Classification

Paper A Syllabic content 5.1

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1. Approaches to Classification
The two major contemporary classificatory systems are ICD 10 (1992) and DSM IV (1994). American
Psychiatric Association produces the DSM system. WHO commissioned ICD 10? DSM-V was released in
2013 but there has been much criticism of this system, and as of yet it has not been adopted widely except
by clinicians communicating with insurers in the USA. It is anticipated that ICD11 will be released in 2017

Both classificatory systems are categorical systems of classification based on clinical descriptions. While
both ICD-10 and DSM-4 are diagnostic and classificatory systems and are meant to provide reliable
diagnosis, they do not provide assessment plans, case formulations or treatment plans.

Various terms are used to describe the characters of classificatory systems. The concept of operationalized
criteria, atheoretical approach, hierarchical organisation and multi-axial classification are important for
MRCPsych Paper A exam and are described below.

Operationalised approach: In DSM-III operationalised diagnosis was first introduced. Operational

criteria include the use of precise clinical description of disorders, together with predefined exclusion
and inclusion criteria and details of the number and duration of symptoms required for diagnosis. It
enables algorithm-based clinical diagnosis using intensity, duration of the symptoms and impairment
tests. This more or less equates to using a checklist for diagnosis, but some rules are necessary while
some are optional for a diagnosis.

Characteristic symptoms are pertinent to the diagnosis, such as the symptom of depression, which is
found in many different disorders. Discriminating symptoms, e.g. thought insertion, are necessary for
diagnosis since they are not found in other diseases. Pathognomonic symptoms, if present, strongly
favour one diagnosis over another. Thus, they are more specific to a condition than other symptoms
(e.g. flashbacks of trauma and PTSD).

Inclusion and exclusion criteria: A hierarchy of symptoms, arranged in order of importance (e.g.
criterion A and B etc.) often accompanies diagnostic descriptions in operationalised systems. These
form the core inclusion and exclusion criteria used in practice to establish a diagnosis. Computerised
scoring systems such as OPCRIT (for ICD10) facilitate the application of such operationalised
diagnoses.

The atheoretical approach means diseases are described according to the observed phenomenology;
classification is NOT based on the understanding of what might be causing the disturbances. So
various aetiological schools such as behaviourism or psychoanalysis, etc. are not employed in
describing a disorder. No theory forms the basis of the classifications; only neutral observations are
taken into account.

The descriptive approach refers to classifying illnesses on the basis of what constitutes the illness
rather than what causes it; Lack of pathogenetic knowledge of most psychiatric disorders makes this
approach more rational. This forms the basis of any atheoretical classification.

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 Categorical vs. dimensional approaches: The current classificatory systems entertain categorical
diagnoses only; i.e. similar to medical diseases. In other words using current systems, we can only say
whether  an  individual’s  clinical  presentation  either  meets  or  does  not  meet  the  diagnostic  criteria  for  a  
particular disorder. A patient either has or does not have pneumonia; she has or does not have
schizophrenia, etc. Contrast this approach with measurement of blood pressure – we use a continuum
from low to high along which measurement is made. (It only becomes categorical when we apply the
label “hypertension”  to  indicate  that  a  patient  has  clinically  troublesome  problem  with  high  BP).  Of all
psychiatric disorders, the need to develop a dimensional system for description is said to be more
urgent for personality disorders.

Categorical approach Dimensional approach

Traditionally doctors are accustomed to thinking in More valid as most emotional and cognitive states exist as a
terms of categories – easy to understand. continuum without clear cut-off point between ill and the
well.
All existing knowledge base about the presentation,
aetiology, epidemiology, course, prognosis, and Severity can be better indicated
treatment is based on these categories.
Need to entertain many comorbid diagnoses may be
Categories are easy to communicate with prevented.
professionals
Research studies using dimensional scales as end points have
Poor validity –vague  categories  such  as  ‘Psychosis  - much greater power to detect differences in groups than
not  specified’  are  needed  to  include  atypical   do studies focusing on changes in dichotomous categories
cases.
Clinical utility is questionable, as dimensions cannot be
directly mapped onto clinical decisions such as starting or
stopping an intervention.
Hierarchical organisation is largely abandoned in DSM and somewhat maintained in ICD-10 in its
organisation of chapters. Hierarchy means that certain disorders take precedence over others while
making a diagnosis. This follows Jasperian ideas (Karl Jaspers: see Introduction to Psychopathology
for more details) – the ladder starts from organic disorders through to substance use issues, psychosis,
affective and neurosis up to personality issues. If a disorder on top of the hierarchy can explain the
observed symptoms, then a diagnosis should not be entertained from down below the hierarchy even
if the constellation of symptoms are suggestive of such a diagnosis. To understand the concepts of
hierarchy consider the following example. Dementia and other brain-based organic disorders can be
associated with any type of psychiatric problem. But a separate diagnostic label is not used for each of
these  psychiatric  syndromes.  For  example,  ‘schizophrenic  symptoms’  occurring  in  the  course  of  
Huntington’s  disease  or  temporal  lobe epilepsy or severe learning disability do not change the
diagnosis  to  ‘schizophrenia’  in  these  cases.  Other examples include the co-occurrence of depression
and agoraphobia, depression and OCD, organic delirium and psychosis – in all these cases the first
diagnosis is primarily entertained instead of the second even if the symptoms could be explained by

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 both diagnoses in a given patient at a point of time. This hierarchy is generally non-reflexive, i.e. each
disorder tends to manifest the symptoms of those lower down but not those of disorders higher up.
Despite such a hierarchical construct, co-morbidity can be still entertained, and this is explicitly
encouraged when using DSM. For example, alcohol used disorder can be comorbid with depressive
disorder.

Multi-axial approach: Recently there has been an upsurge of interest in the multi-axial system for
achieving a complete diagnosis.  This  method  helps  in  a  more  ‘holistic  assessment’ of an individual
patient.

o The multi-axial version of ICD-10 uses three axes. Axis 1 - the mental disorder (also personality
disorder and mental handicap); Axis 2 - the degree of disability; and Axis 3 - current
psychosocial problems.

o The multi-axial system of DSM uses 5 axes. Axis I - Clinical Disorders; Axis II - Personality
Disorders/ Mental Retardation; Axis III - General Medical Conditions; Axis IV - Psychosocial and
Environmental Problems; Axis V - Global Assessment of Functioning. Note that child and
adolescent mental disorders have a different axial system in DSM-IV.

Structure of ICD-10
The first ICD in 1855 was concerned with a nomenclature of causes of death. World Health Organization
(WHO) in 1948 adopted this version after many revisions and called ISCD 6 - Sixth Revision of the
International Statistical Classification of Diseases, Injuries and Causes of Death.

The ICD-10 is a general medical classification system intended for worldwide, multi-specialty use. ICD-10
classification is easy to follow and has been tested extensively all over the world in more than 51 countries
and has been found to be generally applicable.

ICD-10 includes 21 chapters. The Roman numeral V and the letter F denote the position of mental and
behavioural disorders as the fifth chapter in the WHO classification as a whole. The disorders are
identified using an open alpha-numeric system in the form Fxx.xx  from  F00  to  F99.  The  letter  ‘F’  identifies  
the disorder as a mental or behavioural disorder; the first digit refers to the broad diagnostic grouping (e.g.
psychotic, organic etc.); and the second digit refers to the individual diagnosis. The digits, which follow
the decimal point, the code for additional information specific to the disorder such as sub-type, course, or
type of symptoms. For example, F33.10 refers to recurrent depressive disorder, current episode moderate
with the somatic syndrome.

The Schedule for Clinical Assessment in Neuropsychiatry (SCAN), the Composite International
Diagnostic Interview (CIDI), and the International Personality Disorder Examination (IPDE) are
assessment instrument developed based on the ICD-10framework.

Four versions of the ICD-10 classification of mental disorders exist, suitable for different purposes.

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 o ICD-10: CDDG (clinical descriptions and diagnostic guidelines) - for clinical, educational and
service use. It is mainly used by psychiatric practitioners and gives clinical descriptions of each
disorder together with the diagnostic criteria.

o ICD-10: DCR (diagnostic criteria for research) contains more restrictive and clearly defined
clinical features with explicit inclusion, exclusion, and time-course criteria, and is suitable for
identification of homogeneous patient groups for research purposes.

o ICD-10: Primary care version - focuses on those disorders prevalent in primary care settings and
contains broad clinical descriptions, diagnostic flowcharts, and treatment recommendations.

o ICD 10: Clinical Coding Manual - Short glossary containing the coding together with brief
descriptions can be used as a quick reference by practitioners, as well as by administrative and
secretarial staff. It is suitable for clerical workers and for coding purposes.

Structure of DSM-IV
While ICD-10 is a wider general medical classification, DSM-IV describes only mental disorders. DSM-IV
uses a closed, numeric coding system of the form xxx.xx. A single version of DSM-IV is used for both
clinical and research purposes. DSM takes a descriptive approach, and the characteristic signs and
symptoms of each disorder should be present before a diagnosis is made. It is neutral and atheoretical
regarding the causes of mental disorders and does not subscribe to any models of causation of disorders
such as cognitive theories, learning theories, etc. Its diagnoses are non-hierarchical, which implies that
more than one diagnosis can be made. An important step included in the development of DSM-IV was the
attempt to strengthen the reliability of classification. The inter-rater agreement for Axis 1 disorders is very
high (0.73 and 1.00) and has repeatedly demonstrated greater diagnostic stability over time.

Newer Classification Systems

Proposed changes to ICD-11
ICD-11 is under preparation and consultation now and is expected to be released by 2017. Some of the
significant changes expected in ICD-11 are highlighted below. Note that these are subject to updates and
revisions.

Presumed aetiological groupings rather than conventional symptom-based groupings employed

for placing each disorder in a chapter
Neurodevelopmental disorders will be set in chapter 1
Bipolar disorders will be split from depressive disorders and placed in a separate chapter
Dissociative disorders will be split from stress-induced disorders
OCD will be separated from anxiety disorders
Factitious disorders will be placed in a separate chapter
Conditions related to substance use will be split into various chapters
No restriction in number of character places when coding the disorders

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Summary of major changes to DSM-5
DSM-5 is comprised of three sections: Section 1: An introduction and guidance to use; Section 2: An
outline of the diagnostic categories with the newly revised chapters; Section 3: Includes a list of
conditions that require further research before their consideration as formal disorders. It also includes
details on cultural formulations.

A multiaxial system that separately identified personality disorders (Axis II) and medical conditions
(Axis III) has been modified. The new multiaxial system now includes only three axes - psychiatric
disorder, psychosocial and environmental factors associated with them, and the severity of associated
disability. In effect, this means personality disorders are treated with the same importance as other
psychiatric disorders. This has moved DSM’s  multiaxial  system  closer  to  ICD’s  multiaxial  system.

A brief note on other major changes is given below. Further details are provided downstream when discussing the
major disorders.

Psychosis
•Removal of 'bizarre' delusions
•Removal of subtypes of schizophrenia
•3 core symptoms recognised (delusions, hallucinations and disorganised speech)
•Changes in schizoaffective criteria
Mood disorder
•Dysthymia & chronic depression merged
•Bereavement no longer an exclsuion for depression
•Premenstrual dysphoric disorder is a new diagnostic entity

Developmental disorders
•Asperger's syndrome removed and merged with autism as ASD
•ADHD age criteria relaxed
Other changes
•Anorexia diagnosis does not require amennorhea
•Bingeing frequency required to diagnose bulimia relaxed
•OCD and PTSD moved out of Anxiety Disorders to separate chapters
•New labels: Hoarding Disorder, Excoriation Disorder, DMDD - Disruptive Mood
Dysregulation Disorder introduced

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2. Psychoactive substance use disorders

Mental and behavioural disorders due to psychoactive substance use are dealt in Chapters F10 to F19 in
ICD-10. Substances discussed here include alcohol, opioids, cannabinoids, sedatives, cocaine, other
stimulants including caffeine, hallucinogens, tobacco, solvents and the use of multiple substances. Various
clinical syndromes associated with the use of substances are described:

Syndromes Subdivisions

Acute intoxication Transient disturbances in the level of consciousness, cognition, perception, affect
or behaviour, or other psychophysiological functions and responses.
Usually related to dose/levels of consumed substance
Symptoms need not always in accord with the expected physiological properties
of the drug (e.g. a depressant can cause agitation).
Harmful use A pattern of substance use that is causing damage to physical or mental health.
Should not be diagnosed if dependence syndrome or substance-induced
psychosis are diagnosed.
Dependence Cognitive and behavioural phenomena indicating that the use of
The substance takes on a much higher priority for a given individual than other
previously salient behaviours. A checklist of features is described to diagnose
each dependence syndrome (also see Edward & Gross criteria given below).
Withdrawal state The syndrome occurs on absolute or relative withdrawal of a substance after
repeated and prolonged use.

Withdrawal Delirium Withdrawal accompanied by confusional state

Psychotic disorder Psychotic phenomena that occur during or immediately after psychoactive
substance use (esp. auditory hallucinations and paranoid delusions)
Amnesic syndrome Chronic impairment of recent memory with relatively preserved remote memory
and immediate recall.
Late-onset disorders Changes in cognition, emotion and personality or behaviour that persist beyond
the period of expected physiological effects of the consumed substance.

ICD10  has  a  diagnostic  code  for  ‘harmful  use’ where the actual damage is caused to the drinker
physically or mentally, but he has no dependence pattern (yet). In contrast, DSM-IV upholds the
concept  of  ‘abuse’ which refers to maladaptive use
1. Despite problems in social, occupational, physical and psychological domains
2. In hazardous situations
3. At least one month, recurring over a longer period usually.
4. But not dependent on alcohol.
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!
ICD10"alcohol"dependence"requires"at"least"3"out"of"following"list"satisfied"in"last"12"months:"
1. Intense"desire"to"drink"alcohol"
2. Difficulty"in"controlling"the"onset,"termination"and"the"level"of"drinking"
3. Experiencing"withdrawal"symptoms"if"alcohol"is"not"taken"
4. Use"of"alcohol"to"relieve"from"withdrawal"symptoms"
5. Tolerance"as"evidenced"by"the"need"to"escalate"dose"over"time"to"achieve"same"effect"
6. Salience"–"neglecting"alternate"forms"of"leisure"or"pleasure"in"life"
7. The"narrowing"personal"repertoire"of"alcohol"use."
!
DSMDIV"alcohol"dependence"requires"at"least"3"out"of"following"list"lasting"for"at"least"a"month:"
1. Consuming"alcohol"for"longer"period"and"in"larger"amounts"than"intended"
2. Unsuccessful"attempts"to"cut"down"
3. Experiencing"withdrawal"symptoms"if"alcohol"is"not"taken"
4. use"of"alcohol"to"relieve"from"withdrawal"symptoms"
5. Tolerance"as"evidenced"by"the"need"to"escalate"dose"over"time"to"achieve"same"effect"
(at"least"50%"increase"from"start)"
6. Salience"–"most"time"of"life"spent"on"pursuing"alcohol"directly"or"indirectly"
7. Failure"in"role"obligations"and"physical"health"
8. Giving"up"alternate"pleasures"
9. Continued"use"despite"knowing"the"harm"caused"
"
!
Edwards"&"Gross"criteria"(1976)"for"dependencem
"

"
• Narrowed"repertoirem
• Salience"of"alcohol"seeking"behaviour
" • Increased"tolerance
• Repeated"withdrawals
" • Drinking"to"prevent"or"relieve"withdrawals.
• Subjective"awareness"of"compulsion
" • Reinstatement"after"abstinence

"

"

"

"

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3. Organic disorders

Chapter F00 in ICD-10 discusses organic disorders such as dementia. Major categories include
dementia  of  Alzheimer’s  disease,  vascular  dementia,  
dementia in other diseases classified elsewhere DSM-5 AND CATATONIA

(includes  CJD,  Parkinson’s  dementia  etc.),  organic Presence of three catatonic symptoms
amnesic syndromes, delirium, other mental disorders from a total of 12 is required to diagnose
due to brain damage (includes organic hallucinosis, catatonia.
catatonic disorder, mild cognitive disorder etc.) and
In DSM-5, catatonia may be diagnosed
personality change due to brain damage.
as a specifier for depressive, bipolar, and
Depressive pseudodementia: This is not a separate psychotic disorders; as a separate
diagnosis in the context of another
diagnostic entity, but a descriptive term often used in
medical condition; or as another
old age psychiatry. Depression in elderly patients may
specified diagnosis.
present as dementia clinically. This is called depressive
pseudodementia. Here the patient complain of memory impairment, difficulty in sustaining
attention and concentration and reduced intellectual capacity. Major clinical features
differentiating pseudo-dementia from dementia are tabulated below

Pseudodementia Dementia
Onset can often be dated precisely Onset can be dated only within broad limits
Symptoms usually of short duration before seeking help Symptoms usually of long duration before medical help is
sought
Rapid progression of symptoms after onset Slow progression of symptoms throughout course

Patients complain actively of the cognitive impairment Patients often complain little of their cognitive difficulties
(may even conceal disability and appear unconcerned)

Nocturnal accentuation of dysfunction uncommon Nocturnal accentuation of dysfunction common

Attention and concentration often well preserved Attention and concentration usually faulty
On  direct  testing  ‘Don'ʹt  know’  answers  are  typical  (the   Near-miss answers are frequent in cognitive tests (the
patient is not trying hard) patient is trying but not efficient)
Memory loss for remote events may be more severe than Memory loss for current events usually more severe than
for recent ones for remote events
(Adapted from Kaplan & Sadock - Synopsis of psychiatry-10th edition)

Dementia  in  Alzheimer’s  disease  (diagnostic  criteria)

Global deterioration in intellectual capacity and disturbance in higher cortical functions

like memory, thinking, orientation, comprehension, calculation, language, learning

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 abilities and judgement, an appreciable decline in intellectual functioning and some
interference with personal activities of daily living.
Insidious onset with slow deterioration
The absence of clinical evidence or findings from individual investigations suggestive of
organic brain disease or other systemic abnormalities.
Absence of sudden onset or physical/neurological signs

Remember 5As

Amnesia-Impaired ability to learn new information and to recall previously learned

information
Aphasia-Problems with language (receptive and expressive)
Agnosia-Failure of recognition, especially people
Apraxia-Inability to carry out purposeful movements, even though, there is no sensory or
motor impairment
Associated disturbance-behavioural changes, delusions, hallucinations

Some patients exhibit mild cognitive impairment before the onset of full-blown dementia. A
significant proportion of those with MCI does not develop dementia: if they convert to dementia,
the most common dementia to develop is Alzheimer’s  dementia.

Vascular dementia

Presence of a dementia syndrome, defined by cognitive decline from a previously higher

level of functioning and manifested by impairment of memory and of two or more
cognitive domains (orientation, attention, language, Visuospatial functions, executive
functions, motor control and praxis) and deficits should be severe enough to interfere with
activities of daily living not due to physical effects of stroke alone. (NINDS AIREN
criteria)
Onset may usually follow a cerebrovascular event and is more acute
The course is usually stepwise, with periods of intervening stability.
Focal neurological signs & symptoms or neurological evidence of cerebrovascular disease
(CVD) judged etiologically related to the disturbance. CVD defined by the presence of
focal signs on neurological examination, such as hemiparesis, lower facial weakness,
Babinski sign, sensory deficit, hemianopia and dysarthria and evidence of relevant CVD
by brain imaging (CT or MRI)
Emotional and personality changes are typically early, followed by cognitive deficits that
are often fluctuating in severity.

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 Symptoms are not occurring during the course of the delirium

Dementia with Lewy Bodies

Spontaneous motor features of Parkinsonism

Fluctuating cognition with notable variation in attention + alertness
Recurrent visual hallucinations, which are typically well formed and detailed.
A progressive cognitive decline that is severe enough to interfere with normal social and
occupational functioning and memory loss may not be an early feature, but it is usually
evident with progression.
Supportive features: Neuroleptic sensitivity and history of falls

Parkinson’s  disease  dementia: If the Parkinsonian symptoms have existed for more than 12
months  before  dementia  develops  then  a  diagnosis  of  Parkinson’s  disease  dementia  is given. If
both motor symptoms and cognitive symptoms develop within 12 months, then it is conventional
to give a diagnosis of Lewy body dementia.

Frontotemporal dementia

Insidious onset and gradual progression

Early loss of personal and social awareness
Early emotional blunting, Early loss of insight
Behavioural features: Early signs of disinhibition, decline in personal hygiene &
grooming, mental rigidity, inflexibility, hyperorality, stereotyped and perseverative
behaviour
Speech disorder: Reduced output + signs such as stereotypy, echolalia, and
perseveration
Affective symptoms: Anxiety, depression, and frequent mood changes, emotional
indifference.
Physical signs: Incontinence, primitive reflexes, akinesia, rigidity and tremor.

Notable features in other organic disorders

Most cases of delirium recover in 4 weeks; in chronic lung disease, subacute

bacterial endocarditis and carcinoma delirium may last up to 6 months.
In organic hallucinosis, insight may be present.
Encephalitis and CO poisoning can cause organic catatonia.
Influenza can cause post-infective depression.

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4. Classification of psychosis
Schizophrenia
Schizophrenia usually manifests as a severe psychotic illness with onset in early childhood,
characterised by bizarre (i.e. Schneiderian) delusions, auditory hallucinations, thought disorder,
strange behaviour and progressive deterioration in personal, domestic, social and occupational
functioning, all occurring in clear consciousness.

Common symptoms: The International Pilot Study of Schizophrenia survey determined the
commonest symptoms exhibited by 306 acute schizophrenia patients in 9 countries as follows:
Lack of insight – 97% Auditory hallucinations - 74% Ideas of reference – 70% Suspiciousness – 66%
Flatness of affect – 66% Second person hallucinations – 65% Delusional mood – 64% Delusions of
persecution – 64% Thought alienation – 52% Echo De Pensee, Gedankenlautwerden- 50%

Earlier diagnostic criteria

Before DSM-IV and ICD-10, various criteria were put forward to diagnose schizophrenia. Some
of these are MRCPsych favourites:

St Louis or Feighner criteria (Feighner et al. 1972) or National Institute of Mental Health (NIMH) Research
Washington University Criteria Diagnostic Criteria (RDC) predating DSM-III
For a diagnosis of schizophrenia, A through C are Includes a polythetic symptom criterion, a duration
required: criterion and an exclusion criterion.
A. Both of the following are necessary:
o A chronic illness with at least six months of symptoms The symptom criterion lists eight symptoms or groups of
prior to the index evaluation without a return to the symptoms. The first seven symptom groups are Schneiderian
premorbid level of psychosocial adjustment. first-rank symptoms and other delusions or hallucinations, the
o The absence of a period of depressive or manic last one gives diagnostic value to formal thought disorder if
symptoms sufficient to qualify for affective disorder accompanied by either blunted or inappropriate affect,
or probable affective disorder. delusions or hallucinations of any type or grossly disorganized
B. The patient must have at least one of the following: behaviour.
o Delusions or hallucinations without significant
perplexity or disorientation associated with them. The duration criterion requires that signs of the illness have
o Verbal production that makes communication difficult lasted at least 2 weeks from the onset of a noticeable change in
because of a lack of logical or understandable the  subject’s  usual  condition.
organization. (In the presence of muteness the
diagnostic decision must be deferred.) The exclusion criterion describes the differential diagnosis
C. At least three of the following manifestations must be with affective disorders: at no time during the active period of
present for a diagnosis of "definite" schizophrenia, and illness being considered did the subject meet the full criteria for
either probable or definite manic or depressive syndrome to
two for a diagnosis of "probable" schizophrenia.
such a degree that it was a prominent part of the illness.
o Single
o Poor premorbid social adjustment or work history
o Family history of schizophrenia
o Absence of alcoholism or drug abuse within one year

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 of onset of psychosis
o Onset of illness prior to age 40

ICD-10 schizophrenia
ICD 10 description of schizophrenia is largely based on Schneider’s  first-rank symptoms. Kurt
Schneider described a number of symptoms which he believed were of first-rank importance in
differentiating schizophrenia from related illnesses. According to the International Pilot Study of
Schizophrenia, 58% of patients with acute schizophrenia exhibited at least one first rank
symptom. However, at least 20% of schizophrenic never exhibit a first rank symptom while
almost 10% of non-schizophrenic patients exhibit them.

Duration criteria in ICD: ICD10 rejects the assumption that schizophrenia is an illness of
necessarily long duration. Accordingly, acute psychotic episodes are diagnosed for up to one
month; if schizophrenic features are continuous, the diagnosis is reclassified as schizophrenia
after a month. If not, a diagnosis of the acute psychotic episode is valid for up to 3 months, after
which other diagnoses such as a persistent delusional disorder may be entertained. Prodromal
symptoms of schizophrenia are not included in the 1-month criteria for schizophrenia.

Subtypes of schizophrenia

Subtype Most prominent symptoms Less prominent (may or may not be

present)
Paranoid (commonest, with Delusions or auditory hallucinations Disorganized speech or behaviour
onset usually at a later age Flat or inappropriate affect
compared to hebephrenia Catatonic behaviour
and catatonia)
Hebephrenic or disorganised Disorganized speech or behaviour and flat Catatonic behaviour
(poorest prognosis) or inappropriate affect.
Markedly impaired social and
occupational functioning; poor self-care,
poor hygiene, extreme social behaviour
and disorganised behaviour
Catatonic (more common in Motoric immobility (i.e., catalepsy or Oneiroid (dream like) state can
developing nations; usually stupor) occur, and patients may experience
acute onset with episodic Excessive motor activity visual hallucination. Transient
course and complete Extreme negativism or mutism catatonic features can be seen in all
symptom remission) schizophrenia types
Posturing, or stereotypy, mannerisms,
grimacing
Echolalia or echopraxia
(Minimum 2 of the above needed)

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Residual Evidence of full blown acute episode in the Absence of delusions,
past hallucinations, disorganized speech
Currently negative symptoms or or behaviour, catatonia
attenuated forms of 2 or more generic
symptoms (i.e. odd beliefs instead of
delusions, unusual perceptual experience
instead of fully formed hallucinations)

Simple Insidious development of negative symptoms without evidence of positive

symptoms.  Very  rare.  Appears  as  if  one’s  personality  is  gradually  deteriorating  
with increasing emotional bluntness;
Occasional brief psychotic episodes may support the diagnosis.
Undifferentiated Generic symptoms but not falling in other categories
‘Chronic  schizophrenia.' Persistent disability for two years or longer (not a subtype but a descriptive term)

Catatonic schizophrenia is characterised by marked disturbance of motor behaviour and can

present in three clinical forms; (1) excited catatonia (2) stuporous catatonia and (3) catatonia
alternating between excitement and stupor.
Hebephrenic schizophrenia is characterised by marked thought disorder and severe loosening of
associations, emotional disturbances described by inappropriate affect, blunted affect or senseless
giggling, abnormal mannerisms like mirror gazing. ICD 10 recommends a period of 2-3 months of
continuous observation for a confident diagnosis. Hypochondriacal complaints may be seen in
some cases. Philosophical, religious and abstract preoccupations may be seen along with a
preference for solitariness. The onset of hebephrenic schizophrenia is insidious, usually in the early
second decade (15 to 25 years). The course in many patients is relentlessly downhill. Severe
deterioration without remissions often occurs over time. The recovery from the episode classically
never occurs. The term ‘disorganised schizophrenia’ is used to denote hebephrenia in DSM-IV.
Simple schizophrenia is characterised by an early onset (usually in the second decade), very
insidious and progressive course, and presence of characteristic negative symptoms like marked
social withdrawal, loss of initiative and drive or shallow emotional response. People with this
condition drift down the social ladder quickly, living shabbily and wandering aimlessly. Delusions
and hallucinations are usually absent if present they are short lasting and poorly systematised. The
prognosis is usually very poor. Note that for simple schizophrenia – duration criteria is one year,
not one month (ICD-10).
Residual schizophrenia consists of long-term but not necessarily irreversible negative symptoms.
Delusions and hallucinations must have been minimally intense or reduced for at least one year
period. The positive symptoms are gradually replaced by negative symptoms. According to the
ICD 10 diagnosis “residual schizophrenia is characterised by the following features in additional to
the general guidelines of schizophrenia which includes prominent negative schizophrenic
symptoms, evidence in the past of at least one clear-cut psychotic episode meeting the diagnostic
criteria for schizophrenia, a period of at least one year during which the intensity and frequency of

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 florid symptoms such as delusions and hallucinations have been minimal or substantially reduced
and absence of organic brain disease or disorder”.
Post schizophrenic depression is classed under F20s. Some schizophrenic symptoms (mostly
negative) must be present though not dominating the picture. The most recent episode of relapse
must not be more than 12 months ago. If no current schizophrenic symptoms at all then depressive
disorder can be diagnosed. If florid schizophrenia symptoms with minor affective disturbances
noted, then relapse must be suspected.

Contrasting DSM-IV and ICD-10

ICD 10 DSM IV
Characteristic At least one of: At least one of:
symptoms 1. Thought echo, thought 1. Bizarre delusions
insertion/withdrawal/broadcast 2. Third person auditory hallucinations
2. Passivity, delusional perception 3. Running commentary
3. Third person auditory hallucination, running
commentary OR two or more of:
4. Persistent bizarre delusions 1. Delusions
2. Hallucinations
OR two or more of: 3. Disorganized speech
1. Persistent hallucinations 4. Grossly disorganized behaviour
2. Thought disorder 5. Negative symptoms
3. Catatonic behaviour
4. Negative symptoms
5. Significant  behaviour  change
Duration More than 1 month 1 month of characteristic symptoms
With 6 months of social/occupational dysfunction
Subtypes Paranoid Paranoid
Catatonic Catatonic
Hebephrenic Disorganized
Residual Residual
Undifferentiated Undifferentiated
Simple
Postschizophrenic depression
Chapters • F20 Schizophrenia • 295.x Schizophrenia
• F21 Schizotypal disorder • 295.4 Schizophreniform disorder
• F22 Persistent delusional disorder • 295.7 Schizoaffective disorder
• F23 Acute and transient psychotic • 297.1 Delusional disorder
disorders • 297.3 Shared psychotic disorder
• F24 Induced delusional disorders • 298.8 Brief psychotic disorder
• F25 Schizoaffective disorder • 298.9 Psychotic disorder NOS
• F28 Other non-organic psychotic disorders
• F29  Unspecified  non-organic psychosis

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Other ‘schizophrenias’ in ICD-10
In acute and transient psychotic disorders (ICD-10), onset within two weeks is described as acute while
the onset within 48 hours is called abrupt. Complete recovery
within 2 to 3 months is the rule. It can be of polymorphic form or DSM-5 AND SCHIZOPHRENIA
schizophrenia-like in it is presentation. In acute polymorphic
Presence of bizarre delusions or
psychosis, several hallucination and delusions changing in both
hallucinations is no longer sufficient as a
type and intensity from day to day or even same day is noted.
sole criterion A for diagnosing
Schizotypal disorder is diagnosed in patients with eccentric schizophrenia.

manners, social withdrawal, magical thinking, suspiciousness, 2  of  5  ‘criterion-A’  symptoms  required  for  a  
and obsessive ruminations but without resistance. The diagnosis with at-least one being a core
ruminations may have dysmorphophobic contents too. At least a positive symptom (delusions, hallucinations
2-year history with schizophrenia being never diagnosed in the or disorganized speech)
past is necessary for diagnosing schizotypal disorder. Schizotypal
Schizophrenia subtypes (paranoid,
disorder includes older descriptions such as borderline
disorganized, catatonic, undifferentiated,
schizophrenia, pseudo neurotic schizophrenia, etc. Is classified and residual types) have been removed.
along with schizophrenia and related disorders in ICD-10 but
along with Cluster A personality disorders in DSM-4. Schizotypy A dimensional method of rating severity for

is more common in the other first-degree relatives of the core symptoms of schizophrenia is
included. This proposes 8 dimensions
schizophrenic subjects than in the general population and the
(delusions, hallucinations, depression,
relatives of schizotypal subjects have an increased risk of
mania, abnormal cognition, abnormal
schizophrenia.
psychomotor behavior, disorganized speech
and negative symptoms)
Persistent delusional disorders are characterised by a persistent,
often life-long, typically  ‘non-bizarre’ delusion or a set of related
delusions arising insidiously in mid-life or later. Transient
auditory hallucinations may occur, but clear and persistent auditory hallucinations (voices), schizophrenic
symptoms such as delusions of control and marked blunting of affect, and definite evidence of brain
disease are incompatible with
Schizophrenia Delusional Disorder
this diagnosis. However, the
Bizarre delusions are common Non-bizarre delusions (cannot be presence of occasional or
bizarre by ICD-10 definition)
transitory auditory
Daily functioning is significantly Daily functioning is not
impaired significantly impaired hallucinations, particularly in
Apart from delusions may have one These symptoms are almost elderly patients, does not rule
or more of the following: always absent (tactile or olfactory out this diagnosis. The
Hallucinations hallucinations if at all present, are
delusions need not be strictly
Disorganized speech entangled in the content of a
delusional complex) monothematic though this is
Disorganized behaviour
mostly the case. Affect, thought
Negative symptoms
and behaviour are globally
normal, but  patients’  attitudes  

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and actions in response to these delusions are appropriate and DSM-5 AND DELUSIONAL
may lead to dangerousness in some cases. Symptoms should DISORDERS
have been present for at least 1 month (DSM-IV). ICD-10
There is no requirement for delusions to be
specifies at least 3 months for delusional disorder. According to
non-bizarre anymore
DSM-IV delusional disorder – ‘Apart from the impact of the
delusion(s) or its ramifications, functioning is not markedly Delusional symptoms must not be better
impaired, and behaviour  is  not  obviously  odd  or  bizarre’.  This   explained by conditions such as obsessive-
compulsive or body dysmorphic disorder
criterion is not explicit in ICD-10.
with absent insight/delusional beliefs.

Shared delusional disorder is no longer a

separate diagnosis.

DSM-IV subtypes of delusional disorders

Type Description
Erotomania (de An erotic conviction that a person with higher status is secretly in love with the patient
Clerambault Seen most often in women though forensic samples are mostly males; may be associated with
syndrome) stalking or assaultive behaviour
Grandiosity Patients believe they fill some special role, have some special relationship, or possess some
special abilities. They may be involved with social or religious organisations
Jealousy (Othello Characterised by a delusion of infidelity. Patients possess the fixed belief that their spouse or
syndrome) partner has been unfaithful. Often patients try to collect evidence and/or attempt to restrict
their partner's activities. Contributes to both wife battering and homicide.
Persecutory Most common form of the delusional disorder. Patients are often convinced that others are
attempting to hurt or harm them. This leads to them trying to obtain legal recourse, and
sometimes turning violent.
Somatic Varying presentations including patients who have repeated medical consultations requesting
several treatment to those that show delusional concerns about a bodily infestation, deformity
(delusional dysmorphophobia) or odour.
Mixed and Please refer to delusional misidentification syndromes in Descriptive Psychopathology notes
unspecified types

Induced delusional disorders are accepted as a distinct diagnostic category and coded as F24 in ICD-10.
This is a rare delusional disorder characterised by sharing of delusions between usually 2 or occasionally
more persons who often have tightly knit emotional bonds. Only one person has genuine delusions due to
underlying psychiatric disorder, most often schizophrenia or delusional disorder. On separation, the
dependent individual may give up his or her delusions and the patient with the genuine delusions should
be treated appropriately. In induced delusional disorders, induced hallucinations can be present, and this
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does not negate diagnosis. It is also called symbiotic psychosis or DSM-5 AND SCHIZOAFFECTIVE
folie a deux. It is more common in couples and often involves DISORDER
nonbizarre delusions.
A major mood episode (not merely mood
Schizoaffective disorder is placed with F20 (psychoses) not F30 symptoms) must be present for a majority

(affective disorders). In schizoaffective illness, both schizophrenic (not  merely  ‘substantial  duration’) of the
disorder’s  total  duration  after  Criterion  A  
and mood symptoms are seen simultaneously in approximately
has been met.
equal proportion. The presence of mood-incongruent delusions is
suggestive but not in itself sufficient to diagnose schizoaffective Diagnosis takes a more longitudinal
disorder; at least one typical schizophrenic symptom must be perspective compared to DSM-IV
present. (Note - Affect neutral delusions are also included as
incongruent delusions). The aetiology is assumed to be intermediate to that of schizophrenia and affective
disorder. There are 2 subtypes: schizoaffective manic or depressive subtypes. Schizodepressive episodes
are associated with a family history of schizophrenia and are usually less florid. The response to treatment
is variable and may develop chronic negative symptoms. The depressive symptoms are more likely to
signal a chronic course compared to manic presentations. In manic variant symptoms are florid but
recovery is within weeks. Schizomanic episodes are associated with a family history of affective disorders.
These patients respond well to mood stabilisers and recover rapidly.

Various atypical psychotic disorders

These disorders are recognized but not categorised separately in ICD-10.

Bouffée délirante: The classical description of bouffée délirante was given by Legrain.

Psychosis  of  sudden  onset,  ‘like  a  bolt  from  the  blue’;

Polymorphous delusions and hallucinations of any kind;
Clouded consciousnesses associated with emotional instability;
Absence of physical signs, i.e. the disorder is not caused by any organic mental disorder;
Rapid return to the premorbid level of functioning; and
Relapses may occur, but individual episodes are separated by symptom-free intervals.
The episodes develop in a predisposed individual and are caused by psychosocial factors (which also
determine the content and form of the disorder), have a greater tendency to recover and seem never to
end in deterioration.

Process schizophrenia: The concept of process schizophrenia was first described by Langfeldt (1939).
Langfeldt differentiated between two groups of psychoses usually diagnosed as schizophrenia: a group
with  poor  prognosis,  labelled  ‘genuine’  or  ‘process’  schizophrenia,  and  a  group  with  good  prognosis,  
labelled    ‘schizophreniform’  psychosis. (But later studies  that  reclassified  Langfeldt’s  100  cases  concluded  
that  most  of  the  ‘schizophreniform  psychoses’  turned  out  to  be  affective  disorders  with  psychotic  features).

The  term  ‘cycloid  psychoses’ was coined by Leonhard (1957) to describe endogenous psychotic
syndromes characterized by a sudden onset, an admixture of symptoms belonging to the affective
© SPMM Course 18
disorders and of symptoms belonging to schizophrenia and phasic course. Leonhard subdivided the
cycloid psychoses into three forms: motility psychoses, confusional psychoses and anxiety–blissfulness
psychoses. Cycloid psychoses predominate in severe postpartum psychiatric disorders and are more
common among women.

Perris described the diagnosis as follows; psychotic episodes of sudden onset, mostly unrelated to stress,
with good immediate outcome but with a high risk of recurrence, characterized by mood swings (from
depression to elation) and at least two of the following: various degrees of perplexity or confusion;
delusions  (of  reference,  influence  or  persecution)  and/or  hallucinations  not  congruent  with  mood; motility
disturbances (hypo or hyperkinesia); occasional episodes of elation and states of overwhelming anxiety
(pananxiety).

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5. Classification of mood disorders
Depressive disorder
DSM-IV Major Depressive Disorder ICD 10 Depressive disorder
Duration: Most of the day, nearly every day for at least Duration of at least two weeks is usually required for
two weeks. diagnosis for depressive episodes of all three grades of
severity.
Five or more of following symptoms; at least one Criterion A: Depressed mood, loss of interest and
symptom is either depressed mood or loss of interest or enjoyment, and reduced energy leading to increased
pleasure: fatigability and diminished activity
(1) Depressed mood
(2) Loss of interest Criterion B: other common symptoms are:
(3) Significant weight loss* or gain or decrease or (1) Reduced concentration and attention
increase in appetite (2) Reduced self-esteem and self-confidence
(4) Insomnia or hypersomnia (3) Ideas of guilt and unworthiness
(5) Psychomotor agitation or retardation (4) Bleak and pessimistic views of the future
(6) Fatigue or loss of energy (5) Ideas or acts of self-harm or suicide
(7) Feelings of worthlessness or excessive or (6) Disturbed sleep
inappropriate guilt (7) Diminished appetite
(8) Diminished ability to think or concentrate or
indecisiveness
(9) Recurrent thoughts of death, recurrent suicidal
ideation without a specific plan, or suicide attempt or a
specific plan

*To qualify as a diagnostic criterion, this must be an unintentional weight loss of at least 5% weight in one month. Note
that reduced self-confidence is not listed in DSM.

The 4-6-8 rule for severity grading in ICD-10: For mild depressive episode at least 2 criterion A
‘core symptoms’ with four symptoms in total is required. For moderate depression, at least 2
criterion A with six symptoms in total is required. To diagnose a severe episode, at least 2
criterion A symptoms with eight symptoms in total is required.

Both DSM and ICD-10 define recurrent major depressive disorder if there is more than one
episode of depression. In ICD-10, this diagnosis can be
given to a patient with depression if there has been at least DSM-5 AND DEPRESSION

one previous major depressive episode separated by the In DSM-IV a diagnosis of depression
current episode by at least two months. cannot be given in the presence of
bereavement for 2 months after the loss.
This exclusion is now removed.
Bipolar affective disorder (BPAD)
A  specifier  “with  anxious  distress”  is
BPAD is characterized by periods of prolonged and
added to rate the severity of bipolar or
profound depression alternate with periods of excessively
depressive disorders. This takes DSM
closer  to  ICD’s  description  of  mixed  
© SPMM Course 20
anxiety depression.
elevated and irritable mood, known as mania. ICD 10 needs at least two mood episodes before a
bipolar diagnosis can be considered, with complete recovery in between the episodes. The
depressive episode must be present at least for 2 weeks; mania for 7 days (fewer if hospitalized);
hypomania for 4 days and mixed episodes for 2 weeks before they can be diagnosed using ICD
10. In DSM, bipolar disorder can be diagnosed even with a single manic episode.

BPAD is divided into two main broad types; Type 1 is characterised by full-blown mania or
mixed mania and depression. Type 2 is characterised by recurrent depression and hypomania
without episodes of either mania or mixed states.

Except in the elderly, the natural course of mood episodes suggests that mania lasts for 4 months
while depression for 6 months. This becomes longer in the elderly who show shorter periods of
inter episodic remissions and more frequent episodes, which are considerably longer than those
seen in working age adults.

ICD-10 bipolar affective disorder

Current episode, hypomanic
Current episode, manic without psychotic symptoms
Current episode, manic with psychotic symptoms
Current episode, mild or moderate depression
Current episode, severe depression without psychotic symptoms
Current episode, severe depression with psychotic symptoms
Current episode, mixed
Currently in remission
Other bipolar affective disorders: Bipolar affective disorder, unspecified

In line with the depressive episode, a manic mood episode is also operationally defined in ICD
and DSM. According to ICD, mania/manic episode is a distinct period of abnormally and
persistently elevated, expansive, or irritable mood, with 3 (or more) characteristic symptoms of
mania. By definition, the disturbance must be sufficiently severe to impair occupational and
social functioning. Psychotic features may be present.

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DSM IV Manic episode ICD 10 Manic episode
Duration: at least 1 week or any duration if hospitalised Duration: Sustained for at least a week (unless it is
severe enough to require hospital admission).
Criterion A: Abnormally and persistently elevated, A mood that is predominantly elevated, expansive or
expansive, or irritable mood. irritable and definitely abnormal for the individual
concerned.
Criterion B: During the same period three (or more) of At least three of the following must be present (four if
the following symptoms have persisted (four if the mood the mood is merely irritable), leading to severe
is only irritable) and have been present to a significant interference with personal functioning in daily living:
degree: (1) Increased activity or physical restlessness;
(1) Inflated self-esteem or grandiosity (2) Increased talkativeness ('pressure of speech');
(2) Decreased need for sleep (3) Flight of ideas or the subjective experience of
(3) More talkative than usual or pressure to talk thoughts racing;
(4) Flight of ideas or subjective racing of thoughts (4) Loss of normal social inhibitions resulting in
(5) Distractibility (i.e., attention too easily drawn to behaviour which is inappropriate to the circumstances;
unimportant or irrelevant external stimuli) (5) Decreased need for sleep;
(6) Increase in goal-directed activity (either socially, at (6) Inflated self-esteem or grandiosity;
work or school or sexually) or psychomotor agitation (7) Distractibility or constant changes in activity or plans;
(7) Excessive involvement in pleasurable activities that (8) Behaviour which is foolhardy or reckless and whose
have a high potential for painful consequences risks the subject does not recognize e.g. spending sprees,
foolish enterprises, reckless driving;
(9) Marked sexual energy or sexual indiscretions.

Psychotic symptoms: In bipolar disorder, mood symptoms are prominent. However in its more severe
form, mania may be associated with psychotic symptoms (usually mood-congruent, but may also be
incongruent). Delusions and hallucinations are often  ‘changeable’  in  their  quality. Grandiose and
persecutory delusions are common in psychotic mania. Auditory hallucinations are usually the second
person in nature and are often consistent  with  the  patient’s  mood (e.g. religious revelations).

Hypomania/hypomanic episode- ICD description of hypomania is a difficult concept. By definition,

hypomania shares symptoms with mania, but these are evident to a lesser degree, not severe enough to
interfere with social or occupational functioning or require admission to hospital, or include psychotic
features. It includes mildly elevated, expansive, or irritable mood, increased energy and activity, increased
self-esteem, talkativeness, over-familiarity, reduced need for sleep and difficulty in focusing on one task
alone.

Mixed states are cases where manic and depressive symptoms occur simultaneously. The occurrence of
both manic/hypomanic and depressive symptoms in a single episode, present every day for at least 1
week (DSM-IV) or 2 weeks (ICD-10)

DSM IV course specifiers for bipolar disorder:

© SPMM Course 22
 o Rapid cycling: When at least four episodes of bipolar
disorder occur within a period of one year, the condition is DSM-5 AND BIPOLAR DISORDER
described  as  ‘rapid  cycling’.  Some  patients  with BPAD
have more than 4 episodes per year; they are called rapid Criterion A for manic and hypomanic
cyclers. 70-80% of rapid cyclers are women. Some of the episodes now includes an emphasis on
factors associated with the rapid cycling include the use of changes in activity and energy as well as
tricyclic anti-depressant, low thyroxine level, being a mood
female patient, Bipolar type 2 pattern of illness and the
Separate description of mixed episode
presence of neurological disease. Ultra-rapid cycling refers
has  been  removed.  A  new  specifier  “with  
to the situation when fluctuations are over days or even
mixed  features”  has  been  added:  to  
hours.
qualify for this specifier, there is no need
o Postpartum onset refers to the onset of mania, hypomania
to simultaneously fulfill criteria for both
or depression with 4 weeks of childbirth.
mania and major depressive episode.
o Seasonal pattern refers to recurrences over several years
Presence of some features of the opposite
with most episodes typically start (and end) at the same
pole of mood disturbance is sufficient.
time each year.

Secondary Mania: This can occur as a result of misuse of alcohol or illicit drugs and can also occur with
some prescribed drugs such as Levodopa and corticosteroids. The drug induced state wanes with the
clearance of the drug responsible. It can also occur in certain organic conditions such as thyroid disease,
multiple sclerosis and lesions involving cortical and or subcortical areas of the brain.

Bipolar 3 is a variant used to describe minimal depression complicated by antidepressant-induced

hypomania – these patients fall into bipolar spectrum (in ICD: this is coded as unspecified type).

Other affective disorders

Persistent affective disorders: This includes dysthymia and cyclothymia respectively for unipolar and
bipolar patterns of symptoms that fail to meet criteria for severity but which are of long duration and
sufficient to cause impairment.

Dysthymia (ICD-10)/dysthymic disorder (DSM-IV): Chronic, mildly depressed mood and

diminished enjoyment, not severe enough to be considered a depressive illness. Clinical features
include depressed mood (< 2yrs), Reduced/increased appetite, Insomnia/hypersomnia, reduced
energy/fatigue, Low self-esteem, Poor concentration and thoughts of hopelessness. Double
Depression describes episodes of major depression superimposed on Dysthymia; the prognosis
and treatment response may be worse.
Cyclothymia:  There  is  also  a  subclinical  presentation  ”cyclothymia”  in  which  an individual may
experience oscillating high and low moods, without ever having a significant manic or depressive
episode (numerous periods of mild depression and mild elation) and not sufficiently severe or

© SPMM Course 23
 prolonged to fulfill the criteria for bipolar affective disorder or recurrent depressive disorder. An
individual usually perceives these mood swings as being unrelated to life events.

Seasonal Affective Disorder (SAD) is included in ICD-10 in the Annex.

Many patients exhibit a seasonal pattern for their affective illness. The classical presentation is
depression with reversed biological features in winter. These do not constitute SAD. To diagnose
SAD, ICD-10 specifies that 3 or more affective episodes must occur, with onset within the same 90
day period of the year, for 3 or more consecutive years. Remissions should occur within a defined
90-day period of the year. Seasonal episodes substantially outnumber any non-seasonal episodes
that may occur.
The affective episode is most commonly depressive in nature. Atypical features like hypersomnia,
increased appetite, carbohydrate craving and weight gain are common. Most commonly, the onset
is in autumn/winter (when daylight is less), and
DSM-5 AND DYSTHYMIA
resolution is in spring/summer (when daylight is
more). Dysthymia of DSM-IV is now
Phototherapy is a treatment that is popular in reclassified as persistent depressive
SAD. Bright light (10,000 lux) is considered to be disorder, a diagnosis that includes both
superior to dim light. Daily exposure is usually chronic major depressive disorder and for 1
to 2 hours. The benefit may become apparent the previous dysthymic disorder.
within a few days. Maintenance treatment is
given for the next few months until the usual time of remission.

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6. Classification of Neurotic Disorders

Though the term ‘neurotic’  is retained, neurosis is not a major organising principle for classification in
ICD10. DSM abandoned the name completely in 1994.

In ICD-10, ‘Neurotic, Stress related and Somatoform disorders’ have been categorized under seven
headings; phobic anxiety disorders, anxiety disorders (including panic disorder and generalized anxiety),
obsessive compulsive disorders, reaction to severe stress and adjustment disorders, dissociative disorders
(conversion) disorders, somatoform disorders and other neurotic disorders.

In ICD-10, obsessive-compulsive disorder has a separate place in the classification but in DSM-4 it is
classified as one of the anxiety disorders. ICD-10 contains a category of mixed anxiety and depressive
disorder, but DSM-4 does not. In DSM-4, 12 distinct anxiety disorders are listed.

Anxiety disorders include various combinations of psychological and physical symptoms not attributable
to real danger and occurs as a persisting state (generalised anxiety disorder) or occurring either in attacks
(panic disorder)

Generalised anxiety disorder (GAD)

GAD is characterised by prominent tension, excessive worry with generalised free-floating persistent
anxiety and feelings of apprehension about everyday events leading to significant stress and functional
impairment.

To diagnose generalised anxiety disorder, ICD-10 requires duration of at least 6 months and the
symptoms should have been present on most days during 6 months.

The ICD-10 list contains 22 physical symptoms of anxiety whilst there are only 6 in the DSM-4 list.

To diagnose GAD in ICD-10, at least 4 (with at least 1 from  ‘autonomic  arousal) of the following should
be present:

1. Symptoms of autonomic arousal: palpitations/tachycardia; sweating; trembling/shaking; dry

mouth.
2. ‘Physical’  symptoms:  breathing  difficulties;  choking  sensation;  chest  pain/discomfort;  
nausea/abdominal distress.
3. Mental state symptoms: feeling dizzy, unsteady, faint or lightheaded;
derealisation/depersonalisation; fear of losing control, going crazy, passing out, dying.
4. General symptoms: hot flushes/cold chills; numbness or tingling sensations.
5. Symptoms of tension: muscle tension/aches and pains; restlessness/ inability to relax; feeling
keyed up, on edge, or mentally tense; a sensation of a lump in the throat or difficulty
swallowing.

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 6. Other: exaggerated responses to minor surprises/being startled; concentration difficulties/mind
going blank due to worry or anxiety; persistent irritability; difficulty getting to sleep due to
worrying

(List adapted from Oxford Handbook of Psychiatry- edition 2; pg. 357) DSM-5 AND PANIC DISORDER

Panic disorder Panic disorder and agoraphobia are

A panic attack is a discrete episode of intense anxiety. It starts separated in DSM-5. The controversial
abruptly, reaches a peak within few minutes (10 minutes) and issue of the primacy of panic over phobic
then starts to subside within 20-30 minutes. The attacks usually symptoms is now closed with the
tend to occur spontaneously with no obvious precipitants. DSM- introduction of two distinct diagnoses,
IV specifies 13 physical symptoms of which at least 4 must be panic disorder and agoraphobia, each
present to define a panic attack. It also specifies different types of with separate criteria. Comorbid
panic attacks: i.e., situationally bound/cued, situationally diagnosis is still possible.
predisposed, and unexpected/uncued panic.
Only 2 types of panic attacks are
Panic disorder is characterised by recurrent panic attacks, which recognised: unexpected and expected
are not secondary to substance misuse, medical conditions, or panic attacks.
another psychiatric disorder. Frequency of occurrence may vary
from many attacks a day to only a few in a year. It is usually accompanied by persistent worry about
having another attack, phobic avoidance of places or situations and significant behavioural changes
related to the attack.

Symptoms must be present for at least one-month duration to diagnose panic disorder. In ICD-10, panic
disorder is graded as severe if there are more than 4 attacks per week in a 4-week period.

According to ICD-10, for a definite diagnosis of panic disorder, several severe panic attacks should have
occurred within a period of about 1 month:

(1) In circumstances where there is no objective danger;

(2) Without being confined to known or predictable situations; and
(3) With comparative freedom from anxiety symptoms between attacks (although anticipatory anxiety
is common)

According to DSM-IV at least one of the panic attacks, must be followed by at least one of the following
three features for 1 month or more:

(1) Anticipation of further attacks

(2) Worry about implications or
(3) Avoidance behaviour.

Panic disorder can present either alone or with agoraphobia. In DSM–IV agoraphobia is not a distinct
diagnostic entity; it can be only diagnosed along with panic disorder. In ICD-10, agoraphobia is held as a
© SPMM Course 26
primary diagnosis, with panic disorder being a qualifier for subcategorisation, in addition to being a
diagnostic entity on its own but to be used only when no phobic disorder is notable.

Phobic anxiety disorders

According to Marks, the cardinal features of phobia include  the  ‘fear’  which  (1) Is out of proportion to the
situation (2) Cannot be explained or reasoned away (3) Is beyond voluntary control (4) Leads to avoidance.

Phobic anxiety is subjectively and behaviourally indistinguishable from other anxieties. Anticipatory
anxiety is an important feature. Note that the phobic object is almost always external and not ‘currently
dangerous’ for the patient. Internal phobic objects are noted in conditions such as nosophobia and
dysmorphophobia; these conditions are classified under hypochondriasis.

The circumstances provoking anxiety include situations (for example crowded places), objects like
cockroaches and natural phenomena like thunder.

The common types of phobic syndromes are agoraphobia, social phobia and specific (simple) phobias.

Agoraphobia

Agoraphobia is the commonest phobic disorder seen by psychiatrists. Agoraphobia is considered to be the
most incapacitating of all phobias, with a lifetime prevalence of about 6-10% (Weismann and Merikangas
1986).

It is more common in women between the age group of 15-35 and most cases begin in the early or mid-
twenties, though there is a further period of high onset in the mid-thirties. In later life, agoraphobic
symptoms may develop secondary to physical frailty, with the associated fear of exacerbating medical
problems or having an accident.

The first episode typically occurs when a person (often a woman) is waiting for public transport or
shopping in a crowded supermarket. Lack of immediately available escape route or exit is the main
cognitive basis for the anxiety seen in agoraphobia.

The three common themes that provoke anxiety and avoidance are of distance from home, crowding and
confinement. Anticipatory anxiety can start even hours before the patient enters the feared situation.

Avoidance of crowds, public places, or travelling away from home or being alone is a common feature. .
Patients remain symptoms free if avoidance is successful. Symptoms usually fluctuate.

It is not uncommon for agoraphobics to become totally housebound and, therefore, is sometimes called as
housebound housewife syndrome, although not all patients with this condition are necessarily
housewives.

Agoraphobia may be accompanied by panic attacks, whether in response to environmental stimuli or

arising spontaneously.

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As highlighted earlier, ICD-10 considers agoraphobia as the primary disorder with panic attacks being
secondary and indicate severity of agoraphobia. The opposite is true in DSM-IV (but this issue has been
resolved in DSM-V: see the box above).

In cases where depression starts earlier, a diagnosis of depressive disorder should suffice, especially in
late onset agoraphobia.

Social Phobias
DSM-5 AND SPECIFIC PHOBIAS
Social phobia occurs more in small group settings where
In adults, there is no requirement for a
close scrutiny is possible. Two types of social phobia are
subjective recognition that the fear is
noted in ICD-10 - (1) discrete type – anxiety manifested seen
excessive or unreasonable.
in specific occasions e.g. shy bladder (when using a public
toilet) or fear of public speaking or (2) diffuse type – seen
For all ages, duration of 6 months or
with exposure to any generic social task. Fear of vomiting in
more is applied.
public is seen in some with social phobia. Blushing is also
more common in social phobia than other anxiety disorders.

The condition usually begins between the ages of 17 and 30. The first episode occurs in a public place,
usually without any apparent reason.

DSM describes social phobia as a marked and persistent fear of one or more social or performance
situations where one gets exposed to unfamiliar people or to possible scrutiny by others. DSM also
specifies the fear of humiliating or embarrassing oneself as an important feature, which helps to
differentiate it from the anxiety seen in social situations when someone is paranoid. In addition, DSM
stipulates that the sufferer must also recognize that the fear is excessive or unreasonable.

DSM-IV specifies that in children, difficult social situations should involve interactions with peer, but an
appreciation of the unreasonable or excessive nature of the fear is not required. A duration criteria of 6
months is also specified only for children, not adults.

Specific phobias

The age of onset of most specific phobias is in childhood; phobia of animals at average age of 7, blood
phobia at 9, dental phobia at 12 (Ost, 1987) and claustrophobia -20yrs. It is more common among women.

DSM-IV distinguishes 5 subtypes of phobias: animals, aspects of the natural environment,

blood/injection/injury, situational, and other provoking agents.

Specific phobia does not usually fluctuate and remain constant. Disease phobia related to situations where
disease can be acquired and so avoided is still a specific phobia (nosophobia) and not hypochondriasis.

Blood injury injection phobia is different from other phobias in that the response to exposure is not
tachycardia and sympathetically driven heart rate, etc. Instead, a fainting response occurs where the
© SPMM Course 28
patient may drop fainting with low BP and bradycardia. There is a high prevalence of the condition
among first-degree relatives of affected people (Marks 1988)

About 5% of adults have a fear of the dental procedures. It can

DSM-5 AND OCD
become so severe that all dental treatment is avoided, and
dangerous caries develops (Gale and Ayer 1969). A new exclusive chapter has been
created to describe obsessive-compulsive
DSM-IV specifies that in adults, but not children, an appreciation
and related disorders (not clubbed with
of the unreasonable or excessive nature of the fear to diagnose
anxiety disorders anymore).
specific phobias. The duration criteria of 6 months is specified
only for children, not adults; as many irrational fears in children 2 new diagnoses are included in this
may be transient and developmental (this is changed in DSM-V, chapter.
see the box above).
1. Hoarding Disorder with core
Obsessive-compulsive disorder symptom being the inability (or
OCD is characterised by obsessional thinking, compulsive persistent difficulty) to discard or give
behaviour and often associated with marked anxiety and up possessions, regardless of their actual
depression. value.
Diagnosis according to ICD10 obsessions (thoughts, images, or
2. Excoriation Disorder
ideas) and compulsions share the following features, all of
(dermatillomania) with core symptom of
which must be present:
compulsively  picking  one’s  own  skin  for  
(1) Acknowledged as originating in the mind of the
no apparent reason.
patient
(2) Repetitive and unpleasant; at least one recognised as
excessive or unreasonable
(3) At least one must be unsuccessfully resisted (although resistance may be minimal in some
cases)
(4) Carrying out the obsessive thought or compulsive act is not intrinsically pleasurable

Obsessions can occur in several forms such as thoughts, ruminations, doubts, impulses and phobias.
Obsessional slowness can occur as a result of Obsessional doubts or compulsive rituals. According to
ICD-10, either obsessions or compulsions (or both) present on most days for a period of at least two
successive weeks.
Common symptoms: Checking (63%), washing (50%), fear of contamination (45%), doubting (42%),
bodily fears (36%), counting (36%), insistence on symmetry (31%), aggressive thoughts (28%) (Data
from OxfordHandbook of Psychiatry)
Compulsive hoarding may be a neurobiologically distinct form of obsessive-compulsive disorder.
Hoarding is notoriously difficult to treat by either psychological or pharmacological means. Symmetry
obsessions tend to be chronic and treatment resistant.

© SPMM Course 29
 DSM-IV describes OCD as an anxiety disorder along with GAD and PTSD. A change has been made in
DSM-V (see the accompanying box)

DSM-5 AND ADJUSTMENT

Reactions to severe stress DISORDER

Acute stress reaction Reconceptualized as a heterogeneous

Acute stress reaction (ICD) usually starts in an hour; resolution array of stress-response syndromes that
begins within 8 hours (if the stress is hit and run) or 48 hours if it is occur after exposure to a distressing
prolonged. The presence of physical exhaustion, organic factors or (traumatic or nontraumatic) event.
disease states increases the risk. The stressor is usually one that
No longer a residual category for other
poses a serious threat to security, integrity and social position. The
anxiety disorders
patient may initially be dazed with narrowed attention;
disorientation is not uncommon as a result. Sometimes agitation
and overactivity are seen. Partial or complete amnesia for the acute stress reaction is not unheard of.
Dissociative symptoms seem to predominate in some.

Having a history of previous psychiatric disorder does NOT negate a diagnosis of acute stress reaction.

Acute stress disorder is a DSM concept similar to acute stress reaction. It is defined as starting while
experiencing or after experiencing the distressing event, and lasting at least two days to at most four
weeks. The emphasis is on dissociation, with onset specified to be within four weeks with symptoms
lasting up to 4 weeks.

In DSM-4, the diagnosis of acute stress disorder requires marked symptoms of anxiety and 3 from a list of
5 dissociative symptoms- depersonalization, derealisation, a sense of numbing or detachment, reduced
awareness of the surrounding and dissociative amnesia. It also specifies that the response should involve
intense fear, helplessness or horror.

Debriefing is used widely for treatment but with little evidence DSM-5 AND ACUTE STRESS

that it is effective; in some cases it may even be counterproductive. DISORDER

The stressor criterion requires being

Adjustment disorder
Adjustment disorder is a diagnosis in both ICD-10 and DSM-IV. explicit as to whether qualifying
In DSM-IV, it is seen as a residual category for individuals with traumatic events were experienced
clinically significant distress without meeting criteria for a more directly, witnessed, or experienced
discrete disorder such as depression or PTSD. indirectly.

It is a condition that refers to the psychological reactions arising The need for subjective response with
in relation to adapting to new circumstances and occurs in intense fear, helplessness, or horror is
someone who has been exposed to a psychosocial stressor like removed now.

© SPMM Course 30
divorce, separation etc., which is not catastrophic in nature.

The usual presentations include anxiety, depression, poor concentration, irritability, anger, etc. with
physical symptoms caused by autonomic arousals such as tremor and palpitations.

Individual vulnerability plays a greater role in adjustment disorder than any other neurotic disorder. In
adjustment disorder, patients may feel vulnerable to become violent though they rarely are violent.
Conduct problems may be a presentation of adjustment disorder in adolescence; regressive phenomenon
may be seen in children.

The onset is more gradual than that of acute stress reaction, and the course is more prolonged. Social
functioning is usually impaired.

Onset must be within one month in ICD-10 and three months according to DSM-IV. Duration of
adjustment disorder cannot exceed six months except in the subtype of prolonged depressive reaction,
which can last up to 2 years. Brief depressive reaction subtype can last only up to a month.

Also, the DSM-IV  Criterion  A2  regarding  the  subjective  reaction  to  the  traumatic  event  (e.g.,  “the  person’s  
response involved intense fear, helplessness, or horror”)  has  been  eliminated.

Bereavement and grief reaction

Patients who experienced bereavement within last three months cannot be diagnosed to have an
adjustment disorder. Normal bereavement is not coded in ICD 10 Chapter V, but in Chapter XXI.

Normal grief: The classical symptoms experienced after bereavement which would include disbelief,
shock, numbness, and feelings of unreality; anger; feelings of guilt; sadness and tearfulness; pining or
searching, preoccupation with the deceased; disturbed sleep and appetite and, occasionally, weight loss;
seeing or hearing the voice of the deceased (hallucinations of widowhood)

Usually these symptoms gradually reduce in intensity, with the acceptance of the loss and readjustment
(see the table below for the normal phases).

A typical grief reaction lasts up to 12 months with an average duration of 6 months.

© SPMM Course 31
 Phase I includes numbness, disbelief and acute dysphoria
Shock and protest
Phase II includes yearning, searching and anger
Preoccupation

Phase III includes despair and acceptance of loss

Disorganisation

Phase IV gradual return to normality

Resolution

Irrespective of age, a third of those who lose a spouse meet criteria for major depression in the first month
after the death, and half of these remain clinically depressed one year later. However, in normal grief
reactions substantial improvement is expected within two months to 6 months, and those who continue to
meet criteria for major depression after this period should receive antidepressant or psychotherapy.

Abnormal grief: It is also called as morbid or pathological or complicated grief. It is a grief reaction that is
very intense, prolonged, delayed (or absent), or where symptoms outside the normal range are seen: e.g.
preoccupation with feelings of worthlessness, thoughts of self-harm or suicide, excessive guilt, marked
slowing of thoughts and movements, a prolonged period of lack of ability to function, hallucinatory
experiences (other than the image or voice of the deceased)

In ICD-10, abnormal grief reactions are coded as adjustment disorders. Abnormal grief includes
Inhibited grief: Absence of expected grief symptoms at any stage
Delayed grief: Avoidance of painful symptoms within two weeks of loss
Chronic grief: Continued significant grief-related symptoms six months after loss
( Working with grieving adults | BJPsych Advances, http://apt.rcpsych.org/content/10/3/164_br (accessed March 31,
2015).
Likely causes of abnormal grief include sudden and unexpected death of the deceased; insecure survivor;
dependent or ambivalent relationship with the deceased; presence of dependent children and so cannot
show grief easily; presence of previous psychiatric disorder in the survivor.

© SPMM Course 32
Posttraumatic stress disorder
The term PTSD denotes an intense prolonged and sometimes delayed reaction to an intensely stressful
event. The essential features are hyperarousal, re-experiencing of aspects of the stressful event and
avoidance of reminders.
The principal symptoms of PTSD include
Hyperarousal DSM-5 AND PTSD
o Persistent anxiety
o Irritability The stressor criterion requires being
o Insomnia explicit as to whether qualifying
o Poor concentration traumatic events were experienced
Hypervigilance due to re-experiencing and enhanced directly, witnessed, or experienced
startle response
indirectly.
o Intrusions
o Recurrent distressing dreams
The need for subjective response with
o Intensive intrusive imagery (flashbacks, vivid
memories) intense fear, helplessness, or horror is
o Difficulty in recalling stressful events at will removed now.
Avoidance
o Avoidance of reminders of the events- Efforts to avoid Along with the symptom clusters of re-
thoughts, feelings, or conversations associated with experiencing and hyperarousal, the
the trauma. Efforts to avoid activities, places, or
avoidance/numbing cluster is split into
people that arouse recollections of the trauma
o Detachment-Feeling of detachment or estrangement two. So now there are 4 clusters.
from others
o Emotional numbness Irritable, reckless or self-destructive
o Diminished interest in activities (anhedonia) behaviour is added to the description of
Both ICD-10 and DSM-IV require 2 or more persistent arousal symptoms.
symptoms of increased psychological sensitivity and arousal
(not present before exposure to the stressor) to diagnose PTSD. Diagnostic threshold is lowered for
children. In addition, a separate PTSD
PTSD should start within six months of the trauma. In a small
criterion has been added for children less
number of patients the onset is delayed i.e. after six months –
than age 6.
termed  as  ‘probable PTSD’; in others the course may be chronic
> 6 months. Enduring personality changes are also reported
following such trauma. In DSM-IV, a 3-months threshold is used to define chronic PTSD.
Type 1 trauma refers to a single sudden catastrophic event e.g. accidents or rape. Type 2 trauma refers to
a chronic repetitive insult against which the individual has no defence e.g. sexual abuse.

Dissociative (conversion) disorders

Under this chapter in ICD-10 dissociative amnesia, fugue, trance/possession and disorders of
movement/sensation (motor disorders, convulsions, anaesthesia/sensory loss) are included.

© SPMM Course 33
 Dissociation is referred to as loss of integration among
DSM-5 AND DISSOCIATIVE
memories, identity, sensations and movements. It occurs closely
DISORDERS
in time with trauma. Theoretical concepts such as unconscious
Depersonalisation disorder is now motivation or secondary gain are not used to describe this
renamed as condition in ICD 10.
depersonalization/derealization disorder.
Dissociation starts suddenly and terminated abruptly within
Fugue is now a specifier for amnesia; not weeks to months, Treatment is difficult in patients in whom it
a separate diagnosis remains chronic (i.e. nearly a year).

Dissociative identity disorder now The concept of dissociative amnesia is centered on the

includes pathological possession loss of memory for important recent events, which is partial,

syndromes seen in some cultures. Both patchy and selective. The characters of dissociative amnesia are

observed and reported changes in o Episodic memory loss: retrograde only – no

personality are considered in the anterograde deficits.

diagnosis o Amnesia is for events that happened in a discrete

period of minutes to years
o The problem is not vague or inefficient retrieval but the strikingly complete unavailability
of memories which were generally formed and were previously accessible. These events
are traumatic or stressful.
Amnesia can occur as a part of a dissociative fugue as well. In fugue purposeful journey away
from home or   one’s   usual   base occurs. Self-care is usually maintained despite   ‘getting   lost’.
Sometimes new identity can be assumed, and amnesia is present for past identity during the fugue;
on recovery amnesia may be present for the fugue episode itself. As there is no cognitive
impairment, the behaviour is usually normal. Perplexity and la belle indifference are frequent.
Trance is a dissociative state where narrowed consciousness and limited but repeated movements
are seen. Diagnosis of trance is made only if it is involuntary and not a culturally appropriate,
intended practice. In addition, the trance states must be intrusive on activities of life and occur
outside culturally sanctioned situations. Note that Temporal Lobe Epilepsy and head injury can
also cause ‘organic’  trance.

Conversion / hysterical disorder is called a dissociative disorder of motor movement and

sensations. The degree of disability in this disorder is very variable. La belle indifference is not
universal, but common in conversion disorder. Close friends or relatives might have had the actual
organic illness whose symptoms are present in a subject with conversion disorder. A milder and
transient variety is seen in adolescent girls.
Both Ganser syndrome and twilight states are included in dissociative states according to ICD-10.
In DSM-IV, under dissociative disorders, only amnesia, fugue, dissociative identity disorder
(multiple personalities), and depersonalization disorder are included. Conversion disorders and

© SPMM Course 34
 pain disorder are classified along with the somatoform disorder. In other words, all motor/sensory
presentations are classed as conversion while memory/personality presentations are retained in
dissociation category.
Somnambulism is listed as a nonspecific dissociation in DSM-IV.
Dissociative trance Possession trance
Altered narrow consciousness Altered narrow consciousness
Lost personal identity Lost personal identity
No replacement with another identity Replaced with another identity
Stereotypic movements / utterances Stereotypic movements / utterances
Amnesia seen Amnesia seen

Seizures vs. pseudoseizures: At times it may be difficult to distinguish epilepsy from

pseudoseizures (conversion). The following features are taken to be more suggestive of
pseudoseizures:

Seizures vs. pseudoseizures

Avoidance behaviour during seizures (to prevent serious injuries)
Change in symptomatology of  seizure  patterns  e.g.  progression  or  ‘march’  that  is  inconsistent  with  cortical
organization, asynchronous limb movements.
Closing eyes during seizures, especially resisting opening of eyelids when attempted
Dystonic posturing (this can happen in frontal seizures though rare)
Emotional or situational trigger for the seizures and seizures provoked by suggestion
Gradual onset and cessation of seizures (true seizures have a rapid crescendo and decrescendo)
Tongue biting is rare and if present, usually the tip (not the side) of the tongue is bitten.
Pelvic movements (especially forward thrusting) and side-to-side head movements
Prolonged seizures (duration of 2 to 3 minutes); High seizure frequency but no history of injury from
seizures.
Lack of concern or an excessive or exaggerated emotional response
Multiple unexplained physical symptoms
Non response to antiepileptic drugs or a paradoxical increase in seizures with drug treatment
Seizures that occur only in the presence of others or only when the patient is alone

Adapted from Elger RM. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav 2003;4:207.

Somatoform disorders
Under this chapter in ICD-10, somatization disorder, hypochondriacal disorder, somatoform pain
syndromes, autonomic dysfunction and undifferentiated somatoform disorder are included. All
somatoform disorders are characterized by the lack of a psychological appraisal on the patient’s  part  along  
with a resistance to consider presenting problems  as  one  of  ‘mental’  origin.

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Somatization disorder is characterized by (a) at least 2 years of multiple and variable physical symptoms
for which no adequate physical explanation has been found; (b) persistent refusal to accept the advice and
reassurance of several doctors regarding the absence of a physical illness; (c) notable impairment of social
and family functioning due to the symptoms and the illness behaviour. The term Briquet Syndrome or St.
Louis Hysteria is sometimes applied to denote somatisation disorder.

Family history of alcohol use and antisocial personality are

common in women with somatisation disorder. DSM-5 AND SOMATIC-
SYMPTOMS
Hypochondriacal disorder is characterized by 2 conditions (1)
persistent belief of harboring atleast one serious physical illness In DSM-5, somatoform disorders are

even though repeated investigations and examinations have referred to as Somatic Symptom

identified none or a persistent preoccupation with a presumed Disorders (SSD).

deformity or disfigurement (body dysmorphic type); (2)

Diagnosis of Somatization,
persistent refusal to accept the advice and reassurance of several
Hypochondriasis, Pain Disorder and
doctors regarding the absence of a physical illness. Both
Undifferentiated Somatoform disorders
nosophobia and nondelusional dysmorphophobia are
are now eliminated.
classified as hypochondriasis in ICD-10. A 6 months duration
criteria is specified in ICD-Diagnostic Criteria for Research (not SSD can be diagnosed even if there is a
in the regular diagnostic guidelines). medical disorder that explains the
presenting symptoms. The emphasis is
Note that in DSM-IV, body dysmorphic disorder
shifted from the actual physical
(dysmorphophobia) is considered as a separate diagnostic entity,
symptoms to the maladaptive thoughts
within the chapter on somatoform disorders. It is described as a
and feelings that surround these
‘subjective  description  of  ugliness  and  physical  defect  which  the  
symptoms  (‘positive  features’).
patient  feels  is  noticeable  to  others’.  It  is  an  excessive  concern  
(overvalued idea) about trivial or non-existent physical Individuals with high health anxiety but
abnormalities, which are perceived to be deformities. Beliefs no somatic symptoms will be diagnosed
about deformity that are of delusional intensity are classified to  have  ‘illness  anxiety  disorder’
under delusional disorders. With delusional intensity, the
patient is constantly pre-occupied, convinced and tormented by Factitious disorder is placed under
abnormal belief that some part of his/her body is too large, too somatic symptom and related disorders.
small or misshapen, which to other people, the appearance is
Body Dysmorphic Disorder has been
normal or there is a trivial abnormality. The common
moved from somatoform chapter to OCD
complaints are about the nose, ears, eyes, mouth, buttocks, penis,
& related disorders. A  “with  muscle  
breasts, but any part of the body may be involved. The affected
dysmorphia”  specifier  has  been  added  the
person might think that other people notice and talk about his
description of body dysmorphic disorder.
deformity and, therefore, would get involved in time consuming
behaviours such as re-examining, repeated checking, involve in
elaborated grooming rituals to hide the perceived defect and avoidance behaviour. This condition usually

© SPMM Course 36
begins in adolescence and is chronic with some fluctuations over time. It can occur as part of other
psychiatric disorders such as depression or schizophrenia, or may be associated with social phobia or
personality disorders

Men and women are equally affected by hypochondriasis. In hypochondriasis patient looks for diagnosis,
not symptom relief; he/she names the suspected disorder and may be more or less convinced about
having the disorder.

Somatoform autonomic syndrome refers to recurrent symptoms of autonomic arousal, such as

palpitations, sweating, tremor, flushing, which often occur alongside other subjective symptoms referred
to a specific organ or system despite having no evidence of structural or functional deficit in these systems.
Patients refuse to be reassured regarding the absence of a physical illness despite the reassurances of
different doctors.

In somatoform pain syndrome, the major complaint is of persistent, severe, and distressing pain that is
not explained by a physiological process or a physical disorder.

Globus hystericus, psychogenic pruritus, psychogenic torticollis, teeth grinding (bruxism) and
psychogenic dysmenorrhea are also included as  ‘other  somatoform  disorders’.

Other neurotic disorders

Neurasthenia, depersonalization-derealisation syndrome and other specified neurotic disorders (most of
the culture-bound syndromes such as latah, dhat, koro) are included here. Psychogenic syncope and
writer’s  cramp  are also described in this category.

Neurasthenia is classified in F48 of ICD-10 as a neurotic disorder with either persistent and distressing
complaints of increased fatigue after mental effort or persistent and distressing complaints of bodily
weakness and exhaustion after minimal effort. This must be accompanied by at least two of the following
features: - feelings of muscular aches and pains, dizziness , tension headaches, sleep disturbance,
inability to relax, irritability , dyspepsia. The diagnosis can only be made if other disorders classified in
F40-47 section or depression cannot account for the presenting symptoms. Neurasthenia is the closest
ICD-10 equivalent of Chronic Fatigue Syndrome.

Depersonalization-derealization syndrome is diagnosed when either depersonalization or derealization

symptoms are present in the presence of full insight (i.e. an acceptance of the subjective and spontaneous
nature of the symptoms) and a clear sensorium. Depersonalization refers  to  the  perception  that  one’s
feelings and/or experiences are detached, distant, not his or her own, lost (as if phenomenon).
Derealization refers to the perception that objects, people, and/or surroundings seem unreal, distant,
artificial, colourless or lifeless. Note that DSM classifies this condition as a dissociation disorder.

© SPMM Course 37
 Factitious Disorders and Malingering
DSM-IV considered factitious disorder and malingering in a separate chapter.
In ICD-10, factitious disorders are considered along with personality disorders (F68).
Malingering is not an ICD 10 mental disorder category but is coded in Z76.5. Munchausen by proxy is not
coded in Chapter V of ICD10 but is discussed in T74.8.

Comparing and contrasting various disorders with somatic features

Dissociation Conversion
1. Mental effects of a conflict 1. Physical effects of a conflict
2. E.g. Amnesia, Loss of identity, alter personality 2. Paralysis, blindness, ataxia, anaesthesia,
aphonia, seizures
Somatoform/somatisation Conversion
1. Production of a symptom (positive) 1. Loss of function (negative)
2. Pain, vomiting, etc. 2. Paralysis, blindness, loss of balance, etc.
3. GIT and Musculoskeletal 3. Neurological
4. Polysymptomatic 4. Monosymptomati
Hypochondriasis Somatisation
1. Preoccupied with diagnosis 1. Preoccupied with symptoms
2. Concern: ‘One  dreadful  disease.' 2. Concern: ‘One  excellent cure.'
3. Gastrointestinal features most common 3. Musculo-skeletal symptoms most common

Malingering Factitious
1. Clearly intentional 1. ‘Truly puzzling’  with  ‘no  cause.'
2. Often monetary benefits 2. Only gain is sick role
3. Military, compensation claims, etc. 3. Seen in paramedical professionals
4. Munchaussen is severe form – wide doctor
shopping is seen

© SPMM Course 38
7. Disturbances of behaviour and body physiology

This  includes  various  disturbances  in  ‘behaviour’  and  abnormalities  across  a  mixture  of  ‘physiological  
systems’  such  as  weight,  libido,  pregnancy, etc. It also includes non-dependence producing substance
abuse such as analgesic abuse; antidepressant use; laxative use and steroid abuse.

Eating Disorders
The ICD-10 diagnostic criteria for Anorexia Nervosa describes the presence of low body weight as
being 15% or more below the expected norm and BMI as 17.5 or less. Other features include

Self-induced weight loss, avoidance of fattening foods, vomiting, purging, excessive exercise,
use of appetite suppressants.
Body image distortion, dread of fatness: overvalued idea, imposed low weight threshold.
Endocrine disturbances due to HPA axis dysfunction
(Hypothalamic- pituitary-gonadal axis) manifesting DSM-5 AND EATING DISORDERS
as amenorrhoea, reduced sexual interest, raised GH
levels, increased cortisol, altered Thyroid tests, Anorexia Nervosa: The requirement
abnormal insulin secretion. of amenorrhea as a condition for
Delayed/arrested puberty- if onset pre-pubertal. diagnosis has been removed.

While diagnosing anorexia, Quetelet’s  body mass index is Bulimia Nervosa: The required
applicable only if age is more than 16. minimum average frequency of
binge eating/compensatory
In DSM-IV, amenorrhea is defined as at least three consecutive behaviour is changed from twice to
cycles being absent. DSM-IV also specifies two types: once weekly.
Binge-eating/purging type: regularly engaged in binge-
eating or purging behavior (such as self-induced vomiting or the use of laxatives, diuretics, or enemas).
Restricting type: no binge-eating or purging behavior

In atypical anorexia nervosa, one or more of these essential features may be absent, or all are present
but to a lesser degree. Atypical anorexia nervosa is described as “ a disorder that fulfills some of the
features of anorexia nervosa but in which the overall clinical picture does not justify that diagnosis.
For instance, one of the key symptoms, such as amenorrhoea or marked dread of being fat, may be
absent in the presence of marked weight loss and weight-reducing behaviour. This diagnosis should
not be made in the presence of known physical disorders associated with  weight  loss.” (ICD-10)

Several features are noted in patients with atypical anorexia when compared to those with typical
anorexia.

Older age at onset and presentation

Recurring bouts of depression

© SPMM Course 39
 Numerous somatic complaints
Unmet dependency needs, and
Little evidence of distortion in body image is seen.

Differential Diagnoses for Anorexia Nervosa

Physical Disorders Hyperthyroidism; other endocrine disorders; GI disorders resulting in vomiting, loss of
appetite and/or malabsorption; Malignancy; Chronic infection. Hypothyroidism can also
produce amenorrhea.

Psychiatric Depression, OCD with eating abnormalities, delusional behaviour concerning food,
disorders vomiting secondary to conversion (cyclical vomiting)

Adapted from Focus. Fall 2004, Vol. II, No. 4 (p 528)

The ICD-10 diagnostic criteria for Bulimia Nervosa includes the following:

Persistent preoccupation with eating

Irresistible craving for food
Binges- episodes of overeating
Attempts to counter the fattening effects of food (self-induced vomiting, abuse of purgatives,
periods of starvation, use of drugs e.g. appetite suppressants, thyroxine, diuretics)
Morbid dread of fatness, with imposed -low weight threshold

In atypical cases of bulimia, one or more of these features may be absent. Neglecting insulin treatment is
a weight reduction strategy seen in diabetics with bulimia.
In DSM-IV, two types are specified: Purging and non-purging type.

Obesity is not coded under eating disorders in ICD-10, but in chapter E66, which is not a mental disorder.
Similarly  ‘loss  of  appetite’  is  not  considered  as  anorexia  even  if  it  is  ‘psychogenic’.

EDNOS- Eating disorder not otherwise specified is the most common eating disorder in the outpatient
setting and is widely used by clinicians using DSM-IV.

Binge eating disorder (BED) is also increasingly recognised, but in ICD-10 this falls under atypical
bulimia and in DSM-IV under EDNOS. Binge eating disorder is characterized by recurrent episodes of
binge eating in the absence of extreme weight-control behaviour. This is often seen in a background of a
general tendency to overeat. BED is associated with obesity; 5–10% of those seeking treatment for obesity
have BED. Patients typically present in 40s. More males compared to other eating disorders, but only 25%
of all binge-eating population is male. There is a high degree of spontaneous remission noted and stressed
associated overeating is a common phenomenon. Self-help, behavioural weight loss programmes and
CBT/IPT can help.

© SPMM Course 40
Sleep disorders
ICD-10 chapter V (mental health) recognises only non-organic sleep disorders in which emotional causes
are considered to be a primary factor. These are conditions that include dyssomnias (abnormalities in
amount, quality, or timing of sleep) and parasomnias (abnormal episodic events occurring during sleep).

Various chapters where sleep disorders are described in ICD-10

Hypersomnia, sleep-walking, sleep-terrors, nightmares, ICD-10 Chapter V, F51
nonorganic sleep-wake disorder

Kleine-Levin syndrome, Narcolepsy, Disorders of the Chapter VI of ICD-10

sleep - wake schedule, Sleep apnoea

Episodic movement disorders which include nocturnal Chapter II

myoclonus
Enuresis Chapter V, F98 (Childhood disorders)
Primary nocturnal enuresis (considered to be due to Chapter XVIII
delay in bladder development)

Sleep walking and sleep terrors are mostly childhood disorders and if adult onset or adult persistence is
seen then significant psychological disturbance must be suspected; these are sometimes seen in early
stages of dementia especially REM disorders in Lewy body dementia. In sleep terrors, several minutes of
disorientation is noted on waking, and some perseverative behaviour may also be noted; recall if at all
possible may be limited to fragmentary mental images. In contrast nightmares are well recalled; they may
be associated with benzodiazepine, tricyclic or thioridazine use.

Kleine-Levin syndrome is characterised by periodic episodes of hypersomnolence and hyperphagia.

Associated features include a lack of concentration, mood changes, sometimes hypersexuality and anxiety.
Laboratory tests may show some nonspecific changes in the electroencephalogram. However, clinical
presentation and laboratory tests are normal during asymptomatic intervals. It most often presents in
adolescent males, with complete recovery by the 3rd to 4th decade of life. Possible precipitating factors
include excessive workload, febrile illness, and respiratory infections.

Narcolepsy is characterised by excessive daytime drowsiness accompanied by a sudden onset of REM

sleep (sleep seizure or narco lepsy) and sudden loss of muscle tone, provoked by strong emotions
(cataplexy). Sleep paralysis and hynagogic hallucinations may also occur (between wakefulness and sleep)
but are less common. Sleep paralysis is an episode of inability to move occuring between wakefulness
and sleep. These attacks usually occur during adolescence and persist through life. Hypnagogic
hallucinations are usually auditory in nature but may be visual or tactile, occur in about 25% of patients.
Narcolepsy is virtually always familial, and 99.5 % of patients have the HLA Antigen DR-2 (DR15/DQ6).
There is usually no structural brain lesion present in these patients.

© SPMM Course 41
A more commonly used classification system for sleep disorders is the International Classification of
Sleep Disorders ICSD system. DSM closely resembles ICSD. Classification of sleep disorders as per this
system is shown below:

Dyssomnias
Primary insomnia
Primary hypersomnia
Circadian sleep disorders
Narcolepsy
Breathing related sleep disorders
Sleep state misperception
Parasomnias (subdivided according to the phase of sleep with which they are associated)
Arousal disorders (arising from NREM sleep)
Confusional arousals
Sleepwalking
Sleep terrors
Sleep– wake transition disorders
Sleep starts
Sleep talking
REM sleep parasomnias
REM behavioural disorder
Nightmares
Sleep paralysis
Other parasomnias
Sleep bruxism
Sleep enuresis

Sexual disorders

Sexual dysfunctions are coded in F52 group. These disorders include the lack or loss of sexual desire
(sexual aversion disorder, failure of genital response, orgasmic dysfunction, premature ejaculation,
nonorganic vaginismus, nonorganic dyspareunia and excessive sexual drive).

According to DSM-IV, they can be classified into

Sexual desire disorders (sexual aversion, hypoactive sexual desire)
Sexual arousal disorder (female sexual arousal disorder, male erectile disorder)
Orgasmic disorders (female and male orgasmic disorder, premature ejaculation)
Sexual pain disorder (Dyspareunia, vaginismus)
Others (including those due to general medical or substance use disorders)

© SPMM Course 42
Other physiological disorders
Puerperal disorders: F53 codes mild and severe puerperal mental disorders instead of classifying
postnatal   disorders   as   ‘depression’   vs.   ‘psychosis’.   This   is   because,   it   is   well   recognised   that   separating  
postnatal psychosis from depression is often difficult in practice.

Non dependence abuse: F55 codes for the abuse of a wide variety of medicaments, proprietary drugs, and
folk remedies and psychotropic drugs that do not produce dependence, such as antidepressants; laxatives;
and analgesics

DSM-5 AND SEXUAL DISORDERS

Genito-Pelvic Pain/Penetration Disorder

is a new category that merges
vaginismus and dyspareunia.

The diagnosis of sexual aversion disorder

has been removed.

© SPMM Course 43
8. Disorders of adult personality and behaviour
Personality disorders
According to ICD-10, a diagnosis of personality disorders cannot be made in individuals younger
than age 16 or 17.
Unlike other psychiatric disorders, personal distress is not a criterion for diagnosing personality
disorders but this may be a feature seen during the course of a personality disorder.
At least three traits must be present from the list for diagnosing antisocial and borderline
personality; the rest of the disorders requires at least four from the lists provided by ICD-10
diagnostic guidelines.
There are not many differences between ICD-10 and DSM-IV in the description of personality
disorders. The notable exceptions are listed below.
Passive-Aggressive personality disorder and Depressive personality disorder are placed in an
appendix of DSM-IV for research purposes. Passive aggressive is discussed with other personality
disorders category in ICD10.
DSM-IV ICD-10
Personality disorders are grouped into 3 clusters No clustering of personality disorders
Schizotypal disorder is a personality disorder Not a personality disorder, but described as a variant of
psychosis under the chapter on Schizophrenia
Only single entity of borderline personality disorder Emotionally unstable personality disorder can be of
impulsive or borderline type
Features of Cluster A (odd, eccentric) personality disorders

© SPMM Course 44
 Paranoid personality disorder
•Suspicious of other people and their motives.
•Hold longstanding grudges against people,
•Believe others are not trustworthy,
•Emotionally detached
•Feel other people are deceiving, threatening, or making plans against them.
Schizoid personality disorder
•Have difficulties in expressing emotions, particularly around warmth or tenderness.
•Prefer loneliness
•Aloof or remote,
•Have difficulty in developing or maintaining social relationships
•Remain unaware of social trends
•Unresponsive to praise or criticism
Schizotypal personality disorder
•Appear odd or eccentric;
•May have illusions, magical thinking
•Obsessions without resistance
•May be members of quasi-cultural groups
•Thought disorders and paranoia.
•May believe in ESP, clairvoyance etc.
•May have transient psychotic features

Features of Cluster B (dramatic, erratic) personality disorders

© SPMM Course 45
 Antisocial personality disorder
•Lack of regard for the rights and feelings of other people.
•Lack of remorse for actions that may hurt others.
•Ignore social norms about acceptable behaviour,
•May disregard rules and break the law.
•Make relations easily but break them equally easily
•A small proportion may be psychopathic

Borderline personality disorder

•Poor self-image,
•Unstable personal relationships,
•Impulsive behaviour in areas such as personal safety and substance misuse.
•May self-harm, feel suicidal and act on these feelings,
•Experience instability of mood,
•Have episodes of micro-psychosis.
•Feelings of chronic emptiness
•Fears of abandonment – rejection sensitivity hence form intense but short lasting relations

Histrionic personality disorder

•Extreme or over-dramatic behaviour.
•May form relationships quickly, but be demanding
•Attention-seeking.
•May appear to others as being self-centred with shallow emotions
•Being inappropriately sexually provocative.

Narcissistic personality disorder

•Exaggerated sense of own importance.
•Frequently self-centred
•Intolerant of other people.
•Grandiose plans and ideas
•Cravings for attention and admiration.
•Fear of dependency is the core conflictual theme.
•Narcissistic injuries to pride lead to rage reactions.

© SPMM Course 46
Features of cluster C (anxious, inhibited) personality disorders

Avoidant personality disorder

•Fears being judged negatively by other people
•Feelings of discomfort in group or social settings.
•May come across as being socially withdrawn
•Have low self-esteem.
•May crave affection but fears of rejection overwhelming.

Dependent personality disorder

•Assumes a position of passivity,
•Allowing others to assume responsibility for most areas of their daily life.
•Lack self-confidence,
•Feel unable to function independently of another person,
•Feels own needs are of secondary importance.

Obsessive-Compulsive personality disorder

•Difficulties in expressing warm or tender emotions to others.
•Frequently perfectionists
•Often lack clarity in seeing other perspectives or ways of doing things,
•Rigid attention to detail may prevent them from completing tasks.
•Some may be hoarders, scrupulous with money
•May not be able to delegate tasks; workaholics.

DSM IV ICD 10 equivalent

Cluster A (odd or eccentric disorders)

Paranoid personality disorder Paranoid personality disorder
Schizoid personality disorder Schizoid personality disorder
Schizotypal personality disorder NONE - classified as a type of schizophrenia like disorder in ICD
Cluster B (dramatic, emotional, or erratic disorders)
Antisocial personality disorder Dissocial personality disorder
Borderline personality disorder Emotionally unstable: 1. Impulsive 2. Borderline subtypes
Histrionic personality disorder Histrionic personality disorder
Narcissistic personality disorder NONE; mentioned in other personality disorders category
Cluster C (anxious or fearful disorders)
Avoidant personality disorder Anxious (avoidant) personality disorder
Dependent personality disorder Dependent personality disorder
Obsessive-compulsive personality disorder Anankastic personality disorder

© SPMM Course 47
Habit and impulse disorders
Impulse control disorders (DSM-IV) or habit and impulse disorders (ICD 10 –chapter F 63) include the
following: Kleptomania, Pyromania, Trichotillomania, Intermittent explosive disorder (not in ICD-10, but
present in DSM-IV) & Pathological gambling.

These disorders are typified by recurrent behaviours that appear irrational and result in harming the
patient's own and others interests. This definition excludes the habitual excessive use of alcohol or drugs
or sexual (F65.-) or eating (F52.-) related compulsive acts.

A repeated failure  to  resist  impulses  (to  set  fire,  steal,  pull  one’s  own  hair  etc.)  is  a  common  theme.

Gender identity disorders

ICD-10 recognises three disorders: transsexualism, dual role transvestism and gender identity disorders of
childhood.

Gender identity is established  by  3  years;  it  is  an  individual’s  self  perception  of  being  male  or  female  and  
depends on reared sex more than biological sex. It is resistant to change once established firmly.

Gender dysphoria refers  to  feeling  of  incongruence  between  one’s  gender  identity  (I’m  a  man, or  I’m  a  
woman)  and  one’s  phenotypic  appearance  (I  appear  like  a  man  or  woman). Various degrees of gender
dysphoria exist. One mild form is recognized in ICD and DSM as dual role transvestism.

Individuals with dual role transvestism wear clothes of the opposite sex in order to experience temporary
membership in the opposite sex. The individual experiences a sense of appropriateness by wearing clothes
of the other gender. There is no sexual motivation for the cross-dressing. The individual has no desire for
a permanent change to the opposite sex.

Dual role transvestism must be differentiated from fetishistic transvestism where cross-dressing results
in sexual arousal often associated with masturbation or sexual activity. This is classified as a paraphilia
(see below).

A severe form of gender dysphoria is recognised as transsexualism in ICD and DSM. Transsexualism has
the following criteria:

Persistent discomfort with his/her sex or sense of inappropriateness in the gender role of the sex
Strong and persistent cross-gender identification (not merely a desire for any perceived cultural
advantages of being the other sex). This may be associated with the wish to  make  one’s  body  as  congruent  
as possible with the preferred sex through surgery and hormone treatment.
The disturbance is not concurrent with a physical intersex condition and not due to other functional
psychiatric disorders
The disturbance causes clinically significant distress or impairment in social, occupational or other
important areas of functioning
The transsexual identity has been present persistently for at least two years.
© SPMM Course 48
Most adult transsexuals, in fact, have origins of symptoms in
DSM-5 AND PARAPHILIC
childhood itself.
DISORDERS
Gender identity disorders of childhood can also be present
All Paraphilic Disorders now include
in adolescents and children. A duration criteria of 6 months
two new specifiers: In a Controlled
is appreciated for the pre-pubertal group. It is important to
Environment and In Remission.
rule out chromosomal and endocrine problems in this group.
In children, the large element of management is promoting the young person's tolerance of uncertainty
and resisting pressures for quick solutions for the gender dysphoria. Surgical intervention is not justified
until adulthood.

Rarely some patients may have a form of body dysmorphic disorder where there is a persistent
preoccupation with castration or penectomy without a desire to acquire the characteristics of the other sex.
This may be classed as Gender identity disorder - NOS (not otherwise specified) or body
dysmorphophobia. But this is not transsexualism.

A transsexual person need not necessarily be homosexual – In other words, gender identity must be
differentiated from sexual orientation. In gender dysphoria of childhood, 1/3rd to 2/3rd boys later appear
homosexually oriented but very few persist as adult transsexuals.

GIDs, at any age, are more common in males.

Cross-dressing behaviour can also be transient in some associated with stressful times. Also, some
individuals with mild gender dysphoria (to a degree that does not cause undue distress while in a
mentally healthy state) may experience a marked intensification of a low-grade gender dysphoria when
experiencing depressive episodes.

Paraphilias (Disorders of sexual preference)

Paraphilias, impulsive disorders and other habitual problems are coded under F60. In paraphilias, ego-
syntonic urges of sexual deviancy are seen (except in some cases of exhibitionism where the urges are
reported as ego-alien).

Klismaphilia is not a separate entity but is related to use of enemas to achieve sexual arousal. Necrophilia
is  also  an  ‘other  paraphilia’  in  ICD-10. This refers to achieving sexual arousal by using dead bodies or
other death related objects for sexual arousal.

Paraphilias described in ICD-10 & DSM-IV

Exhibitionism Expose genitals to achieve arousal
Fetishism Use of inanimate objects to achieve arousal
Paedophilia Sex with prepubescent child (<13)
Sexual masochism Real, not simulated act of being humiliated, beaten or bound to achieve arousal
Sexual sadism Real, not simulated act of inflicting psychological or physical suffering including
humiliation of victim to achieve arousal

© SPMM Course 49
Fetishistic transvestism Crossdressing in heterosexual male to achieve arousal

Voyeurism ‘Peeping-toms.'
Frotteurism Touching and rubbing against non-consenting individual

Frotteurism  is  coded  as  ‘other  paraphilias’  in  ICD-10, but separate disorder in DSM-IV. Fetishistic
transvestism is termed transvestic fetishism in DSM-IV.

© SPMM Course 50
9. Mental retardation
ICD-10 specifies 4 degrees of mental retardation but advises that the IQ levels for grading severity of
mental retardation be only for guidance and should not be applied rigidly in view of the problems of
cross-cultural validity. Instead, the severity must be graded primarily by functioning ability.

Degree of mental retardation defined using activities of daily life

Profound: a minimal capacity for functioning, needs nursing care; constant aid and supervision required. IQ<20

Severe: Speech minimal; Can talk or learn to communicate. No profit from training in self-help. May contribute
partially to self-maintenance under complete supervision later in life; IQ 20-34
Moderate: Profits from training in self-help; can be managed with moderate supervision. IQ 35-49

Mild: Can develop social and communication skills; minimal retardation and can be guided toward social
conformity. IQ 50-69
The  term  ‘Mental  Retardation’  in DSM-IV is now replaced by  the  term  ‘Intellectual  Disability’ in DSM-V.

Statement of Special Educational Needs (SEN): In England & Wales, following a statutory assessment by
local  authority,  a  ‘statement  of  SEN’  will  be  prepared  to    set  out  what  special  help  the  child  needs,  and  to  
consider the views and wishes of the child and their parents. The SEN statements consist of 6 essential
parts as outlined below. The local educational board usually arranges for statutory assessments and
initially issues a proposed statement, upon which the parents are invited to comment. The final statement
has a legally binding effect on the board. It is possible to ask for reassessmeents to amend the statements.

© SPMM Course 51
 Part 1

•Demographics details
•List of reports gathered when preparing the statement

Part 2

•Description of nature and complexity of learning difficulties

•The needs listed here will determine the care provided by the state.

Part 3

•List of arrangements and provisions proposed to be offered by the local authority/education

board
•Must also include monitoring arrangements
•The outlined provisions MUST be met by the board

Part 4

•Details of school placement

Part 5

•Non-educational (health and social) needs

•NOT legally binding on the local authority

Part 6

•Describes processes in place to meet noneducational needs

© SPMM Course 52
10. Disorders of psychological development

In ICD-10 these include specific developmental disorders of DSM-5 AND AUTISM

speech and language (expressive, receptive language disorders,
Autism Spectrum Disorder is a new
acquired aphasia with epilepsy), scholastic skills (reading,
description that will now include
spelling, arithmetical skills), motor skills and pervasive
autism,  Asperger’s, Childhood
developmental disorders.
Disintegrative Disorder, and Pervasive
In non-pervasive disorders, the domain showing a deficit in Developmental Disorder (not otherwise
development often improves with age. For example, in specific specified) in a single category.
reading disorders of childhood, reading improves significantly
ASD is characterized by 1) deficits in
though spelling difficulties persist longer.
social communication and social
Pervasive developmental disorders include childhood autism, interaction and 2) restricted repetitive
Asperger’s  syndrome,  Rett’s  syndrome,  atypical  autism  and   behaviors, interests, and activities
other childhood disintegrative disorder. (RRBs). If no RRBs are seen, then social
communication disorder is diagnosed.
Autism is defined by the presence of abnormal and/or
impaired development evident before the age of 3 years, with
abnormal functioning in all three areas of social interaction,
communication, and restricted, repetitive behaviour. Unlike children with autism, children with
Asperger’s  syndrome have normal language functions before the age of 3.

Though language development is affected in autism, the children do not remain mute in most cases.
Though not a diagnostic criteria, the presence of persistent gaze avoidance is strongly suggestive of
pervasive  developmental  disorder  such  as  autism  /  Asperger’s.  

Atypical autism is diagnosed if autistic features are seen but either of the age of onset is not satisfied or a
failure to fulfill all three sets of diagnostic criteria is noted.

Rett’s  syndrome is  seen  only  in  girls  in  whom  “apparently  normal  or  near-normal early development is
followed by partial or complete loss of acquired hand skills and of speech, together with deceleration in
head  growth,  usually  with  an  onset  between  7  and  24  months  of  age”  (ICD-10). Children also show hand-
wringing stereotypies, hyperventilation and loss of purposive hand movements. During later ages, trunk
ataxia and apraxia, associated with scoliosis along with choreoathetoid movements are seen. Epilepsy is
also a common feature.

Heller's syndrome or childhood disintegrative disorder is said to resemble dementia that occurs in
childhood. Apparently normal development up to 2 years is followed by a loss of previously acquired
skills and abnormal social functioning.

© SPMM Course 53
Acquired Aphasia with Epilepsy is also called Landau-Kleffner syndrome. It is a disorder in which the
child, despite the previous normal progress in language development, loses both receptive and expressive
language skills (starting from age 3 – 7) but retains general intelligence. Epilepsy with paroxysmal
abnormalities on the EEG is noted; these almost always originate from the temporal lobes bilaterally.

© SPMM Course 54
11. Disorders with childhood onset

Major ICD-10 categories in this chapter are highlighted in the table below:

Divisions Subdivisions

Hyperkinetic disorders (HKD) Rarely used (Attention and overactivity, hyperkinetic conduct
disorder)

Conduct disorders Conduct disorder & oppositional defiant disorder

Emotional disorders specific to Separation anxiety, phobias, social anxiety, sibling rivalry
childhood
Social functioning disorders Elective Mutism, reactive attachment disorder

Tic disorders Transient  tics,  Tourette’s  syndrome  (chronic  combined  motor  

and vocal)
Other behavioural and emotional Enuresis, Encopresis, Pica, Stuttering
disorders

The hyperkinetic disorder is the ADHD equivalent in ICD-10. For ADHD/HKD, the diagnostic criteria
are considered  to  be  more  ‘relaxed’  in  DSM  but  stricter  in  ICD-10. According to DSM-IV criteria, to meet
the diagnosis of ADHD, some symptoms must be present before the age of 7 years, although ADHD is not
diagnosed in many children until they are older than 7 years when their behaviours cause problems in
school and other places.

To confirm a diagnosis of ADHD, impairment from inattention and/or hyperactivity-impulsivity must be

observable in at least 2 settings and interfere with developmentally appropriate functioning socially,
academically, or in extracurricular activities and should persist for at least six months.

ADHD is not diagnosed when symptoms occur in a child, adolescent, or adult with a pervasive
developmental disorder, schizophrenia, or another psychotic disorder.

Conduct disorder is an enduring set of antisocial and aggressive behaviours that evolves over time,
usually characterized by aggression and violation of the rights of others. Diagnostic criteria: Children
with conduct disorder are likely to demonstrate behaviours in the following four categories

Physical aggression or threats of harm to people, cruelty to people and animals

Destruction of their own property or that of others
Theft or acts of deceit
Frequent and serious violation of age-appropriate rules. (Like truanting or running away)
© SPMM Course 55
Other features would include early sexual behaviour, lack of empathy, low self-esteem, and gang
involvement. Usually, the features must be present for a substantial duration of minimum six months
before entertaining the diagnosis. According to DSM-IV criteria, these behaviours should begin before the
age of 13. [Childhood onset type – symptoms present before age 10, Adolescent onset type – symptoms
develop after age 10]

Oppositional Defiant Disorder: An enduring pattern of negative, hostile, disobedient and defiant
behaviour, without serious violations of societal norms or the rights of others. Symptoms must be
persistent and evident for at least 6 months. In oppositional defiant disorder, a child's temper outbursts,
active refusal to comply with rules, tendency to blame others, spiteful and annoying behaviours exceed
expectations for these behaviours for children of the same age.

Oppositional Disorder is seen as a limited form of conduct disorder. According to ICD10, the oppositional
disorder is a subtype of conduct disorder. DSM-IV excludes oppositional disorder if a conduct disorder is
present.

Separation anxiety disorder (SAD) is defined as developmentally inappropriate and excessive anxiety
concerning separation from home or from those to whom the individual is attached. This anxiety will
interfere with normal age appropriate functioning. The essential clinical feature of separation anxiety is
excessive worry about losing or being permanently separated from a major attachment figure.

Reactive attachment disorder: This disorder, occurring in infants and young children is characterised by
persistent  abnormalities  in  the  child’s  pattern  of  social  relationships, which are associated with emotional
disturbance and reactive to changes in environmental circumstances.

Elective Mutism is a disorder characterized by a persistent failure to speak in specific settings (school)
despite the full use of language at home or with family, may be found in younger children with social
phobia. A child with selective mutism may remain completely silent or near silent, in some cases
whispering instead of speaking out loud.

Fear of strangers is a normal phenomenon in the second half of the first year of life. A degree of social
apprehension is normal in early childhood in socially threatening/novel situations. Social anxiety
disorder of childhood is a diagnosis that can be used before the age of 6 years, but only when the anxiety
is unusual in degree and accompanied by problems in social functioning.

© SPMM Course 56
Sibling!rivalry!disorder"is"characterized"by"“the"combination"of:"(a)"evidence"of"sibling"rivalry"and/or"
jealousy;"(b)onset"during"the"months"following"the"birth"of"the"younger"(usually"immediately"younger)"
sibling;"(c)emotional"disturbance"that"is"abnormal"in"degree"and/or"persistence"and"associated"with"
psychosocial"problems”"(ICDL10)."

"

"

"
DSM%5!AND!ADHD!!
"
For'ADHD'the'onset'criterion'has'been'
" changed'from'“symptoms'that'caused'
impairment'were'present'before'age'7'
"
DSM%5!AND!CHIDHOOD!ONSET! years”'to'“several'inattentive'or'
" DISORDERS!! hyperactive-impulsive'symptoms'were'
present'prior'to'age'12”'
" A'new'diagnosis'“Disruptive'Mood'
Dysregulation'Disorder”'has'been'added' Subtypes'have'been'replaced'with'
"
to'reduce'the'misdiagnosis'of'Bipolar' presentation'specifiers'that'map'directly'
" Disorder'in'children.'Features'of' to'the'prior'subtypes'
DMDD'include'a'persistent,'irritable'
" A'comorbid'diagnosis'with'autism'
mood'and'frequent,'major'anger'
spectrum'disorder'is'now'allowed'
" outbursts'or'tantrums'three'or'more'
times'a'week'for'more'than'a'year.'
The'symptom'threshold'has'been'
"
Separation'Anxiety'Disorder'and' changed'for'adults'with'a'cutoff'for'
" Selective'Mutism'have'been'moved'from'' ADHD'of'five'symptoms,'instead'of'six'
“Disorders'Usually'First'Diagnosed'in' required'for'younger'persons,'both'for'
"
Infancy,'Childhood,'or'Adolescence,”'to' inattention'and'for'hyperactivity'and'
" “'Anxiety'Disorders”.' impulsivity.'

"

"

©"SPMM"Course" 57"
DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug related information using external sources;
no part of these notes should be used as prescribing information.

Notes produced using excerpts from:

Cooper, J. E. (Ed.). (1994). Pocket Guide to the ICD-10 Classification of Mental and Behavioural
Disorders: With Glossary and Diagnostic Criteria for Research: ICD-10/DCR-10. American
Psychiatric Pub.

American Psychiatric Association. (2013). DSM 5. American Psychiatric Association.

First, M. B. (1994). Diagnostic and statistical manual of mental disorders. DSM IV-4th
edition. APA. p, 97-327.

© SPMM Course 58
 Clinical Examination
Paper A Syllabic content 5.21 &
5.24 to 26

© SPMM Course

We claim copyright only for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
 1. History Taking & Interview Skills
The four tasks of a psychiatric interview are 1. Build a therapeutic alliance. 2. Obtain the
demographic information required. 3. Interview for diagnosis. 4. Negotiate a treatment plan.

Basic concepts on approaching threatening topics:

1.Use normalizing questions to decrease a patient's sense of embarrassment about a feeling or

behaviour. 2. Use symptom expectation and reduction of guilt to defuse the admission of
embarrassing behaviour. 3. Use symptom exaggeration to determine the actual frequency of a
sensitive or shameful behaviour. 4.Use familiar language when asking about behaviours.

Nondirective Use Example Comments

techniques
Open-ended Qs The opening stage of the What brings you to the Preferable when highly
interview, to allow free hospital? suggestible; not very
narration. Non-directive useful to focus if over-
technique talkative or extremely
poor historian. Usually
starts with ‘tell me’,
‘describe’, etc.
Repetition Repeating the exact Pt: I was having bad Helps patient to feel that
words of the patient dreams last night. doctor is listening actively

Dr: So, you were having

bad dreams last night.
Restatement Similar to repetition but Pt: I was having bad Helps patient to feel that
phrases rearranged dreams last night. doctor is listening actively

Dr: So, you are getting

disturbed by the dreams
you have.
Summation Brief summarisation of ‘So from what you have Helps patient to check if
what the patient has said told so far, you are worried he has said what he
up to a point in the for last 4 months and not intended to say. Helps the
interview sleeping well, and your job doctor to form an idea of
is at risk. Right?’ the narration so far.
Clarification Doctor tries to get details ‘You said you are feeling Helps in avoiding
from patients about what depressed ever since you misconceptions by the
the patient has already can remember. When do clinician. Also shows
said. you feel most clinician’s interest in
depressed?’ knowing more.
Facilitation Helping patients continue Approval nods, leaning Helps patient to feel that
the interview by forward slightly to express doctor is listening actively.
providing both verbal and interest, ‘Yes. And then?’, Encourages flow of
nonverbal ‘yeah, go on…’ ‘Uh-huh’ information.
encouragement. etc.

© SPMM Course 2
Techniques when changing topics: 1. Use smooth transitions to hint at something the patient just
said. 2. Use referred transitions to hint for something said earlier in the interview. 3. Use
introduced transitions to pull a new topic from thin air.

1. Non-directive techniques: These techniques are employed without focussing on a particular

answer.
2. Directive techniques: These are focussed on seeking a particular answer or driven by other
motives of the doctor. Note that these are not necessarily detrimental but must be used
judiciously.

Directive Use Example Comments

techniques
Closed When, where, how many, which and Did you sleep well last Better avoided in early
questions what questions. night? parts of the interview as
Answers can only be ‘yes or no’, in they can produce
most occasions. When clubbed with You have lost weight. prescribed answers lacking
non-facilitative gestures, can be Haven’t you? in detail. Also avoid in
detrimental to interview process. highly suggestible
Stating a presumption followed by patients. Good technique is
tags can be very directive. to start with open; move to
closed by the end of the
interview. Useful to rule
out less likely symptoms.
Question Persisting with a question to seek an Often used when patient
rephrasing answer; so, restating the question in digresses from the topic of
different terms for a second time. discussion. The motive is
to collect the specific
information.
Redirection Gently reorienting patient towards Pt: ‘It is not good if one’s The motive is to keep the
the topic of discussion. parents are divorced even patient on track.
before one goes to school.’
Doc: ‘I’d like to hear more
about your parents, but
first let me get a picture of
what’s happening to you
of late’.
Transition Moving from one to another topic – ‘You mentioned that your Smooth transitions – uses
this is a special skill and preferably mother is a medical the cue off something the
must be done as smoothly as possible secretary. What about patient just said.
to keep the patient interested. yourself? What job do you Referred transitions – uses
do?’ the cue off something said
earlier in the interview.
introduced transitions
-uses a new topic to
proceed.

© SPMM Course 3
Limit setting Useful to manage time pressure, ‘I am going to interrupt To be used cautiously,
especially in garrulous patients. you as there are few overuse may detach
important things we need patient from the doctor.
to cover today’. The motive is to use time
effectively.

© SPMM Course 4
Other methods to elicit information:

Technique Description Example Comments

Confrontation Point out to a patient ‘You seem not to have gained any Must be done in a
something to which weight in last 6 months. Is it possible respectful way. The aim is
the doctor thinks the that your eating has been poor again?’ to help patients face a
patient is missing or difficult aspect rather than
denying. dismissing patients by
showing a negative aspect.
Interpretation Clarifying certain You seem very anxious when talking Sophisticated technique
associations or about your job. Are you having any and should generally be
relationships that the problems at workplace? used only after the doctor
patient may not see. has established some
rapport. Should be stated
as a hypothesis after
sufficient collection of
evidence from the
interview.
Self-revelation Limited, discreet self- ‘Do you like Shakespeare? I was a mad Helps physician feel at-
disclosure by fan when I was at school.’ ease sometimes. Excessive
physicians self-revelation is a
boundary violation.
Silence Silence can be used Relieves patient’s pressure
either to facilitate and he/she may fell relaxed
discourse or to that not every moment
indicate disapproval must be spent talking.
or disinterest.
Sometimes useful and
allows free emotional
expression.
Symptom Without a formal What sorts of drugs do you usually use Defuse the admission of
expectation admission from the when you're drinking? embarrassing behaviour.
patient, asking about (Assuming that the patient uses drugs) May help in reduction of
details of problem guilt. But must be used
behaviour. Doctor with experience and
assumes (rightly) that according to the context.
the patient is involved
in the act.
Symptom When deception or How many times have you taken Also helpful in reducing
exaggeration minimisation is overdoses since your last guilt to certain extent as
expected, overstating a hospitalization? Four? Five? the patient feels that the
guessed frequency in doctor has expected a
order to elicit a true higher amount of problem
answer. that what she/he actually
has brought.

© SPMM Course 5
Supportive techniques – not aimed at eliciting information:

Supportive technique Use Example

Reassurance Used to instil positive hope and ‘The depression may be very difficult for you.
avoid or reduce despair. Must not I think it is very likely with the proper
be falsely reassuring. treatment you can get back to your job’.

Advice Many patients seek advice directly; ‘I think it is best for you to consider ECT at
it is acceptable to provide advice this time. If I am you, I will give this a serious
but based on sound understanding thought.'
of the context. Premature advice can
be obstructive than facilitative.

Postponement Conscious and deliberate ‘I can see that you are uneasy to tell me about
postponement of delicate issues; but your relationships. That’s OK, we can come
must be opened at an appropriate back to this when you feel ready to discuss
time. with me.’
Validation / normalisation Helps to decrease a patient's sense ‘Sometimes when people are very depressed,
of embarrassment about a feeling or they think of hurting themselves. Has this
behaviour. Generally done by been true for you?’
quoting how it is normal for people
to have different emotions/
reactions/ behaviours, etc.

Acknowledgement of Making a remark about patient’s I can see that you look anxious when talking
affect affect can facilitate disclosure. about those voices.

Positive reinforcement Gently uplifting self-esteem by ‘I've never been good at expressing my
statements of praise (but at a problems’.
realistic extent) ‘Well, I think you've described the situation
in a way that helped me understand what you
have been going through’.

Statement of respect Affirmative statements (must be “You have been through a lot.” “I’m
genuine and appropriate) indicating impressed at how you have hung in there.”
respect and dignity along with “You must be a very strong person.”
positive reinforcement

Partnering The interviewer encourages the “I’m here to help.” “Let’s plan on working on
patient to ask questions and to this together.”
express any concerns, encouraging
team working

© SPMM Course 6
Obstructive techniques that may hamper the progress of information sharing:

Obstructive techniques Use Example

Suggestive questions Answers are contained in the question These voices are not from your head. Am I
itself. Misleads both the patient and the right?
doctor. The patient is left with little
choice.

Why questions These questions ask the patient to Why do you keep waking up so early in
discover their own problems, in a way. the morning?
Not useful when used to elicit
information from a distressed patient.

Compound questions Adding two or more questions in a single Do you take a vacation every year, and are
statement. This confuses the patient and you able to relax?
will lead to either a vague response or
non-response.

Negative Nonverbal Facial expression, body posture, and The doctor is yawning or repeatedly
gestures behaviour that indicate lack of interest or checking his/her watch, other repetitive
inattentiveness, gestures like tapping the table, etc.

Disapproval Expressing unhappiness with a topic that ‘Over the last month I have had trouble
the patient wants to discuss; may lead to with sex’. 
withdrawal and not revealing the ‘Dr: We are here to talk about your
important problem faced b y the patient. sleep.'

Setting traps Tricking the patient using his own words. You wanted to see me as nothing had
Often seen as doctor’s attempt to negate gone well for you, but you just said that
patient’s problems. you have got a new job and keeping a
good shape.

Adapted from Kay J & Tasman A. Essentials of Psychiatry, 2 nd edition, 2006. John Wiley & Sons, Ltd.

© SPMM Course 7
Open-Ended vs. Closed-Ended Questions

Open-Ended Questions Closed-Ended Questions

Highly informative answers Low yield answers
They produce spontaneous formulations. They lead the patient.
Low reliability of answers. High reliability.
Non-reproducible at a later date, or by a different
doctor.
Low precision – do not focus on target symptoms. The intent of the question is clear, and so precise, focused
answers elicited.
Not very time efficient. My lead to circumstantial High time efficiency.
elaborations.
Low diagnostic coverage as patient selects the Good diagnostic coverage as doctor selects interested
content revealed. content.
Adapted from Othmer E, Othmer SC. The Clinical Interview Using DSM-IV. Washington, DC: American Psychiatric Press; 1994.

Techniques for a poor historian

 Use open-ended questions and commands to increase the flow of information.

 Use continuation techniques to keep the flow coming.
 The Shift to the neutral ground when necessary.
 Schedule a second interview when all else fails.

Techniques for over-talkative garrulous historian

 Use closed-ended and multiple-choice questions to limit the flow.

 Perfect the art of the gentle interruption.
 Educate the patient about the need to move along in the interview.

Ancillary methods of gathering information:

Behavioural observation methods:

 Observing and recording behavioural events, to study mental state or plan intervention.
Often used when patients are in seclusion.
 Event sampling: e.g. every fifth or tenth event is coded in detail
 Time sampling: observations may be made only every 5 or 10 mins
 ‘Functional analysis' refers to attempts to explain and predict the functions of a
phenomenon by examining any relationships to the outcome. It is a special variant of
behavioural observation methods, where the sequence of antecedent environmental
events, target behaviour and concurrent events and consequent outcomes are observed.
This is also called ABC analysis. Often used in LD setting, dementia care, and challenging
behaviour services.

© SPMM Course 8
Using an interpreter:

 Explain the goals of the interview to the interpreter

 Explain structure and content of interview
 Explain the need for literal translation – not interpreted translation in the Mental Status
Examination
 Ask for feedback when something is hard to translate
 Offer to debrief the interpreter to address any of their own emotional concerns following
the interpretation
 Ask interpreter about the patient’s degree of openness or disclosure
 Preferably work with same interpreter/culture-broker for the same case whenever possible

© SPMM Course 9
 2. Laboratory assessment of physical factors
Depression
Depression is a clinical diagnosis. A physical examination is always required to rule out several
common medical disorders that can present with depression (especially endocrine disorders).
Laboratory tests are required if medical causes are suspected and to assess baseline fitness before
starting antidepressants.

Several chronic medical disorders are associated with depression (e.g. Coronary artery disease,
Diabetes mellitus, End-stage renal disease, HIV infection, various malignancies, degenerative
neurological disorders and stroke) but these do not ‘present’ with depressive features and as
such for a patient presenting with depression, there is no need to exclude all of these medical
disorders before diagnosis depression.

TEST WHY DO WE DO IT?

Full blood count Rule out infectious and inflammatory pathology
Thyroid-stimulating hormone (TSH) Rule out hypothyroidism
Vitamin B-12 Deficiency can mimic depression
HIV test & Syphilis (rapid plasma reagin) In suspected cases of sexually transmitted infections
Electrolytes, including calcium, phosphate, and Deficiency can contribute to fatigue and mimic
magnesium levels depression
GFR and creatinine In preparation for antidepressant use and to rule out
renal insufficiency contributing to depression
Liver function tests (LFTs) In preparation for antidepressant use and to rule out
alcohol-related liver damage in suspected cases
Blood and urine toxicology screen In suspected cases of drug abuse
24-hour urinary free cortisol In suspected cases of Cushing disease; will require
additional confirmation, as this can be positive in a
large number of patients with depression.
ACTH stimulation test Addison’s disease can also mimic depression

The following table displays some common abnormalities. Please note that none of the tests
below are required routinely during a workup for depression.

LAB ABNORMALITIES INTERPRETATION

Dexamethasone Suppression DST nonsuppression (DST-positive result) is seen in many disorders associated with
Test depression e.g. grief reactions (10%), dysthymic disorders (23%), major depressive
disorder (44%), melancholia/somatic syndrome (50%), psychotic affective disorders
(69%), and in depression with serious suicidality (78%). DST-positive patients
respond more favorably to biological interventions. DST nonsuppression is non-
specific; can be seen in chronic pain, patients with anorexia or bulimia, alcoholism,
obsessive-compulsive disorder, or anxiety disorders.
Corticotropin-Releasing HPA axis abnormality in major depression results in blunted ACTH response to
Hormone Test CRH.

© SPMM Course 10
Serum Thyroxine 1% and 4% of depressed patients, esp. women show evidence of overt
Concentrations hypothyroidism; 4% to 40% have subclinical hypothyroidism, contributing to
treatment failure. Serum T4 reductions may accompany treatment with
antidepressants, lithium, sleep deprivation, or ECT, especially in responders.
Thyrotropin-Releasing ~ 30% of depressed patients show blunted TSH response during depression
Hormone Test

Anxiety and other neuroses

A number of medical disorders can directly contribute to anxiety and panic attacks, but in
practice, patients seeking clinical consultations seldom require specific investigations to diagnose
these conditions. Diagnostic possibilities for panic attacks include paroxysmal atrial tachycardia,
pulmonary embolus, seizure disorder, Meniere's disease, transient ischemic attack, carcinoid
syndrome, Cushing's disease, hyperthyroidism, hypoglycemia, and pheochromocytoma. A
physical examination is warranted for all first presentations; extensive medical evaluation for
these disorders is indicated only when other features suggest physical disease.

Lactate infusion: Nearly 72% patients with panic disorder have a panic attack when
administered IV injections of sodium lactate. Therefore, lactate provocation is used to confirm a
diagnosis of panic disorder. Hyperventilation and CO2 inhalation have been used. Panic attacks
triggered by sodium lactate are not inhibited by peripherally acting beta-blockers but are
inhibited by benzodiazepines and tricyclic drugs.

Narcoanalysis: Interviews with amobarbital are very rarely used in current clinical practice
for diagnostic and therapeutic indications. These are sometimes helpful in differentiating
nonorganic and organic conditions, particularly in patients with symptoms of catatonia,
stupor, and muteness. Organic conditions tend to worsen with infusions of amobarbital, but
nonorganic or psychogenic conditions tend to get better because of disinhibition, decreased
anxiety, or increased relaxation. Therapeutically, amobarbital interviews are useful in
disorders of repression and dissociation such as amnesia and fugue. Benzodiazepines can be
substituted for amobarbital.

Psychosis
Differential diagnoses to be considered in the history of presenting illness: head trauma
(subdural haematoma), seizures, new-onset headaches, focal neurological deficits, abnormal
body movements, memory loss, and tremor especially in older patients, recreational drug use,
dietary history (deficiencies of vitamin B12, folate, thiamine, and niacin can all cause psychosis).

Physical examination: vital signs, level of consciousness, evidence of malnutrition, signs of hypo-
or hyperthyroidism or cushingoid features, rashes associated with autoimmune disorders,

© SPMM Course 11
dysmorphic facial features (genetic syndromes e.g velocardiofacial), focal neurological signs and
examination for signs of raised intracranial pressure

Initial tests

TESTS WHY DO WE DO IT?

Full blood count Rule out infectious and inflammatory pathology; the baseline for starting
haemotoxic antipsychotics such as olanzapine, clozapine.
Thyroid profile (TSH, free T4) Rule out hypo or hyperthyroidism. If abnormal carry out free T3 level and
thyroid autoantibodies ELISA for anti-thyroid peroxidase
Blood glucose, lipid profile, ECG Baseline for antipsychotic therapy; metabolic syndrome is common among
patients with psychotic disorders
Prolactin levels Baseline for antipsychotic therapy
In suspected cases of sexually transmitted infections
Electrolytes, including calcium, May be abnormal if there is an underlying metabolic or endocrine
phosphate, and magnesium levels disturbance
GFR and creatinine In preparation for antidepressant use and to rule out renal insufficiency
contributing to depression
Liver function tests (LFTs) In preparation for antipsychotic use; to rule out chronic alcohol abuse and
Wilson's disease in suspected cases
Blood and urine toxicology screen Acute toxic drug effects the most common cause of psychosis; screen for
amphetamines, cocaine, cannabis, and benzodiazepines

SUSPECTED CONDITION TESTS REQUIRED

Delirium with psychosis Blood glucose, Blood alcohol, Urine microscopy and culture, Blood culture, Chest X-ray.

Suspected STDs HIV test & Syphilis (rapid plasma reagin)

Screen for autoimmune Anti-Nuclear Antibodies, CRP and ESR
disorders in suspected cases
Suspected encephalitis NMDA receptor (NMDAR) and voltage-gated potassium channel receptor (VGKC)
syndrome auto-antibodies (IgG)
Cushing's syndrome 24-hour urinary free cortisol test followed by DST and ACTH challenge, evening
salivary cortisol, and the dexamethasone-corticotropin-releasing hormone test
Porphyria Spot urine sample for porphobilinogen during acute attack, and 24-hour urine for
porphyrins, porphobilinogen, and delta-aminolevulinic acid
Hyperparathyroidism Serum calcium and serum parathyroid hormone test
Wilson's disease Serum ceruloplasmin, 24-h copper excretion test
Lysosomal storage diseases Skin biopsy, genetic tests, and the detection of serum alpha-galactosidase enzyme
Homocystinuria Homocysteine in urine and blood and molecular genetic testing
Metachromatic Arylsulfatase A enzyme activity in WBCs or in cultured skin fibroblasts
leukodystrophy
Malnourishment Serum homocysteine and foalte (folate deficiency) , vitamin B12, niacin, tryptophan,
nicotinamide adenine dinucleotide (NAD) and NADP
CNS lesions MRI or CT scan; EEG if TLE is suspected

Porphyrias: Acute intermittent porphyria (AIP) is one of the groups of disorders of haem

© SPMM Course 12
metabolism, characterised by neurological and psychiatric manifestations without obvious
cutaneous markers. AIP manifests itself by abdomen pain, neuropathies, and constipation,
but, unlike most types of porphyria, patients with AIP do not have a rash. It is an autosomal
dominant disorder with the presentation starting between ages 18 and 40. It is episodic in
nature, and the episodes are often triggered by certain medications including estrogens,
barbiturates and benzodiazepines. Diclofenac can precipitate an episode. Psychiatric
manifestations include depression, anxiety, delirium and psycho sis. Most important lab test
is demonstrating increased urinary porphobilinogen during acute attacks. Treatment is
aimed at reducing haem synthesis by administering haemin.

Autoimmune encephalitis presenting as psychosis:

Autoimmune disorders with antibodies produced against crucial neurotransmitter receptors can
present with psychosis. Several anecdotal reports have pinpointed the following receptors as
most vulnerable in this regard.

 Voltage Gated Potassium Channel complex (LGI1, CASPR2, contactin-2)

 N-Methyl-D-aspartate receptor (NMDA)
 AMPA receptor
 GABA-B
 Glycine receptor

Some studies have estimated that 6.3% of first onset psychosis patients have pathogenic
antibodies against brain receptors (Zandi et al., 2011). The most well known of these syndromes
is the anti-NMDA receptor (NMDAR) encephalitis.

 Anti-NMDAR antibodies result in the titre-dependent destruction of synaptic NMDAR

through crosslinking and internalisation.
 Around 4% of patients with anti-NMDAR present with isolated psychiatric symptoms.
 It is more common in females (80%) than males
 ~50% of women with anti-NMDAR have an underlying ovarian teratoma.
 75% of patients first present to a psychiatrist with acute psychosis and/or mania.
 Psychosis associated with anti-NMDAR encephalitis usually presents with a prodromal
illness (fever, headaches, malaise). In suspected cases, the following investigations are
appropriate
o Serum NMDAR and VGKC antibodies
o Test for ANA, CRP, ESR, FBC, U+E (low sodium is seen in those with anti-VGKC
antibodies)
o If there is a strong suspicion EEG (look for encephalopathy with disorganized

© SPMM Course 13
 delta/theta activity) and MRI brain (look for medial temporal hyperintensity, usually
seen in T2 or FLAIR sequences in the hippocampi, frontobasal and insular regions and
basal ganglia; normal in ~50%).
o Confirmatory diagnosis requires CSF analysis: Lymphocytic pleocytosis, elevated
protein and oligoclonal bands are seen in ~60% of cases; almost all have intrathecal
anti-NMDAR antibodies. Note that patients who are cured of anti-NMDAR
encephalitis may continue having detectable antibodies in serum and/or CSF. CSF
antibodies rise during each relapse
o Elevated creatine kinase is a non-specific feature of the anti-NMDAR illness.
o In females with anti-NMDAR, ask for ultrasound or CT pelvis.

Anti-NMDAR encephalitis usually responds to 3 days of methylprednisolone orally or

intravenous followed by oral prednisolone, in association with 5 days of plasma exchange. The
remission thus achieved can be maintained by either (1) steroids alone; (2) steroids with a
steroid-sparing agent, such as azathioprine or mycophenolate mofetil or (3) rituximab.

Regular benzodiazepines may be required. AVOID ANTIPSYCHOTICS as dystonic reactions and

NMS-like syndrome with rigidity, hyperthermia, and autonomic instability might occur on the
use of antipsychotics in patients with anti-NMDAR antibodies.

Dementia
Patients presenting with memory difficulties always require a thorough physical examination to
look for signs of neurological disorders. In addition, several nutritional and metabolic factors can
produce what is called ‘reversible’ dementia – cognitive impairment with no progressive,
degenerative pathology. Laboratory investigations required for initial dementia workup are
shown below.

TEST WHY DO WE DO IT?

Full blood count Rule out infectious and inflammatory pathology; the baseline for starting
antidementia medications.
Thyroid profile (TSH, free T4) Low T4 can cause cognitive impairment
Blood glucose, lipid profile, ECG Baseline before starting antidementia medications; metabolic syndrome is
common among patients with vascular dementia
Thiamine, folate levels Thiamine deficiency can result in memory impairment esp. in alcoholics
Tests for syphilis or HIV HIV is associated with cognitive impairment that can worsen with opportunistic
infections.
Electrolytes, including calcium, May be abnormal if there is an underlying metabolic or endocrine disturbance
phosphate, and magnesium levels causing cognitive impairment
GFR and creatinine In preparation for antidementia medications
Liver function tests (LFTs) In preparation for antidementia medications
CT or MRI brain This is becoming a routine practice though the diagnostic yield of routine
imaging is low in senile dementia of Alzheimer’s type. Recommended when
suspecting vascular dementia, subdural hematoma or tumours.

© SPMM Course 14
EEG No need for routine EEG. But rapid onset dementia may suggest CJD for which
EEG and MRI are warranted.

Anorexia
Several abnormalities are expected in physical investigation in anorexic subjects: (The list below
is adapted from Fairburn & Harrison, 2003)
Endocrine
 Low concentrations of luteinising hormone, follicle stimulating hormone, and oestradiol
 Low T3, T4 in low normal range, normal concentrations of thyroid stimulating hormone
(low T3 syndrome)
 Mild increase in plasma cortisol
 Raised growth hormone concentration
 Severe hypoglycaemia (rare)
 Low leptin (but possibly higher than would be expected for bodyweight)
Cardiovascular
 ECG abnormalities (especially in those with electrolyte disturbance): conduction defects,
especially prolongation of the Q-T interval, of major concern
Gastrointestinal
 Delayed gastric emptying
 Decreased colonic motility (secondary to chronic laxative misuse)
 Acute gastric dilatation (rare, secondary to binge eating or excessive re-feeding)
Haematological
 Moderate normocytic normochromic anaemia
 Mild leucopenia with relative lymphocytosis
 Thrombocytopenia
Other metabolic abnormalities
 Hypercholesterolaemia
 Raised serum carotene
 Hypophosphataemia (exaggerated during refeeding)
 Dehydration
 Electrolyte disturbance
o Varied in form; present in those who frequently vomit or misuse large quantities of
laxatives or diuretics
o Vomiting results in metabolic alkalosis and hypokalaemia.
o In repetitive vomiting, loss of hydrochloric acid from gastric juices leads to metabolic
alkalosis (loss of acid – alkalosis).
o Laxative misuse results in metabolic acidosis, hyponatraemia, hypokalemia

© SPMM Course 15
 o During laxative induced diarrhoea, a large amount of bicarbonate may be lost in the
stool. With normal kidneys, the lost bicarbonate is replaced effectively and a serious
base deficit does not develop. When there is poor renal blood flow due to
hypovolemia/starvation, base deficit and acidosis develop rapidly.
o Acidosis also results from excessive production of lactic acid when patients have
severe diarrhoea.
Other abnormalities
 Osteopenia and osteoporosis (with heightened fracture risk)
 Enlarged cerebral ventricles and external cerebrospinal fluid spaces (pseudo atrophy)

Calculating BMI: BMI = Weight in kg / (height in meters)2. e.g. if weight = 50kg and height is
165cm, then BMI = 50 / (1.65) (1.65) = 50 / 2.7225 = 18.36. BMI categories: Underweight = <18.5;
Normal weight = 18.5-24.9; Overweight = 25-29.9; Obesity = BMI of 30 or greater

Alcohol use disorders

No single lab test can dependably diagnose alcohol abuse. Of available tests such as GGT (a liver
enzyme), Mean Corpuscular Volume, Breathalyzer and Carbohydrate Deficient Transferrin
(CDT), the CDT is the single most specific and sensitive test for detecting heavy alcohol use over
last 10 days. But due to a high degree of intersubject variability it is best to compare CDT levels
with patient’s own baseline. In primary care, AUDIT is often considered to be the best screening
tool.

As alcohol abuse is associated with systemic complications, several other lab tests may be
required when these complications are suspected.

System involved Complications

Neurological Seizures (intoxication or withdrawal), Wernicke's encephalopathy, Korsakoff's
dementia, polyneuropathy, coma, amnesia, alcoholic dementia, cerebellar
degeneration, damage to corpus callosum (Marchiafava syndrome)
Gastrointestinal GI bleeds, peptic ulcer, malnutrition (esp. thiamine), Mallory-Weiss tears,
esophageal strictures, fatty liver, hepatic cirrhosis, portal hypertension,
pancreatitis and hypoglycaemia
Cardiovascular Cardiomyopathy, hypertension, hyperlipidemia
Hematologic Pancytopenia, folic acid and B12 deficiency resulting in MCV changes and
anaemia, clotting disorders due to liver failure, immune compromise
Respiratory Lung cancer, pneumonia due to aspiration under intoxication
Musculoskeletal Muscle wasting, osteoporosis
Renal Renal failure, hepatorenal syndrome, hyponatremia and other electrolyte
imbalances
Endocrine Testicular atrophy, sexual disorders, menstrual irregularities
Pregnancy Low birth weight, foetal alcohol syndrome, developmental delays, neural tube
© SPMM Course 16
 defects due to maternal malnourishment.

Specific investigations

ELECTROCARDIOGRAM:

 The major use of ECG in a psychiatric ward, apart from emergency needs, is to measure QT
interval when treating patients using antipsychotics.
 Prolonged QT can predispose to fatal ventricular arrhythmias such as torsades de pointes
(polymorphic ventricular tachycardia).
 QTc is QT corrected for heart rate. While valuable for classifying risk groups, it is not a precise
predictor of torsade de pointes as it has low positive predictive value.
 There are different methods to arrive at QTc from QT – these give markedly different values.
 As a clinical measure, the risk is said to increase if QTc is beyond normal limits (440 ms for
men; 470 ms for women) – anything more than 500 ms is clearly an increased risk.
 QT varies with gender, time of day, food intake, alcohol intake, menstrual cycle, ECG lead
used.
 Risk factors for prolonged QTc include
• Congenital long Q-T syndrome,
• Underlying heart disease, bradycardia, heart failure, and ischemic disease
• Female gender,
• Extremes of age,
• Presence of liver disease,
• Electrolyte abnormalities (hypokalemia, hypocalcemia and hypomagnesemia),
• Illicit drug use (principally stimulants),
• Starvation or anorexia,
• High physical exertion (agitation),
• High dosages of the drug contributing to the lengthened Q-T interval, and
• Rapid infusion of torsadogenic drugs.

URINALYSIS:

 Testing for drugs: This is one of the most frequently used lab investigations in
psychiatry. When a patient repeatedly gives negative urine samples despite strong
suspicions, a cheap and quick way of checking the sample is by testing specific gravity –
this will reveal any adulteration of urine with tap water. The following table will help
answering some recurrent questions on this theme.

© SPMM Course 17
Substance Time present in urine
Alcohol Up to 12 hrs
Amphetamine Up to 48 hours
Benzodiazepine 3 days (depending on t1/2)
Cannabis Occasional use – up to 3 days. High daily use for long time – up to 4 weeks.
Cocaine 6 – 8 hrs; metabolites up to 2 - 4 days
Codeine 48 hours
Heroin 1 to 3 days
Methadone 3 days or more
Morphine 2 to 3 days
Phencyclidine (PCP) 8 days
Data from Oxford Handbook of Psychiatry & Rudolph’s Paediatrics 21e. p 230

 Renal disturbances in IV drug users: Renal disease in cocaine and heroin abusers has
been associated with the nephrotic syndrome, acute glomerulonephritis, amyloidosis,
interstitial nephritis, and rhabdomyolysis. In a heroin user with a puffy face,
hypertension and weight gain – suspect heroin-related nephropathy. Infective
endocarditis, HIV, and HBV and HBC infections are associated with renal pathologic
patterns similar to those that can be caused by the drug itself. In Black patients, focal
segmental glomerulosclerosis is often seen while in Whites mostly
membranoproliferative glomerulonephritis is noted.

 SIADH: Urine analysis may be important with regard to SIADH induced by

antidepressants or antipsychotics/Psychogenic polydipsia where excessive water
consumption occurs without obvious organic illness and Diabetes insipidus due to
lithium (nephrogenic) or head injury (central). As a rough guide use the following
tables.

Plasma osmolality Urine osmolality

Diagnosis
High (>295mosm/kg) Low Diabetes Insipidus (Central / nephrogenic)
Low (<280 mosm/Kg) Low Psychogenic polydipsia
Low High SIADH - hyponatraemia
Psychogenic / Primary polydipsia Diabetes Insipidus
Gradual onset Acute or sudden
Nocturia is rare Nocturia is common
Plasma osmolality normal/low Elevated plasma osmolality
Urine osmolality normal/low Low urine osmolality

© SPMM Course 18
Plasma ADH levels normal compared to osmolalityLow in central type
NOTE - polydipsia and polyuria are not features of SIADH or hyponatraemia per se.
 The clinical features of SIADH are attributed to water retention, hyponatr aemia, and
hypo-osmolality of the serum. Most hyponatraemic patients have no symptoms or signs
until the serum sodium concentration falls below 125 mmol/L. Initially, the symptoms
include lethargy, muscle cramps, anorexia, nausea, and vomiting. When hyponatraemia
develops more rapidly or more profoundly, coma, convulsions, and death may occur. On
longer term hyponatraemia can cause neurologic signs and symptoms such as altered
levels of consciousness, headache, impaired memory and confusion. If the serum sodium
concentration drops below 110-115 mmol/L, seizures and irreversible brain damage can
occur.

© SPMM Course 19
 3. Physical examination of a psychiatric patient
General examination
SIGNS Relevant conditions
Argyll-Robertson pupil Neurosyphilis; the more common cause is diabetes.
Checker-board abdomen Multiple surgical scars in factitious disorder.
Constricted pupils Opiate intoxication, Horner’s syndrome
Dilated pupils Stimulant abuse or opiate withdrawal, anxiety states
Kayser Fleischer ring Golden Brown pigment around cornea in Wilson’s disease
Generalised lymph node enlargement HIV illness, Lymphomas.
Goitre Thyroid disease, very small number related to lithium use
Gynaecomastia Hyperprolactinaemia, cirrhosis, androgen or steroid abuse
Jaundice Heavy alcohol use.
Lanugo hair Anorexia nervosa
Lemon stick appearance, central obesity Cushing’s syndrome
Lid lag, lid retraction, exophthalmia, Hyperthyroid state
and proptosis
Mask like face Extrapyramidal affect is seen in Lewy body dementia,
Parkinsonism, and in psychomotor retardation of
depression
Parotid swelling Bulimia, mumps
Piloerection Opiate withdrawal
Rapid/irregular pulse Anxiety, delirium states, Drug/alcohol withdrawal and
Hyperthyroidism
Russell's sign Bulimia nervosa – calluses at knuckles
Sialorrhoea Clozapine treatment; parkinsonism; facial palsy of Bell’s,
stroke involving cranial nerves
Splinter haemorrhages, Osler’s nodes, Due to infectious endocarditis in IV drug users.
and Janeway lesions
Xanthelasma Lipid accumulation, related to Olanzapine or another
antipsychotic treatment.
Patients with acute hyperventilation (often in the context of panic attack in a psychiatric clinic)
may present with agitation, increased breathing rate with shallow breaths (tachypnoea), chest
pain, dizziness, palpitations, tetanic cramps (carpopedal spasm), paresthesias, generalized
weakness, and syncope. Paresthesias are due to acid-base imbalance, and occur more commonly
in the upper extremity and are usually bilateral. Unilateral paresthesias are left-sided in
approximately 80% of cases. Perioral numbness is very common.

Minor Physical Anomalies (MPAs) are often observed in a range of developmental disorders.
MPAs are also more frequent in patients and siblings of patients with schizophrenia than in
healthy controls, supporting neurodevelopmental aetiology. MPAs can be rated using Lane Scale
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 Minor Physical Anomalies in putative developmental
disorders
 Preauricular tag
 Preauricular pits
 Lip pit
 Bifid uvula
 Supernumerary nipples:
 Partial syndactyly (generally involving toes 2–3)
 Pigmented naevi
 Cafe-au-lait spots
 Sacral haemangioma
 Prominent or flat occiput
 Prominent or flat forehead
 Primitive shape of ears
 Earlobe crease
 Fine electric hair
 Tongue with smooth and rough spots
 Double antihelix
 Simian crease [Instead of the two usual creases only a single
uninterrupted palmar crease traverses the palm from the radial to the
ulnar border. To be considered as an anomaly, the line should be
uninterrupted].
 Single flexion crease on 5th finger
 Sole crease
 Prominent heel
 Double posterior hair whorl
 Multiple buccal frenula
Neurological  Furrowed tongue examination in
psychiatry  Brushfield spots

Cranial nerves examination:

No. Name Main clinical examination technique

I Olfactory Smell – each side separately
II Optic Test visual acuity using Snellen’s charts (near and distance), colour using
Ishihara charts, field by confrontation/perimetry and pupillary reflexes.
III Oculomotor Eyelid elevation, eye elevation, adduction, depression in abduction, pupillary
reflex for efferent fibres
IV Trochlear Eye intorsion, depression in adduction
V Trigeminal Facial and corneal sensation, muscles of mastication
VI Abducens Eye abduction
VII Facial Facial movement, taste fibres
VIII Vestibular Balance – Romberg / Caloric test
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 Cochlear Hearing – Rinne, Weber tests.
IX Glossopharyngeal Sensation - soft palate, taste fibres
X Vagus Cough, palatal and vocal cord movements
XI Accessory Head turning, shoulder shrugging
XII Hypoglossal Tongue movement
Adapted from Kumar & Clark Textbook of clinical medicine 6 th edition Pg 1179

 The auditory function is tested using 512 Hz – Weber’s test and Rinne’s test; vibration sense
is tested for peripheral neuropathy using a 128Hz fork.
 The Weber test involves holding a vibrating tuning fork against the forehead in the midline.
The vibrations are normally perceived equally in both ears because bone conduction is
equal. In conductive hearing loss, the sound is louder in the abnormal ear than in the normal
ear. In sensorineural hearing loss, lateralization occurs to the normal ear.
 In the Rinne test, the vibrating tuning fork is placed over the mastoid region until the sound
is no longer heard. It is then held at the opening of the ear canal on the same side. A patient
with normal hearing should continue to hear the sound. In conductive hearing loss, the
patient does not continue to hear the sound since bone conduction, in that case, is better than
air conduction. In sensorineural hearing loss, both air conduction and bone conduction are
decreased to a similar extent.
 The vestibular portion transmits information about linear and angular accelerations of the
head from the utricle, saccule, and semicircular canals of the membranous labyrinth to the
vestibular nucleus.
 The Romberg test is performed to evaluate vestibular control of balance and movement.
When standing with feet placed together, and eyes closed, the patient tends to fall toward
the side of vestibular hypofunction. Results of the Romberg test may also be positive in
patients with polyneuropathies, and diseases of the dorsal columns, but these individuals do
not fall consistently to one side as do patients with vestibular dysfunction.
 Provocative tests include caloric testing. Normally on cold water testing, nystagmus is noted
to the opposite side; warm water elicits nystagmus towards the same side. (COWS – Cold
Opposite, Warm Same, can be used as a mnemonic)

Neurological soft signs:

Neurological signs are often referred to as either “hard” or “soft” signs. The ‘hard signs’ refer to
impairments of the basic motor and sensory functions that are localisable to the pyramidal,
extrapyramidal or cranial nerve systems.

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Common soft neurological The soft signs are non-localisable neurological findings thought
signs in psychosis to reflect neurodevelopmental aberrations when seen in
Choreoathetosis (predating psychiatric disorders. These are seen in many psychiatric
psychosis esp. in children)
disorders including schizophrenia, autism, OCD and ADHD.
Abnormal gait
Grimacing However, this distinction between hard and soft signs is artificial,
Abnormal reflexes merely reflecting our inability to define the brain-behaviour
Changes in muscle tone relationship that underlies certain neurological abnormalities.
Abnormal saccades
Frequent blinking There are three groups of symptoms collectively known as soft
Dysdiadochokinesia
signs - abnormalities of motor coordination, sensory integration
Astereognosis
Poor left-right discrimination and signs of cortical disinhibition. In recent times, neuroimaging
Anosognosia studies that parse finer details of the cortex have implicated
Apraxia several parts of the brain in ‘soft’ signs, further blurring their
Gaze impersistence
distinction from hard signs.
Frontal release

Cerebellar signs

The cerebellum provides an important feedback loop for coordination of muscle activity. Midline
cerebellar dysfunction results in ataxia of gait, difficulty in maintenance of upright posture, and
truncal ataxia. The following cerebellar signs are noted in various degrees in psychiatric
disorders. The lateral cerebellar hemispheres (the neocerebellum) controls the movement of the
ipsilateral limbs. The midline vermis is involved in the control of truncal tone, speech and eye
movements. The flocculonodular lobe (also called archicerebellum) is involved in vestibular
functions.

Cerebellar signs
Ataxia Difficulties in coordinating truncal and limb movements, often seen in
midline damage. Tested using tandem walking (heel-to-toe walk) test.
Hypotonia Reduced muscle tone resulting in loss of ‘checking’ effect when passively
manipulated (leg swinging test results in pendular swinging of legs until
passive inertia sets in)
Intention tremor An oscillating tremor that accelerates in pace on approaching the target
Dyssynergia Results in loss of smoothness of execution of a motor activity.
(incoordination)
Dysmetria (past Overshooting or undershooting of a target while attempting to reach an object
pointing)

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Dysdiadochokinesis Inability to perform rapid alternating movements. Tested by asking the
patient to tap 1 hand on the other repeatedly while simultaneously pronating
and supinating the hand

Dysrhythmia Inability to tap and keep a rhythm

Dysarthria Staccato or scanning speech with poor modulation of the volume and pitch of
the speech.
Dyssynergia, dysmetria and tremor can be elicited by finger nose or heel shin test. Dysarthria is
usually a sign of diffuse involvement of the cerebellum.

Meningeal signs:

These signs can be elicited in the presence of meningeal inflammation or irritation due to
haemorrhage/trauma.

Nuchal rigidity or neck stiffness:

 The Brudzinski sign (Flexion of his knees and hips when you try to flex one’s neck
constitutes a positive Brudzinski's sign.)
 The Kernig sign (this is elicited by flexing one hip and knee and then extending the knee
with the hip still flexed). Hamstring spasm may occur; if severe, opposite knee may flex
during the test – positive Kernig’s)

The Lasègue or straight-leg raising (SLR) sign is elicited by passively flexing the hip with the
knee straight while the patient is in the supine position. Limitation of flexion due to hamstring
spasm and/or pain indicates local irritation of the lower lumbar nerve roots.

Reverse SLR sign is elicited by passively hyperextending the hip with the knee straight while the
patient is in the prone position. Limitation of extension due to spasm and/or pain in the anterior
thigh muscles indicates local irritation of the upper lumbar-nerve roots.

Cortical sensory signs:

The cortical sensory system includes the somatosensory cortex and its central connections.
Functions include kinaesthetic sensation, stereognosis, graphesthesia and tactile localization
and tactile 2-point discrimination on both sides of the body.

Position sensation is tested with the subject’s eyes closed. The subject is then tested in the
various directions of passively elicited distal joint movements.

Movement abnormalities:

 Fibrillations are not visible to the naked eye except when the tongue is affected.

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  Fasciculations may be seen under the skin as quivering of the muscle. Although
fasciculation is usually benign (e.g. can occur with fatigue); if widespread it can be
associated with neuromuscular disease, including amyotrophic lateral sclerosis (ALS).
 Asterixis can be elicited by having the patient extend both arms with the wrists dorsiflexed
and palms facing forward, and eyes closed. Brief jerky downward movements of the wrist
are considered a positive sign. Asterixis is commonly seen in metabolic encephalopathies.
(Note pronator drift is elicited by having the patient extend both arms with the wrists
supinated and palms facing upwards and eyes closed – slow unequal drift towards
pronation indicates hemiparetic weakness)
 Myoclonus is a brief <0.25 seconds muscle jerk; generalized and sometimes asymmetric.
These occur alone or in association with various primarily generalized epilepsies; associated
with CJD and also with severe Alzheimer’s.
 In athetosis, the spasms have a slow writhing character and occur along the long axis of the
limbs or the body itself; the patient may assume different and often peculiar postures.
 The term chorea means dance. Quasi-purposeful (patient turn it to appear as if they are
purposive) movements affect multiple joints with a distal preponderance. It is associated
with caudate lesions.
 Hemiballismus is a violent flinging movement of half of the body. It is associated with
lesions of the subthalamic nucleus.

Reflexes

Primitive reflexes: These include the glabellar tap, rooting, snout, sucking, and palmomental
reflexes. These are generally absent in adults. When present in the adult, these signs signify
diffuse cerebral damage, particularly of the frontal lobes (hence the name frontal-release signs).

Superficial reflexes: These are segmental reflex responses that indicate the integrity of
cutaneous innervation and the corresponding motor outflow. These include corneal, conjunctival,
abdominal, cremasteric and plantar (Babinski) reflexes.

 Corneal and conjunctival reflexes – afferent is via 5th nerve while efferent is via 7th
nerve.
 Abdominal reflex can be elicited by drawing a line away from the umbilicus along the
diagonals of the 4 abdominal quadrants. A normal reflex draws the umbilicus toward
the direction of the line that is drawn.
 The cremasteric reflex is elicited by scratching on the medial surface of the thigh to elicit
scrotal contraction or lift in male subjects. A normal reflex results in elevation of the
ipsilateral testis.

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  The best known of this group of reflexes is the plantar reflex or Babinski reflex. The
normal response is plantar flexion of the great toe. This normal response is considered
an absent (negative) Babinski sign. Dorsiflexion of the great toe (Babinski sign present)
suggests an upper motor neuron lesion and is referred to as a positive Babinski sign.
Lack of either response may indicate the absence of cutaneous innervation in the S1
segment or loss of motor innervation in the L5 segment ipsilaterally.

Deep tendon reflexes: Intact cutaneous innervation, motor supply, and cortical input to the
corresponding spinal segment are required for normal deep
tendon reflexes. Deep tendon reflexes include biceps, Muscle Spinal Roots
Biceps C5, 6
brachioradialis, triceps, patellar, and ankle jerks. These get
Brachioradialis C6
exaggerated in UMN lesions and are absent in respective
Triceps C7
LMN lesions. Pseudobulbar palsy is a UMN lesion; Patellar L2-4
exaggerated jaw jerk is noted in patients with this condition. Achilles S4
Bulbar palsy is a result of LMN lesion and jaw jerk is absent in this case.

Neurocutaneous system

 Frontal baldness: Myotonic dystrophy

 Dermatomal eruptions: Herpes Zoster
 Ash leaf macules: Tuberous sclerosis
 Ungual fibromas: Tuberous sclerosis
 Dimples and large moles along the spine: spina bifida occulta
 Cafe au lait spots: Neurofibromata, Tuberous sclerosis.
 Axillary freckling: Neurofibroma

Speech abnormalities

Dysarthria Types Description

Spastic dysarthria Strained and hoarse voice, hypernasality and slow, imprecise articulation
related to bilateral UMN lesions. Often accompanied by swallowing and
drooling difficulties (Palmer 2005).
Flaccid dysarthria Isolated areas of involvement are depending on which motor neurone is
affected. LMN type lesion. The tongue is usually small due to loss of tone if
XII nerve is involved and lies flaccidly on the floor of the mouth. Could be
of nasal quality if IX and X nerves are involved.
Ataxic dysarthria Excess loudness, tremor and irregular articulatory breakdowns (scanning
speech). Intonation, pitch and volume and also be affected, as well as
difficulty with alternate tongue movements. The cerebellum is often
involved.
Hypokinetic dysarthria A breathy monotone voice with reduced loudness and articulation tends to
be accelerated and imprecise. Associated with motor control circuit
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 damage.
Hyperkinetic dysarthria Features strained hoarseness and voice arrests. Associated with basal
ganglia damage.
Mixed dysarthria Similar symptoms to spastic dysarthria, and tends to be accompanied by a
wet sounding voice with rapid tremor, poor laryngeal and tongue
movements and poor control of lips (Damage to more than one motor
system).
Hysterical aphonia The examination is usually normal. Sudden loss of voice, but preserved
vocal cord activity is notable.

Gait

Gait is the motor attitude of a person in the upright position.

 Hemiparetic gait: Seen in patients with stroke affecting the pyramidal system. Typically,
clenched hand with extended knee and plantarflexed ankle. This makes the paralyzed leg
appear longer (pole-like) than the other. The patient resorts to circling it around resulting
in repeated circumduction of the affected leg while walking.
 Ataxic gait: In mild cases this can only be elicited by or tandem walking tests. In severe
cases, a staggering wide-based gait is seen. Unilateral (rather than midline) cerebellar
lesions may result in the patient veering to the side of the lesion (resulting in sailor’s gait).
 Shuffling gait: This is often seen in Parkinsonian patients. The patient takes very short
steps and appears to shuffle legs away or apart rather than propelling them forward.
Progressively short steps result from a tendency of the patient to accelerate (festinating
gait).
 Steppage gait: Here the patient takes high steps as if climbing a flight of stairs while
walking on a level surface. Steppage gait is seen in chronic peripheral neuropathies e.g.
drop foot and dorsal column disorders.
 Waddling gait: It is seen in patients with proximal myopathy. Patients have a broad-based
gait with a duck-like waddle resulting from the dropping of the pelvis to the side of the leg
being raised. A compensatory forward curvature of the lumbar spine adds to the body
swing. This is also be seen in patients with congenital hip dislocation and near term in
pregnant women.
 Scissoring gait: This is seen in patients with spastic paraplegia. Marked rigidity and
excessive adduction of the swinging leg together with plantar flexion of the ankle and
flexion at the knee due to contractures of all spastic muscles leads to forced tip-toe walking
with knees rubbing together and crossing like scissors.

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GAIT Conditions
Antalgic gait Trauma, Osteoarthritis
Broad, unsteady gait Cerebellar lesions
(Drunken/sailor’s gait)
Festinating/shuffling gait Parkinson’s

Gait apraxia Hydrocephalus

(Magnetic gait or failed gait ignition)
High stepping due to foot drop Neuropathic / polio / peripheral lesions in MS
Lurching, chaotic gait Huntington’s disease
Pigeon gait Torsional abnormalities seen in hip dysplasias
Propulsive gait Carbon monoxide poisoning (stiff with head and neck bent)
Stiff, scissoring gait UMN lesions, cerebral palsy, cortical lesions in MS or stroke
Stomping gait Friedreich's ataxia Pernicious anaemia, Tabes Dorsalis (Syphilis)
Trendelenburg gait Weakness of the abductor muscles of the lower limb,
principally gluteus medius
Waddling myopathic gait Pregnancy, proximal myopathy.

Other neurological signs

 Absent ankle jerks, upgoing plantars: This is an odd combination - UMN lesion of
corticospinal tracts is expected to cause exaggerated ankle reflex (i.e. clonus) with upgoing
plantar normally. But in subacute combined degeneration cord, Syphilitic taboparesis and
Friedrich's ataxia and MND we see absence of ankle jerk as spinal reflex pathway is affected
(afferent) while UMN type damage still produces Babinski – upgoing plantar.
 Anisocoria: This refers to pupillary asymmetry, which may result from sympathetic or
parasympathetic dysfunction. Sympathetic dysfunction results in Horner syndrome, in
which the pupil is small but reacts to light. Parasympathetic dysfunction results in the tonic
pupil.
 Argyll-Robertson pupil, seen in neurosyphilis, is irregular and small; it does not react to
light, but does accommodate.
 Anosognosia refers to the denial of illness and typically is seen in patients with right
frontoparietal lesions, resulting in left hemiplegia that the patient denies.
 Asterixis involves momentary loss of tone and flapping of the hand are seen when the
patient extends his arms in front with the wrists dorsiflexed. This is seen in patients with
metabolic encephalopathies

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  Beevor sign is seen with bilateral lower abdominal paralysis that results in upward
deviation of the umbilicus when the patient tries to raise his head and sit up from the
supine, recumbent position.
 Brown Sequard syndrome is due to hemisection of the spinal cord; the full syndrome is
rare. Clinical features are related to various tracts that are severed.

Lateral corticospinal damage Posterior column damage Lateral spinothalamic damage

•Ipsilateral spastic paralysis •Ipsilateral loss of tactile •Contralateral loss of pain and
below the level of the lesion discrimination, vibratory, and temperature sensation. This
•Babinski sign ipsilateral to position sensation below the usually occurs 2-3 segments
lesion level of the lesion below the level of the lesion.
•Abnormal reflexes (UMN
type hyperreflexia)

 Chvostek sign is seen in hypocalcemia. Tapping the cheek at the angle of the jaw
precipitates tetanic facial contractions.
 Doll 's eye maneuver: This refers to turning the head passively with the patient awake and
fixated or when the patient is in a coma. In the former, the eyes remain fixated at the original
focus when all gaze pathways are normal; in the latter, the eyes deviate in the opposite
direction when the brainstem is intact.
 Friedreich’s ataxia is an inherited neurological disease (trinucleotide repeat) with pes cavus,
kyphoscoliosis, cerebellar signs, impaired joint position / vibration, cardiomyopathy, optic
atrophy.
 Gower sign: This sign, seen in severe myopathies, occurs when the patient attempts to stand
up from the floor. Patients first sit up, then assume a quadruped position, and then climb up
their own legs by using their arms to push themselves up.
 Holmes-Adie syndrome - A benign form of the tonic pupil is seen in Holmes-Adie
syndrome, i.e., a tonic pupil with absent patellar and Achilles reflexes.
 Horner's syndrome: Remember PAMELA – Ptosis, Anhidrosis, Miosis, Enophtholmos and
Loss of ciliospinAl reflex. This collection of signs indicates a lesion of the sympathetic
pathway on the same side. Seen in cervical lesions –e.g. apical lung tumour affecting
cervical sympathetic ganglion, carotid aneurysms.
 Kayser-Fleischer ring: This is a brownish ring around the limbus of the cornea. It is best
demonstrated by an ophthalmologic slit lamp examination.
 Marcus-Gunn pupil: This sign requires a swinging flashlight test to assess. As the flashlight
swings from 1 eye to the other, the abnormal pupil dilates as the light swings back from the
normal side. No anisocoria is seen. The phenomenon is also called a paradoxical pupillary
reflex and indicates an afferent (optic nerve) pupillary defect.

© SPMM Course 29
  Mononeuritis multiplex: Painful asymmetric asynchronous sensory and motor peripheral
neuropathy with isolated damage to at least 2 separate nerve areas. Causes: diabetes,
vasculitis, amyloidosis, direct tumor involvement, autoimmune disorders paraneoplastic
syndromes.
 Milkmaid's grip: This refers to the inability to maintain a sustained grip commonly seen in
patients with chorea.
 Myerson sign: Patients with Parkinson disease, particularly those with bilateral frontal lobe
dysfunction, continue to blink with repeated glabellar taps.
 Optic neuritis: The classic triad of optic neuritis consists of (1) loss of vision, (2) eye pain,
and (3) dyschromatopsia. 70% unilateral. Usually recover spontaneously (Multiple sclerosis)
within 2-3 weeks. Movement- or sound-induced phosphenes are seen. Reduction in vision
may worsen in bright light, a symptom that seems paradoxical. The Uhthoff symptom,
described as exercise- or heat-induced vision loss is seen in 50% of patients. Afferent
pupillary defect is noted on testing (i.e. direct light reflex absent; consensual present)
 Subacute combined degeneration is due to vitamin B12 deficiency; causes peripheral
neuropathy, posterior column signs with pyramidal signs below the waist.
 Trombone tongue: This is seen in patients with chorea. It refers to the unsteadiness of the
tongue when the patient tries to protrude it outside the mouth.
UMN Lesion

Rigidity Atonia or hypotonia

Hypertonia Loss of deep tendon
Exaggerated reflexes reflexes

Mild atrophy Atrophic, wasted

(disuse) Fasciculatione.g.
LMN Lesion

e.g. pseudobulbar bulbar palsy

palsy

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 Bulbar Palsy Pseudobulbar palsy

•LMN weakness of 9-12 cranial nerves •bilateral supranuclear (UMN) lesions

•Wasted, fasciculating tongue of lower cranial nerves
•Nasal speech •Stiff tongue; wasting seen only in
•Lost jaw jerk and gag reflex later stages
•emotional lability not seen •Donald-duck speech
•MND, polio, botulism, myasthenia •Exaggerated jaw jerk; preserved gag
gravis, muscular dystrophies reflex
•emotional lability (pathological
emotionalism)
•MND, multiple sclerosis,
multiinfarch dementia and severe
head injury.

Bedside cognitive examination tools

(This section is best read in conjunction with the section on neuropsychological tests in the Applied Neuroscience chapter and
the chapter on Rating Scales)

MMSE: The Mini-Mental State Examination (MMSE) is the standard screening instrument for
dementia introduced by Folstein in 1976. It takes 5–10 minutes to administer and has a median
positive Likelihood Ratio of 6.3 and a median Negative Likelihood Ratio of 0.19.

 Brief tool for grading cognitive impairment in elderly and screening form dementia.
 Not very sensitive to change, but used in anti-dementia drugs’ clinical trials.
 ADAS-Cog may be better suited to detect change.
 Practice effect may occur with MMSE.
 It is a 30point scale
 With less than 9 years of formal education, the cut off for suspecting dementia must be 21/22
and not the usual 23/24.
 Insensitive to early decline.
 Doesn’t pick up frontal executive defects
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 ITEMS in MMSE
o Orientation (10)
o Registration (3) and recall (3) tasks (6 points total)
o Attention task (5)
o Multistep command (3)
o Naming (2)
o Repetition language (1)
o Reading comprehension (close your eyes, 1 point)
o Writing (1)
o Visual construction (copy interlocking polygons, 1 point)
Clinical interview with carers and patients is the best diagnostic tool for any disorder including
dementia; overreliance on MMSE scores can be counterproductive.

The clock drawing test: Clock drawing test requires verbal understanding (comprehension),
short-term working memory to process the instruction and spatially coded knowledge in
addition to constructive skills and planning (executive function). (It does not test orientation to
time!)

 Watson introduced a 7 scores screening method with a good degree of reliability. The
placing of any three digits in a quadrant is considered to be correct. An error score of one is
assigned to each of the first three quadrants containing any errors, and an error score of
four is assigned for the fourth quadrant if it contains an error. Thus, a maximum error score
of seven can be obtained. The normal range for the score is 0-3. A score of 4 or greater in
this scoring system has a sensitivity of 87%, a specificity of 82% and a kappa value of 0.70
for identifying dementia (according to the NINCDS-ADRDA criteria for probable
dementia).
 The test has a high correlation with the MMSE and other tests of cognitive dysfunction.
 It can also be used in diagnosing unilateral neglect and inattention.
 Subjects of low education, advanced age and depression perform more poorly. There are
many methods of administering and scoring.
 Normal clock-drawing ability reasonably excludes cognitive impairment

Addenbrooke’s cognitive examination (ACE-Revised):

 ACE-R evaluates six cognitive domains (orientation, attention, memory, verbal fluency,
language and visuospatial ability). It is useful for detecting dementia and mild cognitive
impairment.

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  Frontal tests such as verbal fluency are also included in the ACE, making it more sensitive
to frontal types of dementia than MMSE. (Hodges R et al., 2000). It is also effective for
differentiating the subtypes of dementia, such as Alzheimer’s disease, frontotemporal
dementia, progressive supranuclear palsy, and other forms of dementia associated with
parkinsonism (Rittman et al., 2013).
 The normative data provided with ACE-R (revised version) states that there are two
defined cut-offs (<88: sensitivity=0.94, specificity=0.89; <82: sensitivity=0.84, specificity=1.0).
The likelihood ratio for a positive test of dementia at a cut-off of 82 is 100:1.
 Language domain receives the major share of the scoring in ACE.

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 4. Imaging of the nervous system
Computed Tomography – CT
 The most widely available scan in clinical practice
 CT scanners effectively take a series of head X-ray pictures from 360 degrees around a
patient's head.
 The CT image contrast is determined by the degree to which tissues absorb X-rays.
 Structures close to bone may appear obscured in a CT image e.g. brainstem
 The difference in the attenuation between gray matter and white matter is not very high.
 CT is limited to one plane of rotation – often axial.
 Appreciation of tumours and areas of inflammation is possible by intravenous infusion of
iodine-containing contrast agents. Iodinated compounds in the vascular compartment
absorb much more irradiation than the brain tissue and so appear bright.
 One feature that is better visualized on CT scanning is calcification, which may be invisible
in MRI.
 CT scans and MRI are the most common neuroimaging tools used in psychiatry. The CT
is widely available with shorter scan duration at a low cost, but exposure to radiation is
a disadvantage.
 CT has poor sensitivity to early ischemia and has poor visualization capacity for
posterior fossa lesions.

Magnetic Resonance Imaging – MRI

 MRI does not rely on the absorption of X-rays but is based on nuclear magnetic resonance
(NMR) principle. MRI magnets are rated in Tesla (T) units of magnetic field strength.
 The nuclei of all atoms spin about an axis that is randomly oriented in space. When atoms
are placed in a magnetic field, the axes of all odd-numbered nuclei (H1 in particular) align
with the magnetic field. This axis deviates away from the magnetic field when exposed to a
pulse of radiofrequency electromagnetic radiation oriented at 90 or 180 degrees to the
magnetic field. When the pulse terminates, the axis of the spinning nucleus realigns itself
with the magnetic field, and during this realignment, it emits its own radiofrequency signal.
MRI scanners collect these signal emissions.
 The images can be in the axial, coronal, or sagittal planes.
 The rate of the realignment of the H1 axis is determined by its immediate environment and
the degree of water content.
 Hydrogen nuclei within fat realign rapidly, and hydrogen nuclei within water realign
slowly.
 Routine MRI studies use 2 different radiofrequency (RF) pulse sequences: T1 and T2.
 T1 images:

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  The RF pulses are brief, and data collection is brief
 Hydrophobic environments are emphasized i.e., fat is bright on T1, and CSF is dark.
 The T1 image most closely resembles that of CT scans and is most useful for assessing
overall brain structure.
 T1 is also the only sequence that allows contrast enhancement with the contrast agent
gadolinium-diethylenetriamine pentaacetic acid (gadolinium-DTPA).
 On T1 images, gadolinium-enhanced structures appear white.
 T2 images
 This RF pulse lasts four times as long as T1 pulses, and the collection times are also
extended.
 Emphasizes signal from hydrophilic areas i.e. brain tissue is dark, and CSF is white on
T2 images.
 Areas of the brain tissue that have abnormally high water content, such as tumors,
inflammation, or strokes, appear brighter on T2 images. T2 images reveal brain
pathology most clearly.
 The proton density sequence
 A short radio pulse is followed by a prolonged period of data collection,
 Useful to see periventricular structures
 Fluid attenuated inversion recovery (FLAIR)
 The T1 image is inverted and added to the T2 image to double the contrast between
gray matter and white matter.
 Very useful for detecting sclerosis of the hippocampus caused by temporal lobe
epilepsy and for localizing areas of abnormal metabolism in degenerative neurological
disorders.
 MRI scans are contraindicated in patients with pacemakers or implants of ferromagnetic
metals. Claustrophobia is a relative contraindication.
 MRI is less useful in emergencies due to limited availability and longer scan duration, in
addition to higher costs. But it involves no radiation and can use water soluble
Gadolinium for contrast studies. It has good sensitivity for early ischemia with better
posterior fossa visualization.

Structures / pathology CT scan T1 image T2 image

Infarct Dark Dark Bright

Bleed (haemorrhage) Bright Bright (unless too Bright (unless too
old / too fresh) old / too fresh)
Tumour Dark Dark Bright
MS plaque Dark Dark Bright

© SPMM Course 35
 (demyelinated)

CSF Dark Dark Bright

Bone Bright Bright Dark
Air Dark Dark Dark
Fat Dark Bright Bright
Tissue Shades of grey Grey matter – grey Shades of grey
White matter - white

Magnetic Resonance Spectroscopy –MRS

 MR spectroscopy can detect several biologically important nuclei with an odd number of
protons and neutrons.

 H-1 proton spectroscopy

MR Potential clinical uses
can be used to quantify N-
molecule
acetyl aspartate (NAA), 1H Magnetic resonance imaging (MRI), Analysis
creatine, and choline- of metabolism – NAA, creatine and choline.
containing molecules.
19 F Measurement of pO2, Analysis of glucose
 GABA and glutamate can be
metabolism
detected using MRS but not Measurement of pH, Pharmacokinetics
dopamine as it is available in 7Li Pharmacokinetics
a very low concentration 31P Analysis of bioenergetics
 Phosphorus-31 MRS can be Measurement of pH
14 N Measurement of glutamate, urea, ammonia
used to determine the pH of
13 C Analysis of metabolite turnover rate
brain regions and the
Pharmacokinetics of labelled drugs
concentrations of 17 O Measurement of metabolic rate
phosphorus-containing
compounds (e.g., adenosine triphosphate [ATP] and guanosine triphosphate [GTP]) that are
important in the metabolic activity of the brain.
 Additional indications include the use of MRS to measure concentrations of
psychotherapeutic drugs such as lithium in the brain. Some compounds, such as fluoxetine
and trifluoperazine (Stelazine), contain fluorine-19, which can also be detected in the brain
and measured by MRS.

Functional Magnetic Resonance Imaging (fMRI)

 Neuronal activity within the brain causes a local increase in oxygen consumption.
Consequently the local concentration of deoxyhaemoglobin increases, relative to
oxyhaemoglobin. While oxyhaemoglobin is diamagnetic (weak magnetic contrast),
deoxyhemoglobin is paramagnetic, producing an MR signal that can be detected with the T2

© SPMM Course 36
 sequence. This is called Blood Oxygen Level Dependent (BOLD) technique. This process is
the basis for functional MRI.
 fMRI is a proxy measure of tissue activity that depends on relative changes in perfusion; it
does not measure the actual neuronal metabolism.
 No radioactive isotopes are administered in fMRI; this is a significant advantage over PET
and SPECT.
 A subject can perform a variety of tasks, both experimental and control, in the same imaging
session. In resting fMRI, the brain regions that have high levels of activity during rest are
studied. These regions include the precuneus, lateral parietal regions and medial prefrontal
cortex. A network of these regions showing higher baseline activity at rest is called default
mode network or DMN.

Single Photon Emission Computed Tomography - SPECT

 SPECT uses radioactive compounds to study regional differences in cerebral blood flow
within the brain. This records the pattern of photon emission from the bloodstream which
varies according to the level of perfusion in different regions of the brain.
 Similar to fMRI it does not measure neuronal metabolism directly.
 SPECT uses compounds labeled with single photon-emitting isotopes: iodine-123,
technetium-99m, and xenon-133.
 Xenon-133 quickly enters the blood and is distributed to areas of the brain as a function of
regional blood flow. Xenon-SPECT is thus referred to as the regional cerebral blood flow
(rCBF) technique. Xenon-SPECT can measure blood flow only on the surface of the brain,
which is an important limitation.
 Assessment of blood flow to the whole brain with SPECT requires the injectable tracers such
as technetium-99m-d,l-hexamethyl propylene amine oxime (HMPAO).
 This is attached to highly lipophilic molecules that rapidly cross the blood-brain barrier to
enter brain cells. Once inside the cell, the ligands are enzymatically converted to charged
ions, which remain trapped in the cell. Thus, over time, the tracers are concentrated in areas
of relatively higher blood flow. This is the ligand most commonly used in detecting
perfusion changes in dementia.
 In addition to studying perfusion, Iodine-123 (123I)-labeled ligands for the muscarinic,
dopaminergic, and serotonergic receptors can be used to study the occupancy and
distribution of these receptors. Iodobenzamide is used for D1/D2 receptors; iomazenil is
used for GABA-A receptors; nor-β- CIT for dopamine and serotonin transporters;
epidepride for D2/D3 receptors.

© SPMM Course 37
Positron Emission Tomography – PET
 PET can be used to study blood flow, receptor distribution and metabolic activity of brain
tissue.
Purpose PET ligand
 A key difference between SPECT and Blood flow C15/H215O
PET is that in SPECT a single particle Glucose metabolism F18 deoxyglucose
is emitted, whereas in PET two Dopamine D2 receptors C raclopride
11

particles are emitted; the latter Dopamine neuron 18F dopa; 18F
density metatyrosine
reaction gives a more precise location
GABA-A receptors 11C flumazenil
for the event and better resolution of
5HT2 receptors F altanserin; setoperone
18

the image.
Striatal D2, cortical 5HT2 C methylspiperone
11

 The isotopes used in PET decay by

Serotonin synthesis rate C methyltryptophan
11

emitting positrons, with the resolution

Muscarinic receptors C scopolamine
11

closer to its theoretical minimum of 3

mm.
 Relatively few PET scanners are available because they require an on-site cyclotron to make
the isotopes.
 The most commonly used isotopes in PET are fluorine-18, nitrogen-13, and oxygen-15. These
isotopes are usually linked to another molecule, except in the case of oxygen-15 (15O).
 The most commonly employed ligand is [18F]fluorodeoxyglucose (FDG). FDG gives direct
information about neuronal metabolism. Other molecules are listed in the table below.

Diffusion tensor imaging – DTI

 DTI combines the principles of nuclear magnetic resonance and molecular diffusion.
 Diffusion refers to the random translational motion of molecules, also called Brownian
motion, that result from the energy carried by these molecules.
 During their random, diffusion-driven displacements, molecules probe tissue structure at a
microscopic scale well beyond the usual image resolution: the predominant direction of the
molecular movement can help determine the integrity and trace white matter tracts.
 In traditional diffusion weighted images only 3 gradient directions are applied; DTI –
diffusion tensor allows multiple (e.g. 16) gradients .
 From DTI, mathematical measures such as the Fractional Anisotropy (FA) can be calculated.
This is an index of the integrity of white matter.
 The principal direction of the diffusion tensor can be used in tractography to infer the white-
matter connectivity of the brain.

© SPMM Course 38
Neuroimaging findings in psychiatry:
Neuroimaging findings in depression
Periventricular and deep WM hyperintensities
Subcortical – thalamic and striatal hyperintensities
Decreased frontal and basal ganglia volumes
Decreased metabolism in prefrontal cortex, Anterior cingulate & amygdale
Higher prefrontal metabolism (esp. anterior cingulate) predict better treatment response
Higher 5HT2A receptor density – higher dysfunctional negative thoughts
Increased MAO-A activity (especially women)
Elevated D2 binding in untreated depression – psychomotor retardation
Therapeutic dose of SSRIs- 80% 5HT transporters occupied
Neuroimaging findings in schizophrenia
Ventricular enlargement
Loss of grey matter – especially insular cortex, anterior cingulate (medial prefrontal cortex)
and medial temporal lobe
Progressive loss of brain volume in first few years of diagnosis
fMRI reveals poor DLPFC activation in executive tasks
Decreased NAA (N-Acetyl aspartate) in PFC (neuronal loss) in MRS
Widespread reduction in DTI (diffusion tensor) – fractional anisotropy: frontal and corpus
callosum – more in chronic treated patients
Neuroimaging findings in Alzheimer’s
Ventricular enlargement
Loss of temporal lobe volume – especially hippocampus
Decreased parieto-temporal fMRI activation and SPECT blood flow

Neuroimaging findings in OCD

Both reduced and increased volumes of caudate nuclei reported.
Higher caudate blood flow due to increased metabolism. This reduces after effective treatment
of the OCD.

(Adapted from Murray, R, et al. (ed)

Essential Psychiatry, Cambridge Press)

Neuroimaging findings in
Childhood-Onset
Schizophrenia: Summary of key
grey matter structural changes
reported from Childhood-Onset
Schizophrenia samples (Rapoport &
Gogtay, 2011). In addition to what is
shown, a ventricular enlargement at
baseline and slower growth rates of
(especially right hemispheric) white
matter are also noted. From Hollis &
Palaniyappan, Rutter’s Child and
Adolescent Psychiatry, Ed: Thapar et
al...6e. Wiley & Sons.

© SPMM Course 39
DISCLAIMER: This material is developed from various revision notes assembled while
preparing for MRCPsych exams. The content is periodically updated with excerpts from
various published sources including peer-reviewed journals, websites, patient information
leaflets and books. These sources are cited and acknowledged wherever possible; due
to the structure of this material, acknowledgements have not been possible for every
passage/fact that is common knowledge in psychiatry. We do not check the accuracy
of drug-related information using external sources; no part of these notes should be used
as prescribing information.

Notes prepared using excerpts from:

 Agrell & Dehun (1998). The clock-drawing test . Age and ageing 27:399
 Lennox, B. Antibody-mediated encephalitis: a treatable cause of schizophrenia. Br J Psychiatry. 2012
Feb;200(2):92-4.
 Barton, JJS. Prosopagnosia associated with a left occipitotemporal lesion. Neuropsychologia. 2008 46(8):2214-
24
 Carlat, DJ. The Psychiatric Interview: Practical Guides in Psychiatry, 2nd Edition, 2005. Lippincott Williams
& Wilkins
 Cartlidge, N. States related to or confused with coma. Neurol Neurosurg Psychiatry 2001; 71(Suppl 1):i18-i19
 Fuller Neurological examination made easy Churchill Livingstone; 4 edition
 Higgins, E S.& George, MS. Neuroscience of Clinical Psychiatry, The: The Pathophysiology of Behavior and
Mental Illness, 1st Edition. Lippincott Williams & Wilkins 2007. Page 16
 http://bestpractice.bmj.com/best-practice/monograph/1066/diagnosis.html
 http://www.emedicine.com/EMERG/topic270.htm
 http://www.emedicine.com/neuro/TOPIC632.HTM
 Jaffe JA & Kimmel, PL. “Chronic Nephropathies of Cocaine and Heroin Abuse: A Critical Review,”
Clin J Am Soc Nephrol 1, no. 4 (July 1, 2006): 655-667.
 Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition. Lippincott
Williams & Wilkins 2007
 Katz DI, Alexander MP. Traumatic brain injury: predicting course of recovery and outcome for patients
admitted to rehabilitation. Arch Neurol 1994; 51: 661–70
 Kay J & Tasman A. Essentials of Psychiatry, 2 nd edition, 2006. John Wiley & Sons, Ltd.
 Kayser MS and Dalmau J. Anti-NMDA Receptor Encephalitis in Psychiatry. Curr Psychiatry Rev. 2011; 7(3):
189–193.
 Kipps & Hodges. J. Neurol. Neurosurg. Psychiatry 2005;76;22-30
 Koyama T, Tamai K, Togashi K (2006) Current status of body MR imaging : fast MR imaging and diffusion-
weighted imaging. Int J Clin Oncol 11:278-285.
 Lewis DA. Structure of the human prefrontal cortex. Am J Psychiatry. 2004; 161[8]: 1366
 Moo et al. J Neurol Neurosurg Psychiatry 2003;74:530-532
 Semple et al (Ed). The Oxford Handbook of Psychiatry 1st edition. Oxford University Press 2005.
 Strub & Black. The Mental Status Examination in Neurology (2000) 4 th ed. F. A. Davis Company.
 Zadikoff C and Lang AE. (2005) Apraxia in movement disorders. Brain 128:1480–97

© SPMM Course 40
  

   
Descriptive  Psychopathology  
Paper  A   Syllabic  content  5.22  
 

© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
©  SPMM  Course   1  
1. Mood and Affect:
The  terms  affective  disorder  and  mood  disorder  are  used  interchangeably  in  clinical  practice.  The  
difference  between  mood  and  affect  has  been  variously  described.  It  is  generally  accepted  that  mood  refers  
to  a  more  pervasive  emotional  state  than  affect  (as  if  climate  =  mood  and  weather  =  affect).    Both  mood  
and  affect  can  have  an  objective  and  subjective  components  though  one  school  of  thought  proposes  to  use  
the  term  mood  for  subjective  and  affect  for  objective  components  of  emotional  expression.    

Aspects of Affect:
Descriptor  
Valence   The  quality  of  affect:  i.e.  happy,  depressed,  perplexed,  anxious  or  angry  

Reactivity   Responsiveness  of  affect  to  environmental  cues  -­‐‑  One  expects  affect  to  be  reactive  to  
cues  in  the  environment;  we  laugh  on  hearing  a  joke,  blush  when  embarrassed,  etc.  If  
the  reactivity  is  conspicuously  absent,  then  this  is  called  blunted  affect  or  parathymia,  
according  to  Bleuler.  Bleuler  proposed  this  feature  as  a  primary  schizophrenic  
symptom.  

Range  of  expression   This  may  be  restricted  or  constricted  in  depression  and  anxiety  states.    

Congruence   Incongruent  affect  may  be  seen  in  hebephrenic  schizophrenia  and  learning  disability.  
For  example,  a  patient  might  maintain  a  silly,  jocular  affect  in  spite  of  receiving  a  bad  
news.    
Stability   This  refers  to  the  reasonable  maintenance  of  an  affective  state  until  a  clear  external  
stimulus  demands  a  change  in  affect.  The  absence  of  such  stability  manifests  as  a  
sudden  unprovoked  change  in  affect;  the  patient  may  break  down  into  tears  for  no  
reason  or  appear  enlightened  with  apparently  no  environmental  cues.  This  is  called  
labile  affect;  it  is  seen  in  histrionic  personality,  borderline  personality,  and  sometimes  
in  PTSD.  
Control   An  extreme  form  of  labile  affect  is  termed  as  emotional  incontinence;  it  is  seen  in  
organic  states  such  as  pseudo  bulbar  palsy  where  frontal  lobe  is  damaged.  Here  the  
patient  bursts  out  into  laughter  or  tears  within  minutes  with  no  control  over  these  
emotions  –  it  appears  as  if  the  patient  has  developed  an  incontinence  of  the  emotion  
filled  ‘bladder’.  He/she  has  little  control  over  these  expressions.  

Coexisting features of mood disturbance:

Mania  is  characterized  by  extreme  euphoria  (disturbed  emotion),  pressured  speech    (disturbed  thought)  
and  too  many  ideas  and  plans  to  be  carried  out  (disturbed  will).  It  is  not  a  pure  mood  or  affective  disorder  
in  this  sense.  The  terms  euphoria,  ecstasy  and  expansiveness,  refer  to  various  degrees  of  an  elevated  mood,  
but  they  do  not  include  thought  or  will  component.  The  same  applies  to  the  term  ‘depression’  in  clinical  
sense  –  it  includes  mood,  will  and  thought  components  and  not  just  sad  affect.  

Melancholia  is  probably  the  oldest  of  terms  used  in  psychopathology.  It  is  defined  as  a  quality  of  mood,  
which  is  distinct  from  grief,  occurring  in  association  with  significant  psychomotor  retardation  often  with  
somatic  symptoms  of  depression  (as  described  in  ICD-­‐‑10).    It  is  very  characteristic  of  depression;  patients  
often  describe  this  as  a  deeply  distressing  affective  state.  

©  SPMM  Course   2  
Mixed  states:  It  is  long  appreciated  that  between  the  extremes  of  mania  and  depression  various  mixed  
states  exist.  In  fact,  mixed  states  are  commoner  than  pure  mania  or  depression,  according  to  the  recent  
literature.    

s.  no   Type   Mood   Will   Thought  

1   Manic  stupor   High   Low   Low  

2   Mania  with  poverty  of  thought   High   High   Low  

3   Inhibited  mania   High   Low   High  

4   Depressive  mania   Low   High   High  

5   Excited  depression   Low   High   Low  

6   Depression  with  flight  of  ideas   Low   Low   High  

Over  the  years,  the  six  Kraepelinian  mixed  states  have  dwindled  into  just  two  varieties:  1.  Dysphoric  
Mania  (when  predominant  mania  is  present  with  some  depressive  symptoms)  and  2.  Depressive  Mixed  
State  (when  full  depression  is  present  with  some  manic  symptoms).    

Other  terms  such  as  agitated  depression  (full  depression  with  psychomotor  agitation),  anxious  depression  
(depression  with  marked  anxiety),  irritable  depression  (depression  with  marked  irritability),  and  mixed  
hypomania  (hypomania  with  some  depressive  symptoms)  are  used  in  this  context  but  are  better  avoided.  

Pain symptoms:
Pain  is  frequently  associated  with  mood  disturbances.  It  is  difficult  to  distinguish  organic  and  non-­‐‑organic  
pain  as  often  there  are  mixed  elements  of  both  in  a  pain  syndrome.  Nevertheless  certain  differences  exist  
as  listed  below.  

Psychiatric  vs.  Organic  pain:    

Organic  pain   Non-­‐‑organic  pain  

Less  diffuse   More  diffuse  
More  anatomical  confinement   Less  anatomical  
Often  fluctuant  and  remits  during  intervals   Often  constant  and  unremitting  
Usually  characteristic  quality   Difficult  to  describe  the  quality  
Progression,  if  occurs,  will  have  tissue  boundaries   Progresses  without  tissue  confinement  generally  

Anywhere  in  the  body   Head  and  neck,  back  are  the  most  common  
Can  wake  patients  from  sleep   Rarely  wakes  one  from  sleep  
Tenderness  may  be  present   Tenderness  very  rare  
May  have  typical  postural  changes  e.g.  intracranial   Usually  no  postural  variation  
pathology  
 

©  SPMM  Course   3  
For  somatoform  pain,  head  and  neck  are  the  most  common  sites.  In  somatisation  disorder,  
musculoskeletal  symptoms  are  the  commonest.  In  hypochondriasis  gastrointestinal  symptoms  
predominate.  

Anhedonia & Alexithymia:

Anhedonia  was  a  term  coined  by  Ribot;  it  refers  to  the  inability  to  derive  pleasure  in  life  often  leading  to  
diminished  interests  in  activities.  It  may  be  of  two  types:  physical  and  social  anhedonia.  Physical  
anhedonia  represents  a  defect  in  the  ability  to  experience  physical  pleasures,  such  as  pleasures  of  eating,  
touching  etc.,  while  social  anhedonia  represents  a  defect  in  the  ability  to  experience  interpersonal  pleasure,  
such  as  pleasure  of  being  with  people,  talking,  etc.  Anhedonia  is  common  in  melancholic  depression  with  
somatic  syndrome  where  it  is  a  core  symptom.  It  is  also  observed  as  a  part  of  the  negative  syndrome  of  
schizophrenia.  In  schizophrenia,  anhedonia  is  considered  to  be  more  social  or  interpersonal  than  a  
personal/physical  deficit.    

Alexithymia  was  first  described  by  Sifneos.  A-­‐‑  Absence  or  defective  +  LEXI  –words  +  THYMIA    -­‐‑  emotion  
i.e.  Difficulties  in  using  words  to  express  emotions.  It  is  often  accompanied  by  
1. Diminution  of  fantasy.  
2. Reduced  symbolic  thinking  
3. Literal  thinking  concerned  with  details    
4. Difficulties  in  recognizing  one'ʹs  own  feelings  
5. Difficulties  in  differentiating  body  sensations  and  emotional  states.  
6. A  ‘robot-­‐‑like  existence’  is  suggested  –  but  patients  rarely  complain  in  these  terms.  
It  is  especially  seen  in  psychosomatic  illnesses,  somatoform  disorders,  depression,  PTSD,  personality  
disorders  and  paraphilias.  Note  that  in  some  cultures  especially  south  Asian,  somatic  metaphors  are  used  
in  describing  emotions  often.  

Mood and perception of time:

This  may  be  altered  in  patients  with  depression  or  mania.  In  a  study  of  32  acutely  depressed,  30  acutely  
manic,  and  31  control  subjects,  the  experience  of  time  was  assessed  both  subjectively  (with  a  visual  analog  
scale)  and  objectively  (with  Chronotest  software  and  the  Trail  Making  Test  (TMT)).  Both  manic  and  
depressed  subjects  were  slow  in  the  TMT,  but  the  subjective  experience  of  time  was  slowed  in  the  
depressed,  sped  up  in  the  manic,  and  unchanged  in  the  control  subjects  (Bschor  et  al.  2004).    

An  allied  phenomenon  seen  in  some  patients  with  schizophrenia  is  the  age  disorientation.  In  chronic  
schizophrenia  patients  may  lose  the  track  of  their  age  and  may  claim  that  they  are  of  an  age  at  least  5  years  
different  from  their  actual  age.  Age  disorientation  is  defined  as  misstating  one'ʹs  age  by  5  or  more  years.  It  
is  observed  in  a  substantial  number  of  chronically  ill,  institutionalized  schizophrenic  patients.  Prevalence  
estimates  have  been  limited  to  data  from  surveys  of  hospitalized  mental  patients  in  chronic  care  facilities,  
where  approximately  25%  of  patients  are  age  disoriented.  The  majority  of  age-­‐‑disoriented  schizophrenic  
patients  understate  their  age.  In  fact,  an  additional  10%  of  schizophrenic  subjects  report  an  incorrect  
subjective  age  that  is  within  5  years  of  their  age  at  illness  onset.  Age-­‐‑disoriented  patients  are  generally  
older,  have  a  longer  current  admission,  and  were  younger  at  first  admission  than  age-­‐‑oriented  patients.  
Age  disorientation  is  associated  with  early  onset  and  poor  prognosis.  
©  SPMM  Course   4  
2. Disorders of perception
Perception   consists   of   two   parts   –   receiving   information   from   a   sensory   modality   (bottom   up)   and  
interpretation   or   processing   of   the   sensation   instantaneously   using   cognitive   faculties   (top   down).  
Normally,  any  perceived  object  corresponds  to  the  stimulus  that  elicited  it.  

Perception   occurs   in   visual,   auditory,   tactile,   gustatory,   olfactory,   kinaesthetic   or   proprioceptive  

modalities  –  any  distortions  in  perception  could  also  occur  in  any  of  these  domains.    

Perceptual  errors  can  occur  at  different  levels  –  

Perceptual  disorder   Stimulus   Corresponding   object   Error  

present?   perceived?  

Perceptual  distortions   Yes   Yes   Object’s  quality  altered  

Illusions   Yes   No   A  different  object  is  perceived  

Hallucinations   No   Yes   Perception  without  a  stimulus  

Negative  hallucinations   Yes   No   No  object  is  perceived  

¬ If  a  stimulus  is  perceived  as  corresponding  object  but  not  accurately  –  changes  in  physical  properties  
e.g.   size,   shape,   intensity   and   colour   -­‐‑     this   is   a   perceptual  distortion.   In   depression   and   hypoactive  
delirium  there  is  dulled  perception;  intense  perceptions  can  occur  in  mania,  hyperactive  delirium  and  
drug-­‐‑induced  states  (hallucinogens).  Hyperacusis  especially  is  seen  in  migraine  and  alcohol  hangover.    

§ Changes  in  the  shape  of  objects  especially  with  the  loss  of  symmetry  are  called  dysmegalopsia.    
§ The  objects  can  shrink  in  size  –  micropsia  or  enlarge  -­‐‑  macropsia.    
§ These   are   usually   organic   –   could   be   ictal   (parietal)   or   ocular   (accommodation   errors   –  
paralysed   accommodation   can   cause   micropsia),   rarely   in   acute   schizophrenia.   Hallucinogens  
(Mescalin)  can  also  change  the  colour  of  perceived  objects  or  make  components  of  an  object  e.g.  
body  parts  –  to  be  seen  detached  in  space.  
¬ Stimulus  is  perceived  as  an  object  but  not  corresponding  to  the  source  –  both  stimulus  and  object  are  
present,  but  different  from  each  other  –  illusions.    
¬ There  is  no  stimulus  but  perception  occurs  –  hallucinations.  
¬ There  is  a  stimulus  but  no  perception  occurs  –  negative  hallucinations.  

©  SPMM  Course   5  
  

The  above  table  has  been  pictorially  represented  below:  

STIMULUS PERCEIVED EXPERIENCE

OBJECT
 

Imagery & Illusions

The  imagery   is   not   a   perception   because   there   is   no   stimulus   involved   and   no   object   perceived;   it   is  
essentially   a   fantasy.   Imagery   refers   to   images   produced   voluntarily   with   complete   insight   that   they  
are  mental,  not  external  phenomena.  They  also  lack  the  objective  quality  of  hallucinations  and  normal  
sense  perceptions.    

One  form  of  imagery  called  eidetic  imagery  is  considered  to  be  a  special  ability  of  memory  wherein  
visual  images  are  drawn  from  memory  accurately  at  will  and  described  as  if  being  perceived  currently.  
This   is   noted   in   children   (2-­‐‑15%   school   goers)   and   may   be   a   part   of   religious   experiences;   no  
pathological  association  is  noted  consistently.  

Illusions   may   be   difficult   to   differentiate   from   hallucinations   if   the   source   of   stimulus   is   difficult   to  
trace  –  e.g.  ‘Did  I  see  the  devil  on  the  wall  or  from  the  wallpaper  pattern?’  But,  fortunately,  these  are  
qualitatively  different  and  so  eliciting  the  description  patiently  can  help.  There  are  three  major  types  of  
illusions:  

©  SPMM  Course   6  
  

Type  of   Context   Quality   Effect  of   Example  

illusion   concentration  

Affect   Prevailing  emotional  state  leads  to   Often   Disappears  on   A  

illusion   misperceptions   fearful,   focussing  the   depresse
emotion   object  with   d  patient  
provoking.   extra   reading  
concentration   ‘deed’  as  
‘dead.'ʹ  

Pareidolic   Formed  objects  from  ambiguous  stimuli,   Often   On  paying   Seeing  

illusion   coloured  by  prevailing  emotion;  not   playful  and   extra  effort,   cars  in  
entirely  due  to  inattention  or  affective   whimsical.   the  object   the  cloud  
change   intensifies  –  
does  not  
disappear.  

Completion   Stimulus  that  does  not  form  a  complete   Due  to   Disappearance   CCOK  is  
illusion   object  might  be  perceived  to  be  complete   inattention   on   read  as  
concentration   COOK  
is  the  rule.  

In  pareidolia,  fantasy  and  imagery  play  equal  parts,  apart  from  the  actual  sense  perception.  It  is  common  
in  delirium  especially  in  children  when  febrile,  hallucinogen  use.  Pareidolia  are  under  some  degree  of  
voluntary  control  and  not  characteristic  of  any  psychotic  illness.  

Pseudohallucinations:
Though   the   distinction   between   these   two   is   not   always   clinically   relevant,   presentation   with   consistent  
pseudo   hallucinations   with   no   other   psychotic   features   should   make   one   question   the   veracity   of   the  
psychopathology.  

Pseudohallucinations:    There  are  two  different  definitions:  

o Involuntary  hallucination-­‐‑like  experiences  occurring  in  inner  subjective  space,  with  a  vivid  outline  
that   are   absolutely   different   from   normal   sense   perceptions   and   hallucinations   (Kandinsky,  
Jaspers  &  Sims).    
o Hallucinations   that   are   recognized   to   be   unreal   and   self-­‐‑originating   are   pseudohallucinations  
according  to  Hare.  European  psychopathologists  use  the  former  definition  more  often.  

Pseudohallucinations  are  not  pathognomonic  of  anything;  they  are  not  always  pathological.    

©  SPMM  Course   7  
They   are   intermediate   between   fantasy   (imagery)   and   hallucinations.   Like   fantasy   they   are   in   subjective  
space,   lack   quality   of   concrete   reality,   have   quality   of   idea   and   so   not   sought   in   other   modalities  
simultaneously  (not  searched  for,  no  attempts  to  reach  out  etc.)  and  appreciated  to  be  observer-­‐‑dependent,  
self-­‐‑originating.  Like  a  hallucination,  they  have  a  clear  outline,  vivid,  retained  for  the  good  length  of  time,  
cannot  be  dismissed  at  will  and  are  behaviourally  and  emotionally  relevant  i.e.  acted  upon  or  felt  for.    

The  hallucinatory  experiences  of  bereavement  and  in  Ganser’s  state  are  pseudohallucinations  

 
TRUE  HALLUCINATION   PSEUDO  HALLUCINATION  
 
 Objective,  outside  spatial  location   Subjective  spatial  location  
Absence  of  insight   The  presence  of  insight,  often.    
Sought  in  other  modalities  (see  text)   Not  sought  in  other  modalities  usually.    
Often  seen  in  psychosis   Often   in   personality   disorders,   following  
trauma,  dissociative  experiences.    

Hallucinations
Hallucinations   have   several   important   qualities   that   are   essential   in   differentiating   from   other   mental  
phenomena:  

1. They   take   place   at  the  same  time   as   other   sensory   perceptions   –   e.g.   the   voice   is   heard   even   when  
music   is   playing,   or   someone   is   talking   to   me.   So   they   are   different   from   dreams   where   no   real  
component  exists  alongside  the  false  perception.  
2. They  take  place  in  the  same  space  as  other  perceptions  -­‐‑   angel  is  seen  standing  at  the  corner  of  my  
room.  This  is  different  from  fantasy  or  imagery  which  takes  place  in  subjective  space.  
3. They  are  experienced  as  sensations  –  not  as  thoughts  –  contrast  from  obsessional  images.  
4. The   percept   has   all   qualities   of   an   object   –   i.e.   it   is   believed   that   it   can   be   experienced   in   other  
modalities  too,  like  a  real  object  which  can  be  seen,  felt,  smelt  and  heard.  This  is  why  hallucinators  
search  for  the  man  behind  the  voice  or  try  and  reach  out  and  touch  visual  percepts.  
5. They   are   involuntary   –   appearance   cannot   be   controlled;   independent   –   will   exist   even   when   not  
perceived  by  the  hallucinators;  may  lack  the  quality  of  publicness  –  not  every  one  could  hear  and  see  
them.  
Auditory  Hallucinations:    

§ Elementary,  unstructured  hallucinations  are  seen  in  acute  organic  states.    

§ Musical   hallucinations   are   similar   to   Charles   Bonnet   syndrome   in   visual   domain   –   can   occur   in  
those  with  deafness,  also  in  organic  conditions.  Formed  auditions  like  voices  –  as  in  thought  echo  –  
cannot  be  elementary.  
Phonemes   are   any   auditory   hallucinations   that   occur   as   human   voices.   Schizophrenic   phonemes   are  
usually  multiple,  may  or  may  not  be  recognizable,  usually  male  with  a  different  accent,  speaking  in  one’s  
mother   tongue   and   usually   episodic   -­‐‑   almost   never   continuous.   When   a   same   word   is   repeated  
continuously,   normal   subjects   hear   phonetically   linked   but   different   words.   Hallucinating   schizophrenia  

©  SPMM  Course   8  
subjects   hear   different   words   that   have   no   phonetic   connection   to   the   original   repeated   word   –   this   is  
called  verbal  transformation  effect.  Patients  could  be  distracted  away  from  their  voices,  but  it  is  the  attention  
paid  to  the  external  stimulus  which  is  more  important  than  the  degree  of  external  stimulus  used  to  distract.  
Alcoholic  hallucinosis  initially  starts  as  fragmented  voices,  later  organised  into  clear  voices.  

Visual   hallucinations:   Occipital   lobe   tumours,   postconcussional   states,   epileptic   twilight   state,   hepatic  
failure  (any  toxic  delirium),  dementia  are  some  causes  for  visual  hallucinations.  30%  of  old  age  psychiatric  
referrals   have   visual   hallucinations.   Solvent   sniffing   and   hallucinogens   can   cause   elementary   visual  
hallucinations  like  light  flashes.  Simultaneous  visual-­‐‑verbal  hallucinations  –  green  man  speaking  to  me  –  
is  seen  in  TLE.  Visual  hallucinations  are  very  uncommon  in  schizophrenia  (But  Andreasen  quotes  30%  in  a  
series   observed   with   acute   schizophrenia).   Reports   of   “black   patch”   psychosis   were   frequent   following  
simultaneous  bilateral  cataract  surgery  in  the  early  era  of  the  procedure,  attributed  to  sensory  deprivation,  
leading  to  the  recommendation  that  only  one  eye  be  operated  on  at  a  time.  It  was  subsequently  recognized  
that   “black   patch”   psychosis   was   a   relatively   uncommon   postoperative   delirium   partly   due   to  
anticholinergic  eye  drops.*  

Charles   Bonnet   Syndrome:     Elderly   patients,   with   normal   consciousness   and   no   brain   pathology,   with  
reduced  visual  acuity  due  to  ocular  problems,  experience  vivid,  distinct,  usually  well-­‐‑coloured  (in  contrast  
to   real   sensation   that   is   blurred   due   to   eye   disease)   formed   hallucinations   –   mostly   humans,   at   times  
animals  and  cartoons.  These  objects  usually  show  movement,  and  can  be  voluntarily  controlled  –  disappear  
on   closing   the   eyes;   insight   about   unreality   is   usually   preserved   –   though   they   may   evoke   emotions  
including  fear  and  joy.  About  1/3rd  are  elementary;  usually  the  hallucinations  are  located  in  external  space.      

Podoll'ʹs   criteria   for   diagnosis   include:   Elderly   person   with   normal   consciousness   with   visual  
hallucinations;  not  in  the  presence  of  delirium,  dementia,  psychosis,  intoxication  or  neurological  disorder  
with  lesions  of  central  visual  cortex;  reduced  vision  resulting  from  eye  disease  (most  commonly  macular  
degeneration).  The  syndrome  can  occur  in  people  with  normal  vision1,2  

Lilliputian  hallucinations  can  occur  in  visual  or  haptic  mode  –  they  usually  involve  seeing  tiny  people  or  
animals   (or   feeling   diminutive   insects   crawling   if   haptic)   and   are   seen   in   delirium   tremens   and   unlike  
other   organic   visual   hallucinations,   Lilliputian   hallucinations   can   be   accompanied   by   pleasure   though  
often   intermingled   with   terror.   These   are   not   the   same   as   micropsia.   Patients   with   DT   often   have   a  
prodromal  affect  or  pareidolic  illusions  before  these  hallucinations.  

Autoscopic   hallucinations   are   the   visual   experience   of   seeing   oneself.   Males   predominate   2:1,   impaired  
consciousness   is   a   common   accompaniment   and  depression   is   the   commonest   psychiatric   cause.   They   are  
also  called  phantom  mirror  images  and  may  take  the  form  of  pseudohallucinations.  Schizophrenia  (usually  
pseudo),  TLE,  parietal  lesions  (organic  states  more  likely  to  have  true  hallucinations)  are  also  implicated.  
In  negative  autoscopy,  one  looks  into  a  mirror  and  sees  no  image  at  all.  

Palinopsia:  palin  for  "ʺagain"ʺ  and  opsia  for  "ʺseeing"ʺ.  It  is  a  visual  disturbance  that  causes  images  to  persist  
even  after  their  corresponding  stimulus  has  left.  It  is  seen  in  LSD  use,  migraine,  occipital  epilepsy,  head  
trauma.   It   is   similar   to   afterimage,   but   colour   inversion   (usually   shadows   or   distorted   colours   noted   in  
afterimages)  is  conspicuously  absent.    

©  SPMM  Course   9  
Somatic   hallucinations:   These   can   be   divided   into   superficial,   visceral   and   kinaesthetic.   The   superficial  
somatic   hallucinations   are   tactile   (haptic   -­‐‑   touch),   hygric   (fluid   –   wetness   etc.)   and   thermic   (heat   or   cold).  
Visceral   hallucinations   are   usually   pain-­‐‑like   sensations   arising   from   deep   viscera   like   liver.   These   are  
sometimes   termed   as   coenesthetic   hallucinations   and   suggest   schizophrenia.   Kinaesthetic   or  
proprioceptive   hallucinations   refer   to   joint   or   muscle   sense,   often   linked   to   bizarre   somatic   delusions.  
They  are  also  seen  in  benzodiazepine  withdrawal  and  alcohol  intoxication.  Formication  (formic  acid  –  from  
ant)   is   a   special   type   of   haptic   hallucination   –   unpleasant   sensation   of   little   animals   or   insects   crawling  
under  the  skin,  seen  in  DT  and  cocaine  intoxication.  Tactile  hallucinations  can  be  seen  in  parietal  seizures.  
Superficial   somatic   hallucinations   are   almost   never   noted   in   TLE   though   the   visceral   sense   of   ‘raising  
epigastrium’  is  seen.  The  common  experience  of  the  phantom  limb  is  a  body  image  disturbance  and  not  a  
hallucination;  though  it  is  in  external  space,  it  does  not  satisfy  other  qualities  of  hallucination  and  patients  
are   aware   of   unreality   usually.   It   is   a   body   image   disturbance   with   a   neurological   basis.   Somatic  
hallucinations   may   or   may   not   be   accompanied   by   passivity   delusions.   Without   the   passivity   delusions,  
they  cannot  be  classed  as  a  First  rank  symptom.  

Olfactory   hallucinations   can   occur   in   the   aura   of   TLE   –   usually   burning   smell   or   urine   smell.   In  
depression,  this  can  be  an  adjunct  to  nihilism.    

Gustatory   hallucinations   e.g.,   bitter   taste   of   poison   can   give   rise   to   delusions   of   persecution   in  
schizophrenia.  They  are  also  seen  in  TLE.  

Extracampine  hallucinations:  Hallucinations  that  occur  outside  the  normal  field  of  perception  e.g.,  images  
seen   behind   your   back,   under   your   sternum   or   hearing   voices   from   Inverness,   etc.   They   occur   in  
schizophrenia,   epilepsy   and   also   in   hypnagogic   hallucinations   of   healthy   people   –   so   not   diagnostically  
important.  

Both  illusions  and  hallucinations  are  not  necessarily  pathological  though  they  both  are  false  perceptions,  
along   with   pseudohallucinations.   For   example   hypnagogic   hallucinations   (hallucinations   when   going   to  
sleep  –  go  for  gogic  -­‐‑  usually  auditory.  Also  seen  in  Narcolepsy-­‐‑cataplexy.  They  can  be  visual  or  tactile  too.  
First   noted   by   Aristotle)   and   hypnopompic  
HYPNAGOGIC  HALLUCINATIONS  
hallucinations   (hallucinations   when   waking   up)  
can   occur   in   normal   individuals.   Hallucinations   3  times  more  common  than  hypnopompic  
also   occur   in   glue   sniffing,   post-­‐‑infective   37%  normal  adults  experience  at  least  once  
depression,   children   with   fevers   and   in   phobic   Hypnopompic  is  more  specific  for  narcolepsy  
anxiety.   Sensory   deprivation   in   normal   healthy   EEG  shows  alpha  rhythm  (subject  not  awake)  
people  can  also  produce  hallucinations.  They  are   Hearing  one’s  name  called  is  the  most  common  
not   more   frequent   in   schizophrenia   than   other  
conditions.  

Functional   hallucinations:   An   external   stimulus   provokes   hallucination,   and   both   hallucination   and  
stimulus  are  in  same  modality  but  individually  perceived.  e.g.  voices  heard  whenever  the  noise  of  water  
running   through   the   tap   is   heard.     They   are   not   illusions   –   as   the   stimulus   is   perceived   appropriately  
(noise  of  water),  but,  in  addition,  there  is  another  perception  (voices)  without  any  appropriate  object.    

©  SPMM  Course   10  
Reflex   hallucinations:   These   are   hallucinations   in   one   modality   provoked   reflexively   by   a   stimulus   in  
another   modality   e.g.   seeing   an   angel   whenever   listening   to   music.   They   are   similar   to   functional  
hallucinations   in   that   there   is   a   stimulus,   which   is   perceived   normally,   followed   by   a   hallucinatory  
perception  –  only  difference  being  the  modality  of  stimulus  and  perception  being  same  in  functional  while  
different   in   reflex   hallucinations.It   is   important   to   differentiate   synesthesia   from   reflex   hallucinations   in  
EMIs.  In  synesthesia  it  is  the  music  that  is  seen  –  the  stimulus  and  object  of  perception  remain  the  same  albeit  in  
different  modalities  -­‐‑   the  patient  does  not  claim  that  she  could  see  Jesus  or  angel.  Also  the  perceptions  are  
simple,  unformed  and  non-­‐‑bizarre  in  synesthesia  e.g  colours;  in  reflex  hallucination  these  are  formed  voices,  
vivid  images  like  angels  etc.  The  stimulus  –perception  sequence  is  usually  completed  before  hallucination  
occurs  in  reflex  hallucination  –  ‘I  heard  the  music  and  then  came  the  angel’;  in  synesthesia  music  itself  is  
seen  as  colour  –  the  experiences  are  simultaneous.  

Synaesthesia:
It  was  Francis  Galton  (1880)  who  first  reported  the  condition  called  synaesthesia.  He  noticed  that  a  certain  
number   of   people   in   the   general   population,   who   are   otherwise   completely   normal,   seemed   to   have   a  
certain   peculiarity:   they   experience   sensations   in   multiple   modalities   in   response   to   stimulation   of   one  
modality.   The   phenomenon   of   perceiving   a   stimulus   of   one   modality   in   a   different   modality   (may   be  
single   or   multiple   modalities)   is   called   synesthesia.   E.g.   tasting   the   music,   hearing   colours   and   smelling  
voices.  It  is  not  a  hallucination  as  the  perceived  object  has  an  appropriate  stimulus.  The  original  stimulus  
is  usually  perceived  in  appropriate  modality  too  when  the  cross  modality  perception  occurs  (syn  –  joint,  
simultaneous).   It   is   common   in   females   4:1   to   6:1,   runs   in  families   and   colour-­‐‑number   synesthesia   is   the  
most   common   form.   It   is   thought   to   be   due   to   extensive   cross   wiring   between   multimodal   association  
regions  in  some  people,  probably  due  to  failed  selective  pruning.  Several  pieces  of  evidence  support  the  
notion  that  indeed  synesthetic  experience  has  a  neural  basis:    

1. There   is   a   remarkable   consistency   of   associations   (e.g.,   sound–color   associations)   over   time.   For  
example,  Baron-­‐‑Cohen  et  al.  found  a  consistency  of  92%  of  color–sound  associations  after  1  year  in  
13  synesthetic  subjects  but  only  a  37%  consistency  (after  1  week)  in  a  control  group.    
2. There   is   evidence   that   synesthesia   can   be  acquired   in   the   course  of   neurological   illnesses   such   as  
multiple  sclerosis,  temporal  arteritis,  tumors  to  the  sella  region,  and  others.  
3. Synesthetic  experiences  can  be  induced  by  ingestion  of  drugs  such  as  mescaline.    
4. There   appear   to   be   differences   between   nonsynesthetes   and   synesthetes   in   measures   of   cerebral  
blood  flow.    

©  SPMM  Course   11  
  

©  SPMM  Course   12  
3. Delusions
 

DSM-­‐‑IV  defines  a  delusion  as  “A  false  belief  …  that  is  firmly  sustained  despite  what  almost  everyone  else  
believes  and  despite  what  constitutes  incontrovertible  and  obvious  proof  or  evidence  to  the  contrary”.  
This  definition,  though  very  useful,  conceals  the  multidimensionality  of  delusional  experience,  which  is  
now  well  endorsed  by  cognitive  psychologists,  phenomenologists,  philosophers  as  well  as  clinicians.  

Do  delusions  exist  in  a  continuum?  

Some  authors  suggest  that  ‘delusions  and  hallucinations  are  commonplace  in  healthy  populations,  with  
prevalence  up  to  approximately  25%  depending  on  the  definitional  criteria,  and  so  psychosis  exists  in  a  
continuum  model’.  This  claim  is  yet  to  be  validated  and  established.  (Lincoln,  2007).    

Using  data  based  solely  on  self-­‐‑report  measures,  Lincoln  (2007)  found  that  high  distress  associated  with  
beliefs  seems  to  be  a  relevant  characteristic  of  delusions  in  persons  with  schizophrenia,  compared  to  
‘delusion-­‐‑like  beliefs  in  common  population’.  The  presence  of  hallucinatory  experiences  accompanying  
delusions  did  not  differ  between  schizophrenia  and  ‘common’  population.    

Are  delusions  really  persistent?  

Though  classically  defined  as  persistent  belief,  doubts  have  been  cast  on  this  of  late.  In  a  follow-­‐‑up  of  
nearly  1100  acutely  hospitalized  psychiatric  patients  who  were  re-­‐‑interviewed  at  10-­‐‑week  intervals  for  1  
year,  it  was  demonstrated  that  most  delusions  exhibited  a  high  degree  of  plasticity;  in  nearly  one-­‐‑third  
delusions  completely  subsided  on  follow-­‐‑up  (Applebaum  et  al.  2004).  

Delusional  ideation  is  more  likely  to  persist  in  never  married,  older  patients,  those  with  schizophrenia,  
and  with  delusions  of  thought  broadcasting,  those  with  higher  degree  of  preoccupation  and  higher  
behavioural  relevance,  and  those  with  more  than  one  primary  delusion.    Even  when  delusional  experience  
persists  in  certain  patients,  this  does  not  mean  that  the  same  delusion  will  be  maintained;  considerable  
change  in  content  was  noted  during  the  follow-­‐‑up.  

What  are  the  dimensions  of  delusions?  

Kendler  (AJP,  1983)  has  listed  the  dimensions  of  delusional  experiences.      

The  dimensions  of  delusions  include    

1. Conviction:  The  extent  to  which  the  patient  believes.  

2. Extension:  The  extent  to  which  the  belief  extends  to  various  spheres  of  life.  

3. Disorganisation  (or  organisation):  the  degree  of  internal  consistency  and  systematisation  of  the  
belief.  

4. Bizarreness:  The  implausible  quality  of  the  belief  (especially  in  schizophrenia).  4%–8%  of  patients  
receive  a  diagnosis  of  schizophrenia  because  of  the  presence  of  Bizarre  Delusions.  Bizarreness  is  
defined  using  the  following  notions:  physical  (or  logical)  impossibility  and  overall  implausibility  or  

©  SPMM  Course   13  
 incomprehensibility  with  the  lack  of  grounding  in  ordinary  experience.  Most  bizarre  delusions  are  
Schneiderian  (i.e.  of  FRS  type).  

5. Pressure:  The  extent  to  which  the  patient  is  preoccupied  and  distressed.  

6. Acting  on  delusion:  The  extent  to  which  the  belief  drives  behaviour    

7. Seeking  evidence:  The  extent  to  which  the  patient  questions  the  veracity  of  belief  or  seeks  to  
strengthen  the  belief.  Often  patients  with  delusions,  do  not  need  any  external  proof  or  evidence,  
and  despite  showing  evidence  to  contrary,  will  continue  to  hold  their  delusional  beliefs.  

8. Lack  of  insight.  

   

 
Conviction
 

  Insight Extension

  DELUSION Disorganis
Evidence ation
 

  Action Bizareness
 
Distress
 

Primary  delusions:  

 These  are  defined  in  two  different  ways    

1.  Jaspers’  concept:  primary  delusions  are  the  true,  un-­‐‑understandable  beliefs  that  arrive  fully  
formed  and  cannot  be  reduced  further  to  any  other  mental  experiences.  This  has  been  challenged  
recently.    

2.  Primary  delusions  are  the  first  psychopathology  to  occur  in  the  course  of  symptoms  (temporal  
sequence).    

Often  both  are  true  i.e.  they  are  irreducible  and  precede  other  mental  phenomena.  

There  are  4  types:  

1. Autochthonous  delusions  or  delusional  intuitions  or  simply,  primary/true  delusions:  These  are  
ideas  that  occur  de  novo,  or  'ʹout  of  the  blue'ʹ  -­‐‑  takes  form  in  an  instant,  without  identifiable  
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 preceding  events,  as  if  full  awareness  suddenly  burst  forth  in  an  unexpected  flash  of  insight,  like  a  
bolt  from  the  blue.  This  can  be  a  quite  elaborate  delusional  system  on  arrival  itself.  Wernicke  
formulated  the  concept  of  autochthonous  delusions.  Autochthonous  stands  for  ‘out  of  soil’,  
‘aboriginal’.  

2. In  delusional  perception,  a  normally  perceived  object  is  given  a  new  meaning,  usually  in  the  sense  
of  self-­‐‑reference  -­‐‑  the  conclusion  being  entirely  unwarranted,  the  perception  is  normal.  Hence,  it  is  
a  two-­‐‑staged  process  –  normal  perception  preceding  the  attachment  of  delusional  significance;  these  
two  steps  need  not  be  simultaneous  -­‐‑  might  even  be  separated  for  years!  The  only  type  of  delusion  
included  in  Schneider'ʹs  first-­‐‑rank  symptoms  is  delusional  perception.  

3. Delusional  mood  or  atmosphere  refers  to  the  sense  of  perplexity  and  uncertainty  that  exists  
during  a  prodrome  of  psychosis,  usually  ending  in  an  autochthonous  delusion  which  will  make  
sense  of  the  perplexity  on  arrival.  Delusional  mood/atmosphere  can  precede  other  primary  
delusions.  It  is  the  only  psychiatric  phenomenon  that  can  directly  precede  and  causally  related  to  
primary  autochthonous  delusion.  Note  that  delusional  mood  is  a  specific  affective  experience  –  not  
thought  content.  

4. Delusional  memory  can  be  of  two  types.  It  can  be  a  retrospective  delusion  where  something  that  
never  happened  and  so  false,  irrational  or  bizarre  is  reported  as  if  occurred  in  the  past  and  
recollected  now.  E.g.,.  A  male  schizophrenia  patient  said  I  had  a  hysterectomy  at  age  3  and  since  
then  I  became  a  man.  Sometimes  a  normal  memory  might  be  delusionally  elaborated  –  “My  dad  
bought  me  a  camera  when  I  was  seven,  now  I  understand  it  is  because  he  was  homosexual”.  It  is  
difficult  sometimes  to  say  what  is  fact  and  what  is  not  though  the  distinction  between  above  two  
variants  is  more  an  academic  exercise.  More  importantly  delusional  perception  can  mimic  
delusional  memory  when  the  first  stage  of  normal  perception  is  actually  a  ‘recollected’  normal  
perception  from  memory.  But  in  spite  of  this  delusional  perception  is  a  two  stage  process  –  e.g.  “I  
saw  an  envelope  yesterday  (normal  perception  but  recollected  from  memory),  I  realised  my  
stomach  is  upturned”.  

Primary  delusions  do  not  carry  any  prognostic  significance  in  schizophrenia  though  they  have  diagnostic  
relevance.  While  primary  delusions  can  occur  in  epileptic  psychoses,  they  are  not  generally  associated  with  
epilepsy  when  they  occur  in  psychotic  disorders.  Primary  delusional  experiences  occur  more  in  acute  
stages  of  schizophrenia  and  are  not  seen  in  chronic  schizophrenia,  due  to  being  mixed  with  secondary  
delusions,  hallucinations,  FTD,  etc.  Other  delusions  that  follow  a  primary  delusion  or  other  mental  
phenomena  like  hallucinations,  affective  disturbances,  etc.  are  termed  as  secondary  delusions.  

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Perception   Delusional  
(factual) Judgement perception

 
 

Delusional  
Perception   Misinterpretati
(factual) Judgement
on

In  delusional  perception,  the  delusional  judgment  or  belief  that  follows  a  perception  will  be  unrelated  to  the  
prior  perception.  

Persecutory  delusions:  Primary  delusions  vary  considerably  in  content  and  are  not  characteristically  
persecutory  in  nature.  In  contrast,  most  secondary  delusions  are  often  persecutory,  making  persecutory  
themes  the  commonest  contents  of  delusions  as  a  whole.  

Paranoid  delusions:  The  term  paranoid  is  very  much  misused  in  psychiatric  practice.  Paranoia  stands  for  
‘besides  mind’.  In  the  strict  sense,  the  term  paranoid  can  be  used  only  for  self-­‐‑referential  delusions,  
irrespective  of  their  content.  For  example,  grandiose  delusion  ‘God  is  sending  a  messiah  to  help  me’,  
persecutory  delusion  ‘mafia  is  after  me’,  referential  delusion  ‘those  kids  are  talking  about  me,  cameras  are  
fixed  to  watch  me’,  hypochondriacal  delusion  or  nihilistic  delusion  ‘my  body  is  rotting  away’  etc  are  all  
paranoid  delusions.  

Monothematic  delusions:  These  can  occur  as  single  delusions  in  various  disorders  though  in  their  
commonest  form  they  occur  in  major  psychotic  illnesses  like  schizophrenia  or  affective  psychosis.  

Delusion   Example  Content  of  monothematic  delusions  

Capgras  delusion   "ʺThat'ʹs  not  my  wife;  it  is  an  impostor  who  looks  just  like  her."ʺ  

Cotard  delusion   "ʺI  am  dead."ʺ  

Fregoli  delusion   "ʺI  am  constantly  being  followed  by  people  I  know,  but  I  can'ʹt  
recognize  them  because  they  are  always  in  disguise."ʺ  

Mirrored-­‐‑self   "ʺThe  person  I  see  when  I  look  in  the  mirror  isn'ʹt  me;  it  is  some  stranger  
misidentification   who  looks  like  me."ʺ  

©  SPMM  Course   16  
De  Clerambault'ʹs  delusion   "ʺPerson  X  is  secretly  in  love  with  me"ʺ  (Person  X  being  some  important  
(erotomania)   or  famous  person  who  has  never  encouraged  this  idea)  

Othello  syndrome   "ʺMy  wife  is  having  an  affair."ʺ  

(pathological  jealousy)  

From  Coltheart,  M,  et  al.  Schizophrenia  and  Monothematic  Delusions.  Schizophrenia  Bulletin  2007  33(3):642-­‐‑647  

Morbid  jealousy  can  occur  in  various  forms  –  delusion,  overvalued  idea,  in  depression  and  in  anxiety  
states;  it  is  not  a  misidentification  syndrome.  It  was  first  described  by  Ey.  It  is  common  in  alcoholics.  It  has  
a  potential  of  violence,  especially  against  rival  than  a  partner  and  can  occur  among  cohabiters  and  
homosexual  couples  too.  

De  Clerambault’s  syndrome  is  a  type  of  delusion  of  love,  in  which  a  woman  believes  that  an  older  man  
who  is  of  higher  social  status  is  in  love  with  her.    It  is  not  related  to  delusional  misidentification.  It  is  also  
called  Old  Maid'ʹs  insanity  where  persecutory  beliefs  coexist.    

Cotard’s  syndrome  is  severe  depression  with  nihilistic  and  hypochondriacal  delusions  tinged  with  
grandiosity  and  a  negative  attitude.    It  is  not  related  to  delusional  misidentification.  Cotards  syndrome  is  
seen  in  schizophrenia  though  more  commonly  in  depressive  psychosis.  It  is  generally  seen  in  the  elderly,  
with  hypochondriacal  and  nihilistic  delusions  with  a  tinge  of  grandiosity  amidst  nihilism  (not  grandiose  
delusions!).It  is  also  reported  in  organic  lesions  and  migraine.  

Hypochondriacal  delusions:  These  are  seen  typically  in  psychotic  depression  especially  in  elderly,  as  a  
part  of  Cotard’s  syndrome.  A  specific  type  described  by  Munro  called  monosymptomatic  
hypochondriacal  psychosis  consists  of    

1. Delusions  of  body  odour  and  halitosis  (olfactory  delusions).  Some  of  these  may  have  olfactory  
reference  syndrome  –  no  olfactory  experiences  but  only  fixed  belief  about  body  order  with  anxiety  
reaction.  Paranoid  personality  disorder  is  often  associated  with  this  syndrome.  

2. Delusional  infestation  (Ekbom’s  syndrome)  It  is  a  delusion  of  parasitic  –  macroscopic  -­‐‑  infestation  
with  classical  matchbox  sign:  An  old  lady  comes  to  clinic  with  a  match  box,  of  skin  scrapings  
usually,  as  evidence  for  the  parasite  that  infests  her  causing  itching.  This  can  predate  the  onset  of  
dementia.  It  may  or  may  not  be  associated  with  a  somatic  hallucination.  

3. Dysmorphic  delusions  (misshaped  nose,  etc.).    

The  various  misidentification  syndromes  (Ellis,  2005)  are    

1. In  Capgras  syndrome,  a  person  believes  that  a  person  usually  close  to  him  has  been  replaced  by  an  
exact  double.  Capgras  syndrome  is  sometimes  referred  to  as  the  illusion  of  doubles  though  it  is  a  
delusion.  First  reported  by  Kahlbaum  (1866)  but  more  extensively  described  by  Capgras  and  
colleagues  (1923,  1924).    The  Capgras  delusion  is  classified  as  a  dangerous  delusion  and  may  be  
associated  with  violence.  Capgras  delusion  is  etiologically  heterogeneous  –  at  least  15  different  
causes  are  recorded.  It  is  now  thought  to  be  mostly  due  to  organic  brain  damage  (>50%,  Lishman)  
apart  from  being  seen  as  a  part  of  schizophrenia  or  isolated  delusional  disorder  including  brain  

©  SPMM  Course   17  
 injury  and  schizophrenia.  It  is  thought  to  be  cognitively  mediated  by  the  combination  of  reduced  
affective  responsivity  to  familiar  faces  plus  impaired  belief  evaluation,  and  neuropsychologically  it  
is  believed  to  be  due  to  the  combination  of  the  disconnection  of  the  face  recognition  system  of  the  
brain  from  the  autonomic  nervous  system  plus  damage  to  a  specific  region  of  right  frontal  lobe.    

2. In  Fregoli  syndrome,  there  is  the  false  identification  of  familiar  persons  in  strangers.  A  familiar  
person  is  thought  to  be  taking  various  disguises.  First  reported  by  Courbon  and  Fail  (1927).    They  
described  a  27-­‐‑year-­‐‑old  woman,  a  domestic  servant  with  a  passion  for  the  theatre,  who  developed  
the  delusion  that  the  actresses  Robin  and  Sarah  Bernhardt  were  persecuting  her  in  the  guise  of  
others.  They  suggested  the  term  Frégoli  delusion  with  reference  to  the  celebrated  Italian  mimic  
Léopoldo  Frégoli.  The  essential  feature  of  this  delusion  is  that  there  is  no  belief  in  actual  physical  
change:    instead  the  patient  believes  that  his/her  persecutors  can  invade  the  body  of  others.  It  is  
rare  compared  to  Capgras.    

3. In  the  syndrome  of  subjective  doubles,  the  patient  believes  that  another  person  has  been  
physically  transformed  into  his  own  self  and  the  patient  is  convinced  that  exact  doubles  of  him-­‐‑  or  
herself  exist.  

4. Intermetamorphosis  -­‐‑  A  becomes  C,  C  becomes  B  etc.  People  keep  transforming  their  physical  and  
psychological  identities.  Courbon  and  Tusques  (1932)  described  Sylvie  G,  a  49-­‐‑year-­‐‑old  woman  
who  claimed  that  objects  and  animals  seemed  altered.  People  could  change  gender  as  she  looked  at  

Feature  recognition   Affect  recognition   RESPONSE   SYNDROME  

(appearance)   (warmth)  
Looks  like  my  dad,  but  he  is   Capgras  syndrome  
not  my  dad,  probably  an  
impostor  
 
 
  My  dad,  but  does  not  look   Fregoli  syndrome  
like  him…  is  he  disguising  
himself?  
 

 
Who  is  he?   Prosopagnosia  (Seen  in  
neurological  disorders)  

   
them.    Many  people  looked  like  her  son  or  her  aunt.    She  could  distinguish  them  from  her  true  son  
only  by  examining  their  feet  (his  were  large  and  were  invariably  shod  in  dirty  shoes).  Her  husband  
might  change  appearance  into  that  of  a  neighbour  (all  except  his  eye  colour  and  missing  finger).  
There  were  no  further  reports  of  intermetamorphosis  for  46  years  since  when  five  cases  have  been  
described,  including  three  by  Young  et  al.  (1990).  

©  SPMM  Course   18  
 5. Paraprosopia:  This  is  very  rare,  re-­‐‑described  by  Ellis.  Here,  a  face  appears  to  transform  within  
seconds  into  a  grotesque  mask,  often  described  by  patients  as  a  "ʺmonster"ʺ,  "ʺvampire"ʺ  or  "ʺwerewolf"ʺ  
[Krauss,  1852].    Most  likely  to  be  reported  by  schizophrenic  children  but  also  observed  in  adults  
(e.g.  Daniel  Paul  Schreber,  1842-­‐‑1911,  President  of  the  Court  of  Appeal  in  Dresden,  saw  two  men  
"ʺas  devils  with  particularly  red  faces…"ʺ).  

The  concept  of  misidentification  is  now  being  extended  to  misidentification  of  time,  a  place  apart  from  the  
person  (reduplication  phenomenon).    

Other  disturbances  in  thought  content:  

Ideas  of  reference  are  seen  in  paranoid  PD  where  the  individual  is  unduly  self-­‐‑conscious  and  feels  that  
people  take  notice  of  him  or  observe  things  about  him  that  he  would  rather  not  be  seen.  It  can  also  precede  
the  development  of  full-­‐‑blown  schizophrenia  where  it  is  called  sensitive  ideas  of  reference  or  "ʺsensitiver  
Beziehungswahn”!  It  is  not  characteristic  of  mania.  

Overvalued  ideas:  Overvalued  ideas  (Wernicke)  are  solitary  abnormal  beliefs  that  are  neither  delusional  nor  
obsessional  in  nature,  but  which  dominates  a  person’s  life  and  his  actions.  They  have  a  poor  prognosis  and  
tend  to  dominate  the  sufferer'ʹs  life.  Common  conditions  presenting  with  overvalued  ideas  are  paranoid  or  
anankastic  personality  disorder,  Body  Dysmorphophobia,  anorexia  nervosa,  morbid  jealousy  &  
transsexualism.  

Folie  a  deux  is  a  shared  delusion,  in  which  a  psychotic  person  transfers  his  delusions  to  one  or  more  
people  close  to  him.    The  non-­‐‑psychotic  victim  usually  exhibits  dependent  traits  on  the  primary  patient.  
Separation  of  the  pair  can  result  in  remission.    

Doppelganger:  This  is  also  known  as  double  phenomenon  –  it  is  the  awareness  of  oneself  as  being  both  
outside  and  inside  oneself.  It  is  a  cognitive  and  ideational  disturbance  as  opposed  to  autoscopy,  which  is  a  
perceptual  disturbance.  It  can  occur  in  the  absence  of  mental  illness  too.  It  is  not  a  delusional  
misidentification  syndrome;  unlike  doppelganger,  the  latter  is  the  pathology  of  familiarity.  

How  are  delusions  formed?  

1. Attentional  biases:  People  with  persecutory  delusions  preferentially  attend  to  threat-­‐‑related  
stimuli  and  preferentially  recall  threatening  episodes.  (Blackwood,  AJP  2001)  

2. Attributional  biases:  An  exaggeration  of  self-­‐‑serving  attribution  bias  is  seen  in  psychosis.  Patients  
excessively  attribute  hypothetical  positive  events  to  internal  causes  (stable  and  global  –  grandiose)  
and  hypothetical  negative  events  to  external  causes  (stable  and  global-­‐‑  persecutory).  The  
attribution  bias  in  paranoid  subjects  shapes  delusional  content  rather  than  form,  as  patients  with  
non-­‐‑persecutory  delusions  do  not  show  this  bias  significantly.  Paranoid  patients  specifically  
attribute  negative  self-­‐‑referent  events  active  malevolence  on  the  part  of  the  other  person  (external  
personal  attribution)  rather  than  circumstances  or  chance  (external  situational  attribution).  
(Blackwood,  AJP  2001).  This  might  serve  to  preserve  the  self-­‐‑esteem  of  paranoid  patients,  acting  as  
a  self-­‐‑defence.  

©  SPMM  Course   19  
 3. Probabilistic  reasoning  bias:  When  deluded  patients  were  shown  sequences  of  black  and  white  
beads  and  were  asked  to  decide  which  jar  [jar  A  had  majority  black  beads  and  B  had  majority  
white]  the  sequence  was  probably  drawn  from,  they  came  to  a  conclusion  with  far  lesser  beads  in  a  
sequence  than  controls.  They  were  also  relatively  overconfident  about  the  accuracy  of  their  
judgement.  This  was  hypothesized  to  be  due  to  impaired  probabilistic  reasoning  (generating  
hypothesis  and  testing  statistical  probability).  But  later  studies  showed  that  when  allowed  to  see  as  
many  numbers  of  beads  as  controls  generally  do,  patients  reached  similar  correct  conclusions  –  
they  were  able  to  generate  hypothesis  and  test  the  probability;  the  defect  being  deficient  data-­‐‑
gathering  (less  information  before  decision).  This  is  called  Jumping-­‐‑to-­‐‑conclusion  style  of  
reasoning.  (JTC).  

4. Mentalising  deficits/bias:  Persecutory  delusions  reflect  false  beliefs  about  the  intentions  and  
behavior  of  others  that  could  arise  from  the  theory  of  mind  deficits.    

©  SPMM  Course   20  
4. First Rank Symptoms:

• Kurt  Schneider,  a  German  psychiatrist  and  a  pupil  of  Karl  Jaspers,  pointed  out  certain  symptoms  as  
being  characteristic  of  schizophrenia  and  therefore  exhibiting  a  "ʺfirst-­‐‑rank"ʺ  status  in  the  hierarchy  of  
potentially  diagnostic  symptoms.    
• The  "ʺfirst-­‐‑rank"ʺ  symptoms  (FRS)  have  played  an  extremely  important  role  in  the  recent  diagnostic  
systems:  in  the  International  Statistical  Classification  of  Diseases,  tenth  Revision  (ICD-­‐‑10)  as  well  as  in  
Diagnostic  and  Statistical  Manual  of  Mental  Disorder,  (DSM-­‐‑III-­‐‑IV),  the  presence  of  one  FRS  is  
symptomatically  sufficient  for  the  schizophrenia  diagnosis  but  FRS  are  not  essential  to  diagnose  
schizophrenia.    
•
FRS  may  also  be  encountered  in  the  nonschizophrenic  conditions,  and,  therefore,  they  are  not  specific  
or  diagnostic  for  schizophrenia  (Palaniyappan,  2007).    
• Kurt  Schneider  proposed  an  empirical  cluster  of  symptoms,  one  or  more  of  which  in  the  absence  of  
evidence  of  organic  processes,  could  be  used  as  a  positive  evidence  for  schizophrenia.  He  did  not  
claim  that  they  are  comprehensive  –  but  they  are  clearly  identifiable,  frequently  occurring  and  occur  
more  often  in  schizophrenia  than  any  other  disorder.      
• FRS  emphasizes  on  the  form  of  the  experience  rather  than  content  i.e.  the  feature  that  voices  echo  one’s  
thoughts  is  more  important  that  what  the  voices  actually  said.    
• Disturbance  of  self-­‐‑image  (ego-­‐‑boundary)  is  the  predominant  underlying  feature  of  all  FRS.    
• In  a  critical  review  of  FRS  studies  published  in  English  between  1970  and  2005,  Nordgaard  et  al.  (2008)  
report  the  following  findings.  The  FRS  are  reported  to  occur  in  22%  to  29%  of  patients  with  affective  
disorders.  Generally,  the  prevalence  of  FRS  in  schizophrenia  is  reported  to  range  between  25%  and  
88%.  This  range  remains  equally  high  in  the  reports  from  western  and  developing  countries  and  in  
studies  of  different  ethnic  groups.    
• In  some  studies,  delusional  perception  is  the  most  frequent  FRS,  whereas  the  same  symptom  is  the  
least  frequent  in  other  studies.  A  number  of  studies  find  no  single  dominating  type  of  FRS.    
• Assessment  of  the  diagnostic  weight  of  individual  FRS  is  absent  with  the  exception  of  Mellor  and  
colleagues  who  suggest  that  "ʺvoices  discussing"ʺ  should  be  given  less  diagnostic  weight  than  other  FRS.    
• The  majority  of  the  reports  conclude  that  FRS  do  not  affect  the  outcome.  No  study  finds  that  the  
outcome  is  related  to  the  number  of  FRS  observed  in  the  individual  patient.  FRS  are  not  of  any  
prognostic  importance  at  all.  They  do  not  specify  any  subgroups  with  the  differential  treatment  
response  or  heritability.    

©  SPMM  Course   21  
The  First  Rank  Symptoms    

3  hallucinations  
Audible  thoughts  (Thought  echo)  
Voices  heard  arguing  (3rd  person)  
Voices  heard  commenting  on  one'ʹs  actions  (running  commentary)  
3  ‘Made’  phenomena  
Made  affect    
(Someone  controlling  the  mood/affect)  
Made  volition    
(Someone  controlling  the  action  –  usually  a  completed  act)  
Made  impulse    
(Someone  controlling  the  desire  to  act  –not  completed  act  but  the  drive.  If  the  action  has  been  carried  
out,  patient  admits  to  ownership  of  act,  not  the  impulse  behind  it)  
3  Thought  phenomena  
(Experiences  themselves  are  more  important  than  later  explanations  or  how  patient  interprets  them)  
Thought  withdrawal  
Thought  insertion    
(External  agency  inserting  thoughts  upon  the  patient)  
Thought  broadcast    
(Also  called  thought  diffusion  –  as  if  in  television  broadcast,  everyone  comes  to  know  about  the  
patient’s  thinking  as  and  when  the  patient  thinks  –  refers  to  the  loss  of  privacy  of  thoughts.  Cf.  
referential  delusion  –  ‘people  act  as  if  they  know  what  I  am  thinking’)  
2  isolated  symptoms  
Delusional  perception  
Experience  of  sensations  on  the  body  caused  by  external  agency  (somatic  passivity)  
Totally  (3X3)  +2.  

What  is  NOT  FRS?  

Command  hallucinations  are  not  first  rank  symptoms.    

Somatic  hallucinations  are  also  NOT  first  rank  symptoms  unless  there  is  a  delusional  elaboration  and  
attribution  of  the  origin  of  sensations  to  an  external  agency  (i.e.  unless  they  are  presenting  as  somatic  
passivity).  Note  that  somatic  passivity  can  follow  a  normal  sensation  like  a  headache,  ascribed  to  a  
‘Russian  neurosurgeon  who  inserted  a  chip  through  my  nose  when  I  was  sleeping’!  

Schneider  described  mood  changes  (depression  or  elation),  emotional  blunting,  perplexity  and  sudden  
delusional  ideas  as  symptoms  of  the  second  rank.  

Thought  alienation:  

©  SPMM  Course   22  
The  three  thought  phenomena  described  above  are  sometimes  grouped  together  as  thought  alienation  or  
delusions  of  thought  control.    These  are  related  to  a  primary  disturbance  in  the  subjective  control  of  
thinking.  This  is  a  high  yield  topic  for  MCQs  –  please  study  the  table  below.  

Phenomenon   Self  –  non-­‐‑ Where  is  the   Who  owns   Who  influences  the  
self   thought  now?   the  thought?   thought?  
difference  
NORMAL   Preserved  (we   Self  (in  our   Self  (it  is  our   Self  (we  can  stop  thinking  
THOUGHTS   know  that  our   subjective  space)   own   when  we  want)  
thoughts  are   thought)  
private)  
Thought   Violated   Self  (with  the   External   External  agency  produced  
insertion   patient)   agency   and  influenced  the  thought  
Thought   Violated   Taken  away  (may  be   Self   Originally  self-­‐‑produced,  
withdrawal   delusionally   now  external  agency  
elaborated)   influences  
Thought   Violated   Diffused  everywhere   Self   External  agency  influences  it  
broadcast   as  soon  as  it  originated  from  
self  
Thought   Not  violated   Unknown   Self   Self  
blocking  
Obsessions  (this   Not  violated   Self   Self   Self  but  disturbed            (the  
is  not  a  thought   thoughts  may  be  against  
alienation)   one’s  values  –  so  ego-­‐‑
dystonic  but  not  fully  
disowned)  
Thought  alienation  table  is  modified  from  Mullins,  S.  &  Spence,  S.A.  Re-­‐‑examining  thought  insertion.  The  British  
Journal  of  Psychiatry  (2003)  182:  293-­‐‑298  

©  SPMM  Course   23  
5. Psychopathology of speech
Aspects of conversational speech:
1. Spontaneity:  Comments  that  are  not  just  responses  to  questions  is  present  in  normal  speech  
2. Turn-­‐‑taking:  Responses  and  comments  are  made  only  when  the  other  speaker  completes  his  
sentences,  or  when  natural  pauses  occur  during  conversations.  
3. Mutual  topic:  Content  is  focussed  and  related  to  the  comments  made  by  the  other  speaker  
4. Animation:  Accompanying  non-­‐‑verbal  behaviours  are  almost  always  present  in  normal  speech  

Disorders of phonation/articulation:
Aphonia  refers  to  the  inability  to  vocalize.  It  refers  to  sound  production  (phonation)  rather  than  sound  
manipulation  (articulation)  –  disturbance  of  the  latter  being  dysarthria.  In  aphonia,  whispering  occurs;  
it  may  be  due  to  paralysed  vocal  cords  or  due  to  hysteria.        

Dysarthria  refers  to  disorders  of  articulation;  it  may  be  due  to  lesions  in  the  brain  stem  (bulbar),  cortex  
(pseudo  bulbar),  cerebellum  or  extrapyramidal  system.  Dysarthria  can  also  be  drug  induced  in  
schizophrenia.    

Stammering:  In  stammering  the  normal  flow  of  speech  is  interrupted  by  pauses  or  by  the  repetition  of  
fragments  of  words  or  parts  of  words.  Tics  often  accompany  stammers.  Boys  stammer  more  often  than  
girls;  usually  reduced  in  adulthood.  

Stuttering  is  difficulty  in  uttering  speech  sounds  at  the  beginning  of  words.  Utterances  are  repetitive,  
prolonged  and  pauses  are  common.  Primary  stuttering  is  seen  in  children,  in  adults  new  onset  stutter  
may  be  related  to  stroke  or  extrapyramidal  symptoms.  

Disturbed speech production:

1. Altered speed of speech:
Quiet  speech  in  low  volume  with  poor  intonation,  reduced  spontaneity  and  prolonged  reaction  time  is  
seen  in  depression.  The  terms  used  here  are  bradyphasia  (decelerated  talking)  while  tachyphasia  
refers  to  accelerated  talking  seen  in  manic  states.    

2. Altered amount of speech:

2.1. Logorrhoea  refers  to  increased  quantity  of  speech,  generally  without  the  pressure  of  speech  
or  formal  thought  disturbances  (see  below)  and  seen  especially  in  early  manic  states.    
2.2.  Alogia  is  a  term  used  to  denote  poverty  of  speech  and  a  decrease  in  spontaneous  talking;  it  
occurs  in  depression  and  schizophrenia.  This  must  be  differentiated  from  the  poverty  of  
content  of  speech  where  the  amount  of  speech  is  adequate  but  conveys  little  information.  
This  is  often  related  to  schizophrenic  formal  thought  disorder  (see  below).    
2.3.  Mutism:  This  denotes  a  complete  lack  of  speech.  Severe  depression  with  psychomotor  
retardation  may  be  associated  with  mutism  though  this  is  relatively  rare  in  the  absence  of  
catatonia.  Mutism  is  almost  always  present  in  a  catatonic  stupor.    
a. Elective  mutism:  Mostly  seen  in  children  who  refuse  to  speak  to  certain  people;  for  
example,  the  child  may  not  speak  at  school  but  speak  at  home.    

©  SPMM  Course   24  
 b. Hysterical  mutism:  This  is  relatively  rare,  and  the  most  common  hysterical  disorder  
of  speech  is  aphonia.  
c. Akinetic  mutism  is  associated  with  lesions  of  the  upper  midbrain  or  posterior  
diencephalons  and  Crutzfeld  Jakob  Dementia.  Here  the  patient  is  mute  but  remains  
aware  of  the  environment  though  cannot  move  or  respond.  

3. Repetitive speech:
Verbigeration:  Repetition  of  phrases  or  sentences.  This  occurs  spontaneously  and  without  any  
goal.  This  should  not  be  confused  with  echolalia.  This  is  not  catatonia.  

Palilalia:  Repetition  of  last  uttered  word,  without  any  apparent  purpose;  seen  in  learning  disabled,  
pervasive  developmental  disorders  and  in  Tourette’s.  Verbigeration  is  a  closely  associated  
phenomenon  though  neurologists  prefer  to  use  the  term  palilalia  for  both.  

Logoclonia:  Repetition  of  last  syllable  of  a  word,  seen  in  Parkinson’s.  

Disturbed Language processing:

Sound  received  by  ears  is  transmitted  to  Wernicke’s  area  and  auditory  association  cortex,  which  processes  
the  language  component.  Arcuate  fasciculus  connects  Wernicke’s  area  to  Broca’s  area.  Broca’s  area  is  the  
higher  motor  area  of  language  production.  Signals  from  Broca’s  area  are  relied  on  onto  the  motor  area  to  
coordinate  the  delivery  of  language  via  the  tongue,  lips  and  vocal  cords.    

©  SPMM  Course   25  
 Wernicke'ʹs  
area
Ears A

Auditory  
association  
cortex

B
Arcuate  
Fasciculus  
(conduction  
aphasia)  
Language  
association  
cortex
Peripheral  
speech  areas   Broca'ʹs  area
(tongue,   C
lips)

 
©  SPMM  Course   26  
Components of Language production:
1.  Fluency:  Production  of  meaningful  words  and  sentences.  Depends  on  intact  Broca’s  area  and  its  
forward  connections.  

2.  Comprehension:  Understanding  words  and  sentences  spoken  by  others.  Depends  on  intact  
Wernicke’s  area  and  its  connection  with  association  cortex  and  sensory  input    

3.  Repetition:  Repeating  what  others  say.  Requires  no  high-­‐‑level  processing;  can  take  place  if  
Broca'ʹs,  Wernicke’s  and  arcuate  fasciculus  are  intact.  It  does  not  need  relay  of  higher  association  
area  to  either  Broca’s  or  Wernicke’s.    

4.  Naming:  Ability  to  use  nouns  especially  the  names  of  objects.  Naming  defects  (anomia)  
accompanies  any  aphasia  but  in  various  degrees.  

Aphasia:
This  refers  to  a  higher  level  ‘language’  problem  –  not  sound  production  or  manipulation  error  but  the  
problem  of  language  reception,  production  and  processing.  Aphasia  is  almost  always  organic.    

 
Type  of  aphasia   Fluency   Repetition   Comprehension   Naming   Adapted  from  
Wernicke’s  sensory   Intact   Lost   Lost   Lost   Harrison’s  
aphasia   Textbook  of  
Broca’s  motor  aphasia   Lost   Lost   Intact   Lost   internal  
Conduction  aphasia   Intact   Lost   Intact   Lost   medicine;  15  e  
Transcortical  sensory   Intact   Intact   Lost   Lost  
aphasia    
Transcortical  motor   Lost   Intact   Intact   Lost  
aphasia    

In  Broca'ʹs  aphasia  the  speech  is  nonfluent;  it  often  appears  laboured  with  any  interruptions  and  pauses.  
Function  words  (prepositions,  conjunctions)  are  most  affected  though  the  good  degree  of  meaning-­‐‑
appropriate  nouns  and  verbs  are  still  produced.  Abnormal  word  order  and  a  characteristic  agrammatism  
are  noted.  Speech  is  telegraphic.  Harrison  textbook  quotes  the  following  example:  "ʺI  see...the  dotor,  dotor  
sent  me...Bosson.  Go  to  hospital.  Dotor...kept  me  beside.  Two,  tee  days,  doctor  send  me  home”.    

In  Wernicke'ʹs  aphasia,  the  comprehension  is  impaired  for  both  spoken  and  written  language.  Language  
output  is  fluent  but  is  highly  paraphasic,  sometimes  with  string  of  neologisms  and  circumlocutions.  Hence,  
it  is  also  termed  as  "ʺjargon  aphasia."ʺ  The  speech  contains  large  numbers  of  function  words  (e.g.,  
prepositions,  conjunctions)  but  few  substantive  nouns  or  verbs  that  refer  to  specific  actions.  The  output  is,  
therefore,  voluminous  but  uninformative.  

Disorders of reading and writing:

As  aphasia  is  a  disturbance  of  language  production,  reading  and  writing  difficulties  too  accompany  all  
aphasias.  In  addition,  some  disorders  of  isolated  reading/writing  problems  have  been  described.  

©  SPMM  Course   27  
 o Pure  word  blindness  (alexia):  Here  the  patient  can  speak  normally  and  comprehend  what  is  
spoken;  he  can  also  write  spontaneously  and  to  dictation,  but  reading  comprehension  is  
impaired.    
o Pure  agraphia:  This  is  an  isolated  inability  to  write  while  other  faculties  of  language  are  
preserved.  It  is  sometimes  seen  as  a  component  of  Gerstmann’s  syndrome  (parietal  deficits)  
o Alexia  with  agraphia  results  in  acquired  illiteracy.    
o Pure  word  deafness:  Patient  can  speak,  read  &  write  fluently,  but  comprehension  is  impaired  
only  for  spoken  language.  Bilateral  (or  left  sided  with  disrupted  connections  to  non-­‐‑dominant  
circuit)  damage  to  the  superior  temporal  pole  is  suspected.    
o Pure  word  dumbness:  Spoken  language  cannot  be  produced  clearly,  but  the  patient  can  
comprehend  language  well,  can  read  and  write  

©  SPMM  Course   28  
6. Disorders of Thought:
Normal thinking:
Normal  thinking is  of  three  types  (or  functions):    

1.  Fantasy/dereistic  thinking  or  autistic  thinking:  There  is  no  goal  direction,  unrealistic  -­‐‑  daydreaming  
type.  Predominant  in  cluster  A  personality,  dissociation  and  pseudologia  fantastica.    

2.  Imaginative  thinking:  Again  fantasy  elements  but  admixed  with  memory,  involving  abstract  concepts  
but  goal-­‐‑directed  and  does  not  cross  boundaries  of  possibility  and  realism.  Determining  the  tendency  of  
thoughts  preserved  e.g.  lateral  thinking.    

3.  Rational  or  conceptual  thinking:  based  on  factual  reality  and  uses  logic.  

Psychopathology  of  thought  includes  1.  Disorders  of  thought  content  (e.g.  delusions)  2.  Disorders  of  
thought  form  (e.g.  tangentiality)  3.  Disorders  of  thought  stream  (e.g.  pressure  of  speech)  4.  Disorders  of  
thought  control  (e.g.  obsessions)  

Elements of thought:
Normally  every  thought  we  have  has  the  following  four  properties:  1.  Form  2.  Stream  3.  Content  4.  
Control.  As  a  student  of  psychopathology,  one  wonders  why  should  the  authors  make  a  fuss  about  the  
stream,  form  and  content  of  thought;  what  is  the  real  difference  among  this  three  concepts?  A  simple  way  
of  understanding  this  is  through  an  analogy  of  buying  fruits  in  the  supermarket.  

Element   Supermarket  Analogy   Refers  to   Disturbances  

Content     Apples,  pears  or  oranges?   What  is  being   Delusions  of  
thought  about?   persecution,  suicidal  
‘the  material.'ʹ  
thoughts,  etc.  

Form   Bags,  boxes,  sold  loose  as   In  what  manner   Loosened  associations,  
single  fruit?   is  the  thought   tangentiality  
present?  
‘the  package.'ʹ  

Stream  or   Packed  as  a  dozen,  a  score,  just   How  is  it  being   The  poverty  of  thought,  
flow   four  only,  half  a  dozen,  etc.     thought  about?   the  pressure  of  speech  
Fast,  slow,  etc.   and  crowding  of  
‘the  amount.'ʹ  
thoughts.  

Control  of   Mango  is  a  produce  of  South   Where  is  it  from?   To  some  extent  
thought   Africa;  tomatoes  are  from   obsessions  can  be  
Spain,  etc.       considered  here,  
passivity  and  first  rank  
‘the  origin.'ʹ  
thought  disturbances.  

Thought  content  could  be  deciphered  from  ones’  behaviour,  but  thought  form  and  stream,  unless  
extremely  deranged,  cannot  be  studied  without  being  expressed  as  speech.  Formal  thought  disorder  (FTD)  
refers  to  disturbances  in  form  and  not  content;  it  is  wrong  to  say  ‘someone  is  deluded  so  he  has  a  formal  
©  SPMM  Course   29  
thought  disorder’.  But  note  that  the  term  FTD  increasingly  includes  both  form  and  stream  errors  (not  
content  errors)  and  scales  that  measure  thought  disorder  do  not  differentiate  stream  from  form  anymore.  

Formal thought disorders (FTD):

Note  that  various  authors  have  used  various  terms  to  describe  the  FTD.  Hence  there  is  a  significant  
overlap  among  the  various  terms  –  the  following  terms  are  not  mutually  exclusive  of  each  other.  

Various  terms  denoting  FTD:  

The  term  paralogia  refers  to  positive  FTD  –  i.e.  symptoms  of  thought  disorder  that  are  identified  as  the  
presence/appearance  of  an  abnormal  element  in  thought  processes  (e.g.  tangentiality).  The  term  alogia  is  
sometimes  used  to  refer  to  negative  FTD  –  symptoms  considered  due  to  the  absence/disappearance  of  a  
normal  element  of  thought/speech  (e.g.  poverty  of  speech  content).    

Kraepelin  used  the  term  akataphasia  for  FTDs  to  convey  the  essence  that  speech  disorders  are  a  result  of  
thought  disorder.    

Blueler’s  term    ‘loosening  of  associations’  is  often  considered  to  indicate  the  presence  of  FTD.    

Classifications  of  FTD:  

Cameron  proposed  4  characteristic  formal  thought  disorders  –  

Metonymy:  imprecise  approximate  expressions  used  as  substitute  words.  For  example  paperskate  
for  a  pen.  

Asyndesis:  This  refers  to  the  lack  of  genuine  causal  links  in  speech.  For  example,  ‘I  got  up  at  eight  
this  morning  as  well  as  few  birds  of  different  colours  on  the  painting,  shrinking  all  the  time  to  drop  
few  coins.  On  the  floor.  All  the  time.’    

Overinclusion:  In  overinclusive  thinking  ideas  that  are  only  remotely  related  to  the  concept  
under  consideration  become  incorporated  in  the  patient'ʹs  thinking;  Conceptual  boundaries  are  lost.  
This  is  used  to  explain  the  thought  disorders  in  schizophrenia  and  is  different  from  the  mechanism  
in  the  flight  of  ideas.  Sorting  tests  can  be  used  to  test  overinclusion.  It  occurs  in  nearly  50%  of  
schizophrenia  patients,  especially  when  acutely  ill.  

Interpenetration:  Irrelevant  thoughts  penetrate  ongoing  stream  of  thoughts.  

Carl  (not  Kurt)  Schneider  proposed  a  different  set  of  5  elements  of  FTD  

Substitution:    one  thought  –  often  inappropriate,  fills  the  gap  between  other  appropriate,  more  
consistent  thoughts.    

Omission:  A  chunk  of  thought  goes  missing  from  stream  of  conversation,  patient  being  unaware  –  
best  analysed  when  written,    

Fusion:  various  thoughts  fuse  together,  leading  to  loss  of  goal  direction.  

Drivelling:  disordered  intermixture  of  constituent  parts  of  one  complex  thought  

©  SPMM  Course   30  
 Derailment  (aka  entgleisen);  In  derailment  normally  flowing  track  of  thoughts  suddenly  change.  
The  determining  tendency  is  preserved  but  is  misdirected.    

Schneider  also  described  desultory  thinking,  sometimes  considered  along  with  driveling.  In  
desultory  thinking,  speech  is  grammatically  correct  but  sudden  ideas  force  their  way  in  from  time  
to  time.  Each  one  of  these  ideas  is  a  simple  thought  that,  if  used  at  the  right  time  would  be  quite  
appropriate.  

Kleist  proposed  that  semantic  disturbance  of  language  was  more  common  than  grammatical  or  syntactical  
errors  in  schizophrenia.    

The  impact  of  semantic  problems  in  speech  could  result  in    

1.  Verbal  paraphasia  –  where  meaningful  sentences  produced  in  spite  of  the  loss  of  appropriate  
words  e.g.  ‘food  filling  muscular  carton’  for  the  stomach  (a  metonym).    

2.  In  literal  paraphasia,  no  one  can  make  out  the  meaning  of  sentence  spoken  except  the  patient.  

Grammatical  or  syntactical  disturbances  include  

1. Agrammatism  refers  to  the  loss  of  parts  of  speech  –  e.g.  propositions  leading  to  disordered  word  
sequences.    
2. In  paragrammatism,  individual  phrases  are  well  constructed  and  meaningful  but  they  do  not  fit  in  
with  the  goal  of  thought.  The  content  delivered  appears  mixed  up,  though  individually  
understandable.  
 

Various  features  of  FTD:  

Neologism  refers  to  making  up  a  totally  new  word  that  is  not  in  dictionary  or  using  a  known  word  with  a  
completely  different  meaning  e.g.  ‘Inkur’  for  pen  (new)  or  ‘roast’  for  pen  (different).  

Stock  words  are  either  newly  synthesized  or  already  known  words  but  used  in  an  idiosyncratic  way  
repeatedly,  often  with  many  meanings  and  in  different  contexts,  sometimes  dominating  any  discourse.  e.g.    
“The  riposte  (?  dog)  runs  into  my  way,  always  active  –  when  my  riposte  (?friend)  is  around,  it’s  OK,  full  of  
riposte  (?energy),  as  everyone  likes  him,  when  you  throw  him  some  riposte  (?food)  he  stops  all  that  
work…  comes  running.”    

Thought  block  is  a  negative  FTD  –  involves  sudden  arrest  in  the  flow  of  thoughts;  sometimes  resembles  
an  absence  seizure  though  there  is  no  amnesia  for  the  idea  that  was  discussed  and  no  motor  
accompaniments  typical  of  absences.  Patients  can  elaborate  on  thought  blocking  with  a  delusional  content  
of  thought  withdrawal.  

Stilted  speech:  This  refers  to  pompous,  formal  speech  often  in  an  inappropriate  context.  Impaired  lexical  
retrieval  may  underlie  stilted  speech  in  schizophrenia.  A  patient  said  ‘  Pliant  rectitude  is  a  trait  more  
appropriate  for  successful  living  than  hot-­‐‑headedness,  which  is  either  stubborn  or  crusady.  (McKenna,  
1994).  This  patient  would  not  have  said’  pliant  rectitude’  or  ‘crusady’  unless  more  common  words  for  the  
same  concepts  were  not  accessible.  

©  SPMM  Course   31  
Flight  of  ideas  is  characteristic  of  mania.  Here  thoughts  follow  each  other  so  rapidly,  that  there  is  no  
general  direction  for  thinking.  Hence,  chance  associations  take  place  to  connect  succeeding  thoughts.  
These  chance  associations  may  arise  from  distractions  in  the  environment  or  distractions  in  the  elements  
of  one’s  own  or  someone  else’s  speech.  An  external  environment  driven  association  could  be  the  following  
one  -­‐‑  when  talking  about  his  breakfast,  hears  rustling  newspaper  and  jumps  to  the  topic  of  Iraq  war  or  
cost  of  petrol  or  elections,  etc.    Being  cued  by  verbal  associations  (i.e.  sound  of  words  spoken)  can  be  of  
three  types:  

1.  Clang  associations  where  thoughts  are  associated  by  the  initial  syllabic  structure  of  words  
rather  than  their  meaning.  e.g.,  clover,  cloud,  clap,  clan,  etc.  Others  include    

2.  Punning:  Here  words  get  associated  as  one  word  has  dual  meaning  e.g.  fast  –  ‘to  starve’  or  
‘speed  up’  and    

3.  Rhyming:  Here  words  get  associated  as  they  have  similar  sounds  e.g.  cat,  rat,  bat,  etc.  In  
schizophrenic  FTD,  clang  occurs  in  more  often  with  first  syllables  as  opposed  to  clangs  in  poetry,  
humour  and  manic  speech  where  they  occur  more  at  the  end  syllables.  

Vorbeireden  is  talking  past  the  point  leading  to  approximate  but  not  accurate  answers  to  questions  asked  
in  an  interview.  It  is  described  as  a  type  of  formal  thought  disorder,  different  from  the  flight  of  ideas.  
Though  often  described  along  with  the  Ganser  syndrome,  it  is  not  exclusive  to  Ganser’s  syndrome.    It  is  
also  seen  in  acute  schizophrenia  and  hebephrenic  schizophrenia.  Vorbeireden  (‘talking  past  the  point’)  is  
often  used  interchangeably  with  vorbeigehen  (‘going  past  the  point’),  although  the  latter  was  originally  
defined  as  part  of  the  ‘Ganser  syndrome’,  whereby  some  criminals  would  give  incorrect  answers  
(‘approximate  answers’)  to  simple  questions  that  none  the  less  suggested  that  the  correct  answer  was  
known  (e.g.  saying  dogs  have  five  legs).  

Circumstantiality:  In  circumstantiality,  thinking  proceeds  slowly,  with  many  unnecessary  details  and  
digressions,  before  returning  to  the  point.  It  is  seen  in  some  patients  with  temporal  lobe  epilepsy  or  
alcohol-­‐‑induced  persisting  dementia,  learning  difficulty  and  in  obsessional  personalities.  It  is  a  formal  
thought  disorder  where  figure-­‐‑ground  differentiation  apparently  fails  but  not  due  to  affective  changes  
such  as  mania.    

Tangentiality:  Circumstantiality  must  be  differentiated  from  tangentiality  -­‐‑  the  patient  never  reaches  the  
point  in  tangentiality,  whereas  they  do   reach  the  point  in  
circumstantiality.  Imagine  a  spiral  that   eventually  touches  its  
centre,  while  tangent  scrapes  through  the   edge  and  never  
reaches  the  centre.  Circumstantiality  may   be  related  to  loosened  
associations  and  usually  develops  within   the  setting  of  a  
delusional  mood  in  schizophrenia;  it  may   be  due  to  an  
impairment  of  a  central  filtering  process   that  normally  inhibits  
external  sensations  and  internal  thoughts  that  are  irrelevant  to  a  given  focus  of  attention.    

Concrete  thinking:  It  is  seen  as  literalness  of  expression  and  understanding,  with  failed  abstraction.  It  is  
recognisable  clinically  but  difficult  to  measure  using  psychometry.  Goldstein  studied  this  loss  of  abstract  
©  SPMM  Course   32  
thinking  which  can  be  tested  using  proverbs  and  similarities  test.  It  seems  concrete  thinking  is  evident  in  
speech-­‐‑disordered  (FTD)  schizophrenia  patients,  but  not  the  non-­‐‑FTD  group  (Allen  1984).  It  is  also  seen  in  
fronto  temporal  dementia.  

Testing  the  linguistics  of  schizophrenia:  

1. Word  association  tests  are  abnormal  in  schizophrenia  –  despite  the  context  of  usage,  patients  
preferred  dominant  meaning  of  a  word  e.g.  court  means  ‘law-­‐‑room’  not  tennis  court,  in  spite  of  the  
context  of  discussion  being  sports.    
2. In  cloze  procedure  parts  of  recorded  speech  are  deleted  to  see  if  meaning  could  be  still  predicted;  
predictability  was  reduced  in  schizophrenia.  In  reverse  cloze  procedure  patients  are  asked  to  
predict  the  missing  elements  of  someone  else’s  speech–  again  schizophrenia  group  performed  
worse  in  prediction.    
3. Type  –token  ratio  refers  to  the  ratio  between  number  of  different  words  used  during  a  discourse  
and  total  number  of  spoken  words.  Impoverished  vocabulary  was  noted  with  low  type-­‐‑token  ratio  
among  schizophrenia  patients.  
4. Cohesion  analysis  (analysing  links  between  sentences  and  words  in  a  discourse)  shows  that  
schizophrenia  patients  use  less  referential  ties  (using  pronouns  without  mentioning  a  subject  in  
first  place)  and  more  lexical  ties  (connected  words).  Also,  patients  make  more  errors  than  controls  
when  asked  to  construct  complex  sentences  from  simple  phrases  (Hunt  test).    
Measuring  FTD:  

Thought  Language  &  Communication  scale  (TLC:  Andreasen)  and  Thought  and  Language  Index  (TLI:  
Liddle)  are  commonly  used  scales.  The  latter  uses  projective  stimuli  from  Thematic  Apperception  Test  to  
elicit  thought  disturbances.    

Of  various  thought  disorders  classified  by  Andreasen,  clanging  and  flight  are  more  common  in  mania  
while  derailment  (loosening)  and  thought  blocking  and  to  some  extent  tangentiality,  poverty  of  content  of  
speech  are  seen  often  in  schizophrenia  -­‐‑  other  items  were  largely  non-­‐‑specific.  FTD  is  suggestive  but  not  
pathognomonic  of  schizophrenia;  it  is  also  seen  in  organic  syndromes  such  as  epilepsy.  

What  causes  Schizophrenic  Speech  Disturbance?  There  are  various  explanations  from  different  scientific  
disciplines.  

1. Von  Domarus  proposed  that  FTD  is  a  result  of  loss  of  deductive  reasoning  –  illogical  thinking.  
(Von  Domarus  law  –  Kiwi  cannot  fly  (premise  1),  Kiwi  is  a  bird  (premise  2)  -­‐‑  so  birds  cannot  fly  
(conclusion);  note  that  the  inferences  are  based  on  insufficient  premises.)  
2. Schizophrenic  thought  disorder  could  be  measured  using  Kelly’s  personal  construct  theory  -­‐‑  based  
repertory  grids  (Bannister).  The  patient  is  asked  to  score  different  elements  (can  be  relatives  or  
friends)  under  different  constructs  (qualities  of  them).  Normally  one  would  expect  congruence  
between  different  constructs  scored  for  an  element,  e.g.  Mum  is  helpful,  and  she  is  also  kind  and  
supportive.  But  in  schizophrenia  the  predictability  of  an  element’s  quality  using  prior  constructs  is  
affected.  (Mum  is  helpful  but  scores  low  on  kindness  and  support  offered).  This  is  called  serial  
invalidation  and  is  more  pronounced  for  peoples  than  objects,  showing  that  thought  disorder  
affects  interpersonal  realm  more  than  other  spheres.  The  scores  can  be  used  to  draw  a  semantic  

©  SPMM  Course   33  
 space,  demonstrating  graphical  connections  between  people  and  qualities  in  the  patient’s  personal  
world.    
3. Mortimer  considered  FTD  to  be  a  result  of  impaired  semantic  memory  –  so  associations  between  
words  and  qualities  are  lost.    
4. Words  carry  a  semantic  halo  –  e.g.  the  word  ‘London’  is  linked,  through  symbolic  meaning  to  
words  like  ‘tube’  and  also  ‘Britain’,  ‘England’,  etc.  Imagine  that  these  words  are  cross-­‐‑wired  in  the  
brain.  So  whenever  the  word  London  is  stimulated,  the  closely  cross-­‐‑wired  words  also  become  
available  readily  for  the  thought  process  to  proceed  uninterrupted.  This  activation  is  called  direct  
semantic  priming.  In  Indirect  semantic  priming,  London  activates  tube;  tube  activates  light  (as  in  
tube  light)  or  pipes,  etc.  This  indirect  priming  is  usually  minimal,  preventing  inappropriate  
deviation  in  determining  the  tendency  of  thought  flow.  In  schizophrenia,  it  is  proposed  that  direct  
priming  is  impaired  but  indirect  one  is  activated  more,  to  explain  FTD.    
5. Theory  of  mind  refers  to  the  ability  to  understand  that  other  individuals  have  mental  processes  
similar  to  self,  leading  to  appropriate  behaviour  and  conversation  e.g.  taking  turns  while  
conversing  (as  others  also  think  and  so  want  to  speak).  This  is  deficient  in  the  development  of  
autistic  children  and  can  become  acutely  deficient  (but  develops  normally)  in  schizophrenia  during  
psychotic  episodes.  This  can  explain  some  pragmatic  errors  in  FTD.  
6. Dysexecutive  problems  are  increasingly  proposed  as  the  basis  of  FTD.  Frontal  lobe  plays  
significantly  in  formation  of  the  human  language  ad  so  the  loss  of  executive  functions  can  result  in  
poor  planning,  error  monitoring  and  correction  of  speech  production.  
 

Stream of Thought:
The  term  pressure  of  speech  refers  to  the  phenomenon  of  having  excessive  thoughts  in  mind  
accompanied  by  rapid  voluminous  speech,  often  disjointed  and  non-­‐‑pragmatic.  This  is  seen  in  mania.    

Crowding  of  thought  occurs  in  schizophrenia.  Here  the  patient  describes  his  thoughts  as  being  passively  
concentrated  and  compressed  in  his  head.  The  associations  are  experienced  as  being  excessive  in  amount,  
too  fast,  inexplicable  and  outside  the  person'ʹs  control.  Experientially,  this  is  different  from  the  manic  flight  
of  ideas.  

Retardation  of  thinking:  Seen  in  depression.  Train  of  thought  is  slowed  down,  though  goal-­‐‑directed,  it  is  
characterised  by  little  initiative  or  planning,  the  long  latency  of  response,  increased  pause  times  when  
speech  is  initiated  and  during  speech.  In  both  the  above  the  mood  state  of  the  patient  dictates  the  flow  of  
thoughts.    

Perseveration:  This  could  be  considered  under  a  stream  of  thought  though  traditionally,  it  is  considered  
pathognomonic  of  organic  brain  disease;  it  is  also  discussed  with  disorders  of  motor  action.  The  thought  
process  tends  to  persist  beyond  a  point  at  which  they  are  relevant.  It  presents  itself  as  repeatedly  same  
answer  or  motor  act  even  if  the  stimulus  that  elicits  the  response  has  changed  and  demands  a  different  
answer  or  motor  act.  Perseveration  also  occurs  if  there  is  clouded  consciousness.  

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 Possession /Control of thought:
Obsessions  are  unwanted,  intrusive,  repetitive,  senseless  thoughts  experienced  by  patients  as  
troublesome  and  resisted;  though  the  appearance  of  the  thoughts  themselves  is  appreciated  to  be  beyond  
their  control,  they  are  not  claimed  to  be  due  to  external  agency.  Patients  often  regard  them  to  be  the  
products  of  one'ʹs  own  mind  but  against  their  values  and  needs;  therefore  they  are  termed  as  ego-­‐‑alien.    
Intrusive  thoughts  occur  before  motor  (compulsive)  acts.  But  it  is  not  necessary  that  every  compulsion  is  
preceded  by  an  obsession  or  vice  versa.  Often  during  the  course  of  OCD  primary  obsessions  fade  while  
compulsions  dominate  clinical  picture;  some  compulsions  can  be  mental  compulsions  like  praying,  
counting,  etc.  Obsessional  slowness  can  occur  either  when  obsessional  thoughts  occur  as  part  of  a  
depressive  illness  or  in  cases  of  severe  OCD  where  primary  obsessional  slowness  ensues.  Still  another  
pattern  is  the  obsession  with  symmetry  or  precision,  which  leads  to  a  compulsion  of  slowness.  Patients  
take  hours  to  eat  a  meal  or  shave,  in  an  attempt  to  do  things  ‘just  right’.  Unlike  other  patients  with  OCD,  
these  patients  do  not  resist  their  symptoms!    

The  most  common  obsession  is  the  fear  of  contamination,  followed  by  pathological  doubt,  a  need  for  
symmetry,  and  aggressive  obsessions.  The  most  common  compulsion  is  checking,  which  is  followed  by  
washing,  symmetry,  the  need  to  ask  or  confess,  and  counting.  Children  with  OCD  present  most  
commonly  with  washing  compulsions,  which  are  followed  by  repeating  rituals.  

Thought  alienation  is  a  general  term  used  to  describe  the  experience  that  one’s  thoughts  are  under  the  
control  of  outside  influences  or  that  others  participate  in  one’s  thinking.  This  term  is  often  confusing  and  
better  replaced  with  components  of  first  rank  symptoms  –  thought  insertion,  withdrawal  and  broadcast.  

©  SPMM  Course   35  
7. Motor symptoms
Fish  classified  motor  symptoms  into  

a.  Abnormal  spontaneous  movements:  Tremors,  Tics,  chorea,  athetosis  and  stereotypy  noted  in  autistic  
spectrum  disorders,  hemi-­‐‑ballismus,  etc.  

b.  
Prominent  catatonic  symptoms   Non-­‐‑catatonic  motor  symptoms  seen  in  
psychiatry  

Ambitendence   Akathisia  
Automatic  Obedience   Perseveration  
Catalepsy   Blepharospasm  
Echo-­‐‑phenomenon   Dystonia  
Gegenhalten   Tardive  dyskinesia  
Grimacing     Tics  
Mannerism   Astasia-­‐‑abasia  
Mutism   Chorea*  
Negativism   Tremors*  
Posturing   Athetosis*  
Stereotypy   Hemiballismus*  
Stuporous  immobility/excitement   *  Mostly  neurological  cause  

Abnormal  induced  movement:  Perseveration,  automatic  obedience,  echo  phenomenon  and  other  
catatonic  signs  

Catatonic symptoms:
Fink  &  Taylor  have  argued  to  include  catatonia  as  a  separate  taxonomy  in  psychiatric  nosology.  Catatonia  
is  decreasing  in  frequency  in  its  classical  form,  largely  due  to  early  diagnosis,  treatment  and  
deinstitutionalisation.  Catatonia  is  defined  as  rigidity  during  involuntary  movements  while  volitional  
movement  is  carried  out  normally.  Note  that  in  neurological  spasticity  the  tone  is  increased  irrespective  of  
passive  or  active  movements.  A  patient  with  catatonia  can  use  the  affected  limb  or  muscle  group  when  
needed  with  completely  normal  tone  –  for  example,  running  out  when  there  is  a  fire.  Catatonia  persists  in  
sleep  and  can  continue  for  weeks  without  improvement.  Catatonia  is  mostly  seen  in  advanced  primary  
mood  or  psychotic  illnesses.  Among  inpatients  with  catatonic  presentation,  25  to  50  percent  are  related  to  
mood  disorders  and  approximately  10  percent  are  associated  with  schizophrenia.  Catatonia  results  in  both  
speech  and  motor  disturbances.  

Ambitendence:  Here  a  schizophrenic  patient  brings  the  spoon  to  his  mouth  dozens  of  times  but  never  
completes  the  act.  In  ambitendency,  the  patient  makes  a  series  of  tentative,  opposing  alternate  movements  
that  do  not  reach  the  intended  goal.  This  becomes  evident  when  the  patient  is  asked  to  carry  out  a  motor  
act  e.g.  asking  the  patient  to  show  his  tongue  will  elicit  repeated  protrusion  and  retraction  of  tongue  as  if  

©  SPMM  Course   36  
the  patient  is  undecided  about  showing  his  tongue.  (Note  ambivalence:  Inability  to  make  a  decision  –  
dilemma  of  the  volitional  faculty.  It  may  also  appear  as  affective  ambivalence-­‐‑  e.g.,  To  love  and  hate  the  
same  person  at  the  same  time  or  intellectual  ambivalence-­‐‑E.g.  Assertion  and  denial  of  the  same  idea.  This  
is  not  a  catatonic  symptom.)  

Automatic  obedience:  Exaggerated  cooperation  with  examiner’s  request  or  spontaneous  continuation  of  
movement  requested.  To  demonstrate  this,  the  examiner  must  ask  the  patient  not  to  cooperate,  but  still  the  
patient  will  carry  out  motor  instructions.  In  days  where  ethics  did  not  hamper  research,  Kraepelin  
demonstrated  automatic  obedience  by  pinching  his  patient’s  tongue  with  a  pin  every  time  he  protruded  it;  
but  the  patient  continued  to  obey  Kraeplin’s  commands  in  spite  of  this!  

Mitmachen  and  mitgehen  are  closely  related  to  automatic  obedience:  

• Mitmachen  can  be  considered  as  a  mildest  form  of  automatic  obedience  where  despite  requests  to  
resist  manipulation,  the  patient  yields  himself  to  be  placed  in  abnormal  postures.    
• Mitgehen  or  “Anglepoise  lamp”  sign:  The  patient  yields  to  slightest  of  pressures,  without  much  
resistance,  similar  to  an  angle  poise  lamp  that  bends  easily.    This  happens  even  if  the  patient  is  
instructed  to  resist  any  manipulation.  This  may  be  a  milder  form  of  automatic  obedience.  It  is  also  
called  ‘magnet  reaction’  as  the  patient  may  even  follow  the  examiner  around  the  room  with  light  
touch  as  if  pulled  by  a  magnet.  

Catalepsy  or  Waxy  flexibility:  Also  called  flexibilitas  cerea.  Here  the  patient  shows  wax-­‐‑like  plastic  
‘mouldable’  quality.  His  limbs  can  be  moved  by  the  examiner  to  occupy  certain  postures,  which  are  then  
maintained,  even  if  these  are  uncomfortable  and  bizarre.      

Differentiating  this  from  mitmachen  /  mitgehen  (Automatic  Obedience)    

¬ Unlike  flexibilitas  cerea,  there  is  an  explicit  request  to  resist  manipulation  in  mitmachen    
¬ The  arm  comes  back  to  resting  position  when  released  by  the  examiner  in  mitmachen,  but  not  in  
catalepsy  
¬ Unlike  mitgehen,  the  manipulation  is  not  gentle  with  finger  tip  but  full  and  complete  in  catalepsy  

Echo-­‐‑phenomenon:  This  is  seen  in  catatonia,  Latah  (a  culture-­‐‑bound  disorder)  and  also  in  Tourette’s  
syndrome.  

Echopraxia:  mimicking  examiner’s  movements  

Echolalia:  mimicking  examiner’s  speech.    

In  Gegenhalten  (aka  paratonia  or  opposition)  there  is  a  resistance  to  passive  movements  with  the  
proportional  strength  to  the  increase  of  muscle  tone  which  seems  to  be  voluntarily  controlled  by  the  patient.  
Patients  with  negativism  resist  or  oppose  all  passive  movements  attempted  by  the  examiner.  This  is  an  
extreme  form  of  opposition  where  apparently  motiveless  resistance  to  all  interference  is  found.    
Negativism  can  be  a  frustrating  symptom  especially  for  carers  involved  in  offering  nursing  assistance  to  
the  patient.  The  catatonic  symptom  of  blocking  or  obstruction  (or  Sperrung)  refers  to  a  phenomenon  

©  SPMM  Course   37  
similar  to  thought  blocking  but  occurs  while  carrying  out  motor  acts.  A  patient  with  obstruction  suddenly  
stops  a  motor  act  for  no  reason,  without  any  warning.  This  may  be  demonstrated  by  asking  the  patient  to  
move  a  part  of  his  body;  the  movement  is  generally  well  begun,  but  then  stops  halfway  without  any  
indication.    

Grimacing  refers  to  the  maintenance  of  odd  facial  expressions.  An  odd  variant  of  grimacing  is  called  
schnauzkrampf,  where  the  patient  cups  his  lips  as  if  they  are  spastic  (snout  spasm).  

Stupor  presents  as  immobility  (usually  the  extreme  opposite  of  excitement  where  no  activity  is  noticeable  
though  the  patient  is  able  to  perceive  stimuli).  This  is  akin  to  akinetic  mutism  of  neurological  states.  
Paradoxically  in  extreme  mania  too,  stuporous  immobility  can  occur.  But  it  is  more  common  in  depression.  
Catatonic  excitement  is  characterised  by  extreme  apparently  non-­‐‑purposeful  hyperactivity,  which  
presents  as  constant  motor  unrest.  Unlike   Some  common  mannerisms  
Tiptoe  walking   Finger  to  lip  moves  
akathisia,  this  is  often  dramatic  with  no  
(‘shushing’)  
subjective  component.   Clicking  sounds  during   Odd  robotic  speech,  without  
speech   contractions  (can  not  instead  of  
Mannerisms:  Odd,  but  purposeful   can’t)  
movements  (hopping,  saluting  passers-­‐‑by  or   Shrugging   Grimacing  
Parakinesia  (contracting   Tapping,  adjusting,  saluting  
mundane  movements).       entire  facial  muscles)  

They  are  also  known  as  idiosyncratic  voluntary  movements  though  the  patient  may  claim  unawareness.  
These  often  have  a  delusional  meaning  in  schizophrenia.  They  are  different  from  stereotypes  as  
mannerisms  appear  as  goal-­‐‑directed  movements.    

Mutism  is  discussed  in  detail  along  with  speech  disorders.  

Negativism  is  an  extreme  form  of  opposition  –  see  above.  

Posturing  refers  to  the  maintenance  of  odd  and  bizarre  postures.  These  might  be  spontaneously  undertaken  
or  derived  from  an  arrested  motor  activity  e.g.  posture  with  swung  arms  as  if  one  is  frozen  when  walking.  
This  is  maintained  despite  efforts  to  be  moved.  It  is  also  called  catalepsy.  Psychological  Pillow:  This  is  an  
extreme  form  of  posturing.  The  patient  holds  their  head  several  inches  above  the  bed  while  lying  and  can  
maintain  this  uncomfortable  posture  for  long  periods  of  time.  

Stereotypes  are  non-­‐‑goal  directed  motor  activity  (e.g.,  spinning  one'ʹs  hands,  repeated  touching,  patting,  
rubbing  self).  These  are  seen  in  catatonia  and  also  in  pervasive  developmental  disorder  and  severe  
learning  disabilities.  

Non-Catatonic symptoms:
Agitation  vs.  akathisia:  Psychotic  agitation  is  very  difficult  to  distinguish  from  akathisia  secondary  to  
antipsychotics.  But  such  distinction  is  important,  as  the  latter  requires  a  decrease,  not  increase,  in  
medications  administered.  Akathisia  has  a  subjective  component  of  restlessness  together  with  objective  
evidence  of  unrest;  at  times  one  may  have  to  resort  to  benzodiazepines  when  the  distinction  is  unclear  

©  SPMM  Course   38  
though  the  dose  required  to  treat  one  may  be  different  from  the  dose  required  for  the  other.  
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1289895/  

Astasia-­‐‑abasia:  Inability  to  walk,  sit  or  stand  upright  without  any  obvious  neurological  deficits  in  motor  
strength  and  innervations.  It  is  described  that  some  patients  with  this  syndrome  cannot  balance  
themselves  upright  but  can  run  with  a  bizarre  posture.  Occurs  as  a  motor  conversion  disorder.  

Blepharospasm  is  a  type  of  focal  cranial  dystonia  that  must  not  be  confused  with  catatonia.  
Blepharospasm  may  be  seen  in  Tardive  Dyskinesia.  It  usually  begins  gradually  with  excessive  blinking.  
Initially,  episodes  are  triggered  by  specific  stressors,  e.g.,  bright  lights,  fatigue,  distress  etc.,  and  disappear  
with  sleep.  Concentrating  on  a  specific  task  (such  as  watching  TV)  often  decreases  the    frequency  of  the  
spasms.  With  time,  the  spasms  may  become  progressively  intense,  functionally  blinding  the  patient  
during  each  episode  wherein  the  eyelids  remain  vehemently  closed  for  longer  periods.    

Perseveration:  This  refers  to  repeatedly  same  response  –  either  verbal  or  motor,  when  different  stimuli  are  
delivered  (questions  or  instructions).  Irrespective  of  changes  in  stimuli  that  demand  variation  in  responses,  
the  response  here  remains  the  same.  It  is  different  from  Verbigeration  (see  below)  where  verbal  repetition  
occurs  spontaneously,  not  just  in  response  to  questions  or  commands.  Also  note  that  perseverative  
responses  are  goal  directed  –  they  intend  to  answer  a  question  or  carry  out  an  instruction,  but  stereotypes  
on  other  hand  are  not  goal  directed.  It  differs  from  echo  phenomenon;  the  latter  is  a  copying  of  other  
person’s  responses,  not  repeating  self-­‐‑responses.    

Tics:  These  are  sudden  involuntary  (but  temporarily  suppressible)  jerking  movements  often  seen  in  facial  
and  vocal  musculatures  though  it  can  affect  any  skeletal  muscle  group  in  the  body.  They  typically  have  a  
waxing  and  waning  course,  worsening  with  low  mood  and  fatigue  and  not  seen  in  sleep.  Some  tics  may  
appear  as  coordinated  complex  acts  such  as  grunting,  uttering  syllables  that  may  amount  to  coprolalia  
(obscenities)  or  echophenomenon.  Tics  seen  in  Tourette’s  differ  from  other  simple  tics  in  that  they  are  
preceded  by  a  palpable  urge  or  prodromal  sensation  before  the  motor  act.  Tics  have  been  conceived  to  
share  the  pathophysiology  of  obsessions.  

Verbigeration:  Repetition  of  phrases  or  sentences.  This  occurs  spontaneously  and  without  any  goal.  This  
should  not  be  confused  with  echolalia.  This  is  not  catatonia.  

Stereotypy   Mannerism  
Meaningless  motor  expression   Behaviour  has  a  special  purpose  or  meaning    
   
Often  repetitive     Not  particularly  repetitive  
   
e.g.  Repeated  hand-­‐‑wringing,  or  rocking   e.g.  wearing  black  goggles  all  the  time,    
movements  
Patient  cannot  explain  the  behaviour   At  times,  patient  can  come  up  with  some  
explanation  that  may  /  may  not  be  delusional  

©  SPMM  Course   39  
8. Miscellaneous topics
Pathology of familiarity:
 Déjà  vu  is  the  feeling  of  having  seen  or  experienced  an  event,  which  is  being  experienced  for  the  first  time.  
The  most  consistent  finding  in  the  de´ja`  vu  literature  is  that  the  incidence  with  which  it  is  experienced  
decreases  with  age.  Brown  (2003)  estimates  that  60%  of  people  have  experienced  it.  De´ja`  vu  occurs  more  
frequently  under  stress  and  fatigue  while  it  declines  with  age.  Reports  of  de´ja`  vu  are  greater  in  
schizophrenics  and  temporal  lobe  (TL)  epileptics.  This  suggests  that  neurophysiological  stimulation  or  
dysfunction  of  the  TL  may  be  involved  in  de´ja`  vu.  However,  the  nature  and  duration  of  de´ja`  vu  in  these  
populations  is  different  to  that  experienced  by  the  general  population,  e.g.  lasting  for  hours  in  
schizophrenia  and  minutes  in  TL  epilepsy,  compared  to  the  typical  duration  of  seconds.  De´ja`  vecu  refers  
to  the  perception  that  events  happening  now  have  been  lived  

through  before.  Déjà  pensee  refers  to  the  pathological  familiarity  for  a  thought  or  idea.  Déjà  entendu  is  a  
pathological  familiarity  for  someone’s  voice.  

Jamais  vu  is  an  experience  that  has  been  experienced  before  is  not  associated  with  feelings  of  familiarity.  
Both  can  occur  in  normal  people,  and  also  can  occur  in  Temporal  Lobe  Epilepsy*.  

Note  that  some  authors  (Ellis,  Young)  include  delusional  misidentification  syndromes  with  the  pathology  
of  familiarity.  

Memory and dissociation:

Confabulation  is  a  falsification  of  memory  occurring  in  clear  consciousness  associated  with  organic  states.  
Suggestibility  is  a  prominent  feature  of  confabulation.  It  is  often  described  in  Korsakov  syndrome.  There  
can  either  be  confabulation  of  embarrassment  or  of  fantastic  nature.  

In  pseudologia  fantastica,  there  is  fluent  plausible  lying  (falsification  of  memory),  with  the  statements  
made  extreme  and  of  grandiose  nature.  Is  usually  associated  with  dissocial  or  histrionic  personality  
disorders.  

In  a  dissociative  fugue,  there  is  narrowing  of  consciousness,  wandering  away  from  surroundings  and  
subsequent  amnesia  for  the  episode.  There  is  marked  memory  loss  and  loss  of  identity,  but  the  patient  can  
carry  out  complicated  patterns  of  behaviour  and  is  able  to  look  after  himself.  There  is  a  gross  discrepancy  
between  memory  loss  and  intact  personality.  

For  some  reason,  there  always  seems  to  be  an  MCQ  on  Ganser’s  syndrome,  considered  as  a  hysterical  
dissociative  disorder.  Ganser’s  syndrome  includes:  

¬ Approximate  answers  
¬ Clouding  of  consciousness  with  disorientation  
¬ Psychogenic,  physical  symptoms  –  analgesia  &  hyperaesthesia  
¬ Pseudohallucinations  –  not  always  present.  
¬ Patients  with  Ganser’s  syndrome  are  amnesic  for  their  abnormal  behaviour.  
Couvade  syndrome  describes  a  sympathetic  pregnancy  that  affects  husbands  (rarely  other  family  
members)  during  their  wives  pregnancies.  Most  frequent  between  3-­‐‑9  months  of  pregnancy  -­‐‑  it  is  a  
©  SPMM  Course   40  
conversion  symptom  not  delusional  as  the  husband  does  not  think  he  is  pregnant!    Pseudocyesis  is  a  
condition  where  a  woman  experiences  clinical  signs  of  pregnancy  without  being  pregnant,  and  the  patient  
is  convinced  of  pregnancy.      

Koro  is  a  culture-­‐‑bound  anxiety  state  where  the  patient  believes  that  his  penis  is  shrinking  into  his  
abdomen,  and  he  will  die  as  a  result.  This  is  considered  to  be  a  desomatization  (organ  specific  
depersonalization)  experience  associated  with  folk  beliefs  (hence  not  a  delusion  as  culturally  relevant).  It  
is  seen  in  Malaysia  and  Singapore.  

In  multiple  personality  disorders,  one-­‐‑way  amnesia  is  common.  (A  knows  B’s  existence,  B  is  not  aware).  
Possession  states  can  occur  as  a  part  of  dissociation  or  in  normal  religious  experiences,  or  under  hypnosis.  
Possession  states,  where  consciousness  is  preserved,  can  occur  in  schizophrenia.  Consciousness  is  altered  
in  dissociative  states.  Lycanthropy  is  a  form  of  possession  where  the  patient  loses  awareness  and  identity  
and  believes  he  has  been  transformed  into  an  animal,  usually  wolf.  

Out  of  body  experiences,  autoscopy,  depersonalisation  and  transcendental  experiences  are  clustered  often  
in  Near  Death  Experiences.  The  neurophysiological  basis  of  near  death  experience  (NDE)  is  unknown.  
Clinical  observations  suggest  that  REM  state  intrusion  contributes  to  NDE.    REM  intrusion  during  
wakefulness  is  a  frequent  normal  occurrence  and  NDE  elements  can  be  explained  by  REM  intrusion.    

A  feeling  of  impending  ego  dissolution  is  noted  in  LSD  intoxication.  

Depersonalisation:
It  is  the  third  most  common  symptom  in  psychiatric  clinics.  It  is  defined  as  a  change  in  self-­‐‑awareness  and  
the  individual  feels  as  if  he  is  unreal.  The  ‘as  if’  quality  differentiates  it  from  psychotic  states.  When  a  
similar  feeling  occurs  for  objects  and  environment  around  an  individual,  it  is  termed  as  derealization  
(Mapother).  It  is  always  subjective,  unpleasant  with  affective  change  invariably,  and  insight  preserved.  
Emotional  numbing,  loss  of  feelings  of  agency  and  self-­‐‑esteem,  disturbed  body  image,  altered  perception  
of  time,  memory  and  sensory  experiences  of  all  modalities  are  reported.  Temporal  lobe  epilepsy  (lasts  for  
minutes),  hysterical  dissociation,  depression,  any  anxiety  state  (lasts  for  seconds)  including  anankastic  
personality,  using  tricyclic  antidepressants,  hallucinogens  and  cannabis  can  cause  depersonalisation  apart  
from  fatigue  or  meditation/yoga  in  normal  people.  ECT  can  worsen  depersonalisation  by  unknown  
mechanisms.  In  psychiatric  population,  the  affect  associated  with  the  experience  is  extremely  unpleasant  
as  opposed  to  the  normal  population.  The  most  common  psychiatric  diagnosis  is  depression  followed  by  
anxiety  disorders.  Dissociation  is  only  infrequently  associated.  Depersonalisation  is  often  difficult  to  
distinguish  from  derealization,  and  they  often  occur  together  though  the  former  being  commoner.  The  
patients  often  do  not  report  the  symptom  as  it  is  difficult  to  express.  This  may  be  related  to  the  pathology  
of  familiarity  wherein  familiarity  of  self  being  lost.  Depersonalisation  is  associated  with  déjà  vu  /  jamais  
vu  where  place  familiarity  is  error  prone.  Depersonalisation  is  frequently  situational  and  almost  always  
episodic.  In  depersonalisation  disorder  (classified  as  a  dissociative  disorder  in  DSM  4)  the  experience  lasts  
for  hours.  Roth  described  a  PAD  –  Phobic  anxiety  depersonalisation  syndrome.  Typically  a  married  
female  in  thirties  with  agoraphobia  and  anxiety  –  worsens  with  ECT  treatment.  This  is  now  relevant  only  
historically.  

©  SPMM  Course   41  
Desomatisation  refers  to  depersonalisation  that  is  localised  to  a  body  part.  Deaffectualisation  is  an  
extreme  form  of  anhedonia  wherein  not  only  pleasure    but  also  the  capacity  to  feel  any  emotion  is  
consistently  lost.  It  is  not  specific  to  any  organic  syndrome.  It  is  never  reported  in  mania.  Patients  score  
high  on  neuroticism  with  introversion  being  predominant.  
 

Insight:
Insight  refers  to  a  multidimensional  concept  which  includes  4  A’s:  

¬ Awareness  of  one’s  own  symptoms  (absence  -­‐‑  anautognosia)  

¬ Attribution  of  symptoms  to  mental  disorder  appropriately  (absence  –      dysautognosia)  
¬ Appraisal  or  analysis  of  consequences  of  such  symptoms  
¬ Acceptance  of  treatment  

Insight  is  not  an  all  or  none  phenomenon;  it  fluctuates  within  an  illness  for  the  same  patient.  More  patients  
with  psychoses  have  poor  insight  than  those  with  neuroses.  Loss  of  insight  is  not  always  related  to  the  
presence  of  delusions;  as  in  manic  states  even  without  delusions  nearly  50%  patients  show  no  insight  
during  the  acute  episode.  This  may  be  different  from  schizophrenic  insight  loss  that  is  seen  even  in  the  
chronic  stage.  Insight  has  not  been  consistently  associated  with  any  psychopathology  of  schizophrenia;  
some  studies  show  an  association  with  disorganisation  symptoms.  In  depression,  insight  may  be  higher  
than  usual,  called  depressive  realism.  In  acute  psychosis  presence  of  insight  is  associated  with  more  self-­‐‑
harm  and  suicides.  Loss  of  insight  has  been  compared  to  anosognosia  following  stroke.  Fronto  parietal  
circuit  may  play  an  important  role  in  insight.  

Levels  of  insight:  

1. Complete  denial    
2. Slight  awareness  of  being  sick  but  denying  it  at  the  same  time  
3. Awareness  of  being  sick  but  blaming  it  on  others,  on  external  factors  
4. Awareness  that  illness  is  caused  by  something  unknown  in  the  patient  
5. Intellectual  insight:  admission  that  the  patient  is  ill  and  that  symptoms  or  failures  in  social  
adjustment  are  caused  by  the  patient'ʹs  own  particular  irrational  feelings  or  disturbances  without  
applying  this  knowledge  to  future  experiences  
6. True  emotional  insight:  emotional  awareness  of  the  motives  and  feelings  of  the  patient  and  the  
important  persons  in  his  or  her  life,  which  can  lead  to  basic  changes  in  behaviour.  

Phenomenology of epilepsy:
Temporal  lobe  epilepsy  TLE:    

¬ Autonomic  sensations  are  the  most  common  of  auras,  causing  epigastric  aura,  salivation,  
sometimes  vertigo,  etc.  
¬ Forced  thinking  The  individual  has  a  compulsion  to  think  on  a  certain  restricted  topic.    
¬ The  evocation  of  thought:  Intrusion  of  stereotyped  words  or  thoughts.    

©  SPMM  Course   42  
 ¬ Sudden  obstruction  to  thought  flow  similar  to  schizophrenic  thought  block  is  also  reported.    
¬ Panoramic  memory:  Here  the  individual  recalls  expansive  memories  in  incredible  detail  as  if  
running  a  video  show  of  the  past.    
¬ Psychic  seizures:  Isolated  auras  with  hallucinations,  depersonalization,  micropsia  or  macropsia,  
déjà  vu  or  jamais  vu  (especially  if  right  sided  origin)  can  occur.      
¬ Uncinate  crises:  Hallucinations  of  taste  and  smell  of  uncinate  origin  associated  with  dream-­‐‑like  
reminiscence  and  altered  consciousness.  
¬ Strong  affective  experiences  are  reported  –  fear  and  anxiety  being  very  common.  Dostoevsky’s  
epilepsy  refers  to  ecstatic  content  in  the  epileptic  aura.  TLEs  are  the  most  common  seizures  with  
auras.  The  term  complex  partial  seizure  refers  to  TLE  generally.  

Parietal  lobe  epilepsy:  

Somatosensory  seizures:  The  most  common  type  of  seizure  in  parietal  epilepsies    -­‐‑  patients  describe  
physical  sensations  of  numbness  and  tingling,  heat,  pressure,  electricity  and/or  pain.  Some  patients  
describe  a  typical  “Jacksonian  march”,  in  which  the  sensation  “marches”  in  a  predictable  pattern  from  the  
face  to  the  hand  up  the  arm  and  down  the  leg.  

Pain  is  a  rare  symptom  of  seizures  as  such  but  is  quite  common  in  parietal  seizures,  occurring  in  up  to  25%    
of  patients.    

Somatic  Illusions:  During  a  somatic  illusion  patients  may  feel  that  their  posture  is  distorted,  that  their  
arms  or  legs  are  in  a  weird  position  or  are  in  motion  when  they  are  not  (kinaesthetic  hallucination),  or  
that  a  part  of  their  body  is  missing  or  feels  like  it  does  not  belong  (body  image  distortion).  Vertigo  is  also  
reported.  

Visual  illusions:  Patients  may  experience  objects  as  being  too  close,  too  far,  too  large,  too  small,  slanted,  
moving  or  otherwise  not  right.    

Frontal  lobe  seizures:    Complex  partial  seizures  of  frontal  lobe  origin  are  usually  quite  different  from  
temporal  lobe  seizures.  Frontal  lobe  seizures  tend  to  be  short  (less  than  1  minute),  occur  in  clusters  and  
during  sleep,  include  strange  automatisms  such  as  bicycling  movements,  screaming,  or  even  sexual  
activity.  Sometimes  a  person  may  remain  fully  aware  at  the  same  time  having  wild  movements  of  the  
arms  and  legs.  A  seizure  from  the  frontal  lobe  may  even  involve  laughing  or  crying  as  the  only  symptom,  
the  former  is  called  gelastic  and  the  latter  dacrystic  seizures.  These  are  also  noted  in  temporal  lobe  
seizures.  

Automatisms:  Epileptic  automatism  is  a  state  of  clouding  of  consciousness  which  occurs  during  or  
immediately  after  a  seizure.  The      impairment      of      awareness      varies.    The  individual  retains  control  of  
posture  and  muscle  tone  but  performs  simple  or  complex  movements  without  being  aware  of  what  is  
happening.  To  the  onlooker,  the  patient  appears  confused,  and  there  is  subsequent  amnesia  for  the  
episode.  Simple  stereotyped  behaviours  (gesturing,  grasping,  lip-­‐‑smacking  and  chewing  movements)  are  
often  exhibited  lasting  few  seconds  to  minutes.  Very  occasionally,  automatisms  are  prolonged  (fugue  

©  SPMM  Course   43  
states),  or  complex  actions  are  carried  out.  If  violent,  these  are  never  premeditated,  seldom  goal-­‐‑directed,  
rarely  involve  the  use  of  complex  tools/weapons  and  are  especially  likely  if  restraining  was  attempted.  

DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug-related information using external sources;
no part of these notes should be used as prescribing information.

©  SPMM  Course   44  
Notes produced using excerpts from:

! Andreasen  N,  Powers  P.  Overinclusion  thinking  in  mania  and  schizophrenia.  Br  J  Psychiatry  1974;  125:452-­‐‑
456.  24.      
! Andreasen,  N.  C.  (1979)  Thought,  language,  and  communication  disorders:  I.  Clinical  assessment,  definition  
of  terms,  and  evaluation  of  their  reliability.  Archives  of  General  Psychiatry,  36,  1315-­‐‑1321  
! Appelbaum,  P.S.  et  al.,  Persistence  and  stability  of  delusions  over  time,  Compr.  Psychiatry  45  (2004),  pp.  317–
324  
! Blackwood,  N  et  al.  Cognitive  Neuropsychiatric  Models  of  Persecutory  Delusions.        Am  J  Psychiatry  2001  
158:  527-­‐‑539  
! Bschor  T,  et  al.  Time  experience  and  time  judgment  in  major  depression,  mania  and  healthy  subjects.  A  
controlled  study  of  93  subjects.  Acta  Psychiatr  Scand.  2004;  109:222–229.  
! Coltheart,  M  et  al  Schizophrenia  and  Monothematic  Delusions.  Schizophrenia  Bulletin  2007  33(3):642-­‐‑647  
! Ghaemi,  N.  Feeling  and  Time:  The  Phenomenology  of  Mood  Disorders,  Depressive  Realism,  and  Existential  
Psychotherapy.  Schizophrenia  Bulletin,  2007;  33:122–130.  
! Kaplan  &  Sadock'ʹs  Synopsis  of  Psychiatry:  Behavioral  Sciences/Clinical  Psychiatry,  10th  Edition.  Lippincott  
Williams  &  Wilkins  2007  
! Liddle  PF,  Crow  TJ:  Age  disorientation  in  chronic  schizophrenia  is  associated  with  global  intellectual  
impairment.  Br  J  Psychiatry  1984;  144:193–199  
! Lincoln,  T.  Relevant  dimensions  of  delusions:  Continuing  the  continuum  versus  category  debate.  
Schizophrenia  Research  2007,  93,  211-­‐‑220.  
! Cermolacce,  L.  Sass,  and  J.  Parnas,  “What  is  Bizarre  in  Bizarre  Delusions?  A  Critical  Review,”  Schizophr  Bull  
36,  no.  4  (July  1,  2010):  667-­‐‑679  
! Manschreck,  T.  C.  (1995).  Pathogenesis  of  delusions.  Psychiatric  clinics  of  North  America,  18,  213    
! Nordgaard,  J.,  et  al.  The  diagnostic  status  of  first  rank  symptoms.  Schizophrenia  Bulletin  2008  34(1):137-­‐‑154  
! Palaniyappan,  L.  The  Schizophrenic  Disguise  of  Complex  Partial  Seizures.  J  Neuropsychiatry  Clin  Neurosci  
2007  19:  479-­‐‑480.  
! Schiltz,   K   et   al.   Neurophysiological   Aspects   of   Synesthetic   Experience.     J   Neuropsychiatry   Clin   Neurosci  
11:58-­‐‑65,  February  1999  
! Sims,  A  (2003)  Symptom  in  the  Mind,  3rd  ed.  London:  Elsevier  Science  
! Swedo  SE,  et  al.  Obsessive-­‐‑Compulsive  Disorder  in  children  and  adolescents:  Clinical  phenomenology  of  70  
consecutive  cases.  Arch  Gen  Psychiatry  1989;46:335-­‐‑41  
! Taylor  M,  Fink  M.  Catatonia  in  psychiatric  classification:  a  home  of  its  own.  Am  J  Psychiatry  2003;  160:1–9  
! Scott,  A.  I.  F.  (1998).  Mental  State  Examination.  In  Companion  to  psychiatric  studies  (eds  E.  C  Johnstone,  
C.P.L  Freeman,  &  A.K.Zealley)  Chapter  9.  Churchill  Livingstone,  Edinburgh.  
! http://www.med.nyu.edu/cec/epilepsy  
! Levenson,  D.  Psychiatric  issues  in  surgery.  Primary  Psychiatry  (2007).  
http://primarypsychiatry.com/psychiatric-­‐‑issues-­‐‑in-­‐‑surgery-­‐‑a-­‐‑part-­‐‑2-­‐‑specific-­‐‑topics/  

 
 

©  SPMM  Course   45  
 Dynamic Psychopathology
Paper A Syllabic content 5.23

© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
1. Defence mechanisms

Defence mechanisms are not descriptions; they are explanations for certain human behaviour and
experiences. Hence they are a part of explanatory psychopathology. These defences operate both
in normal individuals and under pathological conditions. Anna Freud organised Freudian
defences; Klein and later contributors added some more defence mechanisms. Vaillant (1977)
classified them and categorised them to mature, immature and neurotic defences. Kleinian
defences are sometimes called as psychotic defences. Using a narrow repertoire of defences
repeatedly and repeated use of immature or neurotic defences may be associated with disease
states or traits.

How is a defence mechanism formed?

Prohibitions (moral,
Wish or Impulse
social or legal)

Defence
operation

Symptoms formed Signal Anxiety

Mature defences:
SASHA is a mnemonic for the mature defences.

Altruism: Using constructive and gratifying service to others to receive a vicarious satisfaction.
This does not involve giving up one’s pleasures. Altruism is distinguished from altruistic
surrender, in which surrender of direct gratification of instinctual needs takes place to satisfy the
needs of others to the detriment of the self.

© SPMM Course 2
ALTRUISM Conflict Result Process
‘Defeat’ in a situation Unconditional offer of help Replaces aggression and
competition by support: Achieve
vicarious satisfaction

Humour: Here comedy is used to express feelings and thoughts overtly without personal
discomfort and without producing an unpleasant effect on others. It allows the person to tolerate
and yet focus on troublesome aspects.

HUMOUR Conflict Result Process

Failure, loss or destruction of Highlighting amusing aspects of Anxiety converted to comedy or
belongings threat signals or outcome irony

Anticipation: Here one plans realistically for future inner discomfort and expects worse to occur
with mental preparation. Note that anticipation without specific target or goal is nothing but free-
floating anxiety and this is not helpful; Anticipation mechanism is goal-directed and implies
careful planning for potential difficulties.

ANTICIPATION Conflict Result Process

Sudden threat event Predicting probabilities and Matching events and coping
planning countermeasures resources to achieve a sense of
control

Sublimation: Achieving impulse gratification but only after altering a socially objectionable
impulse to a socially acceptable one. Sublimation allows instincts to be channelled, rather than
blocked.

SUBLIMATION Conflict Result Process

Unacceptable impulses Socially acceptable behaviour Rechanneling impulses into
acceptable expressions

Suppression: Consciously or semiconsciously postponing attention to a conscious impulse or

conflict. Issues may be deliberately cut off, but they are not avoided. Discomfort is acknowledged
but minimized.

ALTRUISM Conflict Result Process

© SPMM Course 3
 Painful event or sexual impulse Postponement of painful Intentional blocking of recall
problems and feelings (this is NOT unconscious
forgetting – contrast from
repression)

Neurotic defences:
Neurotic defences act at the level of mental inhibition. As a result the patient is deprived of some
degree of freedom in decision-making, but retains insight.

Displacement: The process by which interest and/or emotion is shifted from one object onto
another less-threatening, often less-retaliating one. For example one who is told off by her
consultant during clinical supervision may displace the anger felt onto her spouse or dog (though
the reaction may be extremely different from these two objects!)

DISPLACEMENT Conflict Result Process

Fear/threat by an object; love or Expression of love/hate/anger or Transfer of feelings from one
hate for an object fear against an unprovoking object to a substitute
stimulus (clinically: phobias)

Dissociation: Temporarily but drastically modifying one's sense of personal identity to avoid
emotional distress. Fugue states and hysterical conversion reactions are common manifestations
of dissociation. Dissociation may also be found in counter-phobic behaviour; here a person with
fear of heights takes up parachute diving and experiences dissociation during the act.

DISSOCIATION Conflict Result Process

Promiscuous, hostile or (clinically: Multiple Temporary alteration of identity
irresponsible behaviour personalities, fugue, amnesia) including consciousness,
memory and perception.

Isolation: Splitting or separating an idea from the affect that accompanies it normally but is now
repressed. Noted in OCD.

ISOLATION Conflict Result Process

Painful emotions or memories Talking about emotional events Separate content from affect,
without feeling (clinically: remove affect completely
obsessions)

Rationalisation: Offering rational explanations in an attempt to justify attitudes, beliefs, or

behaviour that may otherwise be unacceptable. Such underlying motives are usually instinctually

© SPMM Course 4
determined. It often involves finding excuses that will justify unacceptable behaviours when self-
esteem is threatened, often seen in teenagers and those who abuse alcohol and drugs.

RATIONALISATION Conflict Result Process

Low self-esteem along with socially Self-serving explanations False but socially acceptable
unacceptable behaviours and justification of explanations are offered for
behaviours unacceptable behaviours

Reaction formation: This involves transforming an unacceptable impulse into its exact opposite.
Reaction formation is characteristic of obsessional neurosis, but it may occur in other forms of
neuroses as well. If this mechanism is frequently used at any early stage of ego development, it
can become a permanent character trait, as in an obsessional personality.

REACTION Conflict Result Process

FORMATION Feelings of hostility and Devotion, self-sacrificing Substituting wishes/feelings
disinterest behaviour, cleanliness, that are exactly opposite to true
correctness feelings

Repression: This refers to expelling or withholding from consciousness an idea or feeling.

Primary repression refers to the curbing of ideas and feelings before they have attained
consciousness: secondary repression excludes from awareness what was once experienced at a
conscious level. Note that this differs from suppression – suppression is mere postponement not
the loss of thoughts from conscious perception. Repression is the primary defence. Other defences
reinforce it.

REPRESSION Conflict Result Process

Threatening feelings / Gaps in memory; often Banning thoughts and feelings
memories/ fears unnoticed from recall; subject unaware
(not conscious)

Intellectualisation: This refers to excessively using intellectual processes to avoid affective

expression or experience. Here the needless emphasis is focused on the inanimate to avoid
intimacy with people; attention is paid to external reality to avoid the expression of inner feelings,
and irrelevant details are emphasised to avoid perceiving the whole. Intellectualization is closely
allied to rationalization but unlike rationalisation, intellectualisation is not an attempt to
substantiate one’s instinctual impulses.

© SPMM Course 5
INTELLECTUALISATION Conflict Result Process
Disturbing feelings and thoughts Abstract thinking, Removing personal and
(‘dissonance’) doubting, indecisiveness, emotional components of
generalizations an event and focusing only
on factual aspects

Intellectualisation Rationalisation

No instinctual impulses/drives involved Instinctual impulses/urges involved

Avoid experience of unpleasant affect Might experience the affect, but attempts to
reduce the impact

Deals with inanimate objects i.e. emphasize Provides ‘excuses’: e.g. alcohol, teenage
details and facts instead of feelings conduct

Identification with the aggressor: Observed where the victim of aggression begins to assume the
qualities of the proponent of aggression.

IDENTIFICATION WITH Conflict Result Process

THE AGGRESOR Sexual threat or life / limb Perpetrates violent acts Identify with aggressor, may
threatening violence reduce direct resistance and
aid in survival during acute
trauma

Undoing: This is seen in OCD and is associated with magical thinking and rituals. A student
might think that if he taps his table three times before the start of his exam, he will surely succeed!

UNDOING Conflict Result Process

Sadistic wishes, unacceptable Superstitions (compulsive Symbolic negating of an
impulses behaviour clinically) impulse

© SPMM Course 6
Repression Dissociation
Information is stored in the unconscious in Information is stored in a horizontal fashion; all
archaeological way – at various depths. units are equally accessible to retrieval.

Motivated forgetting underlies repression Amnestic barriers maintain dissociation

Information is scattered across time e.g. Dynamic Information is discrete and delimited in time
conflicts.
Information is transformed and disguised Untransformed storage
Uncovering requires repeated trials with later Direct retrieval e.g., hypnosis
interpretation

Interpretation and working through transference Integration of memories and working through
is needed in therapy traumatic events is required in therapy

Narcissistic defences:
Projection and denial are often called narcissistic defences though some authors may dispute this
and regard them as immature defences.

Projection: This refers to perceiving and reacting to unacceptable inner impulses as though they
originated outside the self. For example, the person who attributes hostility to others may be
unconsciously projecting their own hostility. Thus, internal threats become externalised and then
are easier to handle.

PROJECTION Conflict Result Process

Hostility, unacceptable wishes Ideas of reference, prejudice, Attributing one’s own feelings
suspiciousness, injustice to be coming from others

Denial: It is the explicit refusal to acknowledge a threatening reality. It may persist despite
constant explanation of the facts. It is not same as conscious avoidance of painful topics or
thoughts.

DENIAL Conflict Result Process

Painful reality Stubborn and angry negation of Refusal to acknowledge the
reality that is visible to awareness of reality; disavow
onlookers problems at unconscious level

© SPMM Course 7
Kleinian defences:
(SIPDOG – splitting, introjection, projective identification, denial, omnipotence, grandiosity)

Splitting: It is seen most often in those with borderline personality. Here qualities of an object or
person are split into black and white i.e. either good or bad with no grey area in between.

SPLITTING Conflict Result Process

Overwhelming experience of Idealization alternating with Stripping off either all positive
negative qualities of oneself or devaluation (denigration) or all negative qualities of
positive qualities of others others

Idealisation and denigration: These two are often accompanied by splitting in those with
borderline traits. Here an object is either glorified, and supremacy is ascribed (idealised,
omnipotence ascribed) or considered very negatively and cursed! (Denigration). Psychiatrists are
treating such patients often experience phases of both idealisation and denigration.

Projective identification: It is a Kleinian defence. Here an aspect of self is projected onto

someone else. The projector influences the recipient to identify with what has been projected and
projector herself now believes that the aspect originated from the reactor. This may result in the
recipient behaving in a manner similar to the projector. Now the projector identifies his feelings
as reactions to the recipient’s aggression (identification of the origin, but wrongly attributed to
the other person). (Please read psychoanalytic psychology for further explanation). It may be seen
in psychotic paranoid states.

PROJECTIVE Conflict Result Process

IDENTIFICATION Hostility, hate and anger Ideas of reference, prejudice, Converting own hostile
suspiciousness, injustice impulses to justifiable reactions
to the hostility expressed by
others

Ogden’s model divides projective identification into three steps.

 Step 1 is the projection of a part of oneself onto an external object. Step 1a is the blurring of self
and object representations (may or may not be seen).
 Step 2 is an interpersonal interaction in which the projector actively pressures the recipient to
think, feel, and act in accordance with the projection.
 Step 3 is the reinternalization of the projection after the recipient has psychologically processed it

Note that step 3 is absent while step 2 is not necessary to define ‘projection’. Projective identification has
manifold aims:

– It may be directed toward the ideal object to avoid separation, or it may be directed toward the bad
object to gain control of the source of danger.
© SPMM Course 8
 – Various parts of the self may be projected, with various aims: bad parts of the self may be projected
in order to get rid of them as well as to attack and destroy the object, good parts may be projected
to avoid separation or to keep them safe from bad things inside or to improve the external object
through a kind of primitive projective reparation.

Introjection: This involves internalizing the qualities of an object. It is seen in normal

development too.

INTROJECTION Conflict Result Process

Need for gratification Accusing others of causing Internalising the qualities
distress observed in an external ‘object’
e.g. mother, friend, etc

Omnipotence: Original Freudian description pertains to the belief that one can transform or
influence the external world through one's thoughts alone. Seen in OCD (e.g. a woman with
depressive obsessions says ‘I keep getting thoughts that something might happen to my baby: I
am distressed because I think something will actually happen due to these thoughts’).

OMNIPOTENCE Conflict Result Process

Helplessness Obsessions, narcissistic features Attaching great value (‘power’)
to thoughts and believing they
can influence external objects

Grandiosity: Klein’s description pertains to manic defence, closely associated with narcissism.
See the box below for Kleinian definition

GRANDIOSITY Conflict Result Process

Inferiority feelings, guilt Self-glorification, presumption Converting inferiority to
and entitlement superiority feelings

Immature defences:
These are mostly normal in early phases of development and do not essentially convey
abnormality.

Acting out: This refers to the expression of an unconscious wish or impulse through action to
avoid being conscious of an accompanying affect. The unconscious fantasy is lived out
impulsively in behaviour, thereby gratifying the impulse instead of prohibiting it.

ACTING OUT Conflict Result Process

© SPMM Course 9
 Sexual and aggressive impulses Violence, stealing, rape, lies Non-reflective and uncontrolled
wish-fulfillment

Passive aggression: Expressing aggression towards authorities indirectly through passive

obstructive activities. For example to ‘defeat’ one’s boss, one may involve in procrastination, and
take sick leave that affects the boss more than oneself.

PASSIVE Conflict Result Process

AGGRESSION Resentment, hostility, low self- Procrastination, loss of follow- Expression through inactivity
esteem through

Somatisation: Converting psychological states and tension to bodily symptoms.

SOMATISATION Conflict Result Process

Threat or unidentified fear Bodily Complaints Converting mental tension to
physical symptoms

Regression: Moving back into childish or earlier developmental phase to avoid confronting a
conflict. Regression is also considered an essential concomitant of the creative process.

REGRESSION Conflict Result Process

Threat or humility Childish, immature Moving back to earlier
behaviour developmental stages (seen during
normal development too)

Somatosensory Amplification: The tendency to experience bodily sensations as unusually

intense or distressing, and this is thought to underpin somatisation and the somatoform
disorders.

SOMATOSENSORY Conflict Result Process

AMPLIFCATION Threat or fear unidentified Bodily complaints, fear of Oversensitivity to innocuous
catastrophic illness bodily features

© SPMM Course 10
Defences and disorders
Disorder Defenses commonly used
Alcoholism Denial, rationalization
Anorexia Denial, rationalization
Borderline Splitting, idealization, denigration, projection, dissociation, acting out

Depression Regression
Dissocial personality Acting out
Fugue or amnesia Dissociation
Hysteria Repression, conversion
OCD Isolation of affect, undoing, reaction formation, magical thinking
Paranoid delusions Projection
Phobia Displacement, avoidance
Schizoid personality Fantasy, avoidance
Somatoform disorders Somatisation
Narcissistic personality Projection, splitting

© SPMM Course 11
2. Dynamic models of the mind:

Topographical theory
This was elaborated in The Interpretation of Dreams in 1900. Here, the mind is divided into three
regions: the conscious system, the preconscious system, and the unconscious system. The
functions of these regions are based on one of the two principles. The Pleasure Principle is the
innate tendency to avoid pain and seek pleasure. The reality principle is a learned function,
which requires delay or postponement of wish fulfillment according to environmental reality.

The conscious system

 Receives and process information from the outside world.

 Its contents are communicated via speech and behaviour.
 Attention cathexis refers to the investment of psychic energy on a particular idea or feeling
to process it consciously.
 Operates secondary process thinking mainly.

The unconscious system:

 Contains the contents of censored or repressed wishes, etc.

 Characterized by primary-process thinking,
 Governed by the pleasure principle.
 Shift of cathexis happens very often and quickly
 Evident via parapraxes (Freudian slips) and dreams.

The preconscious system:

 As and when needed service

 Interfaces with both unconscious and conscious - contents of unconscious become
conscious by ‘squeezing’ through the preconscious
 Maintains the ‘repressive barrier’ to censor unacceptable wishes and desires (not the
repressed contents).
Problems with topographic theory:
When someone employs defense mechanisms such as displacement, repression etc., he or she are
not aware of the process of this defense. Hence, these cannot be represented by preconscious as
Freud thought – as preconscious is available to conscious as and when needed.

An unconscious need for punishment was frequently noted among Freud’s patients –
topographical theory fails to explain this.

© SPMM Course 12
 Instinct/drive theory
This theory has derived most of its terms from biology. Drive and instinct are often used
interchangeably. An instinct has four principal characteristics: source, impetus, aim, and object.

 Source – part of body where instinct originates from

 Impetus - intensity/force of the instinct.
 Aim - action directed towards the discharge of energy/tension
 Object - the target for action.

Dual instinct theory holds that sexual energy and aggressive energy are the dual instincts.
Libido is the force by which the sexual instinct is represented in the mind. It can also be
considered as a part of Eros. Aggression is an instinct with destruction as aim and originates in
skeletal muscles. It can also be considered as part of Thanatos (see below)

Eros and Thanatos are life and death instincts respectively. According to Freud, the dominant
force in biology is Thanatos.

Hierarchy of anxiety
 Signal anxiety – unconscious perception of external or internal threat leads to resource
mobilization and aversion of threat. This forms the basis of defence mechanisms discussed
earlier.
 Disintegration / annihilation anxiety - concerns about fusion with an external object.
 Stranger anxiety – around 7-9 months age
 Separation anxiety – when mother is recognized as independent object
 Fear of object loss / loss of love – especially in girls at phallic stage
 Castration anxiety
 Superego anxiety – mature form of anxiety – id vs. ego conflicts.

Analytical Psychology (Jungian

Model)
 Jung founded analytic psychology. His
construct of psychic apparatus is shown in
the figure.

 Collective unconscious (CU) – all mankind’s

collective symbolic past. (Something like a
DNA in psychoanalytical terms!). This must
be differentiated from the personal
unconscious (PU), which is same as Freudian
unconscious, a collection of repressed
© SPMM Course 13
 individual memories.
 Archetypes – part of CU. Includes representational images with universal symbolic
meaning (e.g. Hero, Old Wise Man, Tree, etc.)
 Complexes – part of PU and are stimulated by interpersonal interactions. Feeling toned
ideas are developing as a result of the interactions of complexes with archetypes.
 Persona – mask covering one’s personality – presented to outside world
 Anima – unconscious feminine aspect of a man
 Animus - unconscious masculine aspect of a woman
 Shadow – an archetype - a personification of unacceptable aspects of oneself symbolized
as a dark internal alien.
 Individuation – ultimate goal of life where an individual develops a sense of self- identity
 Introduced terms extraversion and introversion

© SPMM Course 14
3. Dynamic interpretation of dreams

Freud was initially trained as a neurologist. Joseph Breuer & Freud together treated Bertha
Pappenheim, (Anna O.), after which hypnosis became a psychoanalytic technique. Freud later
used the cathartic method of abreaction - the process of recovering and verbalizing
suppressed feelings that cause the symptoms. However, Freud encountered patients who
could not recall significant memories – he called this resistance. He later proposed resistance
to being caused actively by largely unconscious forces involved in repression - which leads to
symptom production. This made him abandon abreaction/catharsis and pursue free
association – where patients are allowed to ‘speak their mind’ without censor.

Patients often reported their dreams during free association - Freud noted that dream content
was related closely to repressed memories and unconscious. Freud declared dreams were the
‘royal road to the unconscious’. According to his wish fulfillment theory, dreams are attempts
to fulfill unconscious wishes in a surrogate manner.

The content of dreams may include nocturnal sensory stimuli (e.g. thirst, hunger, etc.), the
daytime residue (thoughts and ideas from waking life), and repressed impulses.

Freud distinguished two types/layers of dream content - manifest content refers to what is
recalled by the dreamer; latent content refers to unconscious thoughts and wishes that
threaten to awaken the dreamer. The unconscious mental operation by which latent content
is transformed into manifest content is called the dream work.
 Condensation - several unconscious impulses are combined into a single image in the
manifest dream content. e.g., One’s father and the horrible teacher may be unified and
occur as a single dreadful monster in a child’s dream.
 Irradiation or diffusion – this is the converse of condensation where multiple images in
dreams represent one unconscious impulse
 Displacement refers to the transfer of energy from an original object to a symbolic
representation of the object. It is not the mere formation of alternate substitute but includes
transfer of affective energy on that substitute – cathexis.
 Symbolic representation - highly charged objects or abstract concepts could be
represented by using innocent images that were in some way connected with the original
object. e.g., a dream of intense dancing may represent one’s desire to attract a colleague
sexually.
 The mechanisms of condensation, displacement, and symbolic representation characterize
the primary process thinking that defies logic, lacks a sense of time and space, can accept
© SPMM Course 15
 the presence of contradictory items simultaneously, and often incoherent. (This primary
process thinking is the modus operandi for Id – refer below).
 A more mature aspect of the ego helps to organize primitive aspects of dreams more
coherently; this is called secondary revision. The process by which secondary revision
occurs is called secondary process – this is logical, with intact time and space boundaries
and is mature.
 According to Freud, anxiety dreams reflect a failure in the protective function of the
dream-work mechanisms.
 Punishment dreams defy wish fulfillment theory – Freud explained that these dreams
existed as a compromise between conscience and repressed wish. The wish for
punishment is supposed to exist as an unconscious wish.

DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug related information using external sources;
no part of these notes should be used as prescribing information.

Notes produced using excerpts from

 Casey, P. & Kelly, B. (Ed) Fish’s Clinical Psychopathology. 3rd ed. RCPsych publications.
 Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition.
Lippincott Williams & Wilkins 2007
 Vaillant GE. Adaptation to Life. Boston: Little, Brown; 1977
 http://www.eric.vcu.edu/home/resources/pipc/Other/Personality/Table_Defenses.pdf
 Semrad E: The operation of ego defenses in object loss. In The Loss of Loved Ones, DM Moriarity,
editor. Charles C Thomas, Springfield, IL, 1967;

© SPMM Course 16
 Rating Scales
Paper A Syllabic content 5.27 &
5.28

© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
1. General principles
Rating scales give clinicians an objective benchmark to support critical treatment decisions.
Regular use of rating scales can provide information that aids in diagnosis, prognosis and
therapeutic monitoring. Further, when self-report scales are used, an item-by-item analysis can
help to identify the exact symptoms that a patient considers most troublesome and challenging so
they can be targeted during the consultation process.

Rating scales can be used for (1) screening for the presence of a psychiatric condition (2)
diagnosis of a psychiatric illness (such scales are often termed diagnostic schedules) (3)
estimating severity of various conditions and their response to treatment (4) assess functional
capacity and well-being.

Rating scales can be either self-rated or observer rated. Some observer-rated scales require clinical
experience (clinician-rated) while trained non-clinical personnel can use others.

Self-rated Observer rated

Beck’s Depression Inventory Dementia scales
Zung Depression Inventory PANSS
Symptoms checklist SCL BPRS
GHQ HAMD
Lunser’s (extrapyramidal) MADRS
Edinburgh postnatal depression scale YBOCS
SCID
Scales are based on psychometric properties; aim to measure dimensions of psychopathology
(symptoms) often at the present state (the duration of which is defined variously). Schedules are
based on clinical expectations; deal with categories of disorders (syndromes) based on known
classification systems. A schedule may be devised to focus on either past or present status or both.

Two types of procedures are used when selecting items (symptoms) for scales. The first method
is based on the previous clinical literature to determine the appropriate items. The second
method is based on calibration. In this method, a large number of questions are tested to find the
most discriminating items between a ‘known ill’ and a ‘presumed well’ group. The items that are
most significant in a statistical sense are chosen to represent the scale that is devised.

Considerations for selecting a screening measure for use in a study include

 Characteristics of the population to be screened,

 Psychometric properties of the instrument,
 Time required to complete the measure,
 Ease of use, and
 Cost of obtaining the measure
© SPMM Course 2
General Health Questionnaire is an all-purpose screening tool that is often used as a first-level
assessment instrument in epidemiological studies before detailed diagnostic schedules are
employed.

 Goldberg introduced the General Health Questionnaire (GHQ)

 GHQ was developed as a screening tool to detect those likely to have or be at risk of
developing psychiatric disorders
 It is available in a variety of versions using 12, 28, 30 or 60 items, the 28-item version is used
most widely.
 Each item is scored as a 4 point Likert (0-3) allowing a total possible score on the GHQ 28 of 0
to 84.
 Using alternative binary scoring method (with least symptomatic items scoring 0 and the
most symptomatic items scoring 1), the 28- and 30-item versions classify any score exceeding
the threshold value of 4 as achieving ‘psychiatric caseness’. The caseness threshold is 3 for
the 12-item version. Psychiatric caseness is a probabilistic term—whereby, if such
respondents presented in general practice, they would be likely to receive further attention.
 It should be noted that the GHQ is not usually used for predictive purposes.
 Reliability coefficients have ranged from 0.78 to 0.95 in various studies.

© SPMM Course 3
2. Diagnostic schedules

Scale Mode of Features

administration
Clinical Interview Clinician administered A revised version for lay interviewers also available (CIS-R).
Schedule (CIS) – fully structured. Used in National Psychiatric Morbidity Surveys of Great
Britain. Developed by Goldberg et al. Aims to identify
common disorders found in primary care & community
settings (focus on neurotic conditions).

Composite Clinician administered CIDI was an improvised schedule that incorporated principles
International of both PSE and DIS. It was produced by WHO to be used with
Diagnostic Interview both ICD and DSM diagnoses.
(CIDI)
Diagnostic Interview Non-clinician- Used in ECA study. Lifetime DSM diagnoses made initially;
Schedule (DIS) administered; fully later a time period can be specified for ‘current diagnoses’.
structured interview.
Hopkins Symptom Trained primary care HSCL has a 58 items self-report version that measures
Check List (HSCL) workers (HSCL-25) or ‘neurotic’ symptom distress in outpatients (somatisation, OCD
self-reported (original) symptoms, interpersonal sensitivity, anxiety and depression)
and a 25 item objective version that measures symptoms of
anxiety (10 items) and depression (15 items). SCL-90R and Brief
Symptom Inventory (BSI) are derivatives of HSCL.
Patient Health Self-report scale It is the self-report version of Primary Care Evaluation of
Questionnaire (PHQ) Mental Disorders (PRIME-MD) developed by Spitzer et al. on
the basis of DSM-III. Aims to diagnose common neurotic
conditions in primary care settings. PHQ-9 is a derivative that
focuses on the 9 depression criteria in DSM-IV. GAD-7 on
anxiety and PHQ-15 on depression with somatic features.
Present State Clinician-administered Provides clinical diagnoses in the lines of ICD system.
Examination (PSE) semi-structured CATEGO is the computerize version of PSE schedule.
clinical interview
Schedule for Clinician-administered Covers all major mental illnesses (depression, bipolar disorder,
Affective Disorders semi-structured schizophrenia and anxiety disorders). A regular, a lifetime and
and Schizophrenia a change version are available. A children version called
(SADS) Kiddie-SADS is also available.
Schedule for Semi-structured Developed by Wing et al. on the basis of PSE and has replaced
Assessment in interview for use by PSE at present. Focused on adult psychopathology. Extensive
Neuropsychiatry trained clinicians (28 sections and 1872 items in total, but many can be skipped)
(SCAN)
Structured Clinical- Clinician- To be used for patients in whom a psychiatric diagnosis is
Interview for DSM- administered semi- suspected. Non-patient version available for epidemiological
IV (SCID) structured studies. SCID-II is available for axis 2 disorders.

© SPMM Course 4
Some general observations on diagnostic schedules currently available in psychiatry

1. Most schedules are either DSM or ICD based; only a few cater both simultaneously.
2. A number of primary-care oriented schedules focus largely on nonpsychotic disorders
3. Many schedules have computerized forms; nevertheless a number of them are time-
consuming to complete routinely or during initial clinical contact.
4. Almost all of them are clinician-administered though self-report forms have evolved in
recent times.

© SPMM Course 5
3. Depression rating scales:
2 Questions scale (also called PHQ-2): An affirmative response to the following two questions
may be as effective as using longer screening measures or may indicate the need for the use of
more in-depth diagnostic tools: (1) "Over the past two weeks, have you ever felt down, depressed,
or hopeless?" and (2) "Have you felt little interest or pleasure in doing things?"

HAMD/HDRS – Hamilton depression rating scale:

 Observer rated.
 17 – 21 items- 2 versions
 Refers to last 1-2 weeks
 More items for biological features
 Remains a reference standard

MADRS – Montgomery-Asberg Depression rating scale:

 10 items version
 Most sensitive to change
 Requires clinical interview like HDRS

BDI – Beck depression inventory:

 Self-rating 21 items
 Max score 63
 Last 2 weeks profile
 0-13 minimal; 14-19 mild; 20-28 moderate; >28 severe
 Lacks discriminatory power among very severely ill
 More psychological than somatic factors included
 Can be repeated at short intervals

Zung Depression Inventory:

 20 items
 Self-rated
 Avoids imbalance towards psychological factors seen in Beck’s
 Poor correlation with observer rating
 Insensitive to change

Visual Analogue Scale (VAS)

 Easiest way to quantify depression severity
 10cm line where patient indicates the state of mood

© SPMM Course 6
Depression screening in special cases:

Children with depression

 Depression screening for children and adolescents are generally appropriate in children who
are at least seven years of age. Reynolds Child Depression Scale and the Children's
Depression Inventory (full version with 27 items; screening version with 10 items) were
developed specifically for children and are written at lower reading levels.

Measure Age appropriateness (years)

Children's Depression Inventory (CDI) 7 to 17
Center for Epidemiological Studies-Depression Scale for Children (CES-DC) 12 to 18
Center for Epidemiological Studies-Depression Scale (CES-D) 14 and older
Reynolds Child Depression Scale 8 to 12
Reynolds Adolescent Depression Scale 13 to 18
Beck Depression Inventory (BDI) 14 and older
Mood and Feelings Questionnaire (MFQ) 8 to 18
Adapted from an online version at www.aafp.org/afp/20020915/contents.html.

 Advantages of the BDI and CES-D include ease of scoring, low-cost, and comparable
psychometric properties.
 MFQ is endorsed by the NICE and has a self and a parent-rated versions.

Perinatal depression:
 The BDI, CES-D, and Edinburgh Postnatal Depression Scale (EPDS) have been used to
screen for depression in women during the antepartum and postpartum periods.
 The BDI and CES-D tend to produce higher scores and more false-positive results in
symptomatic pregnant women.
 Edinburgh Postnatal Depression Scale was specifically developed for assessing
postpartum depression and relies much less on somatic questions.
 Questions on the Edinburgh scale (10 items, can be self or clinician-rated) are framed
within the "past seven days", and the response format is frequency-based.
 Routine use of EPDS during the postpartum period has been shown to increase the
detection of postpartum depression compared with usual care.
Geriatric depression:
 The GDS – Geriatric depression scale was specifically developed for use in geriatric
patients, and it contains fewer somatic items. Questions pertain to symptoms within the
past week, and responses require only a "yes" or ‘no’.
 In patients who have cognitive deficits, interviewer-administered instruments such as the
Cornell Scale for Depression in Dementia or the Hamilton Rating Scale for Depression are
preferred.
© SPMM Course 7
  The Cornell measure should be administered to the patient's primary caregiver.
 The Brief Assessment Schedule Depression Cards (BASDEC) system is designed for
general hospital use and eliminates the likelihood of questions being overheard on
geriatric wards. Patients choose answers from a deck of 19 cards presented one at a time.
Depression in schizophrenia:
 Most depression scales are tuned to assess depression in nonpsychotic patients.
 These scales contain items, which do not distinguish depressed from nondepressed
psychotic patients (e.g. delusions of nihilism that can be present in psychosis in the
absence of depression).
 Calgary Depression Scale for Schizophrenia (CDSS) focuses on symptoms of depression in
the presence of schizophrenia.

© SPMM Course 8
4. Alcohol rating scales:
CAGE Questions: 1. Have you ever felt like cutting down on your drinking? 2. Have people
annoyed or criticized you for drinking? 3. Have you ever felt bad or guilty about your drinking?
4. Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a
hangover (eye-opener)? A positive answer should raise suspicion of an alcohol problem, and a
score of 2 is highly suggestive. The instrument takes less than a minute to administer.

AUDIT: Alcohol Use Disorders Identification Test; Saunders et al., 1993: This is a 10-item
questionnaire, covering quantity, frequency, inability to control drinking, withdrawal relief,
loss of memory, injury and concern by others. A score of 8 or more indicates that the person is
drinking to a degree that is harmful or hazardous, whereas a score of 13 or more in women and
15 or more in men is indicative of dependent drinking. It is widely used and recommended by
WHO for primary care use.

MAST: Michigan Alcohol Screening Test (Selzer, 1971): This is a simple, self-report, 25-item test,
which has yes/no answers. A score of 3–5 is an early indicator of a problem drinker, whereas
someone who scores 6 or more is highly likely to be a problem drinker. There are variants on
this test, e.g. the Brief MAST, which can discriminate problem drinkers from nonproblem
drinkers on the basis of 10 items only. There are also a G-MAST and a Brief G-MAST for older
people with slightly different phraseology.

CIWA: Clinical Institute Withdrawal Assessment for Alcohol: (Sullivan et al., 1989) Health
professionals use this scale to rate the severity of alcohol withdrawal. It consists of 10 items, 9
of which can be scored in a range of 0–7 and one on a range of 0–4 (total of 67). It can be used
regularly throughout the day and night to assess the extent of withdrawal and the impact of
treatment. It covers nausea; tremor; paroxysmal sweating; anxiety; agitation; auditory, visual
and tactile disturbances; headache and orientation.

© SPMM Course 9
5. Scales used in child psychiatry

The Child & Adolescent Functional Assessment Scale:

 A rating scale to assess the degree of impairment in functioning due to emotional,
behavioural, or psychiatric problems.
 It is completed by a clinical staff and takes about 10 minutes.
 It is useful for assessing outcome over time and for directing case management activities.
 It measures aggression and conduct problems especially in age between 7 to 17 years.

The Child Behavior Checklist (CBCL):

 It records the behavioural problems and competencies of children aged 4 through 16, as
reported by their parents or others (e.g., teachers) who know the child well.
 The checklist is composed of 113 items in a Likert scale.
 The instrument provides three scores: a total score and scores on internalizing behaviours
(fearful, shy, anxious, and inhibited) and externalizing behaviours
 (Aggressive, antisocial, and under controlled).
 This instrument can either be self-administered or administered through an interview.
The CBCL can also be used to measure a child's change in behavior over time or following
a treatment.
 Teacher Report Forms, Youth Self-Reports and Direct Observation Forms are also
available for the Child Behavior Checklist.
 Two versions of this instrument exist: one for children ages 1 1/2 - 5 and another for ages 6
- 18.

Diagnostic Interview Schedule for Children (DISC):

 Originally developed in the early 1990s
 Fully structured diagnostic interview for making DSM-based diagnoses in children.

Conners Rating Scales

 A family of instruments that measure a range of childhood psychopathology
 Most commonly used in the assessment of ADHD.
 Teacher, parent, and self-report (for adolescents) versions are available
 Both short and long (up to 80 items) forms are available with

© SPMM Course 10
6. Scales used in old age psychiatry

 The Geriatric Mental State Schedule (GMSS) is a widely used instrument for measuring a
variety of psychopathology in community surveys of the elderly. AGECAT is a computerised
algorithm based on GMSS.
 The Mini-Mental State Examination (MMSE) is a popular cognitive screening instrument for
the elderly. It takes 10 minutes to administer by a trained interviewer. A cut-off score of 23 for
the presence of cognitive impairment has been suggested. Educational status affects MMSE
scores. MMSE does not pick frontal lobe deficits, a major drawback of using it as a screening
instrument for dementias. It is also claimed to have only moderate to minimal sensitivity to
change in mild cognitive impairment states.
 Abbreviated Mental Test Score is a brief 10-point questionnaire to assess memory and
orientation in 3 minutes (Hodkinson, 1972). Its origins can be traced back to the Blessed
Dementia Scale. A cut-off score of 7/8 out of 10 is suggested to suspect cognitive impairment
in the elderly.
 The Alzheimer's Disease Assessment Scale (ADAS) is a standardised assessment of
cognitive function, and non-cognitive features that take 45 minutes to be administered by a
trained professional. The cognitive section is termed ADAS-Cog. It is the gold standard for
measuring the change in cognitive function in anti-dementia drug trials. A fall of about 10%
per year is expected (deemed average) in Alzheimer's disease.
 The BEHAVE—AD is a clinician-administered scale to document behavioural symptoms in
patients with Alzheimer's disease. It covers paranoid and delusional ideation; hallucinations;
activity disturbances; aggression; diurnal variation; mood; and anxieties and phobias.
 The Neuropsychiatric Inventory (NPI) can be used to record severity of associated
behavioural symptoms of dementia over ten domains: (delusions; hallucinations; dysphoria;
anxiety; agitation/aggression; euphoria; disinhibition; irritability/lability; apathy; and aberrant
motor behaviour). It is scored from 1 to 144. The severity and frequency of behavioural
symptoms are independently assessed.
 MOUSEPAD stands for Manchester and Oxford Universities Scale for the Psychopathological
Assessment of Dementia. It is administered to carers by an experienced clinician for the
measurement of behavioural and psychiatric symptoms of dementia (BPSD).
 Clifton assessment procedure for the elderly - CAPE (Pattie & Gilleard, 1979) is intended to
assess the level of disability and estimate need for care in the elderly. It consists of a short
cognitive scale and a behavioural rating scale. The latter has four sub-scales: physical
disability, apathy, communication difficulties and social disturbance. It is quick and easy to
administer.

© SPMM Course 11
 Bristol Activities of Daily Living Scale assesses 20 daily living abilities in patients with
dementia. It is a caregiver-rated scale designed for community use by trained health
professionals.

© SPMM Course 12
7. Other clinical rating scales
SCALE Mode of Features
administration
Positive and Negative Clinician-administered For assessment of severity and monitoring of change of
Symptom Scale (PANSS) rating scale symptoms in patients with a diagnosis of schizophrenia. 30
items are covering positive symptoms, negative symptoms,
and general psychopathology.
Yale-Brown Obsessive- Clinician-administered Allowing rating of severity in patients with a pre-existing
Compulsive Scale (Y- semi-structured diagnosis of OCD.
BOCS) interview
SCOFF SCOFF is a mnemonic Do you
for eating disorder 1. Make yourself SICK when you feel uncomfortably full?
screening (similar to 2. Worry you have lost CONTROL over how much you
CAGE for alcohol). It eat?
has a high sensitivity 3. Recently lost more than 14 pounds within three
(2 or more questions months?
positive). 1. ONE stone's worth of weight
4. Believe you are FAT when others say you are too thin?
5. Would you say that FOOD dominates your life?

Minnesota Multiphasic Results generate A self-report questionnaire consisting of 567 questions

Personality Inventory information useful for covering 8 areas of psychopathology, 2 additional areas of
(MMPI) a broad range of personality type, and 3 scales assessing truthfulness. Results
clinical applications. are compared with normative data from non-clinical
populations. NOT A PROJECTIVE TEST.
International Personality Semi-structured 67 standardized probe questions. 57-item true/false
Disorder Examination clinical interview for questionnaire also included for screening purposes.
(IPDE) use by clinicians
producing ICD-10-
personality disorder
diagnosis.

Clinical Global Clinician rated based A two-item instrument - CGI-S (severity) – the current
Improvement (CGI) on clinical judgment condition on a scale of 1–7 & CGI-I (improvement) – the
extent of improvement since the start of treatment on a scale
of 1–7. Can be used for any psychiatric disorder
encountered in a clinic or ward.

Brief Psychiatric Rating Rated by the Developed by Overall, 1960. One of the most widely used
Scale (BPRS) physician on the basis clinical rating scales. It was originally intended for use in
of a semi-structured controlled clinical trials of new psychotropic drugs.
interview (18 items, 7 However, it has also been widely employed in studies of the
points for each, clinical (that is, symptom) correlates of cognitive and
maximum of 108) neurobiological phenomena. The ratings include
observations as well as patient reports. Factor analysis
yields five factors (hostility-suspiciousness, withdrawal-
retardation, thinking disturbance, depression-anxiety, and
activation).

© SPMM Course 13
Scale for Assessment of Clinician rated based Not intended as diagnostic devices. They have been used
Positive Symptoms on clinical interview primarily in studies of the neurobiological correlates of
(SAPS) and the Scale for symptom groupings. SAPS - 34 items divided into
Assessment of Negative hallucinations, delusions, bizarre behavior, and formal
Symptoms (SANS) thought disorder. SANS comprises 25 items divided into
affective flattening or blunting, alogia, apathy, asociality,
and inattention.
Personality Diagnostic Self-report instrument A brief structured interview (Clinical Significance Scale) is
Questionnaire-4+ (PDQ- assessing 12 used as a follow-up after the self-report to estimate whether
4+) personality disorders (a) the trait is enduring (criterion D for DSM-IV); (b) it is
described in the DSM-
present in the absence of other disorders (criteria E and F);
IV using 99 true-false
and (c) it leads to distress or impairment (criterion C).
items.

© SPMM Course 14
8. Outcome scales in psychiatry
The purpose of clinical intervention in psychiatry is to achieve a desirable outcome for the patient,
his/her family and the society. Treatment outcomes are not single constructs but are
multidimensional. Outcome measures can be broadly classified as follows:

 Psychopathological rating scale: measuring individual symptom severity in a disorder

e.g. PANSS, BPRS. These scales can also provide modified measures such as relapse,
remission, etc. that are sued as outcome variables in various studies.
 Global outcome measure: an overall appraisal of disease severity and its impact on
overall functioning e.g. Global Assessment of functioning (GAF) or Global Assessment
Scale (GAS).
 Generic patient-based outcome measure: measuring several domains of health-related
quality of life applicable to populations irrespective of illness. e.g. Short Form 36 (SF36)
 Disease-specific patient based outcome measure: measuring several domains of health-
related quality of life applicable to specific patient groups.
 Domain specific patient based outcome measure: measuring a specific domain associated
with health-related quality of life e.g. focusing on social function or interpersonal
relationships or cognitive capacity or service-level satisfaction.

Any useful outcome measure must satisfy the following criteria to be incorporated into trials and
clinical practice:

Appropriate

•Is the instrument appropriate to the question addressed by the trial or the benefit desired by the clincial
service?

Reliable & valid

•Is the measure reproducible, internally cosnsitent, precise and accurately reflecting the construct of
interest?

Responsive

•Is it sensitive to change over time?

Readily Interpretable

•Are the scores intuitively meaningful and comparable to real life states?

Acceptable & feasible

•Is the tool readily applicable in clincial settings and not too onerous on clinicans and patients?

Some examples of outcome scales

Global Assessment of Functioning Scale (GAF) is available as an appendix to DSM-IV. It
measures overall psychosocial functioning in patients on a 10-item (100 points) scale, rated on the
© SPMM Course 15
basis of self-report and information from the clinical interview. GAF was used in axis V of
the multiaxial diagnostic system in DSM-IV. It combines symptomatic severity and functional
impairment and is based on the clinician’s appraisal of the functional limitation.

Social and Occupational Functioning Assessment Scales (SOFAS) was proposed as a new axis
in Appendix B of DSM-IV. It is related to GAF but focuses only on functioning and not on
symptoms. SOFAS does not try to discriminate between functional changes related to psychiatric
and nonpsychiatric causes. It is rated by clinicians on a 100-point scale based on all available
information, with descriptors for each 10-point interval. Guided tools for administering SOFAS
(e.g. Personal and Social Performance scale –PSP) are available for use in clinical trials.

Short Form health survey-36 or SF-36 was designed for wide use in a variety of settings: clinical
practice, research, policy evaluations, and community surveys. SF-36 can be self-administered by
persons 14 years of age and older, or by a trained interviewer. It assesses eight health concepts: 1)
limitations in physical activities because of ill health; 2) limitations in social activities because of
physical or emotional problems; 3) limitations in role performance due to physical health
problems; 4) bodily pain; 5) general mental distress and well-being; 6) limitations in role
performance because of emotional problems; 7) vitality (energy and fatigue); and 8) general
health perceptions.

The health of the Nation Outcome Scales (HoNoS): HONOS is the most widely used psychiatric
outcome scale within the NHS. It was developed by the RCPsych and commissioned by the
Department of Health in 1993. It has 12 items measuring behaviour, impairment, symptoms and
social functioning, measured on the basis of routine clinical assessments in various clinical
settings and has influenced various policymaking processes in the English NHS over the last 2
decades.

© SPMM Course 16
9. Psychometry of rating scales:
When developing measurement scales, we are concerned about two important properties. Can
we use this scale to measure the actual phenomenon we want to measure? Can this scale provide
consistent results when it is used? A highly valid scale will measure what it is supposed to
measure – the truth. A highly reliable scale will provide consistent results.

Reliability refers to the replicable nature of research studies / tools. Note that high reliability
does not guarantee scientific validity but guarantees consistency.

 Reliability can be assessed by test-retest correlation by administering an instrument twice to

the same population. The time difference between test and retest must be long enough to
avoid practice effect, but short enough so the underlying state (e.g. depression) does not
change very much: 2 to 14 days range is often used in psychiatry.

 Cronbach’s alpha measures the internal consistency of a test by correlating each item with
the total score and averaging the correlation coefficients. It can take values between negative
infinity and 1 as a maximum; but only positive values make sense. Arbitrary cut-off of 0.70 is
used commonly to call the evaluated test to be internally consistent.

 The split-half reliability refers to splitting a scale into two parts and examining the
correlation.

 Interrater reliability is measured using two or more raters rating the same population using
the same scale.

 The intraclass correlation coefficient is used for continuous variables; it is nothing but the
proportion of total variance of the measurement that reflects true between subject variability.
It ranges between 0 (unreliable) and 1 (perfect reliability). ICC can be measured by either
relative agreement or absolute agreement; the relative ICC is always higher than the
absolute ICC. ICC of 0.6 is considered fair while 0.8 is very good and 0.9 as excellent,
arbitrarily. ANOVA intraclass coefficient is used for quantitative data with more than 2
raters/groups.

 For nominal data that has more than two categories, a kappa or weighted kappa can be used.
(More details are given below)

Validity of an instrument is the extent to which an instrument measures what it proposes to

measure.

 Face validity refers to a subjective measure of deciding whether the test measures the
construct of interest on its face value.e.g., Hamilton depression scale clearly has a face value
in measuring depression; but not for measuring obsessions.

© SPMM Course 17
  Construct validity measures whether a test really measures the (theoretical) construct of
interest or something else. One way of classifying the construct validity is considering
unified construct validity. Here construct validity is taken to consist of both content validity
and criterion validity (referred as unified construct validity).

 Content validity refers to whether the contents i.e. each individual subscales, items or
elements of the test are in line with the general objectives or specifications the test was
originally designed to measure. It looks for a good coverage of all domains thought to
be related to the measured condition. This often cannot be statistically tested, but
experts are called for comments on this aspect of validity.

 Criterion validity refers to the performance against an external criterion such as

another instrument (concurrent) or future diagnostic possibility (predictive).

 Concurrent validity refers to the ability of a test to distinguish between subjects

who differ concurrently in other measures (using other instruments). e.g., those
who score high on a scale of insomnia may score high on a scale of fatigue ratings
too.

 Predictive validity refers to the ability of a test to predict future group differences
according to current group differences in score. e.g., high aggression score in
childhood and high criminal incidents in adult life. (On a similar note, Incremental
validity refers to the ability of a measure to predict or explain variance over and
above other measures)
Another way of considering the construct validity is by classifying it to convergent, discriminant and
experimental/interventional validity:

 Convergent validity refers to agreement between instruments that measure same construct e.g.
between BDI and HAMD for depression. This agreement can be tested in contrasted groups i.e.
depressed and non-depressed, both groups showing a high correlation between the two scales.

 Discriminant validity refers to the degree of disagreement between two scales measuring different
constructs. e.g., to say that HAMD measures some construct (depression) different from that measured
by Hamilton Anxiety scale (anxiety) poor correlation must be demonstrated between HAMD and HAS

 Experimental validity: This refers to the sensitivity to change. An instrument must show the
difference in results when an intervention is carried out to modify the measured domain.

© SPMM Course 18
Note: Factorial validity is a form of
construct validity established via factor
analysis of items in a scale.

Precision and accuracy

Precision is the degree to which a calculated

central value (e.g. mean) varies with
repeated sampling. The narrow the
variation, the precise the value is. Random
errors lead to imprecision.

Factors reducing precision includes 1.

Having wider the limits of the interval 2.
Expecting higher confidence interval (e.g.
99.7% versus 95%). Accuracy refers to the
correctness of the mean value – i.e. how
close is it to the true population value. Precision is comparable to reliability while accuracy is
comparable to validity. Bias in a study compromises validity / accuracy.

VALIDITY QUESTION IT ANSWERS

Face Does this scale appear to be fit for the purpose of measuring the variable of interest?

Content Does this scale appear to include all the important domains of the measured attribute?
Criterion Is the scale consistent with what we already know (concurrent) and what we expect
(predictive)?
Convergent Does this new scale associate with a different scale that measures a similar construct?
Discriminant Does the new scale disagree with scales that measure unrelated constructs?

© SPMM Course 19
10. Risk assessment
Risk is the likelihood that harm will occur. Risk assessment is a process of scientific
(statistical/clinical) calculation of likelihood of an adverse event; this includes specifying

1. What will happen?

2. When will this happen?
3. By whom will this happen?
4. How will this happen?
Risk management is integral to assessment; Assessment is not carried out to label people and
categorise into groups – it is a dynamic process and specific to the event of importance. Risk
cannot be eliminated but only reduced.

Problems with ‘predicting’ risk:

 Low base rate: The events of interest are usually very rare. Hence the predictive value is
generally low. Serious violence is rare amongst the severely mentally ill disordered, killing
or maiming of others is measured in probabilities of less than 1% (Wallace 1998). This low
base rate seriously compromises the predictive utility of risk assessment because of the
false positive rate of even an exceptionally good risk assessment instrument.
 Multifactorial: Risk is dependent on several factors, which tend to change over time.
 Unknown interactions: Comprehensive risk evaluations are time-consuming; often the
degree and nature of interaction among various factors is unknown.

Risk factors for any untoward incident (suicide, crime or violence) can be categorized as static,
stable and dynamic factors (Bouch & Marshall, 2003).

 Static risk factors: These are fixed and historical: e.g. family history of suicide. They cannot be
modified.
 Stable risk factors: These are long term, enduring issues but are modifiable to some extent
and not fixed: e.g. diagnosis of personality disorder.
 Dynamic risk factors fluctuate markedly in both duration and intensity: the e.g. presence of
acute anxiety symptoms or akathisia. A dynamic risk factor can act synergistically and
multiply the effect of underlying static and stable risk factors if not addressed promptly.
Certain dynamic factors may occur only in future (e.g. upon discharge, a patient may feel
helpless).

A comprehensive risk assessment should consider static, stable, dynamic and future risk factors
and include them in devising risk management strategies.

© SPMM Course 20
 Approaches to risk assessment
Clinical approach
In this approach, a clinicians’ subjective, intuitive judgment informed by experience and
knowledge is used to estimate risk and guide decisions about treatment. But professional
opinions are often highly variable for a given case and have poor predictive value, not supported
by many policymakers. Most risk assessment currently performed by clinical methods. They are
based on clinical experience, individuals knowledge and person-specific assessment to reach a
conclusion. Only 1/3rd of pure clinical judgments are estimated to be correct in retrospective
studies.

Actuarial approach
This approach is very popular in forensic services. This uses formal, algorithmic and objective
procedures for quantifying risk as a numerical probability of a future outcome: e.g. patient A has
a 60% chance of killing herself in the next 2 years, etc. It is found to be superior to other methods
of predicting the risk of violence and sexual offending, but does not inform the clinician much
about the risk factors that require targeting to mitigate risk. There are hardly any actuarial tools
available for self-harm and suicide risk, but there are many available for violence risk assessment.

Problems of actuarial tools include:

1. Historical aspects are given more importance – so a pessimistic view of risk with
insensitivity to change results.
2. High false positive rates using these tools.
3. As mentioned above generalisation of actuarial tools developed in one setting to the other
is difficult.
4. Further, actuarial approaches are often too focused on static and stable risk factors rather
than dynamic and modifiable factors. Thus, though actuarial instruments more accurately
identify at-risk groups, structured risk instruments may be more clinically useful for
enhancing clinical decision-making.

Structured professional judgment

Structured professional judgment is an approach that aims to combine the evidence base for risk
factors with an individual clinical assessment to complement psychiatric opinion. A structured,
scales-based assessment is used when formulating risk management plan. Several risk
assessment instruments are available to support structured professional judgment (e.g. HCR–20
to assess risk for violence in forensic settings)

It is important to note that neither actuarial nor structured judgments should replace
conventional clinical assessment; they must be employed as an additional aide for systematically
identifying and addressing relevant risk factors.
© SPMM Course 21
Stages in risk assessment
According to Bouch & Marshall, the following stages are identified for risk assessment and
management.

A. Identifying the need for a full structured risk assessment (not everyone will need this)
B. Assessing static, stable, dynamic and future risk factors and considering protective
factors
C. Individual formulation of risk applied to the context of current presentation
D. Considering possible interventions and the level of support required
E. Anticipating the impact of possible interventions
F. Developing a management plan with specified short and long term implementations
G. Reviewing and revising the management plan with variations in risk factors.

Commonly used tools

Structured Risk Tools
HCR-20 (Webster): It is a popular structured clinical assessment tool for violence risk. HCR-20
(Historical, Clinical and Risk) shows good inter-rater reliability. It has

 10 historical items (history of previous violence, PCLR score, etc.)

 5 Clinical items (lack of insight, diagnosis of PD) and
 5 risk management items (feasibility of plans, lack of support, etc.)

It has been useful in predicting inpatient violence and community violence in discharged patients.

Historical items Clinical items Risk items

Previous violence history Negative attitudes to health services Management plan lacks feasibility

Young age at first incident Active symptoms Exposure to destabilisers (e.g. alcohol)

Unstable relationships Impulsivity Non-compliance

Major mental illness Treatment unresponsiveness Stress

Substance use Lack of insight Lack of personal support

Psychopathy

Employment issues

Personality disorder

Early maladjustment

Previous supervision failure

© SPMM Course 22
SARA: Spousal assault risk assessment guide SARA is a 20 item set of risk factors for use in the
assessment of spousal assault. It can be used to help gauge the risk of future violence in men
arrested for spousal assault.

SVR-20 is a sexual violence risk 20 scale - this is a 20 item guide for assessing violence risk in sex
offenders.

SAD PERSONS Score: 10 major demographic risk factors used in a mnemonic to assess
immediate suicidal risk often in acute general hospital setting. The scores can guide in making a
decision to admit or discharge a patient.

S – Sex: 1 if male; 0 if female; (more females attempt, more males succeed)

A – Age: 1 if < 20 or > 44
D – Depression: 1 if depression is present
P – Previous attempt: 1 if present
E –Ethanol abuse: 1 if present
R – Rational thinking loss: 1 if present
S – Social Supports Lacking: 1 if present
O – Organized Plan: 1 if plan is made and lethal
N – No Spouse: 1 if divorced, widowed, separated, or single
S – Sickness: 1 if chronic, debilitating, and severe

Beck Hopelessness Scale consists of 20 true-false statements focused on pessimism and

negativity about the future. The degree of hopelessness measured using this tool is a good
indicator of suicidal risk with scores: 0 –3 indicating minimal, 4 – 8 mild, 9 –14 moderate, and 15–
20 severe risk.

Beck Scale for Suicidal Ideation is a self-report 24-item scale (5 screening items) that assesses a
patient’s thoughts, plans and intent to commit suicide. The total scores could range from 0 to 48
(each item scored from 0 to 2). Higher scores reflect greater suicide risk though no defined cut-
offs are identified for categorizing the risk profiles.

Actuarial instruments
Group data is obtained from high-risk individuals and then to applied to the patient in question.
It gives a group risk, and it should be applied with caution. Different types include:

VRAG (violence risk appraisal guide – Quinsley 1995) entirely reliant on historical factors.
Validated at Canadian prisons. It is made of 12 items and includes PCL_R as a subscale.

© SPMM Course 23
 Violence risk appraisal guide
PCL-R Absence of schizophrenia (Presence is counted to
decrease risk!)
Elementary school difficulties Victim injury (minimal or none)

Personality disorder Alcohol abuse

Younger age Female victim

Separated from parents before age 16 Failed conditional release/supervision order

Never married History of non violent offence

Violence Risk Scale has 23 dynamic and 6 static variables.

PCL-R (Hare) is a scale to diagnose Psychopathy, informs risk assessment and treatment
decisions. 0 – 40 score range; 0-2 for each item; 20 items in total. Cut off of 25 used to diagnose
psychopathy. In the strictest sense, PCL was not designed to be an actuarial tool for risk
assessment on its own.

The Static-99 is a ten item actuarial assessment instrument created by Hanson and Thornton, for
use with adult male sexual offenders who are at least 18 year of age at the time of release to the
community.

SORA (Sexual risk offender appraisal guide) is a 14 item actuarial instrument that incorporates
PCL_R.

The Manchester Self Harm Rule (MSHR) is an actuarial instrument for self-harm risk
assessment produced by Cooper et al. 2006. It has high sensitivity but low specificity.

© SPMM Course 24
DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug-related information using external sources;
no part of these notes should be used as prescribing information.

Notes produced using excerpts from:

 Achenbach, T. M. (1991). Manual for the Child Behavior Checklist/4-18 and 1991 Profile.
Burlington, VT: University of Vermont, Department of Psychiatry.
 Bouch, J., & Marshall, J. J. (2005). Suicide risk: structured professional judgement. Advances in
Psychiatric Treatment, 11(2), 84-91.
 Burns, A., Lawlor, B., & Craig, S. (2002). Rating scales in old age psychiatry. The British Journal of
Psychiatry, 180(2), 161-167.
 Casey, P. & Kelly, B. (Ed) Fish’s Clinical Psychopathology. 3rd ed. RCPsych publications.
 Cooper J, Kapur N, Dunning J, et al. A clinical tool for assessing risk after self-harm. Ann Emerg
Med. 2006;48:459–466.
 Cox JL, et al. Validation of the Edinburgh Postnatal Depression Scale (EPDS) in postnatal women. J
Affect Disord 1996;39:185-9.
 http://www.static99.org/
 http://www2.massgeneral.org/schoolpsychiatry/screeningtools_table.asp
 https://www.cnsforum.com/educationalresources/ratingscales/psychiatry
 Jackson. C. The General Health Questionnaire. Occupational Medicine 2007 57(1):79;
 Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition.
Lippincott Williams & Wilkins 2007
 Morgan et al.(1999), SCOFF Questionnaire. BMJ 319:1467
 Sharp LK, Lipsky MS. Screening for depression across the lifespan: a review of measures for use in
primary care settings. Am Fam Physician 2002;66: 1001-8.
http://www.aafp.org/afp/2002/0915/p1001.html
 Ware Jr, J. E., & Sherbourne, C. D. (1992). The MOS 36-item short-form health survey (SF-36): I.
Conceptual framework and item selection. Medical care, 473-483.

© SPMM Course 25
Eponyms & uncommon syndromes
somatic complaints across different
Angelman syndrome: Congenital organ systems as a manifestation of
syndrome of mental retardation and anxiety.
epilepsy that is distinctive for puppet-
like movements, compulsive laughter, Brueghel syndrome: Trigeminal
and heritability. dystonia that affects the mouth,
sometimes provoked by antipsychotics.
Anton syndrome: Condition of
blindness in which patient denies he Capgras syndrome: The belief that
cannot see and confabulates; a strangers in disguise have replaced
particular type of anosognosia. This persons known to the patient.
condition is classically but not
exclusively associated with bilateral Charcot-Wilbrand syndrome:
occipital cortex lesions. "Global cessation of dreaming"; the
loss of all or part of dreaming after
Balint syndrome: Constellation of brain injury.
symptoms that include fixation of
gaze, neglect of objects in visual Charles Bonnet syndrome: Visual
surround, and misreaching, usually due hallucinations in the context of reduced
to bilateral superior parietooccipital eyesight.
lesions.
Clerambault-Kandinsky syndrome:
Bell mania: Disorganized The syndrome that includes any
hyperactivity (as opposed to waxy paranoid psychosis in which thought
flexibility and rigidity in lethal insertions predominate, regardless of
catatonia) that can be fatal if untreated; etiology.
the syndrome is rare, probably because
of the widespread use of [Cornelia] de Lange syndrome:
antipsychotics, and the eponym is Congenital mental retardation
antiquated. distinctive for patients' self-injury,
hyperactivity, sleeplessness, and
Binswanger disease: A particular type aggression.
of multi-infarct dementia (a subtype of
DSM-IV Vascular Dementia) in which Cotard syndrome: Patient's belief that
infarcts selectively affect the white he does not exist, that part of him is
matter. not there (e.g., his organs), or that he is
dead.
Briquet syndrome: Somatization
Disorder; the disorder of multiple

Eponyms 1
Creutzfeldt-Jakob disease: Rapidly Gélineau syndrome: Narcolepsy; a
progressive dementia caused by disorder with daytime sleepiness,
transmissible prions (proteinaceous cataplexy, sleep paralysis, hypnagogic
infectious particles) and distinctive for hallucinations, and association with
ataxia, myoclonus, EEG triphasic various human lymphocyte antigens.
waves, and the diffuse spongiform
appearance of the patient's brain after Gerstmann syndrome: Finger
death. agnosia, agraphia, right-left
disorientation, and dyscalculia,
Da Costa syndrome: Panic Disorder; associated with dominant parietal lobe
the condition of debilitating anxiety lesions.
attacks accompanied by attempts to
avoid such attacks. Gerstmann-Sträussler-Scheinker
disease: Transmissible prion disease
De Clerambault syndrome: that causes dementia and affects only
Erotomania, or more specifically a individuals with particular autosomal-
female patient's belief that a wealthier dominant defects of chromosome
older man, whom she does not know,
loves her. Geschwind syndrome: Constellation
Ekbom syndrome: 1) delusional of interictal behavior including
parasitosis, the belief that the skin is hyposexuality, hyperreligiosity,
infested with parasites, sometimes hypergraphia, and "viscosity" (not
associated with cocaine use; 2) restless observing appropriate social
legs syndrome, the condition of boundaries in conversation), all seen in
annoying sensations in the extremities some patients with chronic temporal
that disturbs sleep onset. European lobe epilepsy.
physicians prefer the first definition,
Americans the second. Gjessing syndrome: "Periodic
catatonia"; a disorganized state of
Fahr disease: Idiopathic calcification withdrawal or agitation that fluctuates
of basal ganglia that causes dementia on and off.
and abnormal extra movements, often
comorbid with obsessive-compulsive Hakim-Adams syndrome: Normal
and mood symptoms. pressure hydrocephalus; the
accumulation of cerebrospinal fluid in
Fregoli delusion: Belief that strangers the ventricles without a significant rise
are actually persons well known to the in intracranial pressure, which often
patient, in disguise. causes dementia, gait apraxia, and
incontinence; shunting reverses the
Ganser syndrome: The symptom of dementia if it is identified in time.
answering all questions approximately;
e.g., "2+2=5."27 Heller syndrome: Childhood
Disintegrative Disorder; the loss of
Gardner-Diamond syndrome: milestones in multiple domains after
Purpura associated with psychological age
stress; subcutaneous injection of
patients' own blood reproduces the Hoigne syndrome: Acute psychosis
rash in the (mostly female) sufferers. due to the intravenous injection of
penicillin.

Eponyms 2
Hoover sign: Unconsciously exerted defective purine metabolism and
downward pressure with a healthy leg ferocious self-injury.
when the paretic leg is challenged; its
absence demonstrates a feigned deficit. Lhermitte syndrome: Peduncular
hallucinosis; bizarre hallucinations
Kahlbaum syndrome: Catatonia; a (classically, visions of Lilliputians)
syndrome of waxy posturing or without other psychosis, due to a lesion
purposeless agitation or speech, treated in the midbrain.51
with benzodiazepines and ECT.
Marchiafava-Bignami disease:
Kanner syndrome: Autism; a Dementia due to callosal degeneration,
developmental disorder with abnormal associated with chronic alcohol
communication, impaired social (particularly wine) abuse.
interaction, repetitive behavior, and
symptoms before the age of 3 years. Marinescu reflex: Palmomental
reflex; the movement of the chin after
Kleine-Levin syndrome: Syndrome of stroking the palm, which, when
hyperphagia, hypersexuality, and unilateral, suggests frontal or diffuse
hypersomnia classically described in brain damage.
male adolescents.
Martin-Bell syndrome: Fragile X–
Klüver-Bucy syndrome: Syndrome of linked mental retardation, a condition
temporal lobe damage involving due to trinucleotide repeats on the X
hypersexuality and hyperorality. chromosome that is the most common
genetic cause of mental retardation;
Korsakoff syndrome: Chronic particularly important in psychiatry
amnesia characterized by difficulty in because many patients suffer from
learning new information (anterograde autism and virtually all have attention-
amnesia), manifesting as deficit hyperactivity disorder.
confabulation; caused by thiamin
deficiency and wholly or partially Meige syndrome: Dystonic
reversible in some cases. blepharospasm; recurrent involuntary
blinking caused by a
Kozhevnikov syndrome: Continuous hypodopaminergic state such as that
partial epilepsy leading to progressive induced by antipsychotics.
cognitive deterioration.
Morvan disease: Involuntary muscle
Landau-Kleffner syndrome: fiber activity, hyperhidrosis, and
Continuous partial simple epilepsy sleeplessness that leads to death in
selectively causing loss of language weeks if not treated; possibly
development in children. autoimmune.

Langfeldt psychosis: Psychosis Myerson sign: Glabellar tap reflex; a

without the declining course of failure to extinguish blinking after 4
schizophrenia. taps on the forehead that suggests
frontal, diffuse, or extrapyramidal
Lesch-Nyhan syndrome: Congenital disease.
mental retardation caused by a
chromosome 26 deletion, with Parkinson disease/syndrome: The
"disease" is the idiopathic degeneration

Eponyms 3
of the substantia nigra that causes hyperactivity once known as "minimal
resting tremor, bradykinesia, and brain damage syndrome."67
rigidity; the "syndrome" is these
symptoms due to some other cause, Sydenham chorea: Movement
such as medication. disorder that follows rheumatic fever;
often preceded by obsessive-
Pick disease: Dementia with frontal compulsive symptoms (first described
and temporal atrophy, early personality by Osler) that have been characterized
change, and Pick bodies found recently as "PANDAS" when they
postmortem. occur alone.

Prader-Willi syndrome: a congenital Tourette syndrome: Disorder with

form of mental retardation distinctive both motor and vocal tics (sometimes
for patients' compulsive eating and coprolalia), often comorbid with
self-mutilation; caused by a obsessive-compulsive symptoms.
chromosome 15 deletion.
Von Economo disease: Encephalitis
Rasmussen syndrome: Unilateral lethargica, a syndrome that afflicted
brain atrophy and continuous epilepsy many victims of a viral epidemic in the
that results in cognitive decline until early 20th century and distinctive for
the affected portion of the brain is Parkinsonism, lethargy, and obsessive-
removed. compulsive symptoms.

Rett syndrome: Developmental Wernicke encephalopathy: Triad of

disorder caused by an X-linked delirium, ataxia, and abnormal eye
dominant mutation that is found movements associated with thiamin
mostly in girls and involves acquired deficiency, particularly in alcohol
microcephaly, reversal of cognitive abusers.
and social development, ataxia, and
"hand-wringing (stereotypic hand Williams syndrome: Congenital
movements and manual dyspraxia)." syndrome of mental retardation with a
deletion on chromosome 7, distinctive
Sanfilippo syndrome: Congenital for patients' fluent verbal ability and
mental retardation caused by a "elfin" face.
chromosome 12 deletion, distinctive
for aggression and insomnia. Wilson disease: Congenital recessive
condition of defective copper
Smith-Magenis syndrome: Congenital metabolism due to a defect in
mental retardation distinctive for chromosome 13, characterized by
severe self-injury and "self-hugging" hepatic symptoms and later psychiatric
behavior. symptoms and choreoathetosis as
various organ systems are
Steele-Richardson-Olszewski disease: overwhelmed by copper. It can be
Dementia with ataxia, loss of ability to diagnosed (once the central nervous
look up or down, and parkinsonism. system is affected) by finding Kaiser-
Fleischer rings in the cornea with a
Strauss syndrome: Attention- slit-lamp though these are not
Deficit/Hyperactivity Disorder; the universally present. A more reliable
condition of inattention and/or diagnosis depends on low

Eponyms 4
ceruloplasmin and elevated copper in may be at high risk for psychiatric
urine and liver biopsies. illness.

Wolfram syndrome: Rare autosomal

recessive syndrome caused by a defect
in chromosome 4, with diabetes,
bilateral optic atrophy, and diverse
psychiatric disorders. Heterozygotes
for the Wolfram mutation are
extremely common (occurring in 1%
of the population), and those having
them

DISCLAIMER: This material is developed from various revision notes assembled while preparing
for MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books.
These sources are cited and acknowledged wherever possible; due to the structure of this
material, acknowledgments have not been possible for every passage/fact that is common
knowledge in psychiatry. We do not check the accuracy of drug-related information using
external sources; no part of these notes should be used as prescribing information.

This excerpt is from: Bresch, D. (2002) Beyond Wernicke’s:

A Lexicon of Eponyms in Psychiatry J Neuropsychiatry Clin Neurosci 14: 155-160

Eponyms 5
 Human Development
Paper A Syllabic content 2.1 to 2.18

© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
© SPMM Course rights to Images/Figures with CC-BY-SA license if they are used in this material.
1
1. Conceptualizing development

In psychology, maturity refers to the ability to respond to the environment in an appropriate

manner, usually with a learnt response. Maturity refers to the production of expected behaviour
and actions in a given situation in an age-appropriate manner. Psychosocial maturity is a key
factor in the development of a sense of autonomy and includes processes involving cognitive,
emotional, social and moral development.

Nature vs. Nurture: Development is influenced by both nature (genetic disposition) and nurture
(environmental influences). But the proportional contribution of genetics and environment to the
psychosocial development of personality, intelligence and sexuality is fiercely debated to date.

Studies estimate a heritability of 40-50% for human IQ. But several observations warrant
consideration in this regard.

1. Heritability of IQ varies with age: While the heritability is around 30% in children, it
increases to 80% among adults. This suggests that either the genetic determinants of
intelligence are age-specific or that the non-genetic maturational factors are much more
influential in shaping human intelligence at younger ages.
2. Heritability of IQ is affected by demographics: Scarr et al. observed greater genetic effects on
intelligence in middle-class white groups than in lower-class African American groups,
suggesting that among lower socioeconomic groups, nongenetic influences operate on
development. Irving Gottesman, the proponent of endophenotype concept, famously
stated that genes are weaker than poverty.
3. Genetic influences are likely to be variable: For a construct such as intelligence, which is made
of several sub-constructs, it is likely that no single gene or genetic complex will be
sufficient to account for the variations. Furthermore, at various stages of development, the
genetic factors operating to influence intelligence could vary.
4. Effect of the shared environment: genetic influences are often inferred from the observation
that closer biological relatives (e.g. identical twins) are more similar in their intelligence
than less closely related pairs (non-twin siblings). But, in fact, several observations suggest
that there is indeed a greater similarity between pairs of family members than would be
predicted on the basis of their biological relationship, indicating the effect of shared
environment on intelligence (Deary et al., 2010).

© SPMM Course 2
Models and theories
Developmental theories aim to explain how children grow and learn. Of these stage, theories
refer to theories that consider development as a process that occurs over a 12- to the l5-year
period in chunks of time called stages. Within each stage, a specific set of functioning and
behaviour can be observed. Certain maturational tasks (motor, cognitive and perceptual) are also
achieved in each stage, heralding transition to next stage of development. Piaget’s theory is a
prototype stage theory focused on epistemology (the study of the development of knowledge or
intelligence). According to Piaget, development

1. Occurs in hierarchical stages

2. Each stage is qualitatively different ( not just quantitatively)
3. The stages consist of invariant functions and all children undergo these sequentially

Other stage theorists include Gesell, Freud and Erikson.

Maturational tasks
Age Motor Language Sensory Social development
4-6 weeks Smiles at the parent (social
smile - 6 weeks); can
recognise mum’s face apart;
shows preference to human
faces.
6-8 weeks Cooing

3 months Can hold head up. grasp Babbling Localises Squeals with pleasure
reflex disappears sound appropriately. Discriminates
source smile
5 months Reaches out; oral Spontaneous
exploration babbling and
sound
experiments
6 months Hand to hand transfer Double syllable Localises
rolling over sounds such as sound
Palmar grasp 'dada.' 45cm
lateral to
either ear
9-10 Cruises around and Babbles Looks for Stranger anxiety followed by
months crawls. Sits tunefully toys object permanence
unsupported. Picks up dropped;
objects with pincer grasp Peek a boo

© SPMM Course 3
 game

1 year Stands alone One or two Separation anxiety

momentarily words
18 Walks alone. Holds rails Many Shows rapprochement ( hugs
months and climbs, can jump intelligible when coming back).
with both feet. Can words – up to
build a tower of 3 or 4 40 in some.
cubes and throw a ball (1 Uses
X 3). Can use a spoon. holophrases.
2 years Able to run. Builds Makes Parallel play. Dry by day
tower of 6 cubes (2 X 3) sentences –
telegraphic
initially.
3 years Goes upstairs 1 foot per Speaks in Cooperative play. Imaginary
step and downstairs 2 sentences companions
feet per step. Copies
circle, imitates cross and
draws the man on
request. Builds tower of
9 cubes (3 X 3)
4 years Can skip; copies a cross Toilet trained mostly
5 years Can hop; copies a Fluent speech Dresses and undresses alone
triangle. with grammar
use; uses
function words
6 years Copies a diamond. Can Nearly adult-
count number of fingers like speech

© SPMM Course 4
A brief outline of various developmental theories is presented in the table below. These will be
considered in detail in later sections of this chapter.

Theories Key Concepts

Temperament theory Temperaments are inherent biologically based traits varying from
(Thomas & Chess, difficult to easy (or inhibited to uninhibited). Temperament elicits
Kagan) environmental response that perpetuates a pattern of behaviour

Organismic stage Development occurs in stages with transition occurring as a result of

theory (Piaget) interaction of the child with its environment (child as a scientist)
Attachment theory Innate tendency to seek relationships influence patterns of behaviours in
(Bowlby) later life.
Social learning theory Observational learning in childhood influences later behaviour
(Bandura)
Psychosexual stage Stage-specific behaviours are driven by inner conflicts and resulting
theory (Freud) anxiety signals. Successful resolution of conflicts aid in progressive
maturation.
Psychosocial stage Psychosocial developmental stages are characterized by conflicts, but the
theory (Erikson) successful resolution is not mandatory for further development.
Collaborative Development is not entirely private; child acts as an apprentice in social
learning theory surroundings rather than a scientist. Parents and teachers carry out the
(Vygotsky) role of scaffolding to introduce familiarity for the child to develop its
own expertise (collaborative learning). Zone of proximal development
refers to functions that are not yet fully achieved but are in the process
‘pipeline’ whose development is aided by scaffolding.
Maturational Growth Maturation of the nervous system as the principal driver of the various
theory (Gesell) aspects of human behaviour

© SPMM Course 5
Freud’s psychosexual stages: Gradual, the sequential emergence of genital sexuality from
infantile sexuality is noted in Freud’s model. The stages discussed here reflect both biological and
psychological maturation.

Freud’s Psychosexual Stage Characteristics

ORAL (0 to 1 ½ years) Drive discharge is via sucking; oral erotogenic zone. oral
erotism (sucking, licking, etc.) in early stages; oral sadism
(biting, chewing) in later stages. The ego develops at this
stage.
ANAL (1 ½ to 3 years) Anal erotogenic zone; drive discharge via sphincter
behaviour. Anal erotism refers to the sexual pleasure in anal
functioning. Anal sadism refers to the aggressive wishes
linked to fecal expulsion. Anal fixation is characterized by
OCD like pattern – also ambivalence and sadomasochistic
tendencies are associated.
PHALLIC/OEDIPAL (3 to 5 Genitals become organs of interest; masturbation-like activity
yrs) noted. Oedipus complex – wish to have a libidinal
relationship with opposite sex parent (Electra complex in
girls) with a desire to exclude the rival parent. This lead to a
fear of retaliation from the rival parent in the form of
castration anxiety in boys and loss of mother’s love in girls.
Electra complex in girls include penis envy, a wish to have
penis is accompanied by blaming the mother for absence of
penis; later this becomes a secret wish to displace mother as
object of father’s love and bear his baby. At the resolution of
Oedipus and Electra complexes, identification with the
aggressor i.e. dad for a boy and mum for a girl occurs; super-
ego develops from introjection of parental values. Abraham
divided this into early partial genital (true phallic phase) and
later mature genital phase.
LATENCY (5 to puberty Socialization, interest in peers seen. Sexual energy sublimated
approx.11yrs) towards school work, hobbies and friends
GENITAL (puberty onwards) Biological maturation occurs; genital sexuality is born.

© SPMM Course 6
Adversities and development STRESS VULNERABILITY
A critical period is a time point when an individual is MODEL
acutely sensitive to the effects of external influences - both Zubin & Spring (1977) proposed the stress
positive and negative. This is usually defined by biological vulnerability model. According to this model
and psychosocial events. This concept is related to the notion mental illness, schizophrenia especially, is a
result of two hits. The first hit is the
that there is a gradually decreasing plasticity in functioning
vulnerability or predisposition of an
across the life span. But this is challenged by some individual that may be biologically or
observations that suggest, for example, that maturational psychosocially determined. The second hit is
tasks such as an attachment can be formed even at later ages. the stress factor, which may act as a trigger
or precipitant. This could also be biological,
Early life is the period of most rapid brain development. psychological or social. Low vulnerable
Therefore, this period is a sensitive phase for both positive individuals will require high degree of stress
and adverse factors to influence human development. Severe to develop an illness while highly vulnerable
may respond to hairline triggers.
neglect (e.g. in relation to institutional care) produces
adverse consequences if it occurs in early rather than later In an interesting study of environment-gene
childhood. Similarly, the effects of toxins (e.g. lead and interaction, Caspi et al (2003) noted that
individuals with one or two copies of the
alcohol are far more dramatic when the exposure occurs in
short allele of the 5-HT T promoter
utero or in early life. Apart from early life, adolescence is polymorphism exhibited more depressive
also another critical period in life. Major life transitions symptoms, diagnosable depression, and
influencing development occur during adolescence. suicidality in relation to stressful life events
than individuals homozygous for the long
On the basis of potential to cause enduring physiologic allele.
disruptions, 3 distinct types of stress responses are described
in young children.

 Positive stress response – brief, mild response moderated by the availability of a caring
and responsive adult. e.g. getting an immunization, anxiety associated with the first day at
a nursery. When buffered adequately positive stress responses are growth-promoting
opportunities.
 Tolerable stress response - associated with exposure to non-normative experiences with a
greater magnitude of adversity. The e.g. death of a family member, a serious illness or
injury. When buffered well the risk of physiologic harm and long-term consequences is
greatly reduced.

© SPMM Course 7
  Toxic stress response - strong, frequent, or prolonged activation of the body’s stress
response in the absence of the buffering protection from supportive adults. e.g., child
abuse or neglect, parental substance abuse, and maternal depression. Toxic stress disrupts
the developing brain circuitry during sensitive developmental periods forming the
precursors of later physical and mental illness.

Methodology for studying development

Children of different ages can be compared on a given behaviour in order to determine age-
specific developmental features (cross-sectional design). But, in this case, inter-individual
variations can distort the true picture. Longitudinal designs are often employed where the same
children are studied twice or more over a prolonged period of time with respect to a
developmental feature. This provides more reliable estimates of development though this can be
time-consuming.

As in other scientific disciplines, in developmental psychology, the identification of a risk factor

does not necessarily imply causation as the relationship could be mediated by a third variable
(mediator), the putative risk factor may indeed be the outcome (reverse causality) or due to the
presence of multivariate relationships. Such multivariate factors that partially account for the
relationship between a risk factor and a disorder are termed mediators. The mediator could be a
protective factor or a buffer that reduces the risk in an individual.

© SPMM Course 8
2. Attachment theory
Bowlby’s views: According to Bowlby, attachment begins in infancy and lasts throughout a
lifetime. A newborn baby immediately needs someone to take care of them. This person may be a
parent, a sibling, or a nanny, but whoever it is, there will be a bond formed between them.
Bowlby believed that this primary caregiver is the one that will most shape the child's
personality and character. The primary caregiver is usually the mother (but need not always be),
and strong bonds are formed within minutes of giving birth. It is important for the new parents
and baby to be alone together right after the birth to establish a strong bond. If there are too many
individuals in the room right after birth, the natural process of attachment can be disrupted and
this can have long-term effects on the relationship between the child and parents (Klaus, Kennell,
& Klaus, 1995).

The attachment formation needs caregiver’s presence in early stages; no difference is made if
motherly care is provided late after 30m especially and not in early stages. Attachment
behaviour is more evident when distress is present.

According to Bowlby, the strong innate tendency to attach to one adult female is seen – this is
called monotropy. This attachment is qualitatively different from later attachments made. But it
is shown that multiple attachments are the rule rather than the exception. Around 18m, 87%
infants have multiple attachments; 50% primarily attached to the mother, 18% to father and the
rest to equally both. Attachment process itself is more important than who the attachment figure
is.

Bowlby believed that attachment is innate and adaptive. We are all born with an inherited need
to form attachments, and this is to help us survive. In his terms, the newborn infant is helpless
and relies on its mother/caregiver for food, warmth, etc. and hence the attachment behaviour is
essentially adaptive. Attachment behaviour peaks between 12-18 months but various phases are
notable during development.

1. Preattachment phase (birth to 8 or 12 weeks), babies orient to their mothers,

2. Indiscriminate attachment (attachment in making - 8 to 12 weeks to 6 months): Allows
strangers to handle, infants become attached to one or more persons in the environment
3. Clear-cut attachment (6 through 24 months): Preferential attachment, separation anxiety,
object permanence, stranger anxiety. At the later part, weakened stranger anxiety; other
attachment figures may also present.
4. After 25 months, the mother figure is seen as independent.
Harlow’s experiments: These experiments established the importance of contact comfort as basic
as the need for food in developing mother-infant bonding. Harlow separated rhesus monkeys
© SPMM Course 9
from their mothers during their first weeks of life. Harlow substituted a surrogate mother made
from wire or cloth for the real mother. The infants preferred the cloth-covered surrogate mother,
which provided contact comfort, to the wire covered surrogate, which provided no contact
comfort. This preference was observed irrespective of feeding, i.e. the terry-cloth soft-surrogate
mother was preferred even if it did not have a feeding nipple attached to it.

Ainsworth’s experiments: Strange Situation Experiment

Ainsworth constructed a Situation 1 Both mother and infant enter the room
strange situation Situation 2 A stranger joins them
experiment with 2 Situation 3 Mother leaves now; infant left with stranger
separation and 2 reunion
Situation 4 Mother returns; stranger leaves
episodes. An infant is
Situation 5 Infant left alone; mother leaves now
observed in the presence
Situation 6 Stranger comes back and tries to comfort the child
and absence of its mother
Situation 7 Mother comes back and comforts, stranger leaves.
and a stranger in the
vicinity in seven different combinations. According to the infant’s behaviour it is classified as
type A, B or C.

This classification below correlates highly with 1. Responsiveness and sensitivity of the mothers
to the needs of their children and 2. Total amount and quality of stimulation (holding) provided
by the mothers.

 Type A: Anxious avoidant: 15%. Indifferent attitude to the mother is leaving the room or
entering the room; keeps playing indifferent to mother’s presence. Distress when alone,
not when the mother is leaving. Stranger can comfort the child easily. Highly environment
directed, low attachment behaviour. Greater in the West. Perpetrators of bullying mostly
have this pattern.
 Type B: Secure: 70%. Plays independently when the mother is in the vicinity (secure base
effect). Distress when the mother is leaving; seeks contact on the return of the mother and
gets quickly comforted by the mother, not a stranger.
 Type C: Anxious resistant: 15%. Fussy and cries a lot and cannot use the mother as a
secure base to explore around. Very high levels of distress are seen when the mother is
leaving. But not comforted easily even on her return; appears ambivalent about her return.
Active resistance to stranger’s efforts to pacify. Highly caregiver directed low play
behaviour. Greater in Japanese and Israeli families. Furthermore, this pattern is also
common among victims of bullying.

© SPMM Course 10
  In some cases a fourth type D - disorganised type - is also seen. This is seen in maltreated
or maternally deprived children. The child has an insecure, dazed look and acts as if it is
frightened of the mother. This pattern may be a precursor to later personality difficulties
or dissociative experiences. Mother may have an experience of being abused as a child.

Attachment style may differ with different caregivers; it is a function of the quality of caregiving
and NOT the temperament of a child.

Main devised a semi-structured adult attachment interview with 15 items (AAI). This is based on
the fact that infantile attachment pattern can be predicted reasonably accurately using discourse
analysis of adults when recollecting their childhood. Accordingly 4 patterns are noted.

 Secure autonomous: Those who had secure attachment provide spontaneous and
coherent answers with the ability to talk freely about negative experiences in childhood
type B Ainsworth.
 Dismissing of experiences: Those who had an avoidant (insecure) pattern often minimise
their experiences, do not elaborate on them and do not use colourful metaphors during the
discourse– type A (avoidant)
 Entangled: Those who had insecure but ambivalent (enmeshed) attachment use multiple
emotionally laden responses and ramble excessively, – type C resistant.
 Unresolved disorganised: Broken continuity and interrupted the logical flow of thoughts
is seen in those who had insecure disorganised attachment pattern– type D.

The secure attachment appears to be a protective factor for the development of childhood
disorders, and insecure attachment is best conceptualized as a risk factor for a number of
childhood disorders. It has been demonstrated in various studies that insecure attachment during
early childhood is associated with the development of behavioural problems especially
oppositional defiant disorder at school age. Insecure attachment in combination with other
vulnerability factors such as family dysfunction, difficult child temperament, and poor parental
management can give rise to later childhood disorders

Spitz – anaclitic depression or hospitalism: When children are hospitalised for physical
problems, a short period of separation from primary caregiver ensues; this loss of loved one is
called anaclitic (object loss) depression. It is counterproductive to child’s development. But
recovery is good if the maternal deprivation is kept minimum i.e. less than 3 months. Rare if
prolonged. Surrogate mothering helps the infant when having the anaclitic depression to some
extent.

© SPMM Course 11
 MAHLER’S STAGES
1. Normal autism (0 to 2 m): Child spends most time in
sleep as if the intrauterine aloofness continues. Margaret Mahler described the
2. Symbiosis (2 to 5m): Inner and outer world studied development of a sense of
via senses but perceives mother and self as one unit. identity in young children,
3. Separation – individuation phase: (DPRO) independent of their mothers.
a) Differentiation sub-phase: (5 to 10m) slowly This is called separation-
appreciates the difference between mother and self individuation theory, and the
b) Practicing sub-phase: (10 to18m)
proposed stages are supposed to
A gradual increase in interest on the environment;
be universal in all children.
practices exploration.
c) Rapprochement sub-phase: (18 to 24m) Rutter distinguished deprivation
Alternating drives to be autonomous and from privation.
dependent; Able to explore alone but requires
comfort and reassurance on return.  Deprivation: Attachment
d) Object constancy sub-phase: (2 to 5yrs) is formed but lost temporarily. If
Understand that the mother will not be lost if it is for a short time then protest
temporarily away; hence able to function – despair – detachment phases
independently. (similar to grief) are seen. This is
more common in 8m to 3 yr. old. Boys show more deprivation features than girls. It is
more noticeable if aggressive caregiving e.g. physical abuse was present before separation.
In prolonged deprivation, separation anxiety sets in. Increased clingy behaviour,
psychosomatic complaints, vacillation and aggression are seen in the child.
 Privation refers to the non-formation of attachment; this is very rare and can lead to what
Rutter termed as ‘affectionless psychopathy’ and developmental retardation. Attention
seeking, lack of guilt, antisocial behaviour and indiscriminate attachment patterns are
noted. This is reversible but only to some extent.

Ethology is the systematic biological study of animal behaviour. Greek ethos - custom or habit. It
was coined by Heinroth. Imprinting is a special primitive form of learning wherein during the
early period of development (called critical or sensitive phase) a young animal is highly
sensitive to a certain stimulus that provokes a specific behaviour pattern. Lorenz described the
imprinting in goslings where a moving object in the early period of development provokes the
following behaviour of that moving object. This is useful as almost always mother is the first
moving object for goslings and hence they learn to follow the mother; but when Lorenz disrupted
© SPMM Course 12
this by presenting himself as the moving object, the goslings imprinted by Lorenz followed him
and refused to follow mother goose. Imprinting is particularly resistant to change.

Innate releasing mechanism (IRM) refers to the sensory mechanism selectively responsive to a
specific external stimulus and responsible for triggering the stereotyped motor response. Fixed
action pattern (FAP) is an inherent pattern of behaviour initiated by specific stimuli. It consists of
species-specific, stereotyped movements e.g. following behaviour in goslings.

Object relations theory

According to object relations theory – the ego exists only in relation to other objects, which may
be external or internal. ‘Object’ refers to both living persons and non-living concepts.

Melanie Klein was a major proponent of what came to be known as Object relation theory later.
Other prominent theorists include Fairbairn, Kernberg, Guntrip, Winnicott and Balint.

Kleinian theory:

 Play interpretation was the major technique employed

 Maintained that oedipal development occurred earlier than what Freud envisaged
 According to Klein, an infant possessed instinctual knowledge of the body.
 Weaning is symbolically equivalent to castration
 Klein’s stages are not age specific – but the PSP and DP are said to occur between 0-3
months (very early)
 Kleinian defenses – SIPDOG i.e. Splitting, introjection, projective identification, Denial,
omnipotence and grandiosity

Winnicott’s concepts:

 Children’s psychological development occurs in a zone between reality and fantasy called
transitional zone. Play is an important aspect of development of a child.
 Transitional object refers to a soft toy, towel or any such objects that help in transition
from ideal objects of fantasy to real objects which are not as reliable as those in fantasy.
These serve as buffers against the loss, get invested with primary object’s qualities e.g.
mother’s contact but remain under the control of the child.
 Good enough mother concept refers to the fact that a mother need not be perfect – but
good enough to provide growth sustaining environment (holding).
 Parental control and impositions can lead to the development of a false self-different from
the real self (theory of multiple self-organizations).

© SPMM Course 13
A flowchart describing Kleinian theory of infant’s (‘object-‘) relationship with the mother

Soon after birth, fear of annihilation is present. This cannot be tolerated by the child and projects this destructive
impulse to external objects.

Projection of both bad and good impulses occurs followed by splitting of the external world into good and bad.
Cannot unify these elements into one. Bad objects include nongratifying bad breasts (parts). This leads to
persecutory anxiety, and the child is said to be in Paranoid –schizoid position.

Later the child realizes that both good and bad things emanate from the unified single object (whole). At same
time weaning occurs – perceived as a loss. Subsequent guilt develops for having destructive impulses against the
mother. Depressive position – fear of loss of the love of object.

Reparation phase – creativity emanates as an attempt to repair damage done by ‘destructive impulse’. Continues
lifelong. In the absence of reparation, a maladaptive defense called manic defense can emerge characterized by
denial of reality (refusal to take guilt), omnipotence and grandiosity.

© SPMM Course 14
3. Parenting practices
Parenting style is a psychological construct representing standard strategies that parents use in
child rearing and includes the demands of children and response of parents. With respect to
parenting, quality of care is more important than quantity of time spent. Parenting practices are
specific behaviours.

Types of parenting: Maccoby and Martin described four parenting styles given in the table
below. Corresponding to this classification, Baumrind described 3 response patterns in parents.

Demanding Undemanding
Responsive Authoritative/Propagative Indulgent (Permissive)
Unresponsive Authoritarian/Totalitarian Neglectful

 Authoritative parenting: parents are demanding but responsive; fits propagative

parenting and concerted cultivation
 Authoritarian parenting: restrictive and punishment heavy; follow rules without
explanation. High demand and low responsiveness.
 Indulgent parenting: Low demand, high response, the parents are permissible and lenient
with few behavioural expectations placed on the child – parents try to be friends with a
child. As adults, those with indulgent parents pay less attention to avoiding behaviours
which cause aggression in others.
 Neglectful parenting: low demand, low response. These parents are detached and
dismissive, not involved in the child’s life. Also dismiss child’s emotions and opinions.

Authoritative Authoritarian Permissive Neglecting

Control Good degree High control Low or absent Low or absent
of control control control
Nurturance Adequate Poor High degree of Low
warmth and nurturance nurturance and nurturance; no
nurturance leniency warmth
Maturity Age- High degree of No demands No demands
demands appropriate demands placed on placed
demands placed on growing child
expected growing child
Communication Free flowing, Poor flow of Inadequate Poor
positive communication communication communication

Birth order is shown to have an effect on development through varying parenting practices.

© SPMM Course 15
  First-borns - get more parental time and have higher IQ, are more achievement driven and
are more authoritarian, conservative and conformist
 Middle-borns - receive the least attention at home - have strong peer relationships
 Last-borns – receive most attention, get ‘spoiled’; independent and rebellious

Effect of family dysfunction

Family structure has been known to impact the behaviour of children where those with single
parents or large family sizes have been shown to increase behavioural issues. Single-sex couples
and extended family involvement in upbringing do not cause the same issues.

Dysfunction in families cause discord, rejection of children due to processes such as

disengagement and/or overprotection and over-involvement resulting in enmeshment.

According to the landmark Cambridge study of Delinquent development by Farrington et al,

the most important childhood predictors (during age 8-10) of delinquency were antisocial child
behaviour, impulsivity, low intelligence, low attainment, family criminality, poverty and poor
parent child rearing behaviour.

Parental loss: Most children adapt well to parental divorce if financial support, reasonable
contact with non-custodial parent and successful remarriage of single parent take place. If not,
poor academic achievement, low self-esteem, 2-3 times more antisocial behaviour and higher
rates of later life depression are seen.

 Children of all age groups are prone to short term behavioural difficulties after parental
divorce – evident even in infants who may show changes in eating, sleeping and bowel
patterns, with fearful or anxious responses.
 3 – 6 age group often assume responsibility for parental separation
 7 - 12 age group show decline in school performance
 Adolescents feel hurt, become angry and critical of their parents; they spend most time
away from home as a reaction.
 Recovery usually takes 3 to 5 years.
 One third of all children have lasting psychological effects
 Boys are more affected than girls due to parental divorce; Among boys, physical
aggression is a common sign of distress.
 Recent divorce or separation of the parents predicts suicide in children.
 25% step families dissolve in 2 years, whereas 75% are harmonious.
 ADHD, Antisocial PD and conduct problems are more at homes without father.
© SPMM Course 16
  Children of divorced parents undergo divorce themselves twice more than children of un-
divorced parent.
 Academic and social aptitude suffers due to divorce; asthma, injuries, headaches and
speech defects are more common in divorced families.
 Divorce has more impact than death of a parent on psychological make up of a child
 Suicide rates for children of divorce are very high
 25 % have adjustment problems at teenage.
 Parental death has somewhat lesser impact than parental conflict and separation.
Bereavement causes increase in temper tantrums, depressive reaction (sadness, irritability),
sleep disturbance. Divorce can cause all of the above but protective factors include
positive temperament, relationship with other siblings & joint access.
Day care: Providing day care for more than 4 months at less than 1 year age for >20hrs a week
can increase insecure attachment. If not, day care does not affect development adversely.

Adoption: Research shows that the earlier the age of adoption, the better is the outcome for the
child. When a child is adopted during early childhood, then the chances of forming new
attachments are better. Therefore early adoption is recommended as a matter of social policy.
Children adopted before the age of 4 or 5 have been shown to do well generally. Although late
adoption after the age of eight, does not necessarily lead to problems in adjustment, such children
are more vulnerable and are at risk of developing future problems, like behavioural problems at
home and school (Tizard and Hodges 1978).

Adopted children become aware of their adopted status most often between 2 to 4 years. Parental
disclosure to children about their adoption reduces later psychological trauma.

Institutional care: Tizard and Hodges followed up a group of children who had been in
institutions from infancy, adopted at age 4 and had been looked after by a number of carers who
changed often. At age 8, most children had formed reasonably good attachment with their
adoptive parents. At age 16, although the adolescents appeared to be functioning rather well,
they showed a constellation of features termed as ex-institutional syndrome. These young
people related better to adults than to their peers, were less likely to have a special friend, were
less likely to be selective in choosing their friends and turned to peers less often for emotional
support.

Intrafamilial abuse: Sexual abuse perpetrated by a parent can result in anxiety related symptoms,
sexualized behaviour in the child, borderline personality disorder, substance misuse, dissociation
and depression.

© SPMM Course 17
4. Temperament
This is an aspect of personality studied in infants. It describes individual differences in
behavioural style. Certain aspects of temperaments remain stable over many years. Infant’s
negative emotionality (e.g. fear), and reactions to new situations (inhibition or neophobia) are the
two most stable temperaments.

New York Longitudinal Study is a key study on childhood temperament conducted by Thomas
& Chess. It is a thirty years (initially 6 years) longitudinal study of 138 children, observing
childhood temperaments. It employed parental interviews to ascertain temperamental
dimensions – 9 such dimensions have been used:

1. Activity
2. rhythmicity
3. approach/withdrawal
4. adaptability
5. intensity
6. threshold
7. mood
8. distractibility
9. attention span / persistence
Three behavioural styles were identified using the above 9 dimensions

1. Easy – rhythmic pattern of needs, adapts well, and active – 40%

2. Difficult – less predictable, uncomfortable with new experiences, negative mood, react
intensely to stimuli, difficult to comfort – 10%
3. Slow to warm up children – adapts poorly to change, but less active and responds at
low intensity – 15%
4. Ungrouped – 35%
Difficult temperament may offer some survival benefits as mother pays more attention –
especially in tribal populations. Inhibition (approach/withdrawal dimension), according to
Keagan, is a strongly inborn trait. Behavioural inhibition may be a precursor for later neurotic
disorders including anxiety and depression. In an extreme form of inhibition called neophobia, a
child appears frozen and withdrawn in novel situations.

Goodness of fit (Thomas & Chess) describes the reciprocal relationship between a baby’s
temperament and its social environment whereby a good match between the both results in
positive development later. Chess and Thomas used the term especially to refer to the
harmonious interaction between a mother and a child.
© SPMM Course 18
(Note that the concept of Good-Enough Mothering was proposed by Winnicott; according to
him mothers provide a holding environment. A mother does not need to be perfect, but she must
provide good-enough mothering.)

EAS model (Buss & Plomin 1984) describes three major dimensions: Emotionality – Activity –
Sociability in children. EAS is a strongly biological model that views temperament as inherited
personality traits exhibited in early life.

Resilience to mental illness

Resilience refers to the ability of children to function well in the face of adversity. There are 2 ways
of considering resilience. 1. Resilience as a positive psychological outcome in the face of adversity.
2. Resilience as a dynamic process of psychological functioning that increases positive and
reduces adverse outcomes in the face of adversity (Cummings, Davies, & Campbell, 2000).

Masten and Coatsworth (1998) reported that when children are faced with highly adverse
situations (e.g. parental mental illness, family violence, poverty, natural disasters etc.), personal
characteristics such as good intellectual functioning; appealing, sociable, easygoing disposition;
self-efficacy, self-confidence, high self-esteem; talents; and faith can produce a positive
psychological outcome despite adversity.

Certain family characteristics also convey resilience. These include having a close relationship with
a caring parent figure, authoritative parenting (e.g., warmth, structure, high expectations), higher
socioeconomic status and having extended family networks.

Extrafamilial factors that increase resilience include having bonds to supportive adults outside the
family, being attached to prosocial organizations, and attending efficient schools/institutions.

© SPMM Course 19
5. Cognitive Development
Erikson’s stages
Erikson proposed psychosocial developmental stages. These coincide with Freud’s psychosexual
stages but extend well beyond adolescence. It is not necessary that each stage must be resolved
entirely before further progress. A mixture of positive and negative outcomes is noted for most
people. However, if predominantly negative experiences accumulate at various stages of
development, this may predispose to difficulties in life.

In Erikson’s model autonomy

Crisis Approximate Age
refers to children gaining more
1. Basic trust vs. basic mistrust Birth to 12-18 months
control over activities and
2. Autonomy vs. shame 18 months to 3 years
acquiring new skills. This is
3. Initiative vs. guilt 3 to 6 years crucial for building self-esteem,
4. Industry vs. inferiority 6 to 12 years failing which a sense of shame is
5. Identity vs. role confusion Adolescence felt.

6. Intimacy vs. isolation Young adulthood During 6 to 12 years of age we

7. Generativity vs. stagnation Middle adulthood are capable of learning, creating
8. Ego integrity vs. despair Late adulthood and accomplishing numerous
new skills and knowledge, thus
developing a sense of industry. This is also a very social stage of development, and if we
experience unresolved feelings of inadequacy and inferiority among our peers, we can have
serious problems in terms of competence and self-esteem.

Identity vs. role confusion. This stage occurs during adolescence between the ages of
approximately 12 to 18. Up to this stage, according to Erikson, development mostly depends
upon what is done to us. But from teenage onwards, our development depends primarily on
what we do. Teens need to develop a sense of self and personal identity. During adolescence,
children explore their independence and start to form a sense of self. This phase of transition
from dependent child to an independent adult is associated with confusion and insecurity. Teens
also experiment with different social roles at this stage. According to Erikson, this is important to
the process of forming a strong identity and developing a sense of direction in life.

The inherent strength of young adulthood is love, and the major task is intimacy and formation
of a future bond partner.

A middle aged adult seeks satisfaction through productivity in career and family / social network.
This is referred to as generativity.
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An older adult reviews/cherishes life accomplishments prepares for end of life by pursuing
lifelong interests etc. This is referred to as integrity

Piaget’s model of cognitive development

According to Piaget, a schema is defined as the basic building block or unit of intelligent
behaviour. Schemas consist of organized past experiences to understand future experiences. We
have physical schema such as bike riding schema and mental schemas such as addition,
multiplication and division schema.

Within each developmental stage, functioning is generally internally consistent and stable and
thus said to be in equilibrium. Stage-to-stage transformation occurs as a result of interaction with
environment, whereas existing schemas cannot solve the environmental realities.

Adaptation is the process of fitting schemas to environmental information. Adaptation can occur
either as assimilation or accommodation. In assimilation new information is incorporated into
existing schemas without restructuring the schemas. In accommodation, the schemas are
restructured to ‘accommodate’ newly learnt information.

Equilibration is achieved when all information properly fit into the schemas via either processes
of adaptation. During each developmental stage, the child will experience cognitive
disequilibrium, which through adaptation, gets solved, and equilibration results. Each time that
equilibration occurs, the child produces more effective schemata or mental structures.

Approx. AGE STAGES FEATURES

(not delineated by
Piaget)

0 to 2 years Sensorimotor Exercising reflexes (0 to 1 m) to smoothen them; Primary

circular (1 to 4 m) reactions where reflexes extend to objects;
secondary circular ( 4 to 10 m) where goal direction seen; object
permanence starts by 9m; coordinated actions with added
element of curiosity forms tertiary circular ( 12 to 18 m)
reactions – here novelty is sought. Mental combinations occur;
thoughts dominate actions.
2 to 7 years Pre- Preconceptual stage 2 to 4 years; intuitive stage 4 to 7 years.
operational
7 to 11 years Concrete Ability to decentre, conserve, seriate and declining egocentrism
operational noted. Perspective taking starts to develop. But transitivity tasks
still pose a challenge. E.g. ‘4>2, 2>1, which is the greatest of all?’
- is still difficult.

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> 11 years Formal Here manipulation of ideas and propositions are seen – 1st order
operational operations; soon, reasoning solely based on verbal argument
construction develops – 2nd order operations. Hypothetico-
deductive reasoning develops in a proportion of children after
age 12.

Sensorimotor stage: (SPIRO)

 Symbolic thought: Language starts developing and thought starts to dominate actions.
 Representational Play: Mimics one object with another e.g. cup for a hat.
 Deferred Imitation: remembers an act and replays it later.
 Recognition of self: Primitive self recognition begins.
 Object permanence: Understanding that object that disappears from field of perception
has not ceased to exist; if searched well this object can be found or it will reappear. Hence
peek-a-boo games are understood and enjoyed. Initially this is limited as the hidden
objects are searched at where they were last seen (around 9 to 12 months); not at where
they were hidden. Around 18 months invisible displacements are inferred and object
permanence is completed.

Preoperational stage: (FAT PILES)

 Functional attribution: Objects are referred to by their function rather than appearance.
 Artificialism: ‘Sky is blue because someone painted it’
o & Animism: Inanimate objects are treated as living objects.
 Transductive reasoning: Cats have 4 legs, Dogs have 4 legs. So cats and dogs are the same
(called Von Domarus law).
o & Telegraphic speech: No functional propositions noted but verbs and nouns are
used
 Phenomenalistic causality: In a similar logic to transductive reasoning, causality is
inferred if two events occur with some temporal association e.g. lightning and rain come
together; hence lightning brings rain.
 Imminent justice: See moral development
 Lack of seriation, conservation, and reversibility:
o Seriation is the ability to sort or categorise based on dimensional variations of items.
In centration only single dimension can be focussed at one time (akin to syncretic
thought, see below). Conservation refers to the ability to perceive that a quantity
(such as count, weight, volume etc) is unchanged if the same amount of a material is
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 transformed into a different shape or structure. E.g. 1 litre of water remains the same
1 liter irrespective of whether it is present in a half full 2 litre bottle or two complete
500ml bottles. Concept of compensation refers to the fact that magnification in one
dimension and reduction in another dimension can nullify each other’s effect.
Reversibility refers to the ability of mentally calculating and understanding that
what is done can be undone without loss of material.
 Egocentrism: This does NOT refer to self-centredness or selfish attitude. It refers to the
restricted ability of viewing the world from a single point of view at this developmental
stage. This was demonstrated using the Mountains task where a child at this age group
could not say what a person would see from other side of the desk when only one side of a
toy mountain was visible from each view.
 Semiotic function: Signifiers are symbols and signs that represent or stand for something
else. For example, drawing a matchstick man. Thus signifiers represent a meaning, serving
semiotic function. This is vital for developing play activities.
 Syncretic thought: Links neighbouring objects and events on the basis of common
instances e.g. red square with red sphere with blue sphere with blue cube etc.

Concrete operational stage:

Conservation of liquid develops around 6 years, followed by conservation of length, count,

weight and volume (around 11 to 12 years) in a vertical decalage fashion (i.e. not parallel but one
by one development of these abilities). Note that if the same question about quantity is asked
before and after manipulation of materials in front of a child, the child answers differently for the
second question as he/she interprets that the question is asked twice as the answer given was
wrong in the first instance. If the pre-transformation question is dropped, the conservational
ability could be demonstrated at earlier stages. Also using an external ‘accident’ such as naughty
teddy that disturbs a heap of coins, conservation could be demonstrated earlier than what Piaget
thought.

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6. Language development
Basic speech sounds are called phonemes. In English language, there are 46 speech sounds. Most
children can differentiate speech sounds before being able to produce them. The basic
meaningful part of the language is called morpheme. The rules for combining words into
phrases and sentences are called syntax.

Language is slower to develop in boys, in twins, in large families, in those from social classes 4
and 5 and those that lack speech stimulation e.g. deaf and neglected children.

Stages of language development:

The pre-linguistic state (0 to 12 m): Crying is an important form of communication. A one-

month-old child is able to distinguish speech sounds although these phonemes are almost
identical sounds. This categorical speech perception is supposed to be innate. By six weeks, the
child starts cooing. By six months, babbling is seen. Babbling is nothing but the repetitive
production of speech sounds. Spontaneous babbling refers to the situation when the child enjoys
making these sounds alone. All babies around same age irrespective of the culture start bubbling.
Even the deaf babies of the deaf-mute parents start marbling but stop at 9 to 10 months. The
phonemic expansion refers to the expansion of production of phonemes even if such phonemes
are not seen in the native language.

One word stage (12 m to 18 m): Jargon words and babbling continue up to 18 months. First
words are often self-invented but carry meaning and consistently match with the same meaning.
There is a clear intention to communicate. Earliest words are context bound; sometimes they do
not have any communicative purpose but are used as performatives to refer to actions. A child
says ‘teddy’ only when the teddy is thrown up into the air while playing; thus teddy refers to
‘throw up’ action rather than the doll. Holophrases are one-word substitutes for whole phrases
or sentences. At this stage, a child understands more words than it could produce. Gradually
words get decontextualised and fall into one of the following functions;

1. Nominals – specific e.g. Sarah, or general – e.g. ball pen

2. Action words e.g. bye, look.
3. Function words e.g. the for, what, etc. propositions and grammatical functions.
4. Modifiers – e.g. red, big, etc.
5. Personal and social function – e.g. oops, ouch, etc.
Two-word sentences / stage 1 grammar (18 to 30m): Telegraphic speech is seen where
meaningful words are used without connecting words. At this stage adults interact with children

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in a ‘motherese’ – short simple raised pitch paraphrased language directed at infants. As object
permanence is achieved by this stage, words start to have representational functions.

Stage 2 grammar (> 30m): Mean length of utterances

increase largely due to the use of function words – AGE & LANGUAGE
propositions, etc. DEVELOPMENT

Noam Chomsky: Children are born with an innate language 3 months-babbling

acquisition device. Transformational grammar is important
9 months-repetitive babbling
in understanding language development. All languages
have a surface structure where the syntax is accurate and 12 months-speaks three words
actual words are used to construct language; and a deep
18 months-speaks up to 40 words.
structure where the most semantic sense is made without
similar syntactical rules. A single surface structure can have 24 months-telegraphic speech,
several deep structures. Children are born equipped with grammatically pairs words and

the ability to decipher the transformational grammar of deep vocabulary more than 240 words

to surface structure conversion. Hence, years up to puberty 36 months-early comprehension of

are sensitive though not critical fro language development. grammar and syntax

Social interaction view of language development: Adults 48 months-correct use of grammar

such as mother act as LASS (language acquisition support
60 months-language akin to adult
system). This is essential for the function of language is
speech
social interaction.

The elaborate language code is characterized by longer, complex sentences that are context-
independent. It focuses on the past and future, employs pronoun ‘I’ commonly and allows for the
expression of abstract thought. Restricted language code is characterised by short, incomplete
sentences, which tend to be context-dependent, frequently uses like ‘you know’, focuses on the
present, employs pronoun I rarely and has little room for expressing abstract thinking. People in
lower socioeconomic classes more commonly use the restricted code whereas the middle class
and upper class children often use elaborate language code. Such differences emerge from the
influence of social interactions in language development.

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7. Social competence and peer relationships
Through friendship, children learn cooperation, sharing and conflict management. They also
learn empathy and group belonging. Studies suggest that peer rejection can later result in
depression, school drop out and other psychiatric issues. (Cairns, Cairns and Neckerman, 1989)

Social competence is a complex concept involving social, emotional, cognitive and behavioural
skills. It is the foundation upon which ability to interact with others is built and also perceptions
of own behaviour is developed. There are several approaches involved.

Peer regard/status Define social competence based on popularity amongst peers

Social skills Behaviours demonstrating social skills are used to determine social
competence
Relationship Social competence is based on the ability to form and quality of
relationships
Functional Context-specific, it is concerned with the identification of social tasks

Peer groups are comprised of children of similar age, background, social status and often with
similar interests. This primary social group can influence several behaviours and beliefs. Children
look to join peer groups that accept them, even if they are involved in negative activities
disapproved by parents.

Peer acceptance: the extent to which a child I viewed by peers as worthy and likeable companion.
This is assessed using sociometric techniques

Popularity: Popularity is not the same as having many friends - many popular children do not
count having a large number of friends.

1. Popular children: liked by many disliked by few

2. Rejected children: disliked by many liked by few
3. Neglected children: neither liked nor disliked (few nominations in sociometric
measurements in a classroom)
4. Controversial children: liked by many but also disliked by many
5. Average-status of acceptance: nearly 1/3rd of the class – liked or disliked by a moderate
number of peers

Popular children show the following characteristics:

 Respond positively in unfamiliar environments

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  Initiate interaction in new social groups
 Comment constructively in groups
 Blend smoothly with new peers
 Pleasant temperament
 Academic skills
 Display ease when interacting with opposite gender

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8. Moral development
Freudian theory: According to Freud, boys have unconscious wishes to compete with the father
for mother’s love. This leads to castration anxiety as fear of being punished for competing sets in.
This anxiety drives the repression of such desire and leads to identification with one’s father from
whom the superego morality is incorporated; thus moral development is achieved via the
development of the superego. In girls Oedipus complex is not seen; instead penis envy (Electra
complex) is noted. Father is the love object here, and unconscious wish for having a baby from
the father is present, but without a strong anxiety as seen in boys, the identification with mother
and imbibing of superego occurs. Hence, Freud claimed that superego or morality is weaker in
women than men.

Piaget described qualitative differences in older vs. younger children in terms of morality that
was based on the ability of older children to have social perspective (an extension of the Theory
of Mind concept); he did not describe stage-by-stage development of morality. Cognitive
development is essential but not sufficient for moral development. Moral development lags 2
years behind the cognitive development.

Piaget’s Moral Development Theory

5 to 9 years Older than 10 years
Unilateral respect for the external law: seniors Mutual respect for the self-invented law: could
make rules; they are sacred and should not be be changed by consensus and for fairness.
broken, but get violated periodically for
pleasure.
External responsibility holds for crime; Internal responsibility holds for crime; intent
severity of outcome or loss decides the degree or motivation decides the degree of
of punishment warranted. punishment warranted.
Moral realism: Strong penalty should be paid Moral relativism: Punishment should match
for any crime; can accept collective the crime; does not accept collective
punishment to deliver justice (punishing the punishment.
wrongdoer is more important than not hurting
the innocent)
Imminent justice: Wold is just – a misfortune No imminent justice.
will punish the deserved for a misdeed.
Heteronomous morality: Subject to rules Autonomous morality: Rules can be self-made.
written by others.

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Kohlberg’s theory of moral development: This is a stagewise process where reasons for making
a judgment in a hypothetical experiment (Heinz Dilemma) are studied in children; reasons are
more important than the actual judgment made. On this basis, Kohlberg identified 3 levels and 6
stages.

 Level 1 Pre-conventional morality (7-12 years to middle childhood): In this stage, the
children decide right or wrong according to the consequences. If an action leads to
punishment it must be bad and if it leads to reward it must be good.

i. Punishment and obedience orientation: Obedience to rules to avoid punishment

ii. Reward orientation/ Instrumental relativism: What brings rewards is right. ‘tit for
tat’ approach seen.
 Level 2 Conventional morality (approximately 13-16 years): Here the children believe
that social rules and the expectation of the others determine what acceptable or
unacceptable behaviour is.

iii. Concordance orientation: What pleases others is right. What the majority thinks
right is right. Also called Good boy/good girl orientation. Conforms to avoid
disapproval and meet expectations of others. Being good is important and having
good motives and showing concern
iv. Social order or Authority orientation: Upholds laws and social rules to avoid the
censure of the authorities and feelings of guilt about not doing one’s duty.
Maintaining social order is the goal.
 Level 3 Postconventional morality (approximately 16-20 years)- Here what is right is
based on an individual’s understanding of universal ethical principles. These are often
abstract and ill-defined, but it might include the preservation of life at all costs and the
importance of human dignity

v. Social contract or legalistic orientation: Actions guided by principles commonly

agreed by one’s group on as essential to public welfare (relative values) and
democracy is upheld while individual’s life is given more respect than written
codes of law.
vi. Universal Ethical orientation: Actions guided by self-chosen ethical principles.
Laws and social principles usually valid because they are based on these
principles. Social rules can be broken if universal morality is not upheld.
Level 3 cannot be considered a part of the normal or expected course of development and instead
represents a philosophical ideal. Only 15% eventually achieve level 3. Formal operational thought
is necessary but not sufficient to achieve level 3 morality. Kohlberg’s stages are criticized to be

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androcentric (all male sample) and Eurocentric. Though they are well correlated with ‘moral
reasoning’, they are not so well associated with actual behaviour.

Eisenberg’s stages: Both Kohlberg’s and Piaget’s theories were based on the prohibition of the
wrong; Eisenberg’s was based on prosocial reasoning where helping or altruistic behaviour was
studied.

Social learning theory argues that while actual reinforcement is not needed for ‘learning‘ about
morality, the performance of a moral deed can be reinforced (either directly or vicariously).
Vicarious punishment is more effective than vicarious positive reinforcement in this regard.

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9. Emotional literacy and fears
Emotional literacy is a term used interchangeably with emotional intelligence (Steiner, 1997).
Components of emotional literacy includes:

1. Knowing your feelings

2. Having a sense of empathy
3. Learning to manage our emotions
4. Repairing emotional problems
5. Emotional interactivity – putting it together

Emotion regulation describes an individual’s ability to gauge the appropriate level of emotional
response required and respond to environmental stimuli with a range of emotions in a controlled
manner (Panfile and Laible 2012).

Emotion regulation develops throughout the lifespan (Cole et al., 2009). Infants have limited
emotional regulation, shown by gaze aversion and vocalising. Around 1 year of age children are
able to unconsciously regulate their emotions. Between 3 and 5 years (at kindergarten) children
may tolerate ordinary, brief frustrations and handle minor disappointments (Cole, 1986; Cole et
al., 2003).

In a detailed longitudinal study, (Development of Toddlers Study (D.O.T.S.)) Cole et al.

observed the child in spontaneous situations at 4 time points (18, 30, 36, 42 months). Their
observations are tabulated below:

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 18 to 24 months
• were quick to express anger
• slow to distract themselves
• might try to distract themselves but only briefly
• bid to mother but angrily

36 months
• quickly bid to mother (but thru words not anger)
• were somewhat quicker to distract
• anger was briefer, distractions longer

48 months
• quickly & briefly bid to mother (verbally)
• quickly distracted themselves
• eventually focused on gift & then showed anger

Imaginary companions are often a part of emotional development.

 Preschool years mostly (between 3 to 10 yrs age, 50% may have),
 Usually in children with above-average intelligence
 Usually in the form of persons rather than animals/things
 Usually friendly and help to reduce loneliness and anxiety.
 Mostly disappear by age 12, occasionally persist into adulthood.
Developmental fears
 Fear of animals-age 3
 Fear of the dark-age 4 or 5
 Fear of imaginary creatures - 5 plus
 Fear of open spaces arises in later childhood or adult life
 Fears that arise in late childhood or adult life: fear of sex/open spaces.
 Teenage onwards-failure, illness and death
 Fears that show no particular age trend-fear of snakes or storms

Simple fears are often linked to early negative childhood experiences or learnt from other family
members (such as a sibling’s fear of spiders may influence a child). Maintenance of phobias is
due to avoidance of the anxiety-provoking stimuli relieving unpleasant emotions, which becomes
a reward itself.

Children of age 3 to 6 yrs are aware of their body and show a preoccupation with illness or injury,
- every injury must be examined and cared for – hence this phase is also called Band Aid Phase.

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10. Sexual development
Gender identity typically forms around the age 3-4 and remains established. Gender typing
describes the process where an individual acquires a sense of gender-related traits within the
society they are born. It usually starts with clothing at a young age.

Gender role: behaviour an individual engages in that identifies with their gender e.g. use of
cosmetics.

Theories of Gender Identity development

 According to Social Learning Theory of gender development, girls and boys learn to behave
differently because the society treats them differently (pink dresses for girls, Barbie dolls for
girls, etc.). Fathers treat children in a more gendered way than mothers. This sex typing is
reinforced by further observational learning by the child and reinforcement that results on
accomplishing gender specific developmental tasks.
 Cognitive Developmental Theory stresses the importance of child’s participation in gender
identity. A child’s discovery about his/her biological sex leads to identification with a group
and conformity as a result. Thus three stages have been identified:

1. Basic gender identity / gender labelling: Around age three, a child understands she/he
is female or male.
2. Gender stability: By age 4 – 5 recognise that gender is retained life-long and will not
change!
3. Gender constancy / consistency: Age 6 -7 understand that gender is immutable even if
physical changes are carried out. It is a type of conservation achieved akin to Piaget’s
cognitive development
 According to Gender Schema Processing Theory, gender identity alone provides children the
motivation to assume sex-typed behaviour. Following this they observe and learn to be of a
specific gender in the society. Thus, a gender schema of the particular culture gets deeply
incorporated and serves as a standard for comparison.

Sex drive exists from birth but increases in adolescence due to raised androgen secretion. Sexual
orientation is explored during adolescence. There are arguments for and against the biological
determination of sexual orientation vs. shaping in childhood.

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 Sexual Behaviours in Childhood

Preschool (age  Exploring private parts through touch and rubbing or showing to
<4 years) others
 Trying to touch women’s breasts (including mother)
 Exposing oneself and attempting to see other exposed people
(adults and children)

Young  Stimulating genitals (masturbating) sometimes when others are

Children present
(approximatel  Kissing, or holding hands
 Talking about genitals without grasping the meaning in full
y 4-6 years)
 Exploring private parts with peers e.g. “playing doctor”, “I’ll show
you mine if you show me yours.”

School-Aged  Masturbating privately

Children  Playing courtship games (“mummy and daddy”)
(approximatel  Gazing at pictures of naked people; viewing sexual content in
media (
y 7-12 years)
 Wanting more privacy
 Showing reluctance to discuss sexual issues with adults
 Being sexually attracted to peers

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11. Adaptations in adolescence & adult life
Adolescence is the period between childhood and adulthood and is described in many of the
developmental models (Piaget – formal operational, Freud - genital stage, Erikson – identity vs.
role confusion).

Conflict with parents is common during this time due to developing a sense of self and autonomy.
This could be attributed to a second separation-individuation phase.

Anna Freud described affective instability as the oscillation between behavioural and affective
excess and scarcity during adolescence induced by endocrine changes, sexual maturity and
instability of ego defenses.

Erikson described adolescent turmoil as a temporary maladaptive state that was due to identity
diffusion. According to him all adolescents passed through this state. But later studies (Offer &
Offer 1975) showed that while upheaval and turmoil are common in adolescence, they might not
occur in all adolescents. Nearly 23% showed continuous linear development during adolescence,
while 35% were late bloomers who were less introspective and had some frictions with their
families. Around 21% had recurrent conflicts with their parents and chose less competitive
careers.

Marcia’s theory on adolescence: A mature self-identity is possible only if an individual

experiences several crises, finally arriving at a stage of commitment. Successful maturation
during adolescence depends on both the degree of crises faced and commitment achieved, with
different levels of maturation as shown in the table below.

Degree of crises
HIGH LOW
Degree of
HIGH Identity achievement Foreclosure
commitment
LOW Moratorium Role confusion
 Identity achievement: Most mature achievement – most desirable.
 Foreclosure: Avoids anxieties by prematurely committing to safe and conventional
parental and societal goals and beliefs.
 Moratorium: Experiences height of crises but postpones decisions until alternative
identities are tried.
 Role confusion: a unresolved state of adolescence

Puberty trends:
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  In the UK the average age of onset of puberty in males is 11.2 years; for females it is 11
years. Menarche on average is at 12.5 years for females.
 There is a general trend for falling in menarcheal age globally over last 50 years.
Compared to US and other European countries this falling trend is smaller in UK (by
about 6 months in 30 years).
 Social stress is also a puberty accelerator, with familial disruption and father absenteeism,
being one of the most effective stressors.
 Precocious puberty is suspected in boys before age 9, and girls before age 8.

As children develop through adolescence into adulthood, they hold increasingly complex
orientations to the self and to the interpersonal world. Jane Loevinger described 9 stages of ego
and personal identity development involving childhood, adolescence and adulthood.

1. Presocial – the baby is unable to differentiate itself from the world

2. Impulsive – the child is concerned with bodily impulses
3. Self-protective – the child has a notion of blame but externalises to the situation or other
people
4. Conformist – around school age, they conform to socially approved codes/the norm
5. Self-Aware – (conscientious-conformist) transitional stage – increased self-awareness and
self-criticism; deepened interest in interpersonal relations
6. Conscientious – internalisation of rules is complete; goals/ideals are acknowledged, and
there is a new responsibility – feel guilt for hurting others rather than rule-breaking
7. Individualistic – respect for individuality and interpersonal ties
8. Autonomous – ‘synthesizers’ – able to conceptually integrate ideas
9. Integrated – rarely attained stage “learning is understood as unavoidable…the
unattainable is renounced.”

Pairing occurs often within the same cultural and socioeconomic background (homogamous
mate selection). Equity theory suggests that individuals consider the cost-benefit ratio for each
person in a relationship; reinforcement theory suggests that individuals chose their partners on
the basis of reinforcement of attraction with rewards.

The midlife transition occurs around age 40 to 45. The term ‘Midlife Crisis’ was coined by Elliot
Jacques who distinguished it as a critical phase in development as the transition between the
forties and early sixties, and is often associated with coming to realise mortality, unrealized goals,
menopause or children leaving home. Downshifting refers to voluntary opting out of a

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pressurized career and giving up well-paid job for more fulfilling life (anti-urbanism). Empty
nest distress refers to the feeling of loneliness when children leave home.

Bereavement is usually used to describe loss if a person, but can be loss of anything e.g. marriage,
employment, and refers to being in a state of mourning (a process influenced by culture and
society in which grief is resolved).

The classic work on stages of grief came from Erich Lindemann, who studied 101 bereaved
people and published in 1944; an article titled “Symptomology and Management of Acute Grief”.
In this article he described a set pattern of reaction to a loss event (grief): After an unexpected
death, there is the initial shock that lasts 10-14 days. After the initial shock comes a period of
intense sadness, and the grieving person may withdraw from social contact. Next comes anger,
as the grieving person seems to ‘protest’; the unexpected death. Finally, within a year or so, the
grief is resolved, and the person returns to normal. These stages were further refined by Parkes.

5 stages of bereavement (Parkes)

1. Alarm
2. Numbness
3. Pining for the deceased (illusions or hallucinations of the deceased can occur)
4. Depression
5. Reorganisation (recovery)

Physiological events such as pregnancy and childbirth could also be stressful in adult life. The
psychological stress during pregnancy can have physiological implications on the growing fetus.
Release of corticotrophin releasing hormone (CRH) from the placenta increases with stress, and
with this an increased risk of intrauterine infection, preterm labour and low birth weight is seen.
Pre-term infants are susceptible to complications later such as developmental delay and increased
rate of mortality. Babies subject to stress in utero can have the difficult temperament and are
irritable. There is additional data to suggest that stress in utero can result in increased risk of
chronic health issues in adulthood e.g. hypertension and diabetes.

Psychological symptoms following childbirth include intrusive thoughts, avoidance, anxiety,

depression, social dysfunction and somatisation. Significant psychological distress is noted in 37%
of mothers and 13% of fathers. Factors predicting acute maternal psychological distress included
being a single parent, multiparity and previous traumatic birth. At six week and six months,
psychological distress symptoms fell to that of general population level indicating that in most
people, this is a short-term distress.

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12. Adaptation with ageing
Age is the first social category learnt by a child even before number concept develops.

The effect of ageing on cognitive abilities: The mass of the brain reduces with ageing (in some
cases this can be pathological). Memory is often cited as the cognitive function most susceptible
to decline with age – particularly working memory and incidental memory. Attention also
declines with age.

The effect of ageing on body physiology: Bone loss results in a reduction of mechanical strength,
collagen fibres deteriorate causing loss of elasticity of the skin, and the efficacy of organs
deteriorates with age.

Ageing and socioeconomic independence: Older adults are an economically vulnerable group
and with an increasing older population, there are concerns they may outlive their financial
resources. The decline in socio-economic status can result in a decline in their physical and
mental health. Reduced mobility from physical health problems impacts their independence and
ability to maintain social ties.

Old age – theories of role change:

1. Social disengagement theory: Mutual withdrawal of society and the individual occurs;
increased individuality and shrinking life space are inevitable moves towards death.
2. Social (non) reengagement theory (aka activity loss theory): Ageist society reduces the
social interaction that older adults can have; withdrawal is not mutual but forced.
3. Social exchange theory: Age robs people of the ability to engage in reciprocal roles;
retirement is a special social contract wherein productivity is exchanged for increased
leisure and decreased responsibilities.
4. Socio-emotional selectivity theory: Wise investment of social energy in old age is to limit
social interaction to those who are most familiar.
Phases of retirement:

1. Pre-retirement phase: Increasing anxiety with the retirement of friends and colleagues.
2. Honeymoon phase: Immediate post retirement phase where increased freedom is enjoyed.
3. Disenchantment: Slowing down occurs, feels let down, worse if inadequately prepared for
retirement.
4. Reorientation – explores new avenues, more realistic.
5. Stability –makes choices, mastery attained in chosen leisure.
6. Termination – frailty, death.

© SPMM Course 38
13. Genetic influences on development.

Brain development is genetically programmed. For example, the cortical thickness in lateral
prefrontal, medial prefrontal, parietal, and temporal cortices is highly heritable. Regions crucial
for evolutionarily advanced functions (such as higher‐order cognition, sociality, and language)
show both high heritability and an increase in heritability with age during development. This
pattern is similar to the age-related increase in heritability for traits such as IQ (discussed earlier).
This could be either due to an age‐dependent gene expression or due to gene‐environment
interaction.

Gene-environment interaction refers to the influence of the relationship between genotype and
the environment in shaping a phenotype. Consider the example of phenylketonuria, a genetic
condition caused by the lack of an enzyme that breaks down the amino acid phenylalanine,
resulting in intellectual disabilities. However, the usual dietary environment of a child can be
altered by the use of phenylalanine-free foods, which results in normal development.

Waddington proposed the concept of canalization in developmental genetics. Certain behaviour

traits are strongly genetically determined (canalized), so development follows these behaviours
(e.g. crawling). Other behaviours are poorly canalized (e.g. cycling), so environmental factors will
influence these traits. Further, some traits appear to be heavily canalized early in development
(e.g., language development), but less so later on (e.g., reading ability).

Gottesman put forward the notion of a range of reactions. The genetic make-up of a child does
not shape any behaviour in its entirety; instead genes only set limits (or range) within which the
individual variability is shaped by the environment.

Scarr & McCartney proposed the concept of ‘niche-picking’ in developmental genetics (1983).
The genetic make-up of a child does not contribute to skills or behaviours as such; instead genes
only contribute to propensities toward certain skills and abilities; children then seek activities
that are compatible with their genetic endowment

Three types of G-E interaction are notable:

 Passive GE‐Interaction: A child’s environment is influenced in part by parental genes

which are in turn correlated with the child’s genes. Thus, the phenotype is not a direct
result of the child’s genotype; but results from environmental influences that are indirectly
associated with the parental genes. This kind of passive G-E will show decreasing
influence over development. e.g. a boy who does not inherit the same tallness and

© SPMM Course 39
 physique as his father may still develop into a good basketball player in line with the
father due to repeated exposure to basketball sessions.
 Evocative GE‐Interaction: A child’s environment is influenced in part by genetically
shaped behaviour. Thus, the phenotype is not a direct result of the child’s genotype; but
results from environmental influences evoked by the child’s own genes. This kind of
evocative G-E will show stable influence over development. e.g. a girl who inherits
impulsivity may evoke an abusive parental reaction, leading to later depression, though
depression itself is not inherited.
 Active GE‐Interaction: A child’s environment is influenced in part by an active choice of
the child to complement genetically shaped interests. Thus, the phenotype is not a direct
result of the child’s genotype; but results from environmental influences that are actively
associated with the child’s own genes. This kind of active G-E will show increasing
influence over development. e.g. a girl who inherits impulsivity may choose to gamble,
losses in which may lead to later depression though depression itself is not inherited.

© SPMM Course 40
14. Neuroimaging and neurodevelopment
(This section is best read in conjunction with the section on neuroimaging in the Clinical Examination chapter)

A neural tube is seen 2-3 weeks after the formation of the human fetus. By week 5, the ectodermal
tissues differentiate to precursors of different brain regions. This is followed by birth neurons
from stem cells (at ventricular proliferative zone, by week 8), neuronal migration (week 12-20),
formation and pruning of axons, dendrites and synaptic contacts, myelination of axons and
apoptotic removal of excess cells.

One of the earliest neurodevelopmental events that can be visualized using neuroimaging in
human fetuses is the migration of neurons. Around 17 weeks’ of gestation, a transient layer of
cortical subplate of migrating neurons is visible beneath the cortex; by 20 weeks the subplate
withers away and replaced by more permanent cortical sheet at 24 to 28 weeks.

A cortical folding pattern consisting of sulci and gyri become visible on fetal MRI by 20 weeks.
Around the 28th week of gestation, the neuronal count in the human brain is at its peak - around
40% greater than in the adult. Dendritic formation accelerates at this time (but cannot be seen in
MRI), and along with the disappearance of the proliferative zone and cortical subplate, an
increase in cortical thickness is notable on fetal MRI.

Synaptogenesis peaks around 34th week of gestation in (~ 40,000 new synapses formed per
second) and continues in postnatal life alongside active synapse elimination; eventually the net
number of synapses begins to decrease at puberty (pruning). Synaptic pruning cannot be
observed directly with neuroimaging, but a prominent progressive cortical thinning of frontal
and parietal cortices is noted in MRI studies during adolescence and is attributed to synaptic
pruning. An indirect indicator of synaptic removal is the glucose metabolism measured using
positron emission tomography (PET).

Myelination of the visual cortical white matter begins prenatally (last trimester); by 9 months of
postnatal life, myelination extends to frontal cortex (posterior-to-anterior maturation starting
with sensory pathways motor pathways, and finally the higher-order association areas).

Landmark longitudinal studies of brain volumes in children were conducted in the Child
Psychiatry Branch of the NIMH, USA. These studies report the following observations

1. White matter volume increases linearly up to age 20 years in all brain regions;
2. Frontal, parietal, and temporal gray matter volumes follow an “inverted U-shaped”
developmental curve (increase before adolescence, frontoparietal peak at 12 years and
temporal peak at 16 years of age, followed by universal reduction thereafter)

© SPMM Course 41
 3. The cortical thickness decreases with advancing age in “back-to-front” progression
starting from sensorimotor areas, progressing to the dorsal parietal, superior temporal,
and dorsolateral prefrontal cortices later. In other words, sensorimotor area mature
earlier than higher-order regions.

Cortical thinning may occur either due to synaptic pruning or myelination (with myelination, the
brain tissue that is identified as white matter in MRI scans increase in proportion, reducing the
relative grey matter thickness).

Diffusion Tensor Imaging, a technique used to study the integrity of white matter tracts, reveals
that in children, with advancing age, the directionality of diffusion in white matter pathways
continues to increase especially in the prefrontal regions and in basal ganglia. This suggests that
frontostriatal systems myelinate progressively during adolescence. DTI studies also show that the
frontotemporal pathways may continue to myelinate until age 30 years.

Magnetic Resonance Spectroscopic measure of N-Acetyl-Aspartate, an indicator of neuronal

integrity, reveals low levels around birth that increase rapidly during the first 2 years of life,
slowing down thereafter; this may represent synaptogenesis during childhood.

Functional MRI studies reveal age-related increases in activation left frontal and temporal
cortices (language areas) supporting the expansion of reading and phonological skills during
childhood.

© SPMM Course 42
 DISCLAIMER: This material is developed from various revision notes assembled while
preparing for MRCPsych exams. The content is periodically updated with excerpts from
various published sources including peer-reviewed journals, websites, patient information
leaflets and books. These sources are cited and acknowledged wherever possible; due
to the structure of this material, acknowledgements have not been possible for every
passage/fact that is common knowledge in psychiatry. We do not check the accuracy
of drug-related information using external sources; no part of these notes should be used
as prescribing information.

Notes produced using excerpts from:

 Burman, E. (2007). Deconstructing developmental psychology. Routledge.

 Cole, P. M., Martin, S. E., & Dennis, T. A. (2004). Emotion regulation as a scientific construct:
Methodological challenges and directions for child development research. Child development,
75(2), 317-333.
 Deary IJ, Penke L& Johnson W (2010). The neurosciences of human intelligence differences.
Nature Reviews Neuroscience 11, 201-211.
 Farrington, D. P. (1995) The development of offending and antisocial behaviour from childhood:
key findings from the Cambridge Study in Delinquent Development. Journal of Child Psychology
and Psychiatry, 36, 929–964.
 http://www.learning-theories.com/eriksons-stages-of-development.html
 http://www.personalityresearch.org/papers/lee.html
 Marsh, R et al. Neuroimaging Studies of Normal Brain Development and Their Relevance for
Understanding Childhood Neuropsychiatric Disorders. J Am Acad Child Adolesc Psychiatry.
2008 Nov; 47(11): 1233–1251.
 Shonkoff, J. P., Garner, A. S., et al. (2012). The lifelong effects of early childhood adversity and
toxic stress. Pediatrics, 129(1), e232-e246.
 Sigelman, C., & Rider, E. (2014). Life-span human development. Cengage Learning.
 Skari H, Skreden M, et al. Comparative levels of psychological distress, stress symptoms,
depression and anxiety after childbirth--a prospective population-based study of mothers and
fathers. BJOG. 2002 Oct;109(10):1154-63.
 Slee, P. T., & Shute, R. (2014). Child Development: Thinking About Theories Texts in Developmental
Psychology. Routledge.
 Thambirajah MS. Psychological Basis of Psychiatry. Churchill Livingstone, 2005

© SPMM Course 43
 Basic Psychology
Paper A Syllabic content 1.1

© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
 1. Learning Theory

The psychological construct of learning refers to the development of a relatively lasting change in
behaviour as the result of a single or repeated experience.

Non associative learning: These are simple forms of learning demonstrated in lower animals where only
single events are used in learning paradigm - no pairing or ‘operation’ on the environment is required.

- Habituation is a non-associative learning in which repeated stimulation leads to a reduction in

response over time as the organism ‘learns’ the stimulus.
- Sensitization is an increase in response to a stimulus as a function of repeated presentations of
that stimulus. Similar to habituation, repetition of exposure is required to elicit the learning
effect, but the response rates go up, not down (i.e. opposite to the effect seen in habituation).
- Pseudoconditioning (cross-sensitization): The emergence of a response to a previously neutral
stimulus simply as a result of exposures to a different but powerful stimulus.

Associative learning: Here learning occurs through the association of two events.

- Classic conditioning: learning takes place through repeated temporal association of two
events. The learning organism is passive, respondent (i.e. shows an innate, reflexive response
such as salivation) but not instrumental (i.e. does not actively operate on its environment).
- Operant conditioning: learning results from consequences of one’s actions – operations. The
learning organism actively operates (instrumental) on the environment.
- Social learning theory: combines both classic and operant models of learning, and includes
cognitive processes and social interaction to be relevant in human learning.

Classical conditioning is produced by repeatedly pairing a neutral conditioned stimulus (CS e.g. bell)
with an unconditioned stimulus (UCS e.g. food) that naturally evokes an unconditioned response (UCR
e.g. salivation). Eventually the neutral stimulus alone eventually evokes the desired response (salivation –
now called conditioned response, CR). It is a relatively rapid process and depends upon the nature of the
unconditioned stimulus. Pavlov first demonstrated this paradigm in dogs.

The development of the association between the CS and the UCR resulting in a CR is called acquisition.
For animals this takes around 3 and 15 pairings; if sufficient emotional involvement is present acquisition
can occur with even one pairing.

Type of conditioning Pairing procedure

Delayed or forward conditioning. CS (bell) presented before UCS (food); the CS+ UCS pairing
continued till UCR (saliva) appears
Backward conditioning. UCS (food) presented before CS (bell) – not useful in
animals; used in advertising
Simultaneous conditioning. UCS + CS presented together – often the case of learning in

© SPMM Course 2
 real life situations.
Trace conditioning. CS presented and removed before UCS presented –
conditioning depends on memory trace.

A delay of less than 0.5ms is proposed to be the optimum for trace conditioning.

Temporal contiguity (time between stimulus and response) is important for conditioning according to
Pavlov. But Rescorla showed that predictability is more important than temporal contiguity in humans i.e.
if one can predict painful tooth extraction on hearing the dentist’s drill, then the noise gets conditioned to
elicit fear response better than two unconnected, unpredictable events having temporal contiguity. Note
that for classical conditioning it is not necessary that the organism understands an association in cognitive
terms but such awareness facilitates the learning.

Higher-order conditioning refers to the use of an already conditioned stimulus CS1 as UCS for the next
level of conditioning and eliciting a CR for another stimulus CS2. In this way second order and
subsequently higher order conditioning are possible. Animals do not respond higher than 4th order
usually.

Pavlovs’ experiments were conducted using human subjects by Watson & Rayner. Watson produced
‘phobia’ in an infant called Little Albert. By exposing him to loud frightening noise whenever he was
shown a white rat, eventually Albert became fearful of the white rat, even when he heard no loud noise. A
similar fear response was seen when any furry white object was shown to Albert. This ‘spread’ of
associative learning from one stimulus to other is called stimulus generalisation.

Discrimination is a process diametrically opposite to generalization; in many situations associative

learning can be very selective. In such cases, learned responses are made only to specific stimuli and not to
other similar stimuli e.g. a child may be afraid of dogs but not all four-legged animals.

Extinction: reduction/disappearance of a learned response when the UCS – CS pairing (or the reinforcer in
operant conditioning; see below) is not available anymore. Faster extinction may mean weaker learning.
Extinction does not mean loss of learning, but only a suppression of behavioural response. Spontaneous
recovery refers to regaining a previously extinguished learned response after a period of time.

Counter conditioning is a form of classical conditioning where a previously conditioned response is

replaced by a new response that may be more desirable. Utilised in behavioural therapy - systematic
desensitisation, aversion therapy.

Latent inhibition: A delay in learning the association between UCS and CS is seen if previous exposure to
an isolated presentation of CS is present.

An organism learns an appropriate behaviour after many trials because the right behaviour is followed by
appropriate (desirable) consequence. This forms the basis of the concept of operant conditioning; this

© SPMM Course 3
phenomenon is termed the law of effect and is often demonstrated using trial-and-error learning
experiments originally described by Thorndike.

A conditioning that leads to increase in the frequency of behaviour following learning is called
reinforcement. A conditioning that leads to decrease in the frequency of behaviour following learning is
called punishment. Both reinforcement and punishment can be positive (i.e. something is given) or
negative (something is taken away).

Positive Reinforcer Food for pressing a lever (given)

Negative Reinforcer Ceasing of electric shock on pressing a lever (taken away)
Positive Punishment Points on your driving license for speeding (given)
Negative Punishment A monetary fine from a parking ticket (taken away)
Primary Reinforcer Stimulus affecting biological needs (such as food)
Secondary Reinforcer Stimulus reinforcing behaviour associated with primary reinforcers
(money, praise)
Both positive and negative reinforcement increase the desired response.

The use of a “star chart,” with a variable interval schedule so that about 2 or 3 stars are administered per
day depending on the good behaviour, and none for bad behaviour. This part would be positive
reinforcement by giving something additional to increased the desired response

In a patient with OCD, compulsions provide short-term relief of obsessional anxiety via negative
reinforcement. When carrying out compulsive rituals, anxiety is reduced acutely. This provides a
reinforcement to engage in the compulsions repeatedly - the termination of the aversive anxiety cued by
obsessions, increases the compulsive behaviour that removed the anxiety, without addressing the core of
obsessions.

Reinforcement Schedules

A reinforcement schedule refers to how and when behaviour is reinforced on the basis of the number of
responses.

Reinforcement Schedule Explanation/Example

Continuous (aka Reinforcement every time the positive response occurs - e.g. food pellet
contingency every time a rat presses a lever in an experiment
reinforcement)
Partial Only some of the positive responses result in positive reinforcement – the
reinforcement is determined by number of responses (ratio) or time
(interval)
Fixed Interval Reward occurs after a specific period of time regardless of number of
responses e.g. a monthly salary irrespective of your level of performance!
Variable Interval Reward occurs after a variable (unpredictable) period of time, regardless

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 of the number of responses e.g. an angler catching a fish - the first may be
after 10 minutes, the next after 45, then 5 minutes etc.
Fixed Ratio Reward occurs after a specific number of responses e.g. after completing
20 MCQs, you give yourself a coffee (or chocolate) break.
Variable Ratio Reward occurs after a random number of responses e.g. gambling slot
machines. Your first win of £20 on a gamble may occur after 3 tries; then
the next win may not occur even if you play 30 times, while the third win
may follow in quick succession after the second.
Important points to note:

 In fixed schedules, a pause in response is seen after reinforcement as the organism knows the
reinforcement will not be happening for some reasonable time or attempts hereafter. The pause for
fixed interval schedule is greater than the pause for fixed ratio schedule. When we interpret an
operation to be under control (as in fixed schedules) we learn more quickly.
 Variable schedules generate a constant rate of response as the chance of obtaining a reward stays
the same at any time and for any instance of behaviour. In general, partial schedules are more
resistant to extinction than continuous schedule though they take longer to learn. Variable ratios
are the most resistant to extinction. This may explain why gambling is such a difficult habit to
eradicate.
 Another important determinant of operant conditioning is contingency - learning the probability
of an event.

Premack’s principle (a.k.a. Grandma’s rule): high-frequency behaviour can be used to reinforce low-
frequency behaviour e.g. “eat your greens and you can have dessert”. An existing high-frequency
behaviour (eating dessert) is used to reward low-frequency behaviour (eating greens).

Avoidance learning: an operant conditioning where an organism learns to avoid certain responses or
situations. Avoidance is a powerful reinforcer and often difficult to extinguish. A special form of
avoidance is escape conditioning seen in agoraphobia where places in which panic occurs are avoided /
escaped from leading to a housebound state eventually.

Aversive conditioning: This is an operant conditioning where punishment is used to reduce the
frequency of target behaviour e.g. the use of disulfiram (noxious stimuli) to reduce the frequency of
drinking alcohol.

Covert reinforcement: In covert reinforcement schedules, the reinforcer is an imagined pleasant event
rather than any material pleasure e.g. imagining MRCPsych graduation event to reinforce the behaviour
of practicing MCQs.

Covert sensitization: The reinforcer is the imagination of unpleasant consequences to reduce the
frequency of an undesired behaviour e.g. an alcoholic may be deterred from continuing to spend on
alcohol by imagining his wife leaving him, being unable to support himself and ending up broke and
homeless.
© SPMM Course 5
Flooding: An operant conditioning technique where exposure to feared stimulus takes place for a
substantial amount of time so the accompanying anxiety response fades away while the stimulus is
continuously present e.g. a man with a phobia of heights standing on top of the Burj Khalifa or the Shard.
This will lead to the extinction of fear. When a similar technique is attempted with imagined not actual
exposure then this is called implosion.

Shaping (a.k.a. successive approximation): This is a form of operant conditioning where a desirable
behaviour pattern is learnt by the successive reinforcement of behaviours closer to the desired one. Note
that shaping is used when the target behaviour is yet to appear (i.e. it is novel and does not exist already).

Dog runs towards Runs and makes Runs, jumps Runs, jumps Circus on show
a wheel but a jump close to through the through the
doesn’t jump the wheel wheel wheel on fire
Gets a bone Gets a bone Gets a bone Gets a bone Behaviour is shaped

Chaining: This refers to reinforcing a series of related behaviours, each of which provides the cue for the
next to obtain a reinforcer. Chaining is used when the target behaviour is already notable in some form
but not in the fully formed sequence. An example is teaching a child to write his name. The shape of
individual alphabets is first taught using reinforcers and forward chaining can be used to link each
alphabet in the correct order, finally reinforcing the completed name. Backward chaining starts at the end
e.g. when making cupcakes, the child is first taught how to sprinkle over a fnished cupcake, the next time
icing the cake and sprinkleing, the next time placing the prepared cake mixture into cupcake wrappers
then icing then sprinkling etc.

Incubation: An emotional response increases in strength if brief but repeated exposure of the stimulus is
present. Rumination of anxiety-provoking stimuli can serve to increase the anxiety via incubation. This is
a powerful mechanism that maintains phobic anxiety and PTSD.

Stimulus preparedness (Seligman) explains why snake and spider phobia are commoner than ‘shoe
phobia’ or ‘watch phobia’. In evolutionary terms, the stimuli that were threatening to hunter-gatherer men
has been hard wired into our system, reflexively eliciting responses immediately – and phobia develops
more readily for such ‘prepared stimuli’.

Learned helplessness (Seligman): initially put forward as a behavioural model for depression. When
confronted with aversive stimuli from which escape is impossible, an animal stops making attempts to
escape. This was shown experimentally with a dog on an electrified floor unable to escape. After a while,
the dog stopped trying, as if accepting its fate. This paradigm is frequently invoked to explain the
dependence seen in victims of domestic abuse.

Reciprocal inhibition (Wolpe): If stimulus with desired response and stimulus with the undesired
response are presented together repeatedly, then the incompatibility leads to a reduction in frequency of
the undesired response. This is evident when your dog barks at your friend; try hugging her in front of

© SPMM Course 6
your dog every time the dog barks and slowly the dog will stop barking at your friend. This is used in
relaxation therapy for anxiety and in systematic desensitisation.

Cueing (a.k.a. prompting): specific cues can be used to elicit specific behaviours – e.g. in a classroom a
teacher puts her finger on her lips to reduce chatter and elicit the response of silence. The process of
unlearning such cue associations is called fading.

Bandura’s social learning theory: Bandura believed that not all learning occurred due to direct
reinforcement, and proposed that people could learn simply by observing the behaviour of others and the
outcomes. According to behaviourists, learning is defined as a relatively permanent change in behaviour
but social learning theorists differentiate actual performance from learning a potential behaviour.

Social learning theorists emphasize the role of cognition in learning; awareness and expectations rather
than the actual experience of reinforcements or punishments are sufficient to have a major effect on the
behaviours that people exhibit.

Cognitive processing during social learning:

1. Attention to observed behaviour is the basic element in learning.
2. Visual image and semantic encoding of observed behaviour memory
3. Memory permanence via retention and rehearsal
4. Motor copying of the behaviour and imitative reproduction
5. Motivation to act.
Reciprocal causation: Bandura proposed that behaviour can influence both the environment and the
individual and each of these three variables, the person, the behaviour, and the environment can have an
influence on each other. The most commonly discussed experiment illustrating Bandura’s theory is the
Bobo Doll experiment. Children watching a Stages Gagne’s learning hierarchy
model showing aggression against a bobo doll 1 Classical conditioning (signal learning)
learnt to display the aggression without any 2 Operant conditioning
reinforcement schedules. 3 Chaining
4 Verbal association
Cognitive learning (Tolman): reinforcement
5 Discrimination learning
may be necessary for a performance of learned 6 Concept learning
response but not necessary for the learning 7 Rule learning
itself to occur (latent learning). He inferred that 8 Problem solving
rats can make cognitive maps of mazes – called
place learning - which consists of cognitive expectations as to what comes next.

Insight learning (Kohler) is diametrically opposite to associative learning and views learning as purely
cognitive and not based on S-R mechanism - a sudden idea occurs and the solution is learnt.

Hierarchy of learning: Gagne’s hierarchy of learning (see the attached table) describes that simple or
basic learning steps are prerequisites for later complex learning. This pattern of learning can also be seen
during human development and in the hierarchy of evolution.

© SPMM Course 7
 2. Basic principles of visual and auditory perception

When perceiving an object it needs to be differentiated from its background. Determinants of figure vs.
ground differentiation include

1. Contour – surroundedness
2. Size
3. Orientation
4. Symmetry
This is also influenced by perceptual set (see below).

Reversal of figure-ground perception frequently occurs so that sometimes, the ground is perceived as
figure and vice versa e.g. try googling for images of Rubin’s vase illusion. This indicates that same stimuli
can produce more than one perception. Figure-ground differentiation is also crucial for perceiving
auditory stimuli e.g. when we are at a crowded party we are still able to filter our friend’s voice and have
a conversation amidst all noisy background (cocktail party phenomenon). Shadowing is an experimental
extension of this effect where two different messages are given to the right and the left ear and the subject
is asked to follow one and suppress the other. These experiments are called dichotic listening tests (see
below for further information in ‘attention’ section).

The principle of Gestalt: Gestalt means shape or form; it also refers to the global whole of an object.
Gestalt law of perceptual organisation includes

Proximity

•Objects close to each other are perceived as one figure

Closure

•Incompletely closed figures are perceived as fully closed

Continuity

•Continuous items are perceived as one object.

Similarity

•Similar items are grouped together based on colour or shape etc.

Common fate

•Things moving together are perceived as one object.

According to Gestalt laws, global processing occurs before local processing of components. The whole is
different from the sum of its parts. This is true at least for 2 dimensional objects though ecological validity
is lower for 3D objects.

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Depth perception depends on pictorial and non-pictorial primary cues. The non-pictorial cues are
generally binocular cues and include

a. Retinal image disparity

b. Stereopsis
c. Accommodation (monocular)
d. Convergence

Pictorial cues (secondary) include largely monocular elements such as

a. Size
b. Brightness
c. Superimposition
d. Texture
e. Linear perspective (rails converge at distance, wide apart when closer)
f. Aerial perspective (colour – blue mountains means a distant sight)
g. Motion parallax (closer it is faster it seems)

Visual cliff is an apparatus used to test an infant’s perception of depth. A pane of thick glass covers a
shallow drop and a deep drop. The underlying surfaces of both deep and shallow sides are covered with
the same chequered pattern. Children of six months and older will not venture to the ‘deep side’ and this
is taken as an indication that the child can perceive depth.

Perceptual constancy is defined as the ability to perceive objects to be the same and unchanging in
character despite varied inputs. It consists of

1. Size constancy
2. Shape constancy e.g. a door is always a door no matter which angle it is showing to the viewer
3. Location constancy – movement of the head gets nullified somehow so we do not perceive
objects around us getting relocated as we move our head!
4. Brightness, hue and colour constancy

Autokinesis refers to the phenomenon that if light is shown from a small, dim, and fixed light source for
an extended period of time in a dark room, it will appear as if the light source is moving. This visual
illusion can explain UFO sightings and can also affect pilots.

The phi phenomenon is a perceptual illusion described by Wertheimer. This refers to the phenomenon in
which a false perception of motion is produced by a succession of still images shown with fixed time
interval rapidly.

Theories of perception:

Bottom-up theory: Gestalt is an example of a bottom-up theory. According to bottom up theories,

perception is purely data driven and directly starts with the optic array. Piecing together of basic elements
of the data gives rise to more complex systems. This makes the original elements sub-systems of the
‘emergent system’. But perception is not just seeing, it is ‘seeing as’.
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Top-down theory: Gregory’s constructivist theory is an example of a top-down theory. According to this
theory, retinal images are sketchy and cannot explain the complex and fully formed perceptions that we
experience. Perception is best defined as a process of using information known already to formulate and
test a hypothesis. It is driven from the ‘top down’ – i.e. from higher cortical areas. Illusions such as Muller
Lyer (i.e. when you compare >----< and , despite the horizontal line being of same length in both
instances, the first one may appear to be longer) support top-down processing.

A perceptual set is defined as the readiness to perceive selected features as an object. This is related to the
level of motivation e.g. hunger, emotional state, values, beliefs, context and expectations (e.g. UFOs are
sighted only by those who believes in them and ‘expects’ them).

Illusions and hallucinations

Illusion is defined as any perceptual situation in which a physical object is perceived but appears different
from what it really is e.g. a white wall appears yellow if a yellow light is shone on it.
A hallucination is an experience in which an object (e.g. sound or light) is perceived in the absence of any
corresponding object in the real world. A hallucination is often indistinguishable from genuine perception.

Human visual perception

The development of human visual perception is an illustration of a constitutional-environmental
interaction. Most of the time during development, complex visual stimuli such has human faces are
preferred. Innate visual processes such as visual scanning, tracking, fixating, figure-ground
discrimination are present from birth. Learnt visual processes include size constancy, shape constancy,
depth perception, shape discrimination.

From birth we have the ability to discriminate brightness and carry out eye tracking, visual acuity is
significantly impaired and focusing is fixed at 20cm. At 2-4 months – depth perception is apparent (as
evidenced by visual cliff experiments). By 4 months – accommodation and colour vision seems to be
present in most children. By 6 months – 6:6 acuity is achieved.

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 3. Information processing and attention
Focused or selective attention refers to the mechanism by which certain information is registered while
others are rejected.
Capacity or divided attention refers to the upper limit of the amount of processing that can be performed
on incoming information at any one time.
Many studies of attention have used auditory tasks.
 Dichotic listening refers to feeding one message into the left ear and a different message
simultaneously into the right ear. Participants have to repeat one of the messages aloud. This process
is called Shadowing (first used by Cherry). This is a method to study selective attention. Divided
attention can be tested using a dual-task technique whereby the individual is asked to attend and
respond to both or all incoming messages.
 Cocktail party effect: It is a concept related to selective attention. It is a term used in early attention
research ‘to describe the ability of people to be able to switch their attention rapidly to a non-
processed message’. The cocktail party effect shows that certain types of stimuli can elicit switching
between messages e.g. the physical location of the speaker, the pitch of the voice or the use of
familiar stimuli such as the listener’s name. (Lunch-queue effect)
 Broadbent’s early selection filter theory:
o Our ability to process information is capacity limited.
o A temporary buffer system receives all information and passes it to a selective filter.
o The selection is based on physical characteristics of the information – one source is selected and
others are rejected.
o Processing two different pieces of information will take longer and will be less efficient as
switching takes a substantial period of time.

sight
short Selected
sound term stimulus
smell memory

Senses STM Selective Filter

 Triesman’s attenuation theory:
o Treisman (1964) proposed that physical characteristics and semantic relevance (meaning) are
used to select one message for full processing while other messages are given partial processing.
 Deutsch-Norman late selection filter model:
o This model rejects Broadbent and suggests that filtering occurs only later, after all inputs are
analysed at a higher level. This is also called the pertinence model.
 Pigeon-holing:
o Later Broadbent revised the early selection filter theory and stated that apart from filtering,
pigeon-holing can also take place.

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 o Pigeonholing is similar to filtering but selection is not based on physical characters; it is based on
categorization.
o E.g. if one is asked to attend to the names of animal (a category) from many stimuli, this will take
place irrespective of physical characters such as volume, pitch etc.
 Automaticity
o Automatic processing:
 Does not require conscious attention
 Unaffected by capacity limits
 Difficult to modify
 E.g. driving a car or listening to the radio
o Controlled processing:
 Requires attention
 Heavy demands
 Slow and capacity limited
 E.g. reading this notes!
 Closed loop control: when we first learn a task it is under conscious attention system. When we
become skilled at it, open loop control takes over. Open loop is controlled by automatic motor
processes. It is fast and allows conscious attention to be diverted to other activities.
 Stroop test and letter cancellation tasks can test selective attention.

Focused The ability to perceive individual items of information (respond discretely to the specific
attention modality of stimuli).
Sustained The ability to maintain a consistent behavioral response during continuous and repetitive
attention activity. Also called as vigilance or concentration
Selective The ability to avoid distractions from internal or external cues and maintain a behavioural
attention or cognitive set in the face of competing stimuli.
Alternating The ability of mental flexibility that allows individuals to shift their focus of attention and
attention move between tasks having different cognitive requirements.
Divided This is the highest level of attention and it refers to the ability to respond simultaneously to
attention multiple tasks or multiple task demands. It is much more difficult to achieve within same
modality (e.g. visual) as it is between different modalities (visual and auditory)
A hierarchical model of attention: Sohlberg and Mateer proposed a clinically useful model of evaluating
attention in a hierarchical fashion based on the sequential recovery of attentional ability in patients with
brain damage. Five different kinds of activities of growing difficulty are described in the model
connecting with the activities that patients could do as they recover gradually. This model has been
clinically useful in terms of rehabilitation of brain-damaged patients.

Studies of attention in schizophrenia suggest that there is an underlying attentional abnormality for those
with a genetic predisposition for psychosis. The overall reaction time is much slower in patients with
schizophrenia and their relatives; sustained attention, distraction, verbal memory and controlled
processing are also affected.

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 4. Memory
In all cognitive operations involving memory 3 different processes are thought to occur.

 Encoding - It leads to the formation of initial memory traces and receives information from the
outside.
 Storage - Retention of information and maintenance
 Retrieval - Accessing and recovering information from memory stores

William James divided memory to primary (short term) and secondary memory (long term). In fact 3
forms of memory are now recognised.

1. Sensory memory: This is modality specific, has a large capacity but gets disrupted by the inflow of
new information in the same modality. Each sense has its own sensory memory e.g. iconic (visual)
lasting 0.5 seconds, echoic (auditory) lasting 2 seconds etc. No processing is involved in sensory
memory. If attention is paid to the sensory memories during perception, sensory memory gets
consolidated or ‘moves’ into the short-term memory system.
2. Short term memory: The capacity of STM according to Miller is 7+/- 2 items. This is evident while
testing digit span (but see below for chunking). Unaided, STM lasts 15 to 30 seconds. By
maintenance rehearsal, this duration can be increased further up to indefinite periods. If
maintenance rehearsals are prevented, then by 15 seconds the original material is completely
forgotten. Brown Paterson task involves introducing distraction (such as counting a three digit
number backwards) immediately after the digit span test in order to prevent rehearsal. STM uses
acoustic coding (mostly) or visual coding. Recall of information is effortless and usually error-free.
Information is held in STM by the process of rehearsal. Loss of information from STM occurs mainly
through displacement (newly acquired items entering STM displaces existing material) and decay
(older materials have a weaker trace strength than the recently acquired items). In order for memory
to move from temporary to long-term storage, elaborative encoding (Daniel Schacter) must take
place.
NOTE: The term working memory is increasingly used to describe a large part of what was called as
STM in the past. Working memory allows cognitive processes to be performed on data that is briefly
stored in short-term memory.

3. Long term memory: This has unlimited capacity and lasts for an indefinite duration. The coding is
largely semantic, though visual and acoustic coding can occur to some extent.
According to Atkinson &
STM LTM
Shiffrin, STM and LTM are
regarded as structural Encoding Acoustic Semantic
components. Rehearsal is
Retrieval Error-free Error-prone
supposed to be the transient
control process that can aid Capacity 7+/-2 chunks Unlimited
maintenance of STM and
transfer to LTM. Other control processes include encoding, retrieval strategies and decision to

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 remember. Rehearsal may be maintenance/rote rehearsal or elaborative rehearsal where encoding is
semantically elaborated or changed. It is proposed that rehearsal can take place at 3 levels of
processing. Shallow processing where surface features are only rehearsed, phonemic processing
where sound features are rehearsed or semantic processing where deeper encoding and meaning
related associations are made. Higher level of processing depends on time available and nature of the
material processed.

[The terms often used in psychology are short term memory (corresponds to immediate memory in clinical
psychiatry) and long term memory (recent memory and remote memory in psychiatry). STM (immediate
memory) is tested by the recall of digits immediately after their presentation (Digit span).]

Other classifications:

Recent memory is the ability to remember what has been experienced within the past few minutes
(recall of items after five minutes), hours (recall of last meal), days (recall of recent news items).
Remote memory is the ability to remember events in the distant past (weeks to years). This can be
tested by inquiring about important dates in their lives such as date of birth, date of marriage, how
many siblings they have etc.

Tulving elaborated multistore model (LTM) to have two forms - declarative (explicit – includes
semantic and episodic memory) and non-declarative (implicit) memory.

Procedural or Implicit memory: This cannot be consciously inspected. This is not affected by an organic amnesia of
hippocampal origin. It is made of procedural memory for skills and habits, priming, classical conditioning and non-
associative learning.
Episodic memory is autobiographical, self-focused, spatio-temporal memory.

Semantic memory includes factual knowledge of the world. It is proposed to be made of multiple episodic memory
components.
Priming is a form of learning that occurs without conscious recall of the episode of learning;
performance demonstrates that the information is learnt but conscious episodic recall is absent.

Baddley & Hitch proposed a working memory model. Working memory is proposed to have central
executive and 2 arms – phonological loop and visuospatial sketchpad. The central executive is
capacity limited but modality free, similar to attention system. The phonological loop consists of
auditory rehearsal loops while visuospatial scratch pad consists of pattern recognition and movement
perception components. It is proposed that dyslexia may be related to erratic phonological loop. The
4th component of WM is sometimes called episodic buffer. This is a multimodal store that integrates
info from the slave systems onto LTM. This buffer is important for chunking.

Working memory is important for various processes including executive functions, decision-making,
error detection and correction, new learning (anterograde memory formation) and judgement.

Serial position effect: While memorising and recollecting a list of words both primacy and recency
effects are seen. Regardless of the length of a list, the initial words (primacy) and last few words
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 (recency) are remembered better than those at the middle of the list. Primacy is supposed to be due to
LTM as consolidation has occurred in the sufficient time between learning the first word and testing
recall. Recency effect is due to STM wherein last heard words are freshly retained.

In those with organic anterograde amnesia, recency is better preserved than primacy. Here the
problem is in transferring to LTM from STM and/or retrieval from LTM. In retrograde amnesia, the
physical establishment of LTM memory (called consolidation) fails.

Retrieval:

Modes of retrieval (i.e. moving from LTMSTM) are through

 Recognition (solving MCQs)

 Recall (actively searching and reproducing), FLASHBULB MEMORIES

 Reintegration/reconstruction (recollection of past

Distinctly vivid long-lasting
experiences based on certain cues). An eyewitness testimony
memories of a personal circumstance
is a reconstructive memory, which is a mode of retrieval
surrounding a person’s discovery of
from long-term memory. However, reconstructive memory
shocking events.
of events as in eyewitness testimony is affected by the type
of questioning asked to elicit the memory. These are not as accurate or
Forgetting: permanent as photographic
memories but forgetting curve for
Hermann Ebbinghaus plotted the forgetting curve by plotting
the flashbulb memories is far less
the proportion of words retained in memory against time. The
affected by time than other types of
curve shows a sharp drop over the first nine hours and
memories.
particularly during the first hour. After nine hours, the rate of
forgetting slows and declines little thereafter, even after the These memories are often associated
lapse of 31 days. The main findings from his and other studies with important historical or
are; autobiographical events. Such
events could include, for example,
 Forgetting is maximum in the first few hours, and the
the 9/11 or 7/7 etc.
rate of forgetting gets less with time.
 Forgetting is never complete, and some information is
retained over longer periods of time, even for life.
 Recalling the material during the test period increases the probability of remembering items
or events.
 Continuous motor skills, such as cycling and swimming, show no forgetting at all. But
discrete motors skills such as typing are lost more quickly.
Problems with encoding (registration), retention or retrieval, can all result in forgetting.

Decay theory states that neural engrams breakdown with time. This means that disuse with time is
the cause of forgetting, but no evidence exists that neurological decay occurs. Also what happens
before and after learning is more important than the mere passage of time in forgetting.

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 Displacement theory states that due to capacity limitation new info replaces old information.

Retrieval failure theory states that due to lack of proper cues to recall we forget things. According
to encoding specificity principle, anything we encode during learning can be a cue/tag for later
retrieval. Recall improves if same cues are available when recalling, but this holds true only for
recall, not recognition. Hence, some times recall is better than recognition! Such cues can be the
context (place, external state) specific or emotion/ inner state specific.

According to interference theory forgetting occurs due to interference. When newly learnt
material interferes with recall of old material, this is called retroactive interference. Proactive
interference refers to the interference of new learning from older learnt material. There is a low
ecological validity for interference model as most experiments were conducted with memorizing
word lists, a skill that is rarely required in daily life.

Strategies to improve encoding include – order and sorting info, chunking, mnemonics, using imageries,
adding importance and salience to the info and using primacy-
recency effects. Retrieval can be helped by cueing and RIBOT’S GRADIENT
reinstatement of learning context.
Theodule Ribot first suggested that
Chunking is a method of increasing the capacity of short-term
recent memories might be more
memory by combining units or information (usually numbers)
vulnerable to brain damage than remote
into chunks. By doing so, impressive feats of memory can result.
memories in 1881.
For example the numbers 1,5,2,3,5.2,5,8,5,3,7,8 would normally
After damage to the hippocampal
overload our short-term memory but if they are arranged into
memory system, patients tend to lose
chunks 152, 352, 585, 378, they become a lot more manageable.
more of their recent than of their remote
The more similar the retrieval situation is to the encoding memories. This pattern, unique to
situation, the better retrieval. This is called encoding specificity organic amnesia, is called the Ribot
principle. gradient.
This may be related to the dependence of
Amnesia refers to a marked impairment in episodic memory, retrieval on hippocampal systems, while
although other types of memory such as working memory, consolidation gradually ‘pushes’ stored
semantic memory and procedural memory may remain relatively memories to the neocortex, making them
intact. independent of the hippocampal system.

Anterograde Amnesia: The loss of the ability to form or

retain new episodic memories after an injury/lesion/event

Lack memory for events taking place in immediate future after an event
Classic cases often involve hippocampal damage
The subject cannot learn anything new.
Nothing can be moved from STM to LTM.

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 Retrograde Amnesia: The loss of episodic memories that were stored before brain damage had
occurred.

 Lack memory for immediately preceding events.

 Follows head injury
 The subject never consolidates the information that is already in STM (retrieval failure i.e.
fails to move from LTM to STM).

Transient global amnesia is caused by transient cerebral ischemia causing a temporary lack of blood
supply to the regions of the brain concerned with memory functions. The main features include sudden
onset of severe anterograde amnesia with a retrograde amnesia for the preceding days or weeks.

Sometimes amnesic episodes may occur in patients who have had no brain injury but suffered a traumatic
or emotionally disturbing life event (hysterical or psychogenic amnesia). There are two types-Global and
situation specific.

Fugue state is a type of psychogenic global amnesia in which there is a sudden loss of all autobiographical
memories, knowledge of self and personal identity. Usually, there is a period of wandering, and there is
an amnesic gap upon recovery. It usually last a matter of hours or days. Memory recovery is complete
after few hours or days. In most cases, the fugue states will clear over a few days and the amnesia is
mainly transient. If not, the patient usually adopts a new name and identity and begins a new life. As in
organic amnesia, fugue patients will normally retain their procedural and semantic memories. The patient
may have episodic memory loss that is usually only retrograde memory loss and no anterograde
impairment.

Situation specific amnesia: Offenders, as well as victims of crimes commonly, claim amnesia regarding
the offence. In 25-45% of homicides, 8% of other violent crimes and a small percentage of non-violent
crimes, offenders claim amnesia (Kopelman 2002a). Amnesia for an offence is associated with alcohol or
substance misuse and acute psychosis, but purely psychological amnesia is often limited to crimes of
passion.

In people with PTSD anterograde memory dysfunction has been demonstrated with some reduction in
hippocampal volume on MRI (Bremmer 1999) attributed to effects of glucocorticoids (Markowitsch 1996)

Amnesic syndromes: Various disorders can give rise to amnesic syndromes (e.g. hypoxia, herpes
encephalitis) and the features would include

1. Immediate memory is unimpaired.

2. Anterograde amnesia- inability to acquire new information (impaired delayed recall)
3. Retrograde amnesia of variable extent and severity-The degree depends on the extent of brain
damage
4. Preserved global intellectual abilities
5. Preserved implicit memory
© SPMM Course 17
Korsakoff’s syndrome: It is a form of an amnesic syndrome caused by thiamine deficiency. The patient
may have severe anterograde amnesia and extensive retrograde memory loss. This retrograde memory
loss includes autobiographical memory loss with relative sparing of the most distant memories. Working
memory and procedural memory are unimpaired. Bedside tests: Three words learning task (e.g. apple, table,
penny) is a test of anterograde memory and learning, useful to investigate Korsakoff’s syndrome.

Post-traumatic amnesia: The time between the injury and recovery of normal continuous memory, seen in
head injury patients. The longer the PTA, the more severe the brain damage and poorer the prognosis for
the recovery. PTA Retrograde amnesia is also possible after head injury – tested with recent
autobiographical questions (what did you eat for dinner yesterday?). In most cases, the amnesic gap is
short and (< 1 min). It is not a good indicator of prognosis.

Memory loss following ECT: The impairment is usually temporary. There may be both anterograde and
retrograde amnesia, both of which reduce rapidly in most patients. A third of patients report persistent
memory loss following ECT (Rose et al. 2003). Memory impairment is less pronounced with unilateral
ECT.

Tests of memory:

Digit span is the commonest test of auditory, verbal working memory. Both forward and backward digit span are
tested in routine clinical practice. The average range of digit forwards is 6+/-1 and for reverse digit span is 5+/-1
Three words learning task (e.g. apple, table, penny) is a test of anterograde memory and learning.
Name and address recall task (7 items) is the commonest test of recent (verbal) memory. Here the subject is asked to
recall as many items, without prompts, in five or ten minutes
Rey-Osterrieth complex figure test is one of non-verbal memory test. Here the subject is first asked to copy a complex
geometric figure and then to draw from memory after an interval of 30 minutes. The recall is impaired in patients
with dementia and amnesic syndrome.
Wechsler memory tests: Here the subject is asked to read a short story from the Wechsler memory scale containing 25
elements and both immediate and delayed recall after an interval of 30 minutes is tested.

Infantile amnesia: The average age of the earliest retrieved memory is 3.5 years. There is a total lack of
memories for events occurring during the first few years of life, and there is a variable degree of amnesia
for events that occurred in the first 2 to 5 years. This is termed infantile amnesia.

Emotion and retrieval:

Retrieval is reconstructing past experiences and is influenced by a number of variables including emotion.
Current mood affects what is attended, encoded and retrieved. The mood-congruent effect refers to the
ability to more easily recall information if it is congruent with the current mood e.g. in a depressed mood,
negative thoughts and circumstances are more readily retrieved. Mood-state dependent retrieval refers to
the phenomenon wherein retrieval of information is easier if the emotional state at the time is the same as
the emotional state at the time of encoding.

© SPMM Course 18
Elaboration: Material that is fully elaborated produces stronger memory trace as it is believed that
consolidation is linked to the depth with which the data is processed.

Schemas are mechanisms for elaborating and for reconstructing memory at test. They are organized sets
of facts. During recall, distortion can occur in order to ensure the information fit the schemas or to fit
cultural stereotypes. This then impacts the recall of the information.

Inference is a method where known, easily accessible information is used to piece together the retrieved
information, resulting in a biased recall.

Brain imaging and neuropsychological studies provide strong evidence that

a. The brain areas mediating performances in STM are principally the pre-frontal lobes
b. The phonological STM system is mediated by the left hemisphere regions of Broca's’ area and
prefrontal cortex.
c. The visuospatial STM system is mediated by the parietal and prefrontal areas of the right
hemisphere.
d. The brain areas responsible for LTM includes the regions of the limbic system especially the
hippocampus and the entorhinal cortex of the medial temporal lobe

© SPMM Course 19
5. Thought & language

There are several different theories that consider how language can affect thoughts and behaviour.

Sapir-Whorf Grammatical structure of mother tongue influences how we perceive the

Hypothesis world e.g. a language that does not have a word for a specific colour makes
that colour less likely to be remembered - this has largely been disputed as
very little experimental data has been produced in support.
Behavioural economics People are more likely to believe events that are verbally described more
vividly (e.g. availability heuristics)
Prospect theory People make different economic choices based on how something is framed
Cognitive distortions Challenging our 'internal dialogue' can change our cognitive distortions (as
in CBT)
Counting Some cultures do not have numbers above 10, or even 2 - instead using the
word 'many' to describe any number above the highest. This indicates a
conceptual difference in how some people would interpret 100 vs. 1000 vs. 1
million.
Neuro-linguistic A theory that language patterns can affect behaviour, such as influences a
programming consumer in a sale setting.

Concepts, prototypes and cores

Constituents of thoughts are defined as concepts and are important to psychological processes such as
learning, memory and decision-making. There are several theories of concepts – one of which is the
prototype theory.

Let us consider a lexical concept termed X. This concept may not yet have a defined structure but many
constituent features of X are well defined. In this case we can conceptualize that something will fall under
the concept X, if sufficient number of constituent features are satisfied. In other word, we obtain a
prototype of a concept using the linguistic components, thus acquire further knowledge of the world
around us. Consider the concept of FRUITS – most fruits are rounded. Now consider the properties of
apple and banana.

Apple Banana
Edible Edible
Red Yellow
Sweet Sweet
Crunchy Soft
Rounded Elongated

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Using this model, apples would be judged to be more typical of fruits than bananas as the idea of an
APPLE shares more of its constituents with the idea of a FRUIT.

Deductive and Inductive reasoning: Reasoning is broadly divided into deductive and inductive
reasoning. Deductive reasoning starts with a theory with which we form a hypothesis and collect
observations to confirm or dispute our hypothesis. This is often known as top-down reasoning.

THEORY  HYPOTHESIS  OBSERVATION  CONFIRMATION

Inductive reasoning starts with observations and formulate tentative hypotheses that are then explored
and a theory is formed. This is known as bottom-up reasoning.

OBSERVATIONS  PATTERN  HYPOTHESIS  THEORY

Inductive reasoning is open-ended and exploratory in comparison to the narrow nature of deductive
reasoning.

Problem-solving: Two methods of information processing have been described in problem-solving.

 Algorithmic method involves step-by-step search which guarantees solution but it is time-
consuming and more useful in simpler and smaller magnitude problems.
 Heuristic method uses rules of thumb; more likely solutions are tried before others – hence
solution is not guaranteed but it is more quick and ‘dirty’! Means-end analysis is a type of
heuristics in which the solution is sought from working backwards and may include reduction and
breaking down of a complex problem into easily solvable steps.

Heuristics in decision-making:

1. Availability heuristics: the decision is based on readily available information without systematic
search.
2. Representativeness bias: fitting a problem into one of the well-known categories and solve it in a
similar fashion.
3. Gambler’s fallacy: an outcome is due as it has not happened for some time. A gambler thinks that
more he loses, the more chances that he wins later.
4. Base rate fallacy: tend to ignore the relative frequency of occurrence of events but stick to
stereotypes. Consider that a very good student fails an exam, the probability of which is not
negligible. Someone has earlier said that this student could fail only if the examiner gets annoyed
by his handwriting and does not read his answer fully. One believes this has happened even
though the probability of such an event is ridiculously small, as the primary event of that student
failing has now occurred.
5. Sunk cost bias or entrapment: no choice than to continue to a decision, as one believes withdrawal
would not justify the cost incurred.

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6. Personality

Theories of personality consider the following different dimensions:

1. Personality as an enduring and consistent feature (dispositional) vs. differing with and influenced by
situations (situationalism)
2. Personality traits are shared and comparable (nomothetic) vs. traits are unique to individuals and not
comparable (idiographic)

Various theories of personality differ in the degree to which they embrace situationalism (vs.
dispositionalism) and the notion of idiography (uniqueness).

•Shared features •Variable and

(nomothetic) situational
•Consistent/enduring •Shared features
(dispositional)

Eysenck's
factors Psychoanalytic
theories
Cattell's traits

Situationlism
Kelly's personal
construct theory Humanistic
school

•Unique features •Unique features

(idiographic) •Variable and
•Consistent and situational
enduring

(Adapted from Gross Psychology 9e Page 731)

Allport’s theory: Allport analysed 18000 adjectives used as ‘trait labels’. A trait refers to an enduring
disposition viewed as a continuous dimension. He described three types of traits:

1. Cardinal traits: influential, core traits

2. Central traits: 5 – 10 traits, less general
3. Secondary traits: least important, least consistent traits that only close friends can notice.

Cattell’s approach: Cattell selected 4500 traits from Allport’s work, and further reduced them to 171
elements before factor analyzing them to identify 16 dimensions. Surface traits are correlated to one
another but not important for understanding one’s personality and Source traits that are basic building
blocks of the 16 PF questionnaire devised by Cattell. Cattell undertook oblique factor analysis to identify
these source traits. Cattell’s factors are a larger number of less powerful somewhat correlated (not fully
independent) factors arising out of first order analysis – called traits. Cattell maintained that a
© SPMM Course 22
fundamental discontinuity exists between normal and abnormal personalities (categorical). During his
work Catell identified 3 types of data that reveal qualities of one’s personality: 1. Q-data: obtained from
questionnaires 2. L-data: Obtained from lifetime records (e.g. report cards, friend’s accounts etc.) and 3. T-
data: test based data (e.g. Thematic Apperception Test etc.).

Eysenck’s approach: Eysenck used second order analysis (orthogonal factor analysis) that identified small
number of powerful independent factors. This method yielded 3 dimensional traits. These are neuroticism
(vs. stability), psychoticism and extraversion (vs. introversion). Eysenck’s personality questionnaire
contains a lie scale. Biologically, extraversion is related to arousal and ascending reticular activating
system; neuroticism may be related to sympathetic system reactivity. Introverts are said to be easily
aroused. Hence they are also more easily conditionable than extraverts; this may explain why introverts
stay indoors more often. Extraverts have low arousal state; hence they are not easily conditionable.
Eysenck maintained that no fundamental discontinuity exists between normal and abnormal personalities
(dimensional view).

Cloninger’s psychobiological model of personality includes four dimensions of temperament (each 50 to

60 % heritable), which manifest early in life and 3 components of character, which are shaped by
environment. The temperamental dimensions include
 Novelty-seeking (includes frustration avoidance, impulsive decision-making)
 Harm-avoidance (pessimistic worry about the future, passive avoidant behaviour, fear of
uncertainty);
 Reward-dependence (sentimentality, social attachment, and dependence on praise and approval)
 Persistence (high perseverance and tolerance of frustration)
The character dimensions are self-directedness, cooperativeness, and self-transcendence.

DSM identifies 3 clusters of personality disorders. In general Cluster A personalities are associated with
low reward-dependence. Cluster B personality with high novelty-seeking and Cluster C personalities with
high harm-avoidance traits.

Rotter’s locus of control theory is a single trait theory – where external and internal loci are used to
measure personality attributes. Note that both Cattell’s and Eysenck’s are multitrait theories.

Big Five Traits– McCrae & Costa 1992:

1. Openness
2. Conscientiousness
3. Extraversion
4. Agreeableness
5. Neuroticism

(OCEAN)

The Big-Five concept has provided a unified framework for trait research. NEO decreases with age; AC
increases with age.
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Kelly’s personal construct theory: Kelly proposed an idiographic theory of personality influenced by the
humanistic school. According to him one’s personality can be deciphered only when observations
regarding interpersonal relationships are made and hypotheses are formulated and tested. For this
purpose, Kelly used a repertory grid. Initially a list of important people is generated (called elements). 2
elements are chosen and contrasted with the third one to see what themes emerge – called constructs.
Such constructs are applied to elements down the list till all are exhausted and sufficiently descriptive.
Such constructs and elements can also be used for measuring formal thought disturbances (Bannister grid).

Humanistic or phenomenological school of personality focuses on the individuals’ view of the world
rather than their unconscious impulses. In contrast to trait-based approaches that view personality as
relatively enduring and shared, the humanistic school emphasises on the uniqueness of an individual’s
personality and the capacity for growth in an optimistic manner. Therapeutic models such as Roger’s
Client Centred Therapy originated from humanistic school.

Interactionism: A major issue with trait theories (nomothetic approaches) is the poor correlation between
one’s traits and observed behaviour. This led to a raise in the prominence of the so-called situationalism
that contends that all are apparently enduring behavioural patterns are in fact a result of environmental
demands on an individual. A middle path is the concept of interactionism (Magnusson and Endler, 1977),
which proposes that personality and the environment interact with each other to produce the observed
behaviour.

Typology: Early personality theorists such as Sheldon and Kretschmer used body shape based physical
types to describe associated personality traits. Kretschmer related body types to personality variations and
dispositions to major psychoses (1921).

 Asthenic – thin body; aloof individuals; correlated with schizophrenia

 Pyknic – plump individuals; childish with swings in mood; correlated with manic-depression
 Athletic – well-built individuals with a steady temperament.

Based on the study of thousands of nude photographs of first year college students, Sheldon proposed
three body types (1954).

 Endomorphic - plump and round people who are relaxed and outgoing.
 Mesomorphic - strong and muscular people who are energetic and assertive.
 Ectomorphic - tall and thin people who are fearful and restrained; associated with schizophrenia

Friedman & Rosenman introduced Type A / Type B personality classification. Type A persons show
impatience, excessive time consciousness, insecurity, high competitiveness, hostility and aggression and
are incapable of relaxation. They may be high achievers and workaholics. Type B persons are relaxed, and
easy-going; creative, often self-analyze and evade stress but cope poorly when under stress. Type A was
first described as a risk factor for coronary disease but MRFIT study later concluded that there is no
difference between Type A and Type B in regard to coronary proneness. This classification has poor

© SPMM Course 24
psychometric construct and content validity. The hostility component of Type A is the only significant
risk factor for CHD association.

Measuring personality traits:

Projective tests are individually administered tests to obtain information about emotional functioning.
They are based on the principle that ambiguous unstructured open-ended situations stimulate projection
of an individual’s internal emotional world onto the stimulus (environment). Murray was a major
proponent of projective tests. But the first projective test introduced was Rorschach’s inkblots. Thematic
Apperception Test (Murray), Draw-a-person test, sentence completion tests are other examples. Projective
tests do not have much place in contemporary practice.

 Classification of projective tests:

1. Association inducing: verbalizing response pertaining to a stimuli e.g. Rorschach.

2. Completion tests: completing unfinished stimulus e.g. sentence completion test
3. Choice or ordering: rank order or categorise stimuli.
4. Construction: develop or construct story or narration e.g. TAT.
5. Self-expression: create something without stimulus e.g. Draw a man (Goodenough), House Tree
Person (Buck).
 Rorschach is the most commonly used, consists of 10 inkblots, sequentially presented and asked
to describe. Has two phases – free association and inquiry phase – both are analyzed later. Can be
scored using Exner’s system. Needs extensive training to be used.
 Thematic Apperception Test (Murray) TAT has 20-30 pictures and one blank card and the subject
has to make a story from each depicted picture; not all cards are used. Stimuli somewhat more
structured.
 Jung introduced Word Association Test (WAT). In WAT and sentence completion tests, time
pressure is usually applied.

Minnesota multiphasic personality inventory (MMPI) is a popular inventory for measuring personality.
It has 10 scales with clinical labels. It is NOT a projective test.
 Self-report inventory
 Most researched personality inventory
 Developed by Hathaway & McKinley
 567 statements included
 Empirically derived 10 clinical scales are used to score responses
1. Hypochondriasis
2. Depression
3. Hysteria
4. Psychopathic deviance
5. Masculinity-femininity.
6. Paranoia.
7. Psychasthenia.
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 8. Schizophrenia.
9. Hypomania.
10. Social introversion
 Also contains lie scale (validity component)
The Q-sort technique developed from client-centered therapy involves a person sorting cards with self-
descriptive statements(e.g. ‘I don’t trust my own emotions’, ‘I like to be around friends’) on them into
ordered piles under the headings ‘self’ and ‘ideal’. A numerical discrepancy score between ideal and real
self can be thus computed.

The International Personality Disorder Examination (IPDE):

 Psychometric trait instrument for the clinical assessment of personality disorders (for those > 5
years age).
 IPDE comprises both a pencil-and-paper self-report screening questionnaire (77 true/false), and
semi-structured diagnostic interview rated by trained clinician.
 Compatible with both ICD 10 and DSM IV.
 Allows for a definite, probable, or negative diagnosis with respect to each personality disorder
 Translated into several foreign languages
 Ratings can be based either on the patient's answers or informant responses.
 Allows a "past personality disorder" diagnosis prior to the past 12 months
 Allows a "late onset" diagnosis when the diagnostic criteria have only been met after age 25 years.

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7. Motivation: needs and drives

Motivation refers to the process involved in initiation, direction and energisation of behaviour. It can have
various dimensions including internal vs. external, innate vs. learned, conscious vs. unconscious and
mechanistic vs. cognitive.

Maslow identified deficiency needs called D motives and growth needs (or ‘being’) needs called B
motives. He proposed a hierarchy of human needs with phylogenic and ontogenic evolution through the
hierarchy. The needs become less biological as one ascends through the hierarchy.

The higher needs come into focus

only when the lower needs are
satisfied at least to some extent. Once
an individual has moved upwards to
the next level, needs in the lower level
will no longer be prioritized. If a
lower set of needs is no longer being
met, the individual will temporarily
re-prioritize those needs by focusing
attention on the unfulfilled needs, but
will not permanently regress to the
lower level.

Some authors place aesthetic needs

and cognitive needs (need to know & understand) in between esteem needs and actualisation.
Transcendence can be placed above self-actualisation. The need for self-actualisations is "the desire to
become more and more what one is, to become everything that one is capable of becoming."

According to Maslow, the following characters are seen in self-actualizing people:

 Spontaneous in their ideas and actions.

 Creative.
 Interested in solving problems.
 Appreciate life.
 Have a system of internalized independent morality.
 Able to view all things in an objective manner.

Law of Effect related to learning theories can also be considered as a theory of motivation. A satisfying
effect strengthens behaviour; a dissatisfying effect weakens behaviour. So behaviour is contingent on the
consequences ( the basis of behaviourism) (Thorndike, 1911).

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Drive-Reduction Theory (Hull): According to this, the physiological aim of drive reduction is
homeostasis- the tendency for organisms to keep physiological systems (e.g. temperature) at equilibrium.
Any imbalance in homeostasis creates a need – a biological requirement for well-being. The brain responds
to such needs by creating a psychological state called drive – a feeling of arousal that prompts action to
reduce drive. According to Hull, primary drives stem from biological needs; secondary drives are
psychological and learned from primary drives (e.g. self-esteem, power etc.) Similarly Murray (1938)
divided needs into primary or vasculogenic needs that are physiological (e.g. air, water, food, sex) and
secondary needs that are acquired or learned through experiences e.g. money etc.

Yerkes-Dodson Law: An inverted U-shaped curve relates the level of arousal with the performance of an
act. Optimum arousal (moderate) is required for best performance; too low or too high arousal proves to
be a hindrance e.g. sexual performance. But it is demonstrated that the relationship is not as simple as
proposed as task difficulty varies highly. So, difficult or intellectually demanding tasks may require a
lower level of arousal (to facilitate concentration). But tasks demanding stamina or persistence may be
performed better with higher levels of arousal (to increase motivation). Because of task differences, the
shape of the curve can be highly variable.

Curiosity is an intrinsic motivator – it is stimulated when something in our environment attracts our
attention. There are two types of curiosity that can stimulate intrinsic motivation – sensory curiosity
(change in tone of voice or level of contrast e.g. typing bold letters) or cognitive curiosity (learner believes
it may be useful to modify existing cognitive structures e.g. improving knowledge in statistical models in
order to improve understanding of baseball batting averages).

The optimal discrepancy is the strongest curiosity when information appears different from what we
know but is not so dissimilar as to be considered strange or irrelevant.

Cognitive consistency theory focuses on the cognitive balance that is created when inconsistencies result
in tension, which motivates our brains/body to respond. The theory suggests people see imbalances and
correct them through the motivation to make things consistent.
1. People expect consistency.
2. Inconsistencies create a state of dissonance
3. Dissonance drives us to restore consistency.

Need for achievement (nAch) refers to the individual’s desire for significant accomplishment and
mastering skills to a high standard. First used by Henry Murray, it is associated with a range of actions.
Need for achievement motivates an individual to succeed in competition. People high in nAch are
characterised by a tendency to seek challenges and a high degree of independence. nAch is a personality
trait measured in the Thematic Apperception Test (TAT).
Sources of high nAch include:

1. Parents who encouraged independence in childhood

2. Praise and rewards for success

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 3. Association of achievement with positive feelings
4. Association of achievement with one's own competence and effort, not luck
5. A desire to be effective or challenged
6. Intrapersonal strength
7. Desirability
8. Feasibility
9. Goal Setting abilities

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8. Emotions

Ekman identified 6 primary human emotions – surprise, fear, sadness, anger, happiness and disgust.
These are universal, innate and ready-wired responses, also seen in primates to some extent.

An emotion has 3 components – 1. Subjective ‘cortical’ experience 2. Physiological ‘visceral’ changes 3.

Associated behavioural (‘skeletal’) changes.

James-Lange theory of emotions:

 Perception of a stimulus leads to bodily (skeletal and visceral) changes. The peripheral responses
send feedback to the cortex via thalamus leading to the perception of the emotion.
 A modification is a facial feedback hypothesis, according to which different facial movements
elicit different emotional perceptions.
 But wide repertoires of bodily changes are not available to explain the widely variant emotions
perceived. Also, emotional perception occurs faster than that could be explained by a feedback
theory.
 Studies on peripheral features of emotions have shown that anger is associated with the maximum
rise in temperature, while fear and disgust are associated with a drop in temperature. The increase
in heart rate produced by sadness is usually greater than that produced by happiness.

Cannon-Bard theory: On the perception of a stimulus, thalamus coordinates signals to cortex leading to a
conscious experience and simultaneously sends signals to hypothalamus leading to physiological changes.
The thalamus is considered to be cardinal in the emotional appraisal.

Schachter-Singer labelling theory: On the perception of a stimulus, both physiological changes and a
conscious experience of general arousal take place simultaneously. This generic arousal is then interpreted
to either positive or negative and labelled appropriately according to the situational cues. This is also
called jukebox theory or two-factor theory. If an appropriate label is not found, by default, negative
appreciation of arousal occurs (e.g. ‘dysphoria’ when experiencing boredom).

Lazarus cognitive appraisal theory states that appraisal precedes affective reaction – hence affective
primacy cannot be supported. Cognitive appraisal refers to the immediate, intuitive, personal evaluations
of a situation that gives an idea of how the individual subjectively experiences their environment.
Roseman and Scherer propose eight cognitive appraisal dimensions to distinguish emotional
understanding, rather than the traditional two (pleasantness and arousal). A third group of theorists
suggest that each emotion is categorised by a unique pattern of cognitive appraisals.

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 9. Stress: physiological and psychological aspects

Stress is an organism’s response to a challenge in the environment or stimulus. The response, deemed
fight-or-flight, is via the activation of the sympathetic nervous system. Though the sympathetic nervous
system activation is short-lived (as the parasympathetic system calms down the physiological response),
prolonged stress can have systemic effects (e.g. cardiac dysfunction).

The neuroendocrine system plays an important role in regulating response to stress. (see the chapter on
Neuroscience for further details.)

In psychological terms, stress is the feeling of pressure – positive stress or ‘eustress’ is a small amount of
stress that improves motivation and ability but large amounts of negative stress (‘distress’) can be
detrimental to mental health. As well as the external environment, stress can also be caused by internal
cognitions, which can be addressed in CBT for anxiety.

Stress can be classified into four categories:

 Crises/catastrophes  Completely out of the control of the individual e.g. natural disasters, war – can
lead to post-traumatic stress disorder
 Major life events  Going to university, marriage, birth of a child, the death of a loved one (NB not
all life events produce detrimental stress; the context of occurrence is important).
 Daily hassles or  Meeting deadlines, making decisions, irritating colleagues.
microstressors
 Ambient stressors  Low-grade environmental e.g. pollution, traffic, noise

Stressors can result in various levels of conflicts.

 Approach-approach conflict: choosing between two equally attractive options e.g. which restaurant to
have dinner
 Avoidance-avoidance: choose between two unattractive options
 Approach-avoidance conflict – attractive and unattractive traits e.g. going to university but incurring
significant debt

Stress Vulnerability model (Zubin and Spring, 1977) proposes individuals have strengths and
vulnerabilities for dealing with stress. On the diagram shown here, person a has low vulnerability and
thus can deal with a high deal of stress without much negative consequences, whereas person c has high
vulnerability and therefore even moderately low stress can cause them to become mentally unwell. This
model applies to a wide variety of psychiatric disorders including psychosis. Causes of increasing
vulnerability include genetic factors, childhood loss and trauma. This is a simplistic model and more

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sophisticated models exist. Medications, psychological interventions and training to improve coping skills
can build resilience and reduce vulnerability.

The Stress Vulnerability Model

SEROTOIN TRANSPORTER &
LIFE EVENTS

In an interesting study of environment-

gene interaction, Caspi et al (2003)
noted that individuals with one or two
copies of the short allele of the 5-HT T
promoter polymorphism exhibited more
depressive symptoms, diagnosable
depression, and suicidality in relation to
stressful life events than individuals
homozygous for the long allele.
.

Coping process: Lazarus (1999) developed the most popular model of coping – the cognitive-mediation
model which explains why different individuals respond differently to the same types of stressors, and
why the same individual may respond differently to a similar stressor at different times. This model
proposes three stages in the coping process.

Three stages:

Primary appraisal Evaluation of stressor

Secondary appraisal Evaluation of resources and options to manage the stressful situation
Coping stage Choose and use strategy to cope with stressor

Coping strategies may be divided into either problem-focused coping, where an individual attempts to
change the stressful situation or the relationship between oneself and the stressful context, or emotion-
focused coping, in which the individual alters his or her appraisal or emotional reaction to the stressful
situation.

Locus of control refers to the extent to which individuals believe that they control events affecting them. It
is one of the four core dimensions affecting self-evaluation, the others being neuroticism, self-efficacy and
self-esteem. Locus of control concept is aligned with the framework of the social-learning theory of
personality (Rotter 1954).

According to the locus of control, outcomes of an individual’s actions can be attributable to the 4
features shown in the box.

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 ABILITY EFFORT
(Internal & stable) (Internal unstable)
Learned resourcefulness is a concept that is related to TASK DIFFICULTY LUCK
(External stable) (External unstable)
Seligman’s concept of learned helplessness. It refers to
the conscious appreciation of the acquired repertoire of behaviour and skills that aids a person to self-
regulate internal events (emotions, cognitions), which would otherwise interfere with ability to execute
target behaviour.

Psychological resilience: individual’s ability to appropriately adapt to stress and adversity. Factors
developing and sustaining resilience: communication and problem-solving skills, ability to manage strong
feelings/impulses, ability to make and execute plans, confidence in own ability. Both learned
resourcefulness and helplessness can explain how stressors are appraised in their context.

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10. States and levels of awareness
Consciousness is defined loosely as human awareness of stimuli. There are many theories of
consciousness, e.g. Sigmund Freud’s Topographical model of the mind. The topographical model was
elaborated in The Interpretation of Dreams in 1900. Here, the mind is divided into three systems: the
conscious system, the preconscious system, and the unconscious system.

The conscious system

 Receives and process information from the outside world.

 Its contents are communicated via speech and behaviour.
 Attention cathexis refers to the investment of psychic energy on a particular idea or feeling to process
it consciously. Cathexis is ‘stable’ in the conscious mind.
 Operates secondary process thinking mainly.

The unconscious system:

 Contains the contents of censored or repressed wishes.

 Characterized by primary-process thinking, and is governed by the pleasure principle.
 Shift of cathexis happens very often and quickly
 Evident via parapraxes (Freudian slips) and dreams.

The preconscious system:

 As and when needed service

 Interfaces with both unconscious and conscious - contents of unconscious become conscious by
‘squeezing’ through the preconscious
 Maintains the ‘repressive barrier’ to censor unacceptable wishes and desires (not the repressed
contents).

Problems with a topographic theory: When someone employs defense mechanisms such as displacement,
repression etc., he or she is not aware of the process of this defense. Hence, these cannot be represented
by preconscious as Freud originally proposed – as preconscious is available to the conscious ‘as and when’
needed. Further, an ‘unconscious need for punishment’ was frequently noted among Freud’s patients –
topographical theory fails to explain this.

The role of the unconscious mind in decision-making is still greatly debated. Unconscious cognition is
processing of memory, thought, learning and perception without awareness. Freud believed the
unconscious stored memories and desires that influenced an individual's thought process. Freud believed
the unconscious could be accessed through dream analysis and random association. Carl Jung categorised
the unconscious into personal unconscious (holding individual memories/experiences) and collective
unconscious (holding memories/experiences of a species passed down through generations).

Arousal: physiological and psychological state of being awake/reactive to stimuli. Activation of the
reticular activating system in the brain stem, along with the autonomic nervous system leads to an ‘alert

© SPMM Course 34
state’ – raised blood pressure and heart rate, alertness and readiness to respond. Arousal regulates
consciousness and attention, important for fight-or-flight response and sexual activity. Arousal is also
crucial for the appraisal of emotion (see notes for emotion theory) and motivation (see notes for
motivation).

Alertness is a state of heightened awareness of environmental stimuli resulting in ability to act promptly
to danger.

Biorhythms: Chronobiology refers to the study of biological rhythms. Various biological processes of the
human body repeat themselves in a cyclical fashion indicating the presence of a biorhythm. Processes
repeating approximately every 24 h are considered to have a daily rhythm (circadian e.g. sleep-wake
cycle); those with cycles lasting less than a day are called ultradian (e.g. daily arousal levels, phased brain
activity patterns during sleep) while those lasting more than a day are called infradian (e.g. menstrual
cycles last 28-30 days). Infradian rhythms may also occur as a result of seasonal changes in animals e.g.
migration cycles in birds and hibernation in some mammals - these are called circannual rhythms.
Biorhythms are driven mostly by endogenous factors but are entrained by external time cues (called
‘zeitgebers’ or time givers). For example, light is an important zeitgeber without which the sleep-wake
circadian cycle may indeed be a 25h cycle instead of the entrained 24h cycle that we have. Social
zeitgebers are external social cues that function to entrain biological rhythms, e.g. the need to go to work
by 8AM, etc. Life events that disrupt social zeitgebers can increase one’s vulnerability to depression/manic
episodes. The suprachiasmatic nucleus is an internal pacemaker located in the anterior hypothalamus
that regulates many biorhythms. More details on this neuroendocrine system are given in the Neuroscience
section along with details regarding sleep structure and parasomnias.

Sleep deprivation: Most cognitive processes cope surprisingly well despite sleep deprivation. In early
stages, sleep deprived individuals show reduced arousal and perform poorly on monotonous tasks, but
optimally on interesting tasks, indicating that the motivation to perform is more affected than one’s
performance capacity. With further deprivation, 2-3 second periods of micro-sleep (wherein the individual
is unresponsive) are noted. The individual also complains of ‘hat phenomenon’ a feeling that “something
is gripping one’s forehead and temples”. Further deprivation results in delusional ideations, paranoia, loss
of sense of identity and difficulty in social interaction including disorganized speech; this syndrome is
termed sleep-deprivation psychosis.

Upon deprivation, sleep debt accumulates over time, some of which is ‘paid back’ when an individual
resumes sleep after the period of deprivation. REM sleep deprivation has profound effects on
concentration and other psychological functions. REM phases of sleep recover better than NREM sleep, a
phenomenon known as REM rebound.

Hypnosis: the state of consciousness involving focused attention and reduced peripheral awareness.
There are two theories about what occurs – altered state: hypnosis is an altered state of mind with a level
of awareness different from normal; non-state: hypnosis is a form of imaginative role-enactment.

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Normally preceded by ‘hypnotic induction’, non-state theory suggests the client becomes more focused,
heightens expectation.

The term suggestion (instruction or suggestion of subject into the hypnotic state) was not used in the
initial description of hypnotism, but suggestion now forms part of the language associated with hypnosis.
Some state that ‘suggestion’ is communication directed at the conscious mind whereas others believe it is
communication with the unconscious. Braid defined hypnotism as focused (conscious) attention upon a
dominant idea (or suggestion). Other hypnotists (e.g. Erickson) who believed that responses are mediated
through an ‘unconscious mind’, employed indirect suggestions such as metaphors.

Meditation is defined the practice of training one’s mind or inducing a mode of consciousness for the
benefit or as an end itself. It often involves self-regulation and clearing the mind. It can help reduce blood
pressure, help with anxiety and depression. Mindfulness-based therapy is about increasing awareness of
emotions/cognitions in order to address them.

Trance is a state of consciousness other than normal waking consciousness. It can be associated with
hypnosis meditation, prayer and illicit substances. It denotes any state of awareness or consciousness
other than normal waking consciousness.

© SPMM Course 36
11. Intelligence

The two-factor theory of intelligence was postulated by Spearman. Spearman carried out a factor analysis
of the result of children’s performance on a number of tests and concluded that all tests measured both a
common factor of general intelligence (g) and a specific factor (s). He believed that individual differences
were due to differences in g.

Triarchic theory of intelligence: Sternberg's Triarchic Theory of (Successful) Intelligence contends that
intelligent behaviour arises from a balance between analytical, creative and practical abilities, and that
these abilities function collectively to allow individuals to achieve success in particular sociocultural
contexts (Sternberg, 1999). Analytical abilities enable the individual to evaluate, analyze, compare and
contrast information. Creative abilities generate invention, discovery, and other creative endeavours.
Practical abilities tie everything together by allowing individuals to apply what they have learned in the
appropriate setting.

To be successful in life, the individual must make the best use of his or her analytical, creative and
practical strengths while at the same time compensating for weaknesses in any of these areas.

Three sets of components are essential for this process:

1. Knowledge-acquisition components: used in obtaining new information.

2. Meta-components: executive processes used in problem-solving and decision-making.
3. Performance components: processes that actually carry out the actions that the meta-components
dictate.
Flynn effect: An interesting feature of IQ measurements is the observation that IQ scores increased from
one generation to the next for all of the countries in which generational cohorts have been studied to date
(Flynn, 1994). This is called Flynn phenomenon. In general, countries have seen generational increases
between 5 and 25 points. The largest gains appear to occur on tests that measure fluid intelligence
(problem solving: These tests on average have shown an increase of about 15 points or one standard
deviation per generation e.g. Raven’s progressive matrices) rather than crystallized intelligence (verbal
and math skills: These tests on average have shown an increase of about 9 points per generation e.g.
Weschler’s tests).

Salient features of Flynn effect:

1. Non-verbal IQ has risen more rapidly than has verbal IQ.

2. Performance gains are smallest on the most culturally specific tests, and largest on the most abstract
tests.
3. Performance gains, as they occur over time, are roughly constant for all age groups.
4. Problem-solving abilities have seen the biggest performance gains.

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What causes Flynn phenomenon?

 Artifacts (i.e. IQ tests do not actually measure the construct of intelligence but measure something
that has a link to intelligence that can change with generations)

 Test sophistication (e.g. improvement in test taking strategies across time)

 Actual intelligence increases (e.g., due to improved nutrition, improvement in early childhood
education).

 Regression towards the mean (repeated resampling tends to reveal the true mean value)

Paradoxes of the Flynn Effect: There are several observations that highlight the baffling nature of the Flynn
Effect.

 The factor paradox: Prior factor analysis research suggests that a single factor, ‘general
intelligence’ or ‘g,’ underlies IQ. The Flynn Effect does not affect all sections of the intelligence
tests to the same degree. Hence if we’re getting smarter every generation, some parts not all of our
intelligence is getting smarter, and this is difficult to explain.

 The interaction paradox: As Flynn Effect suggests, a difference of some 18 points in the average IQ
over two generations exist. In that case, it ought to be highly visible when the elderly interact with
the young! This is not the case though.

 The mental retardation paradox: If Flynn effect was true then in 1900, average IQ was 75, just
above mental retardation range; this assumption predicts a very high frequency of persons with
mental retardation. But no such phenomenon has been noted.

 The identical twins paradox: Twins raised apart tend to have very similar IQ scores, but the Flynn
Effect suggests that intelligence as measured by IQ is more subjected to environmental effects than
genes.

Commonly used tests for measuring IQ

 Stanford-Binet Scale is the first formal IQ test introduced before 1st World War in 1905 (used for
ages 2 to 18).
 Wechsler Adult Intelligence Scale (WAIS-Revised version) is for individuals aged older than 16.
 Wechsler Intelligence Scale for Children (WISC-Revised) is for those aged 6 to 16.
 Wechsler Preschool and Primary Scale of Intelligence (WPPSI) is for children aged 4 to 6.

© SPMM Course 38
 DISCLAIMER: This material is developed from various revision notes assembled while preparing
for MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books.
These sources are cited and acknowledged wherever possible; due to the structure of this
material, acknowledgments have not been possible for every passage/fact that is common
knowledge in psychiatry. We do not check the accuracy of drug-related information using
external sources; no part of these notes should be used as prescribing information

Notes prepared using excerpts from:

 Carskadon MA, Dement WC. Normal human sleep: An overview. Philadelphia: Elsevier Saunders;
2005. pp. 13–23.
 Eysenck MW (2004). Psychology: An International Perspective. Taylor & Francis.
 Fox, J. (1996) Projective testing. In Jacobson & Jacobson (ed.) Psychiatric secrets, Hanley & Belfus.
Page 22.
 Gross, R (2012). Psychology: The Science of Mind and Behaviour 6th Edition. Hatchette UK.
 Hiscock, M (2007) 'The Flynn effect and its relevance to neuropsychology', Journal of Clinical and
Experimental Neuropsychology, 29:5, 514 – 529
 Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition.
Lippincott Williams & Wilkins 2007
 Mates, M (1992). "Altered Levels of Consciousness in Schizophrenia". Journal of Orthomolecular
Medicine 7 (4): 216–220.
 Mischel, W. (1999). Introduction to Personality. 6th edn. Orlando: Harcourt Brace Jovanovich. An
interesting introduction to personality research.
 Salvatore etal.Biological rhythms and mood disorders. Dialogues Clin Neurosci. Dec 2012; 14(4):
369–379.
 Williams, R. B. (2001). Hostility: Effects on health and the potential for successful behavioral
approaches to prevention and treatment. In A. Baum, T. A. Revenson & J. E. Singer (Eds.) Handbook
of Health Psychology. Mahwah, NJ: Erlbaum.
 McKay, GC & Kopelman MD. Advances in Psychiatric Treatment Mar 2009, 15 (2) 152-158;
http://apt.rcpsych.org/content/15/2/152

© SPMM Course 39
 Social Psychology
Paper A Syllabic content 1.2
© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
1. Attitudes
Attitudes are “learned predispositions to respond in a consistently favourable or unfavourable
way towards a given object, person or event” (Fishbein & Ajzen,1975).

An attitude is a combination of beliefs and values.

 Beliefs are based on our knowledge of the world and link an object to an attribute. They
are non-evaluative and objective e.g. ‘USA is a nation built on capitalism’.
 Values relate to the importance or desirability of the object. It is largely subjective and has
preferential patterns attached e.g. ‘I do not like capitalism’. Values can turn beliefs to
attitudes – ‘I dislike American people’.

Three-component model of attitudes:

1. Affective component: what the person feels about the object (favourable/ unfavourable
evaluations) – e.g. I love chocolate
2. Cognitive component: thoughts, beliefs, knowledge about the object – e.g. Chocolate
keeps me active
3. Behavioural component: actual or intended responses to the object e.g. I eat chocolate
every day

Functions of attitudes: (Katz)

 Knowledge function: attitudes are frames of reference that simplify the world, help make
quick appraisals of situations
 Value expressive function: reflect fundamental self-concepts – self-expressive and
maintains personal integrity e.g. vegetarianism
 Social adjustment function: help to function in a group setting, social acceptance
 Ego-defensive function protects from character or personal deficiencies – this function
makes attitudes very resistant to change

Why do attitudes change?

1. Cognitive dissonance theory: (Festinger)

People strive for consistency between thoughts, feelings and actions. If there is a discrepancy
between different attitudes (cognitive dissonance) or between attitudes and behaviours
(attitude-behaviour discrepancy), then this initiates and drives either a change in attitudes (more
common) or a change in behaviours.

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For example, in smokers, discrepancy between cognitions (‘smoking is injurious’) and behaviour
(repeated smoking) may influence behaviour leading to a cut down, or alternatively, may alter
the cognitions (‘there is too little evidence available to link smoking to poor health’).

1-Dollar 20-Dollar experiment: All subjects in an experiment were asked to do a very boring
repetitive task for 30 minutes. The first group was a control group; the second group (called 1-
dollar group) was paid $1 to say that the task was fun and interesting, the third group (called 20-
dollar group) was paid $20 to say that the task was fun and interesting. All participants were
asked to rate how enjoyable they had found the task. Contrary to popular belief, the group,
which was paid more, did not appreciate the boring task. As they obtained a good incentive, they
did not develop a dissonance. They lied about its usefulness but in fact they did not change their
belief about the boring nature of this task. In contrast, the lowly paid group did experience a
cognitive dissonance between the two facts - ‘This task is boring’ and ‘I am doing this task
without much incentive’, hence they changed their initial attitude towards the task and, in fact,
started liking the task. This highlights the processes relating to counter-attitudinal behaviours.

How to reduce dissonance? Apart from modifying attitudes or behaviours, one can have
selective exposure to information to avoid or prevent dissonance; to reduce a dissonance one can
make a commitment after which primary attitudes get stronger e.g. after betting on a horse, the
belief that the horse will win strengthens!

Other methods are

1. Removal or denial of the dissonant cognition

2. Trivialising the dissonant cognition
3.Adding a new consonant cognition to counterbalance the dissonance

Self-perception theory: According to Bem, self-report of attitude after a behaviour is usually an

inference of one’s own behaviour and context. Dissonance cannot explain this adequately. In the
1 dollar/20 dollar experiment, the 20 dollar group made situational attribution (‘I did it for money,
it was boring) while 1 dollar group made dispositional attribution (‘There is not much incentive,
but I really liked it’). Hence, while cognitive dissonance explains both counter-attitudinal
behaviour and attitude-attitude discrepancy; self-perception applies better when attitude
congruent behaviour occurs, but it cannot explain attitude-attitude discrepancy.

Measuring Attitudes
Attitudes are largely subjective and so cannot be measured directly. Attitude measures usually
rely on self-report, assume that the same statement has the same meaning for all respondents and

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assume that subjective attitudes can be quantified meaningfully. An alternative method of
measurement is to observe behaviours, but behaviours do not always reflect attitude.

 Thurstone scale: While constructing a Thurstone scale, hundreds of statements are

initially produced pertaining to a particular topic. These statements are presented to a
sample (similar to a panel of judges) who is asked to score the statements on an 11 point
scale. A set number of statements e.g. 10 each on both extremes (positive and negative
attitude) are chosen based on the consistency of scores given by the judges. Each of these
statements will carry a value, which is the average of 100 judgments on the 11 points scale.
These 20 statements are clubbed together in producing an attitude scale, which is
administered to the subject. The subject will then indicate what statements he agrees to. It
is not often used because the method is too tedious. The 11 points (used to rate each
statement) are assumed to be intervals and averages are used to obtain the value scores.
This is not entirely accurate as the 11 points scale is, in fact, ordinal.
 Likert scale includes graded ‘agree’ to ‘disagree’ measures. This is one of the most popular
and statistically more reliable measures. It is easy to construct, and no assumptions are
made about the equality of intervals.
 Sociometry is used to measure interpersonal attitudes in a repertory grid-like fashion i.e.
who like whom tables. These are called sociograms.
 Guttman introduced scalograms that include cumulative statements where accepting a
statement usually means accepting all that comes below a statement, in a step-wise
fashion.
 Osgood’s semantic differential scale is used to measure verbally expressed attitudes. It
allows different attitudes about a particular topic to be measured on the same scale. It
includes various factors constituting an attitude; e.g. while expressing one’s attitudes
regarding a politician, one can rate him using an evaluative component (good ---- bad),
activity component (active ----- inactive) and potency component (powerful ---- weak) etc.
With these bipolar adjectives being the two extremes, a 7 points scale is designed, and the
subject is asked to indicate a score for each factor. Osgood’s semantic differential assumes
that every concept can be represented in a hypothetical semantic space with two extremes.

Attitude behaviour correlation

Attitudes and behaviours are not correlated in simple linear fashion. Attitudes are only
predispositions; actual behaviours depend on:

1. Perceived consequences.
2. Social desirability.

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 3. Habitual behaviours.
4. Situational factors

If attitudes are measured with specified assessment of target, action, context and time element,
however, then measured attitudes will be closer to actual behaviour e.g. if one wants to measure
public attitude on the issue of abortion, simply eliciting attitudes on abortion may not be
appropriate. Instead if we measure attitudes on legal abortion in a married woman after 3 months
of marriage, it may provide a more accurate measure of the actual behavior of the respondents
when the issue arises in their personal or family life. Single instances of behaviours are unreliable
indicators of attitudes. Various attitudes aggregate to result in behaviour; also the strength of an
attitude is proportional to its influence on behaviour.

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2. Self psychology
In self-psychology, various concepts are often used to describe the nature of self.

 Self-consciousness: Awareness of distinct self, compared to other objects in the

environment. Only humans are thought to possess full self-consciousness.
 Self-image: This refers to an answer one might give for the question ‘who are you?’ It
includes one’s description of social roles (social self), personality traits and physical
characters (bodily self).
 Self-esteem: This refers to a personal judgment of worthiness expressed in the attitudes
one holds towards oneself. Self-image is descriptive, but self-esteem is evaluative.
 Ideal self: This represents ‘what we would like ourselves to be’. One’s self-esteem
depends on the discrepancy between one’s ideal self and self-image.

We develop self-concept depending upon:

1. Reaction of others (Theory of looking glass self by Cooley suggests that like a mirror,
others around us reflect our self-image)
2. Comparison with others
3. Social roles we play
4. Identification with role models
Self-recognition could be demonstrated in a growing infant by using a mirror. Gallup conducted
the famous ‘touching the dot’ experiments to demonstrate self-recognition. It is noted that only
higher primates and humans older than 20 months successfully demonstrate ‘touching the dot’.
When a red dot is unknowingly placed on the face of a child, the child starts touching its face to
explore the dot when a mirror is shown. This ‘touching the dot’ phenomenon does not occur less
than 15 months of age. 5 to 25% infants touch the dot by 18 months while nearly 75% touch the
dot by age 20 months. It is thus concluded that self-recognition rapidly develops between 18 to 20
months. Object permanence is necessary for self-recognition. Mirror recognition by primates
may be a reflection of behavioural recognition i.e. ‘the one in the mirror is same as me’ rather
than self-recognition i.e. ‘the one in the mirror is me’.

Autobiographical memory in humans develops around age 3 ½ to 4 ½ yrs.

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3. Interpersonal issues
Attribution
This is the process by which we make judgments about causes of behaviour. Heider (1958) was
the first to propose a psychological theory of attribution - he called this “naïve” or
“commonsense” psychology. In his view, people act like amateur scientists, trying to understand
other people’s behaviours by piecing together information until they arrive at a reasonable
explanation or cause. During this process, we make a distinction between intentional vs.
unintentional behaviours in others and make internal vs. external attribution of the cause of the
observed behaviour.

We tend to attribute behaviours to events that co-vary with those behaviours over time. e.g. if A
is an event that occurs when the behaviour B is observed, then we often assume A causes B
(Kelly’s co-variation model). When making such covariant related observations, three elements
are important to ensure validity of the inference.

Consider a student X, who arrives late for a physiology lecture. Another student wants to infer
the cause behind this. To make an appropriate attribution, he/she needs to consider

1. Consensus: Does everyone come late or is it only student X?

2. Distinctiveness: Does student X come late to other classes too?

3. Consistency: Does student X come late to physiology lecture every time?

Consistency is most used in attribution; consensus is least used.

Generally speaking if consensus is low, dispositional attribution is made (student X has a

problem). If consistency is low, situational attribution is made (something must have happened
to him today, perhaps, he missed his train). If distinctiveness is high, stimulus or target is
considered to be at fault (the physiology class is so boring that X always comes late).

Weiner developed a systematic attributional theory. Accordingly there are 3 dimensions

identified in the process of attributions

1. Locus: external/internal

2. Stability: transient/permanent

3. Controllability: controllable/uncontrollable

External stable and uncontrollable cause attributed to a negative event generates a sense of
failure with anger.

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Some consistent errors (attribution bias) are noted in making attributions.

Fundamental attribution error or correspondence bias: This refers to overestimating dispositional

factors and not situational factors while attributing causes for other’s behaviours. This allows a sense of
predictability to be developed about the other person. It is more pronounced if the attributed behaviour is
negative and undesirable.

Actor-observer effect: When one is involved as an agent in a specific behaviour then he/she attributes
external causality to the behaviour. For the same behaviour, others who are merely observers without
direct participation may invoke internal causality (intentional and dispositional).

Self-serving bias (SSB): the actor observer effect is most pronounced when judging negative behaviours
This may be absent or reversed for positive behaviours. Hence such self-serving bias offers self-
enhancement and defense. In depression, an exception to SSB is seen - The patient takes excessive self-
blame for personal failures.

Just world hypothesis refers to the idea that ‘I am a just person living in a just world; everyone here gets
what they really deserve’. ‘Bad things happen to bad people’, leading to blaming-the-victim culture.

False consensus effect and illusion of in group homogeneity: This refers to the tendency to view other
person’s behaviour to be representative of a group’s behaviour (culture or racial stereotypes are thus
formed).

 First impression effect: (primacy effect). Generally first impressions on people count more
unless specific instruction is given to attend or repeatedly observe. A positive first
impression is more likely to change than a negative first impression. Primacy is more
important in strangers; recency effect plays more in evaluating friends and others who will
come into repeated contacts.
 Halo effect is the tendency to perceive other persons as wholly good or bad based on few
observed traits (e.g. physical attractiveness); i.e.making inferences about people using
limited, superficial information. Thus a person's positive or negative traits "spill over"
from one area to influence the total perception of their personality. Investigators
evaluating crime suspects are susceptible to halo effect (to be accurate – reversed halo
effect or devil effect or association fallacy). For example, a policeman may conclude
someone is guilty by association with attributes he has previously seen in other criminals.
Mere similarity of a person to a suspect often causes the police to associate the innocent
wrongly with a guilty act.
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  The term Barnum effect or Forer effect refers to the widespread predisposition to believe
that general and vague personality descriptions or predictions (often given by astrologers,
horoscopes, and palmistry) have specific relevance to certain individuals. This effect has
frequently contaminated research on personality assessment.
 Hawthorne effect refers to a short-term improvement caused by observing worker
performance.
 Pygmalion effect or Rosenthal effect is a form of self-fulfilling prophecy wherein students
with poor expectations from their teachers internalize their negative label and perform
poorly, and those with positive expectations internalise their positive labels and succeed
academically.

Theory of Mind
Theory of Mind (ToM) develops around age 3 ½ to 4 years. ToM refers to the understanding that
other persons do have mental processes similar to self; in this context it forms an essential part of
the social attribution process. Lack of development of the theory of mind (trait related) could
explain the apparent lack of empathy seen in autism. In acute psychosis, state related deficits in
ToM are noted i.e. the deficit is not pervasive but seen only when relapsing into positive
symptoms. Poor ToM in association with reduced empathic ability is also demonstrated in
conduct disorder and in antisocial personality disorder.

First-order false belief tasks

These tasks relate to the understanding that other people can have their own thoughts about a
given situation. First-order tests involve inferring one person’s mental state e.g. What Jim thinks.

Wimmer and Perner (1983) noted that three-year-olds tend to fail whereas four-year-olds tend to
succeed a false-belief task called Sally-Anne Test. Children are first shown the picture of Sally,
leaving a chocolate on the counter before departing the scene. Anne later comes in and moves the
object from the counter to a box. The children are then asked to predict where Sally will look for
the chocolate when she returns to the room. Children aged 4 and above generally grasp the
notion that Sally will hold a false belief and look at the place where she left the chocolate initially.
3-year-olds fail to ascribe this false belief to Sally.

In the deceptive container task, a child is shown a closed candy container and is asked, “What’s
in here?” When the child answers ‘candy’, the container is opened, revealing a pencil. Later when
the child is asked what she originally thought was in the container when she was first asked,
Three-year-olds incorrectly answer “a pencil,” demonstrating a lack of false belief whereas 4-
year-olds correctly say “candy.”

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Flavell et al. (1986) noted that children older than 4 years old distinguish appearance from reality
and show an ability to discuss objects that have misleading appearances (‘it looks like an apple
but it is really a ball’).

Note that when task demands are reduced, even 15-month old show some signs of ToM.
Furthermore, many children with autism and Asperger’s syndrome, can pass first order tests
albeit at a developmentally later age (average 5.5 years according to Happe et al., 1995)

Second-order false belief tasks

These tasks relate to the understanding that other people (a second person) can have their own
thoughts about another (third) person’s state of mind. Second-order tests involve inferring one
person’s thoughts about another person’s mental state e.g. What Jim thinks that Varun thinks.
These tests are usually passed by the age of 6 years in typically developing children. Children
with autistic spectrum disorders may never pass second-order false belief tasks or pass only by
teenagers.

Key neural regions for normal ToM are considered to be the amygdala, orbitofrontal cortex,
inferior parietal and medial frontal cortex.

Interpersonal relationships
Following factors influence relationships:
1. Proximity: minimal requirement for most relationships.
2. Exposure refers to reciprocal disclosure – this may enhance the relationship. Females
do more self-disclosure than males.
3. Similarity – may increase self-esteem in a relationship as one gets validation for similar
interests.
4. Complementarity – not so important initially but increases in importance as a long-
term relationship develops.
5. Compatibility is proportional to both similarity and complementarity.
Types of love:
 Companionate love: True or conjugal love where intimacy and commitment seen; passion
is not high.
 Passionate love: intimate and passionate but not much commitment – obsessive, romantic
and infatuated.
 Consummate love: intimacy, passion and commitment all well mixed.

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  Fatuous love: passion and commitment but no intimacy seen.
According to SVR theory, – relationships proceed from Stimulus (external attributes) to Values
to Role stage.

Linguistics of interpersonal communication

Some linguists view language as a “system of signs that have been developed to serve the
communicative needs of people living in a social context”. Thus language is a product of
sociocultural evolution. In this context, language serves 3 functions:

1. Ideational Function: enable people thinking with language to interpret experience.

2. Interpersonal Function: enable people acting with language to communicate experience
and thoughts
3. Textual Function: enable people organise of a message with language.

Fields of enquiry in linguistics

• Phonology: The study of sound structure
• Morphology: The study of sound structure
• Syntax: The study of sentence structure
• Phonetics: The study of physical act of speaking
• Semantics: The study of the connection of language to meanings. Semanticists consider
that meanings are inherent in sentences; while communication-intentionists consider that
meaning is not inherent but comes from something that people do when using language
• Pragmatics: The study of the connection of context to meanings.
• Sociolinguistics: The study of the connection of language to social situations
• Semiotics: The study of signs and symbols in relation to their form and content

Whorfian hypothesis or Sapir-Whorf linguistic relativity hypothesis states that the semantics of
a language can affect the way in which its speakers perceive and conceptualize the world.
Language determines the basic categories of thought and that, as a consequence, speakers of
different languages think differently. This extreme position is also called linguistic determinism.
Noam Chomsky argues against this stance (see Language Development section in the notes on
Human Development).

Persuasive communication
Techniques of persuasive communication (e.g. used by sales representatives) include

1. Ingratiation: eliciting likeableness

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 2. Reciprocity: doing a favour first, making one indebted.
3. Arousal of guilt
4. Scarcity: ‘offers valid only till stocks last; so hurry!’
5. Social validation: ‘everyone is going to Argos? What about you?’
6. Multiple requests
1. Foot in the door technique: if one agrees to small request this increases the
likelihood of saying yes again.
2. Door in the face technique (concession effect): when a larger request is turned
down initially this increases the likelihood of agreeing to a smaller subsequent
request.
3. Low-ball tactic: hiding the costs and disadvantages initially but revealing after
an agreement is reached.
When attempting to persuade others, one-sided arguments may strengthen existing beliefs but
two-sided arguments more effective in changing beliefs/attitudes. Similarly, highly fear-inducing
messages may increase anxiety but may not result in behaviour change (Jansis & Feshback 1953);
while moderately fear-inducing messages can produce greater behaviour change in some
instances. Thus, an inverted U-shaped curve relates fear and attitude/behaviour change. Feeling
vulnerable also increases behaviour change. The credibility of a perceived message has been
found to be a key factor affecting persuasive communication (Hovland & Weiss, 1951); if we read
a report about health in a professional medical journal, we are more easily persuaded than if we
read it from a tabloid.

Propaganda refers to mass suggestion or influence via emotional manipulation of an individual.

While educating an individual about an issue gives independence for making a judgment,
propaganda over an issue provides ready-made judgments to be adopted by the individual. This
may be done using

1. Induction of stereotypes
2. Substitution of names to facilitate scapegoating and scaremongering
3. Selected facts presentation
4. Repeating same messages in various forms
5. Presenting assertions instead of rational arguments
6. Pinpointing an enemy

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4. Leadership, social influence, power and obedience
Conformity & obedience
Conformity is a process where no explicit requirement is made to do a certain task, but peer
influence, and the need for acceptance pushes one to carry out the task. Obedience refers to
conditions where the individual is explicitly asked to do a task, and this instruction comes from
an authority.

Conformity can be either true internalisation of values or compliance externally without

changing one’s private beliefs. Men conform less than women; people with lower intelligence,
poorer ego strength, poor leadership abilities and having inferiority feelings conform more often.

Sherif used an autokinetic effect (the apparent, false perception of movement of a pinpoint of
light in a dark room, aka Phi Phenomenon) to study conformity. Individuals initially provided
idiosyncratic responses (individual norms) when asked about the distance moved by the light
source. But when
subjects were CONFORMITY OBEDIENCE
grouped together, No explicit instruction given Instructed explicitly
individuals Peer influence is the source Authorities are the source of pressure
compromised on Mutually a subject can influence Mutuality absent as it is one
their assessments othersfor acceptance
Need directional
Need for compliance
and gave modified Done by ‘example’ Done by ‘directions.'
answers, so as to conform to the rest (group norms emerged).

Asch used an unambiguous paradigm (length assessment test) to study conformity. It was noted
that the size of group majority up to 3 to 5 people influenced conformity; a much larger majority
did not influence individual decisions. Further, the more unanimous/consistent the majority was,
the more the conformity of the rest. Giving opinions privately reduced conformity. Collectivist
cultures showed more conformity than nuclear cultures.

Can minorities effectively influence the majority? This is possible if the minority is consistent,
perceived to
be Factors increasing obedience Factors reducing obedience
autonomous Authority figure providing instructions Proximity to shocked victim
Administering by proxy Remoteness of authority
and having
Relieving the subject from responsibility Peer rebellion against instructions
real interest in for actions Increased sense of responsibility for
the issue at Achieving ‘agentic state.' plight of the victim
hand, appear Authoritarian personality of subjects
(they obey more!)
to have

© SPMM Course 13
balanced flexibility, and if the minority appeared to have some similarity to the rest of the group.

Milgram’s experiments on obedience: Subjects were recruited by an authoritative university

faculty and were asked to administer electric shock to victims kept in a different room by
pressing buttons. The sham victim would make crying sounds in pain on increasing the dose of
electricity.

Group processes
There are various processes that influence individuals when making decisions as a part of a
group. The group can make more risky decisions than what an individual him/herself can. This is
called risky shift.

A group discussion process can strengthen average individual inclinations and polarise the
group in the direction where most individuals were heading already. This is called group
polarisation.

While making extreme decisions, the desire to agree with other members of a group can override
rational judgment applicable in individual decision-making. This is called groupthink.

Group processes, especially polarization, are considered to be due to three underlying

phenomena:

 Normative influence: People have a need not to appear odd or ‘stick out’ like a sore
thumb. So they say yes to what others in the group say.
 Informational influence: Having more information after group discussion can facilitate
decision-making
 Social identity: A group norm is established soon after a group is formed. This creates a
social identity and pressure to conform to maintain the belongingness.

Robert Bales made observations around small group communication in early 1950s. In small
groups, discussion initially tended to shift back and forth quickly between a task and its
relevance to the group members. This helped to balance task completion and group cohesion.
Later a linear phase emerged – the discussion moved from a mere exchange of opinions to
evaluating values underlying a decision and then to making a decision. He also noted that no
matter how large the group, the most talkative member spoke for 40-50% of the time, and second
most talkative 23-30% of the time – dominating the conversation to the detriment of the others.

Social power
French and Raven identified 6 sources of social (or organizational) power. They used the term
Bases of Social Power to describe these factors.

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 1. Reward Power - based on the perceived ability to give positive consequences or remove
negative ones
2. Coercive Power - the perceived ability to punish those who not conform with your ideas
or demands
3. Legitimate Power - based on the perception that someone has the right to prescribe
behaviour due to election or appointment to a position of responsibility
4. Referent Power - through association with others who possess power
5. Expert Power - based on having distinctive knowledge, expertness, ability or skills
6. Information Power (Similar to 5) - based on controlling the information

Leadership
Lewin (1939) identified the following leadership styles.

 Autocratic – leader’s decision-making occurs without consultation from the others and
causes the most discontent. It works if no need for input on decision i.e. that motivation
would not be affected by not being consulted.
 Democratic – leader’s decision-making involves others though the decision may
ultimately made by the leader having facilitated group discussion and discussed opinions.
It is a well-regarded process but can be time-consuming.
 Laissez-Faire – leader’s involvement in decision-making is minimal, so others make their
own decision. It works well if those involved are capable and motivated, and no need for
central coordination.

Social Influence
Kelman described three psychological factors that underlie the process of influence of one person
on the other in social settings.

 Compliance – responding favourably to a request (implicit or explicit) from another. It is a

change of behavior rather than a change in attitude (i.e. one can hold private objections but
still comply). Satisfaction from compliance is due to the positive social effect (i.e. reward or
avoid punishment).
 Identification – change in attitude/behavior due to the influence of someone that is liked
e.g. celebrity endorsement. A resultant desired relationship the identifier relates is the
reward.
 Internalisation – process of acceptance of a set of norms established by a person/group
influential to the individual. The content of the influence is intrinsically rewarding.

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5. Intergroup behaviour
Prejudice
Prejudice is essentially an attitude. It has

1. Cognitive component – stereotypes

2. Affective component – hostility
3. Behavioural component – which according to Allport can be
a. anti-locution
b. avoidance
c. discrimination
d. physical attack or
e. extermination in terms of increasing severity.
Prejudice can be positive or neutral as well as negative though the term is mostly used to describe
negative prejudice.

Theories of prejudice

 Adorno’s authoritarian personality theory: Authoritarians are prejudiced in a generalised

manner; difficult upbringing and disciplinarian rules in childhood may lead to a projection
of difficulties on minorities. But this theory does not explain the sudden surges of
prejudice that occur in history. It has no experimental proof either.An allied theory says
that ideological dogmatism in rigid, authoritarian people can explain prejudice.
 Scapegoating theory: It is related to the frustration-aggression model of Dollard. In
situations of extreme frustration when the source of such frustration is too powerful, we
may tend to displace aggression towards a soft target – the scapegoat. The choice of
scapegoat depends on the prevailing social mood. Hence, the society provides the content
of one’s prejudice though one’s personality may predispose to such prejudice according to
Adorno.
 Relative deprivation theory: This supplements scapegoating theory. The discrepancy
between actual attainments and expectations of a society is called relative deprivation.
Any acute changes can cause a sudden substantial relative deprivation, leading to unrest
and scapegoating follows. Note that the relative deprivation is subjective to individuals in
a group, and the competition may be within individuals (egoistic) or between groups
(fraternalistic).
 Realistic conflict theory: This asserts that the mere suggestion of competition is enough to
trigger prejudices. Famous Robber’s Cove experiments by Sherif supported this theory.
The mere perception of another group’s existence can spark discrimination. At a summer
camp at Robber’s Cove, two groups were created from unrelated individuals. Even when
© SPMM Course 16
 these groups were allowed to interact freely, they developed strong in-group preferences
and anti out-group ideas. When a competition was introduced, the groups exhibited a
high degree of aggression and hatred against each other. Sherif concluded that mere
competition is sufficient to create conflicts, and no real lack of resources or acute
deprivation is necessary.
 Social identity theory: An individual’s positive self-image depends on both personal and
social identities. So each individual strives to improve his group’s success to foster his own
image. This leads to prejudice against other groups.

How to reduce prejudice?

 Blue eyes and brown eyes experiment (Elliott): Prejudice exhibited by a person could be
lesser when he/she himself experienced such prejudice in the past. In a class room, blue-
eyed children were initially treated badly by instructing brown eyed pupils that blue eye
stood for inferiority and weakness. When the roles were reversed later, and opposite
information was now provided, supporting the supremacy of blue-eyed children, the
amount of aggression shown was lesser. This suggested that when one experiences
prejudice first hand, his own discriminatory behaviour reduces later.
 Contact hypothesis (Allport): When contact occurs between opposite group members
under equal status and in pursuit of common goals, this can reduce prejudice. Personal
friendship is not needed though. Due to lack of knowledge about what happens in the
other group a degree of autistic hostility exists. This reinforces negative stereotypes as
mirror image phenomenon i.e. ‘we are right, so they are wrong’, etc. Also, one group starts
believing that the members of the opposite groups all are alike – illusion of out-group
homogeneity.

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6. Aggression
There are several types of aggression as outlined below.

 Hostile aggression: aimed solely at hurting someone.

 Instrumental aggression: used as a means to an end – may be self-defense or to attain
something. Instrumental aggression is carried out for the purpose of achieving a particular
goal e.g. kidnapping for ransom. Hence, it is often planned and not impulsive. Hostile
(also called angry or affective) aggression is motivated by the need to express negative
feelings, such as anger.
 Positive aggression: combating prejudice, self-defense.
 Pathological aggression: violence for the sake of being violent- may be associated with
pathological personality.
 Overt aggression: This is readily observable, either reactive & impulsive or proactive,
planned aggression.
 Covert aggression is much more subtle, e.g. telling lies, spreading rumours, excluding a
child from a group of friends, etc. It is seen more in girls than boys.

Hydraulic or build up models

 Psychoanalysis Theory: Human aggression is due the death instinct Thanatos - an

instinctive biological destructive death related urge that gradually builds up in everyone
and must at some point be released.
 Evolutionary Theory: Through the process of natural selection, aggression ensures
survival of the aggressor’s genes passing from one generation to the other. It helps in the
fight for the survival of the fittest.
 Lorenz studied animal aggression and proposed that features such as territorial
imperative are linked to the survival benefits of aggression. According to him aggression
is a fixed action pattern elicited by specific sign stimuli. But he found non-human
aggression to be mostly constructive. Ritualisation refers to a series of stereotyped fight
scenes, carried out by animals without actual physical harm to both the victor and the
vanquished. Appeasement rituals or gestures form a part of such ritualisations in which
certain behaviours (e.g., lying down, dropping and tucking one’s tail) can reduce
aggression expression.

Non-hydraulic models

These models refute the notion of ‘building up’ and ‘release’.

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  Genetic theory: It is controversial whether aggression is inherited; it is often the case in
animal species. But in humans however, people may not necessarily inherit the tendency
to be aggressive; instead they may inherit certain temperaments, such as impulsiveness,
that in turn make aggression more likely (Baron and Richardson, 1994).
 Social learning theory: Bandura’s ‘Bobo Doll’ experiments provide impressive
demonstrations of the power of observational learning. When children observe an
aggressive model, they often reproduce many of the model’s acts precisely, especially if
the model’s aggression was rewarded. Vicarious conditioning refers to a kind of
observational learning where learning is influenced by seeing or hearing about the
consequences of others’ behaviour. Observational learning can occur even when there are
no vicarious effects of reinforcement, but the performance of an aggressive behaviour is
more likely if vicarious reinforcement was observed instead of just seeing behaviour in
isolation without knowing its consequences.
 The frustration-aggression hypothesis was originally proposed by Dollard et al. (1939). It
holds that frustration always results in aggression and conversely aggression will not
occur unless a person is frustrated. But this is not true as sometimes frustration produces
depression or withdrawal instead of aggression. The modified frustration-aggression
hypothesis considers aggression to be one of the many possible products of frustration. In
a meta-analysis including 49 studies, Marcus-Newhall et al. (2000) found consistent
evidence that frustrated individuals show displacement of aggression from the source of
the frustration onto a less powerful or more accessible target.
 Berkowitz (1993) later modified Dollard’s proposal. This is called aggressive cue theory or
weapons effect: Frustration produces not aggression but a readiness to respond
aggressively; once this readiness exists, cues in the environment (e.g. knives, guns, etc.)
will often lead a frustrated person to behave aggressively; neither frustration nor cues
alone can trigger the aggressive behaviour.
 Generalised arousal theory maintains that arousal (e.g. physiological) from one source
may energise some other response. This is called transferred excitation (Zillman).
 Festinger’s deindividuation theory: According to this, people in-group context act
uncharacteristically more aggressive as a sense of identity and belongingness and
diffusion of responsibility occurs in groups. Similarly, uniforms can reduce individuality,
promoting expression of aggression (hence its use in Police and military forces). But
deindividuation does not always cause aggression.

Media influences on aggressive behaviour: TV can influence through modelling effects. In a

natural experiment at St Helena Island when TV was first introduced, some increase in prosocial
behaviour was recorded, surprisingly. Media influence is mediated via

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 1. High arousal
2. Disinhibition – ‘this is happening everywhere; it is not uncommon.'
3. Imitation: e.g. copycat crimes and suicides – Shannon Matthews incident in UK (2008) is
speculated to be akin to a channel 4 drama episode (Shameless).
4. Desensitisation: due to repeated showing
5. Priming- enhancing automatic associations of certain stimuli with a crime.

Family background and aggression: Aggressive children tend to commit violent and non-violent
offences in adulthood. Antisocial behavior is much more common in men. Harsh and inconsistent
discipline and an absence of positive parenting may be an aetiological factor in aggression.

Note that cultural differences exist in expression of aggression; it is said to be much more
common in individualist than in collectivist cultures (Oatley, 1993)

Stress and aggression among primates

 In most species, dominance ranks influence the extent of sustaining stressors. It is too
simplistic to say higher / lower ranking individuals have the highest stress or aggression
levels. The actual amount of stress and aggression depends very much on group’s social
structure and dynamics.
 Ability to avoid confronting dominant individuals will reduce stress levels. When this is
lost in captivity (artificial environments) the subordinates show high-stress hormones. For
example dominant wolves have more cortisol in the wild; subordinates have higher levels
in captivity.
 The most frequent context in which aggression is seen is in defense of status. But the best
fighter does not become the highest-ranking individual in a group all the time (ability to
form coalition and source social support are important).
 In some species, aggression is a primary cause of mortality.
 The most important modulating influence on aggression is social dominance; once it is
established the rate of aggression drops substantially.
 Aggressive encounters are highest among adolescent males during group migrations.
Aggression is also higher under conditions of crowding.
 Males are generally more aggressive than females, but once dominance is stabilized, males
have a substantial drop leading to females showing higher aggression than or as high as
males.
 Mating competition can increase male-to-male aggression. The presence of children can
act as agonistic buffers to reduce aggression among both males and females in some
species.

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  Socially living primates learn social cues of aggression and restraint from the early period
of development by observing their parents and older individuals; they later practice these
skills with their peers. In fact, parental control is essential for the development of cortical
areas involved in impulse control.
 Coping outlets for stress include social support (grooming, coalition formation and
physical contact). Reconcilative behaviour immediately after a competition may help the
loser to cope. Poor availability of this support with low presence of kin will increase stress
among subordinates.

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7. Altruism
Any action that is intended to help others is called Prosocial Behaviour in psychology. Altruism
is often considered to be a motivation behind people’s prosocial acts. Altruism refers to the wish
to help others with no expectation of reward.

Bystander apathy: When alone, individuals will typically intervene if another person is in need
of help: this is called bystander intervention. But intervention becomes less likely to an extent
that no single person will intervene from a crowd or group of observers when someone is in need
of help. This is called bystander apathy or Genovese effect.

Pluralistic ignorance: This refers to members of a crowd looking at each other for signs of
distress but remaining calm themselves, leading to misappraisal of the situation being safe
leading to lack of intervention. Bystander competence is usually not required for intervention
except in ambiguous situations where technical help is required e.g. blood at the scene.

According to arousal/cost-reward model, emotional arousal on seeing a victim increases

motivation to act. But a cognitive appraisal of costs and rewards occurs before an intervention is
carried out. If the cost of helping is high, the bystander undertakes a cognitive reinterpretation -
calling the situation as non-urgent, blaming the victim or diffusing or dissolving responsibility.

Diffusion of responsibility: Similar to social loafing – ‘I have some responsibility, but so do

others; let someone else help.'

Dissolution of responsibility: Not knowing what others are doing, rationalizes that someone
would have helped the victim.

Males show higher agentic help and intervention while females show higher communal help and
empathy.

Social loafing: This is also called Ringelmann’s effect. It is seen in games such as tug-of-war and
in clapping hands after a performance. The larger a group is, the less the individual performance
- as one thinks the others will do the job

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 DISCLAIMER: This material is developed from various revision notes assembled while preparing
for MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books.
These sources are cited and acknowledged wherever possible; due to the structure of this
material, acknowledgments have not been possible for every passage/fact that is common
knowledge in psychiatry. We do not check the accuracy of drug-related information using
external sources; no part of these notes should be used as prescribing information

Notes prepared using excerpts from

 Sapolsky, R. (2005) The Influence of Social Hierarchy on Primate Health Science, 648-652
 Thambirajah, MS. Psychological Basis of Psychiatry, Elsevier 2005
 Gross, R. Psychology: The Science of Mind and Behaviour, Hodder Education; 6th Revised edition
 Wolff, P., & Holmes, K. J. (2011). Linguistic relativity. Wiley Interdisciplinary Reviews: Cognitive
Science, 2(3), 253-265.
 Baron-Cohen, S., Leslie, A. M., & Frith, U. (1985). Does the autistic child have a “theory of mind”?.
Cognition, 21(1), 37-46.
 J. French and B. Raven, The bases of social power in D. Cartwright and A. Zander (eds.), Group
dynamics (pp. 607-623). New York: Harper and Row, 1960

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Sociocultural Psychiatry
Paper A Syllabic content 1.3

© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
© SPMM Course rights to Images/Figures with CC-BY-SA license if they are used in this material. 1
 1. Social Classification

In Britain occupational classification forms the principal mode of social classification:

Classes Categories The social class of a household is

1 Class 1: Professional, managerial and determined on the basis of the head of a
2 Class 2: Intermediate family.
landowners
3 Class 3: Skilled, manual, clerical
4 Class 4: semi-skilled Dominance and dependence are two
5 Class 5: unskilled essential underlying themes behind the
6 Class 6: unemployed
categorical divisions of social classes.
Most psychiatric disorders are more common in lower social classes; with controversial
exceptions noted for anorexia, alcohol use and bipolar disorders.

Anorexia: It is debatable whether social class affects the true prevalence of anorexia or
whether the differential rates noted in various studies reflect variations in help-
seeking/referral pattern. At present the growing consensus is that the social classes 1 and 2
are more prevalent in clinical (as opposed to community-based) samples but there are no
differences in distribution of various clinical features across the social groups. The quality of
family relationships and types of family constellations are also broadly consistent across the
social classes in affected families. A prodrome of excessive diet consciousness and the actual
onset of the disease itself are noted at somewhat younger ages in social classes 1/2.
Community studies have shown that the degree of urbanization has a significant impact on
the prevalence of anorexia, bulimia and binge eating disorder (Favaro et al., 2003). Social
class, professional status, and education are not associated with an increased risk of reporting
an eating disorder in such community samples.

Bipolar disorder: An overrepresentation is found in the higher occupational class in bipolar

probands' brothers and children. It is consistently noted that the family of origin in bipolar
probands belong to a higher social class though the patients themselves might be at a lower
social class. Tsuchiya et al., (2004) showed that higher social class of parents together with
longer paternal education history and larger possession of wealth increased the risk of
bipolar disorder in the offspring. It is speculated that ‘bipolar genes’ may offer some survival
benefits such as superior creativity or productivity, which uplifts the families to higher social
status.

Suicide: The relationship between suicide and social class has not been conclusively
established as of yet. While some authors have reported that higher social class is related to
higher rates of suicide, most other studies indicate that lower social class is associated with

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higher rates of suicide. It is shown that among mentally ill, the higher the social class, the
more the risk of suicide (Silverton et al. 2008).

Alcoholism seems to defy social class boundaries. A Swedish conscript study (Hemmingson
et al., 1999) reported that intergenerational social mobility that is associated with health-
related factors, but not alcoholism itself, makes a significant contribution to explaining
variation in the rates of alcoholism among the different social classes. The class-related
differences in alcoholism among young adults seem to be influenced heavily by factors that
are established by adolescent years. But such adverse conditions did not seem to be well
reflected by social class of origin. By far, a significant influence on the prevalence of alcohol-
related harm seems to be the public health policy regarding pricing and the sales of alcohol.

In all aspects of health including life expectancy, infant and maternal mortality, there is a
discrepancy between social classes, despite the existence of
the NHS, which was developed to combat this. There is a
JARMAN INDEX
question of whether the low social class has lead to poor
health or if poor health leads to deterioration in social status
A scoring system developed by the
(as suggested in the Danish bipolar study above). There is a
British general practitioner Brian
consideration for cultural differences among social classes Jarman for the level of social deprivation
in terms of diet, exercise, alcohol intake and awareness of in a community, using census data on
mental health problems and the treatments available. percentages of old people living alone,
single-parent families, children younger
than 5 years of age, unskilled and
unemployed persons, ethnic minorities,
overcrowded dwellings, changes of
address in previous year, etc. Although a
valid indicator, it is not generally
accepted outside the United Kingdom.

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 2. Sick role and illness behaviour
The sick role is a concept described by the American sociologist Talcott Parsons with 4
characteristics:

The sick person is freed or exempted from carrying out normal social roles. The more severe the
illness, the more is the freedom from normal social roles. This is granted to everyone in society
irrespective of social status.
People who are ‘sick’ are not directly responsible for their disease. They are not blamed or expected
to take the blame, and if one takes self-blame, this is viewed as odd behaviour.
It is necessary that a sick person tries to get well. The sick role is regarded as a temporary stage that
should not be prolonged if at all possible.
A sick person must seek competent help and cooperate with medical care to get well. This implies
that a doctor is an agent of social control – one that restores people’s social roles.
The concept of disease:
Disease: refers to actual pathology (e.g. a process that results in illness)
Illness refers to personal experience (a set of symptoms suffered by a patient)
Sickness refers to social consequences (e.g. absence from work)
Health behaviours are seen in healthy people who try to maintain their health – these are
related to primary prevention of disease and are intended to reduce susceptibility to disease
in the first place. Mechanic and Volkart, 1961, proposed the concept of illness behaviour
which refers to any behaviour undertaken by an individual who feels ill to relieve that
experience or to better define the meaning of the illness experience. Illness behaviour is an
active process “that involves interpreting symptoms, evaluating possible responses and,
finally, deciding whether to try to alleviate those symptoms or simply to ignore them”.

Abnormal illness behaviour (Issy Pilowsky, 1969) is an extension of the concept of illness
behaviour; it is defined as the persistence of a maladaptive mode of experiencing, perceiving,
evaluating, and responding to one’s own health status, despite the fact that a doctor has
provided a lucid and accurate diagnosis and management plan (if any), with opportunities
for discussion, negotiation, and clarification, based on adequate assessment of all relevant
bio-psycho-socio-cultural factors. These can be excessive illness affirming (e.g. somatoform or
malingering) or denying behaviours (e.g. loss of insight in psychosis).

Factors influencing individual response to illness

 Symptom visibility & their perceived importance

 Assessment of symptom’s significance
 Potential for symptoms to disrupt community
 Symptom denial for fear of confirmation of serious illness
 Deferring response to symptoms because of competing social demands
 Assessment of social & economic costs of responding to symptoms versus
potential health-related benefits

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  Available information knowledge & cultural assumptions & understandings
 Symptom frequency & persistence
 Competing interpretations of symptoms
International Classification of Impairments, Disabilities and Handicaps (ICIDH) provided a
descriptive conceptual framework of consequences of illnesses.

Impairment: interference with structural or psychological functions (that is, parts of the
whole person e.g. loss of an arm’s function due to fracture).

Disability is interference with activities of the whole person in relation to the immediate
environment (simply ‘activities of daily living' e.g. not able to cook for oneself due to the
fracture)

Handicap is the social disadvantage resulting from disability (e.g. loss of work and inability
to meet friends due to restricted driving secondary to fracture)

Health Beliefs Model: The health beliefs model was developed with the observation that
patients have their own beliefs about disease risks and treatment benefits. According to HBM
patients’ beliefs about their disease states may be more influential than medically determined
disease information. The health beliefs model identifies several factors for which patients’
beliefs may affect their treatment participation:

(1) Patient’s beliefs about the severity of their condition,

(2) Patient’s beliefs about their susceptibility of acquiring the disease or complications of
the disease,
(3) Patient’s beliefs about cost of treatment adherence (including costs in inconvenience,
effort, time, and money),
(4) Patient’s beliefs about benefits of treatment adherence, and
(5) Patient’s beliefs regarding the environmental and social cues to action that may assist in
their treatment adherence.

The Transtheoretical Model (TTM) was developed by Prochaska and DiClemente (1982).
This was developed largely in response to increasing divergence in the practice of
psychotherapy, and the authors attempted a (transtheoretical) synthesis among the various
therapeutic systems. They identified five common processes of change that are applicable to
how individuals can be motivated to change their illness-related behaviours. These processes
are

(1) Consciousness raising – helping the patient gather information about self and the
problem
(2) Choosing – increasing awareness of healthy alternatives,
(3) Catharsis – emotional expression of the problem behaviour and the process of change,

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 (4) Conditional stimuli – includes stimulus control and counterconditioning,
a. Stimulus control: Avoidance of stimuli associated with the problem behaviour
and the operant extinction cueing effect of the stimulus on behaviour.
b. Counterconditioning: Training an alternative, healthier response to the cue
stimuli.
(5) Contingency control: Positive reinforcement from others and self-appraisal and
improving self-efficacy by self-reinforcement.

From these five processes of change, Prochaska and DiClemente identified six stages of
change. These are (1) precontemplation, (2) contemplation, (3) Preparation, (4) action, (5)
maintenance, and (6) relapse. In the precontemplation stage, a person is not even
considering changing his or her behaviour, does not see the behaviour as a problem,
minimizes and denies associated risks, and avoids information to the contrary. In the
contemplation stage, the person has become aware of why the behaviour is a problem but is
ambivalent about changing, and likely sees equal or more benefits than costs from the
behaviour. During preparation, the person has made a decision to change, and is planning a
strategy for change, but has not yet taken action. In action, the person has implemented a
plan and is changing the behaviour. In maintenance, the person has been able to sustain the
change and avoid reverting to problem behaviour for a significant period of time. In relapse,
the person does revert to problem behaviour, ‘back to square one’.

 These stages are not linear in sequence but rather cyclical, in that a person can
relapse and reenter at a later stage such as preparation.
 The stages do not operate in an invariant sequence (unlike Piaget’s models).
 Each stage can be moved into back and forth (reversibility).
 The stages are not qualitatively different.

Motivational Interviewing (Miller & Rollnick, 1991) is often used together with TTM and
stages of change.

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 3. Social role of doctors
General Medical Council (UK) and other professional organisations have expounded the
concept of multitude roles expected from a doctor. The RCPsych has adapted this to suit the
psychiatric practice.

Doctors as scientists

•Accessing, interpreting and assimilating new knowledge critically

Doctors as health professionals

•Listening and communicating appropriately, the ability to work as part of a team,

non-judgmental behaviour, compassion and integrity

Doctors as leaders

•Making day-to-day clinical decisions based on medical knowledge to assess the

impact, risk and likely outcome of decisions; apply skills in the development of policy,
strategy, service design, and clinical processes.

Doctors as health advocates

•Acting as critical decision makers with responsibility for allocation of significant

health resources; influence to advocate for increased resources to improve health
outcomes for their patients and populations

Doctors as teachers

•Accepting duty to contribute to the education of other professionals and patients in

addition to carrying a responsibility for continued personal education.

Doctors as health sector representatives

•Sharing a responsibility to positively influence the culture and the environment in

which they work

The Consensus Statement on the Role of the Doctor (from medschools.ac.uk) highlights the
social role of the doctor:

 To support patients in understanding their condition and what they might expect,
including in those circumstances when patients present with symptoms that could
have several causes
 To identify and advise on appropriate treatment options or preventive measures
 To explain and discuss the risks, benefits and uncertainties of various tests and
treatments and where possible support patients to make decisions about their own
care.

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  All doctors have a role in the maintenance and promotion of population health,
through evidence-based practice.
 The doctor must appreciate the needs of the patient in the context of the wider health
needs of the population. For all doctors, the patient must come first but they will
achieve this in different ways and in different settings.

The social role of a psychiatrist includes being an appropriate role model providing effective
support and guidance for those seeking treatment for psychiatric disorders and various
societal dilemmas related to them. Some leaders extend this role as being a public figure in
one’s community whose opinions are valued by laymen as well as other professionals and to
serve as an ambassador for the profession by educating the public via various media outlets
to erase misperceptions about mental illness or psychiatry (Henry Nasrallah in The model
psychiatrist: 7 domains of excellence, 2011).

Professionalism: There has been a great deal of interest in defining and adopting the concept
of professionalism in psychiatry. American Board of Internal Medicine Foundation sets out
three core principles specific to medical professionalism that is widely adopted by doctors in
the US, the EU and the UK. The 3 principles are the primacy of patient welfare (based on
dedication and altruism), patient autonomy and social justice. These principles are further set
out in the 10 commitments recommended for developments to promote professionalism in
medical practice (from Bhugra & Gupta, 2010):

1. Professional competence
2. Honesty with patients
3. Patient confidentiality
4. Maintaining appropriate relations with patients
5. Improving quality of care
6. Improving access to care
7. Just distribution of finite resources
8. Scientific knowledge
9. Maintaining trust by managing conflicts of interest
10. Professional responsibilities (including maximising patient care, self-regulation,
remediation, disciplining)
Health advocacy is the process of supporting and empowering patients and carers to express
their opinions, ideas and concerns and enabling them to access appropriate information and
services and promote their rights.

Dual loyalty: World Medical Association’s Medical Ethics Manual highlights this issue when
discussing professionalism. “When physicians have responsibilities and are accountable both
to their patients and to a third party, and when these responsibilities and accountabilities are

© SPMM Course 8
incompatible, they find themselves in a situation of ‘dual loyalty’. Third parties that demand
physician loyalty include governments, employers (e.g., hospitals and managed healthcare
organizations), insurers, military officials, police, prison officials and family members.
Although the WMA International Code of Medical Ethics states “A physician shall owe
his/her patients complete loyalty,” it is generally accepted that physicians may in exceptional
situations have to place the interests of others above those of the patient. The ethical
challenge is to decide when and how to protect the patient in the face of pressures from third
parties.” One such situation pertains to the issue of resource allocation.

Resource allocation: In most countries governments decide the overall healthcare budget;
institutions and local bodies decide the allocation to each service provided locally; doctors
and healthcare professionals decide on the tests to be ordered, services to be offered and
treatments to be provided. From the overall allocated budgets, the distribution of around 80%
of healthcare expenditures is controlled by end-providers. Where resources are limited, all
patients are entitled to a fair selection procedure for that resource. WMA recommends that
this choice must be based on medical criteria and made without discrimination.

In practice, physicians balance the principles of compassion and justice and are called to
employ several approaches for resource allocation depending on where and when the need
arises.

LIBERTARIAN Resources distributed according to market principles (patient is a consumer; if he/thy have
the willingness to pay, the resources will be made available to them).
UTILITARIAN Resources distributed according to the principle of maximum benefit for all.
EGALITARIAN Resources distributed according to the need (estimated by the provider).
RESTORATIVE Resources should be distributed with a positive discrimination towards the disadvantaged
(e.g. poor gets priority over the rich who can pay for private care).

WMA notes “physicians have been gradually moving away from the traditional
individualism of medical ethics, which would favour the libertarian approach, towards a
more social conception of their role”.

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 4. Family life in relation to major mental illnesses
Family is essentially the most basic social unit and microcosm of an individual.

The General Systems Model of families holds that families are systems where every action
in a family produces a reaction in one or more of its members. Such a system has external
boundaries and internal rules, and every member is supposed to play a relatively stable but
interchangeable role.

Family cycle:

 Stage 1: formation of the new family: 2 individuals unite - the  first child is born.
Tasks include formation of working dyad and restructuring relationships with
families of origin.
 Stage 2: child rearing stage: birth of child  adolescence
 Maintaining satisfactory marital relationship amidst the demands of childrearing is a
major task.
 Stage 3: child launching: Children leave home. Tasks include re-establishing
individual interests and reexamining the marital relationship.
 Stage 4: return of independence – growth and extension of family leads to the task of
maintaining ties across generations
 Stage 5: dissolution of the family: occurs due to decline or demise of partners.

Family instability can affect children to a various extent depending on sex (boys affected >
girls), age (younger affected > older children), and temperament hyperactive affected >
placid). This has a demonstrable effect on a child’s cognitive achievements; the most common
psychopathology noted is a behavioural difficulty. Family systems have been studied in
detail with respect to schizophrenia especially.

Lidz studied family systems in relation to schizophrenia and described two

‘schizophrenogenic’ family patterns:

 Marital schism: family is in a state of disequilibrium due to repeated threats of

parental separation. Parents downgrade roles of each other and may even attempt to
collude with children and exclude partners.
 Marital skew: family is at an equilibrium that is skewed and achieved at an expense
of the distorted parental relationship. One parent may be dominant and other
submissive, making the marriage ‘a stable fit’.

Wynne and colleagues described certain communication patterns that may relate to the later
development of perceptual and thought disorders in schizophrenia. Pseudo-hostility and
pseudo-mutuality refer to the disjointed or fragmented communication where the child is

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forced to accept and develop a pattern of communication that will negate and deny the
existence of meaningless relationships in the family.

Bateson described the double-bind relationship where superficial verbal communications

contradict the behavioural and deeper communications among the members of a family.
These mixed messages keep a growing child in a double bind (cannot be correct either way)
that can later increase the risk of psychosis.

Freida Fromm-Reichmann coined the concept of schizophrenogenic-mother. These mothers

were described as 'rejecting, impervious to the feelings of others, rigid in moralism
concerning sex and had a significant fear of intimacy'.

Causal links between the above four family functions and schizophrenia are disputed, and
these models have fallen out of favour in recent times. There is no experimental evidence to
support these claims and any small data regarding the above theories are poorly
reproducible.

Expressed emotions concept was developed by Brown & Rutter in 1966 as a part of the
Camberwell Family Interview [CFI] and later modified by Vaughn & Leff in 1976. The
ratings were based on content and prosodic aspects and emphasis of speech. Five measures
are considered;

1. Critical comments
2. Positive remarks
3. Emotional over involvement
4. Hostility
5. Emotional warmth
The final scores of emotional over-involvement, critical comments and hostility were the
most predictive measures for relapse of schizophrenia. CFI is a long interview process where
individual members of a family are interviewed (including the patient). If one relative is
classified as high EE person, then the whole family could be classified as a high EE family.
CFI ratings based on interviewing parents singly have the most predictive value. A Five
Minute Speech sample (FMSS) measure was introduced as a substitute for CFI, but it tends to
underestimate EE. FMSS is more useful for measuring professional or staff carers’ level of EE.

Studies have indicated:

 Worldwide the proportion of high EE in carers of patients with schizophrenia is 52%.

Lowest rates are found in India and other developing nations.
 The strength of association between relapse and EE is identical for both genders.

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  A meta-analysis of EE data reveals that for patients living in situations rated as
showing high expressed emotion, the relapse rate is 50%, whereas in the ‘low
expressed emotion group’ the rate is 21%.
 In a majority of the studies, high expressed emotion was predictive of relapse in
symptoms of schizophrenia 9 months later for both genders. A significant amount of
face-to-face contact (more than 35 hours per week) with a relative with a high
expressed emotion score increased the risk of relapse, but in households with a low
expressed emotion score, high levels of contact appeared to be protective.
 Pakistani families in the UK were more likely to be rated as high expressed emotion
than White families, indicating that components such as emotional over-involvement
may be cultural rather than pathogenic traits (Hashemi & Cochrane, 1999).

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 5. Life events
(This section is best read in conjunction with the section on Stress in Basic Psychology chapter)

The impact of social and family life events on mental health can be measured in two ways.

a. Ranking various events according to the degree of association with mental difficulties in
a sample and use this list to study other populations. This is the method followed by
Holmes & Rahe (1967) Social Readjustment Rating Scale where 43 life events in the last
2 years are rated using arbitrary ‘stress’ units. The death of spouse generates 100 units of
stress while divorce tops the rest of the list of stressors list with 73 units.
b. Brown and Harris popularized a different method whereby life events are graded
according to the inherent meaning of the events to the individual concerned – i.e.
contextual rating of the social adversity. Accordingly the effect and impact of a life event
is understood in light of one’s current social context and self-perspective. LEDS – Life
events and Difficulties schedule was devised by Brown and Harris.

Types of life events

1. Loss includes events such as death, respondent initiated separation (long-term separation)
and other key losses which are rated as ‘high’ by the subject. If the lower loss is felt by the
subject, these are placed at lower dimensions.
2. Humiliation includes other-initiated separation from a spouse or partner or a falling out,
quarrelling, or rift in a relationship involving a close tie with a reasonable inference that
the separation would be permanent or long duration event. Here the separation or
estrangement is either initiated by the other person or “forced” by circumstances such as
the infidelity of the subject or marked violence. The delinquent behaviour of a child or a
criminal act committed by a close tie could be a humiliation. ‘Put down’ events are events
such as rejection or verbal or physical attack by a close tie, or any other person if the event
is highly public. This may be humiliating or threaten a core role. It includes all rapes; if
the subject feels responsible in some way this might increase the humiliation felt.
3. Entrapment includes long-term sustained entrapment includes serious difficulties that
can only get worse or persist according to the subject; or a failed positive event where a
potential fresh start went disastrously wrong within 1-2 wk, leaving the person stuck in
‘square one’.
It is recognised that the unidimensional measure of severity of life events (either loss or
threat, etc.) is not sufficient to explain the effects on mental illness. Combined loss and
humiliation events are more depressogenic than a threat or other individual types of
events. Humiliation events induce defeat and submission responses which may be
directly related to depression. In a study by Kendler et al. (2003), humiliation predicted
onsets of pure major depression but not pure generalised anxiety episodes, and danger

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 predicted pure generalised anxiety but not pure major depression episodes. But the
results had only moderate strength in prediction.

Depressed patients may recall more stressful life events due to cognitive bias. It is shown that
the frequency of desirable or entrance life events in the depressed population is comparable
to controls – so the absence of positive events cannot be the simple explanation for
depression. It is demonstrated that those with a recurrent episode of depression have less
preceding life events than those with the first episode of depression. This may be related to
kindling phenomenon.

Genes and life events: Kendler (1997) examined the relationship between genetic
vulnerability to depression and the risk of experiencing stressful life events. A reverse
causality effect (i.e. vulnerability to depression itself could explain the occurrence of more
frequent stressful life events) was demonstrated. In a sample of over 2000 female twins,
genetic liability to depression was associated with a significantly increased risk of
experiencing an assault, serious marital problems, divorce/break-up, job loss, serious illness,
major financial problems, and trouble getting along with relatives/friends. Similarly, the
genetic liability to alcoholism impacted on the risk of being robbed and having trouble with
the law. Hence, genes can probably impact on the risk for psychiatric illness by causing
individuals to select themselves into high-risk environments. Therefore, life events are
‘heritable’ to some extent.

Life events measures

Semi-structured interviews  Life events & Difficulties Scale (Brown & Harris)
 Interview for Recent Life Events (Paykel)
Life events scales  Social Readjustment Rating Scale (Holmes & Rahe)
 Adverse Childhood Events Scale
 Hassles & Uplifts Scale (Lazarus & Folkman)

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 6. Social factors and mental health issues
Society as a risk factor
Engel’s model of biopsychosocial approach is widely used in aetiological formulations in
psychiatric practice, highlighting the prominence of social factors in the practice of
psychiatry.

Social Causation Theory: According to this concept, mental illnesses are caused by social
deprivation. Most psychiatric disorders are seen in lower socio-economic class as a mental
disorder is seen as directly due to the poverty and social conditions. This theory may hold for
some conditions such as depression or alcohol misuse, but not for others such as bipolar
disorder or schizophrenia.

In a survey sampling males aged 25-34 on first

admission of schizophrenia, an expected excess
of social class V was noted but social class
distribution of fathers of the patients was the
same as the general population suggesting that
schizophrenia results in a downward drift of
economic status rather than poverty being a
cause for schizophrenia. This Social Drift or
Social Selection Theory was first suggested by
Faris & Dunham on the basis of their ‘Chicago
study 1922 – 1934’ that explored the relation
between the spatial distribution of psychosis and
social organization by applying the concentric zone
model of urban organization (see the figure from
university of Manitoba, Centre of Health Policy
website). In this model, the social organization increased with distance from the epicenter.
(Inner urban zones = most disorganized and unstable communities; outer zones = most
organized and stable communities). Faris and Dunham found that the least socially
organized inner urban zones had the highest rates of schizophrenia; they argued that this
effect was due to the downward drift in economic status after developing the illness.

Factors mediating the effect of social class: Several factors such as lower educational levels,
poverty, immigration, overcrowding, poorer physical health and nutrition influence the
higher prevalence of mental illness in some social classes. For example, high parental
education levels are associated with a lower risk of ADHD, especially in boys. There is no
proven link with food additives but lead exposure is associated with risk. Similarly,

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pregnancy complications such as toxaemia or eclampsia, poor maternal health, maternal age,
foetal post-maturity, long duration of labour, foetal distress, antepartum haemorrhage, low
birth weight and prematurity are associated with ADHD, increasing the likelihood of its
prevalence among lower social classes.

In fact, Rutter’s landmark studies revealed six inter-related risk factors in the family
environment that correlated significantly with childhood mental disturbances in general:

1. Severe marital discord

2. Low social class
3. Large family size
4. Maternal mental health disorder
5. Paternal criminality
6. Foster placement.
Rutter observed that the aggregate of these adverse factors, rather than the presence of any
one factor, impaired development.

Poverty and psychopathology: The Great Smokey Mountains study looked at groups of
white American and American Indian children grouped into ‘poor’, ‘never-poor’ and ‘ex-
poor’ (ex-poor were those whose income increased annually at later times due to a casino
being built on American Indian land). The results showed that before the casino opened poor
and ex-poor children had more psychiatric issues, but the levels in the ex-poor fell to the
same as never-poor after the casino that produced good income for the ex-poor families
opened. The most prominent psychiatric issues responding to poverty were conduct and
oppositional defiant disorders while the prevalence of depression and anxiety remained the
same.

Sociology of mental illness

Mental illness as deviance: Society tends to see odd and abnormal behaviour to be against
acceptable norms and values and some of these are grouped as mental illnesses. Hence, the
deviance becomes an important determinant of illness concept in psychiatry. Edwin Lemert
developed the idea of primary and secondary deviance as a way to explain the process of
labeling.

Primary deviance is any general aberration from expected normality before the person showing such
an aberration is identified as a ‘deviant. For example, primary deviance may refer to minor rule
breaking in society such as over-speeding.

With repeated instances of primary deviance, the subject gets labelled, and the institutions react to the
deviant actions. This leads one to become secondary deviant. Secondary deviance refers to the
actions carried out by a person identified as a ‘deviant’ by institutions such as the society or the
justice system. This refers to the maintenance of primary deviance as a repercussion of the label given.
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Thus, societal reaction initiates sociological/psychological processes which sustain deviance, making
it more central to the life of the "deviant."

Formal deviance includes breaking a written law or code of constitution as in criminal act;
informal deviance includes breaking unspoken social rules of living.

Deviancy amplification spiral: Originally applied to crime reporting, the theory identifies a
spiral that starts with a ‘deviant’ act. The media report such acts as newsworthy and start
regularly adding non-newsworthy items similar to this act (‘sensationalism’) setting up a bias
against the so-called deviant act. As a result, minor problems look serious and rare events are
perceived as common. A mounting public concern is the next stage in this spiral, forcing law
enforcement to focus more resources on the particular deviancy than it actually warrants.

Social construction theory explores how variations in human experience have come to be
classed as illness categories; the method used for such investigation is ‘deconstruction’ or
discourse analysis. According to the theory, the reality of mental illness is socially
constructed and complicated by cognitive interests of social groups – doctors, lawmakers,
politicians.

Some examples include:

1. Agoraphobia as a concept developed around the time when the social emancipation of
women occurred. The condition thus might be partly originated from problematized use of
public space.

2. Sexual role stereotypes may play a role in anxiety disorder constructs and psychopathy.

3. Most major mental problems are circularly defined – e.g. a patient with schizophrenia is
termed ‘psychotic’ as he hears a voice. When this patient enquires why he hears a voice, he
gets told that he hears a voice because he is psychotic. Thus, most labels are circular
descriptions constructed by the society.

Social labelling or societal reaction theory: Labelling theory originated from the concept of
symbolic interactionism. Each person plays many different social roles sanctioned by the
society; in each role, interaction occurs with other people and meanings of such interactions
are dependent on the role assumed. Thomas Scheff in his book Being Mentally Ill (1966)
expanded labelling theory to mental illness.

 According to Scheff, the social routine is made of numerous, uncategorisable residual

rules. These are unspoken and taken for granted often.
 Residual deviance occurs when these rules are broken, but often these are not noticed
unless certain specific circumstances arise. Thus in certain circumstances rule breaking
is accepted, ignored or normalised, but labelled deviant on other occasions.

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  Thus societal-labelling may occur in one-off crises situations or as a gradual shift
from acceptance to labelling, depending on contingencies i.e. the effect of such
deviances on others concerned. This might explain the fact that numerous voice
hearers live in the community without a diagnosis of schizophrenia and the results
from community surveys always showing higher prevalence compared to clinical
samples for almost all mental illnesses.
 Once labelled as mentally ill, the labelled person takes up the role of being a mentally
ill individual in the society. This new identity sanctions him certain privileges as a
compensation for the loss of other privileges. Apart from the societal reaction, self-
labelling will serve to strengthen beliefs with regard to the given role.

Original labelling theory is empirical without much experimental support. A modified

labelling theory is now used to explain the effect of stigma on relapses of mental illnesses.

Suicide and sociology

Durkheim, often adored as the father of sociology, described a sociological model of suicide
and described 4 types of suicides. According to him, both an unusually ‘tight’ bondage and a
weak adherence to defined societal values can contribute to suicide. These are called
altruistic and anomic suicides respectively. Other 2 types are described below.

Durkheim’s model Explanation

Altruistic suicide Individual is overly attached to social norms and dies for the sake of the society
(i.e. for others in the society) e.g. self-molestation among Buddhist monks in
Tibet
Egoistic suicide Excessive individualism, but low social integration. No cohesive group
attachment
Fatalistic suicide Society’s control on the individual is very strong such that it interferes with
moral values and personal goals
Anomic suicide Individual feels that he has no guidance or regulations from the societal
system; feels disillusioned

The Social Origins of Depression

Brown and Harris (1978) studied social & economic circumstances associated with the onset
of depression in women living in inner London in 1978. They identified 4 ‘vulnerability
factors’:

1. Absence of a close confiding relationship;

2. Loss of mother before age of 11;

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 3. Lack of employment outside home;
4. Having 3 or more children under 15 living at home.

Brown et al.’s further work has revealed the following factors for depression (elaborated by
Morris & Morris, 2000);
1. Predisposing factors: these occur before the age of 17.
a. Sexual abuse
b. Parental indifference
c. Parental loss
d. Physical abuse
(See Brown & Harris original vulnerability factors above)
2. Precipitating factors include
a. Acute severe life event
b. Chronic stress more than 4 weeks
c. Lack of social support
3. Maintaining factors include
a. Further negative life events
b. Persistent poor quality social support
c. Poor coping style:
i.Self-blame and helplessness
ii.Denial of problems
iii.Inability to solve problems
iv.Blaming others or external forces
d. Inability to obtain adequate social support:
i.Fear of intimacy
ii.Denial of need for intimacy
iii.Enmeshed intimate relationship
e. Low educational level
4. Relieving factors may include
a. Positive life events such as
i.Fresh or potential fresh start: new role, positive change
ii.Removal from source of stress: e.g. separation from violent husband
iii.Anchoring: role change and increased security
iv.Difficulty neutralisation: ending a difficulty
v.Goal attainment.
b. Improved quality and consistency of support

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Social factors in schizophrenia
The significant social disadvantage (e.g. experience of racism, discrimination, economic and
employment disadvantage, the perception of ‘outsider status’) is evident in populations with
a higher risk of schizophrenia. According to the social defeat hypothesis, “long-term
experiences of social disadvantage lead to sensitization of the... dopamine system and (or) to
increased baseline activity of this system, thereby, to an increased risk for schizophrenia."
Immigrant populations exemplify this link between social factors and schizophrenia.

Stress and Social Adversity: Social adversity is associated with high degree of stress that can
be exceptionally harmful in the context of vulnerability to psychosis. This has been
demonstrated in many animal studies.

Childhood Abuse and Family Dysfunction: While child abuse is not seen as a specific risk
factor for schizophrenia, it is now accepted that childhood abuse may be a marker for other
potential relevant risk factors, such as family dysfunction that increases the risk.

Neighbourhood effect: In neighborhoods with ethnic minorities (non-white) that were at an

increased risk, the risk reduced when the population of minorities increased. Similarly,
natives had an increased risk in neighborhoods where minorities were larger in number,
supporting the notion of social adversity in increasing the risk of schizophrenia.

Urban Effect

 There is a large deal of evidence now to support that in most parts of the globe,
children born in urban environments are at an increased risk for psychosis (OR:1.61;
CI: 1.4 – 1.8).
 This urban-birth effect is not consistent among all countries; some Australian
research has no increase in psychosis among urban areas.
 Marcelis et al. (1998) (Dutch National Psychiatric Register study) found that the
effect of urbanicity on all psychosis was greater for men than for women.

 The effect of urban birth was greatest for individuals from the most recent birth
cohorts and with an early-onset disease even after correcting for the length of follow-
up.

 Another study noted a positive correlation between admission rates for

schizophrenia and degree of urbanization. There is a consistent dose–response
relationship between urbanicity and risk of schizophrenia; the larger the town of birth,
the greater the risk.

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Immigration and schizophrenia

Though the frequency of most mental illnesses are found to be higher in migrants that the
natives, schizophrenia has been studied the most. Conflicting explanations have been offered
to explain why migrants have more schizophrenia. Cooper has revisited and reappraised the
data available and summarised the main findings as below:

a. The excess risk is not specific for African—Caribbean immigrants. It is also

present among African-born Black immigrants to the UK, and to a lesser extent among
immigrants from Asian countries. Hence, any explanation cannot be purely biological
and not simply race specific.

b. Incidence rates of schizophrenia in Caribbean countries are similar to those

found in the indigenous UK population; this excludes country of origin theory which
proposes that the immigrants carry such higher incidence rates from where they come
from. The rate for schizophrenia in second-generation African—Caribbean people born
in the UK appears to be higher than in the first generation, which is strongly suggestive
of an environmental rather than a genetic effect.

c. According to this notion of prepsychotic segregation, individuals who are

psychosis prone find it hard to survive in the countries of birth and so immigrate to
other regions. There is no evidence for selective immigration from the Caribbean as
part of a pre-psychotic segregation. Also notable is the fact that apart from 1st
generation immigrants having higher rates of psychosis, the 2nd generation children
of immigrants also have a very high rate of psychosis (in some cases, higher than their
parents), negating the probability of psychosis-induced immigration.

d. The immigrants’ pathways to psychiatric care are characterized by long delays

in seeking professional help, a lower likelihood of psychiatric referral, and frequent
involvement of the police and emergency services and high proportions of compulsory
and intensive care and secure (locked) ward admissions. The long-term outcome tends
to be correspondingly unfavourable for immigrants.

Hospital admission rates are consistently noted to be higher among ethnic minority
population as a whole but variations between groups. In UK, highest rates of hospital
admissions were noted among Irish migrants followed by people born in Caribbean. The rate
of mental illness among South Asian population is notably lower than UK-born white
population. It is unclear if these are effects of migration or social disadvantage or
organisational differences in pathways of care. Census of inpatients, 2005 showed that 9% of
in-patients were black or mixed black-white ethnicity while black patients were 44% more
likely to have been sectioned & 50% more likely to have been put in seclusion. Black

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Caribbean men were 29% more likely to have been subject to control and restraint. It is
speculated that an association with the use of substances may be a confounder.

Schizophrenia and ethnicity: Aetiology & Ethnicity in Schizophrenia and other Psychoses
(AESOP) study was conducted in London, Bristol and Nottingham. It reported 2-fold higher
rate of incidence of psychosis in London compared to the other 2 centres. Afro-Caribbeans
had a 9-fold increase in rates of psychosis. In addition, minority ethnic groups had a far
higher likelihood to be detained on first presentation, accessing health often via police than
GPs.

Social factors in addictions

Patterns of substance use across the world are strongly influenced by the sociocultural milieu
of human communities. Several social factors shape the population prevalence of substance
use behavior. Contextual factors such as neighborhood deprivation appear to be strong
determinants of cigarette and alcohol use. Family and social network norms and social
support are also important in the cessation of drug use. Factors that are consistently
identified in association with substance use and alcohol are listed below (Galea et al., 2004)

Smoking Alcohol use Illicit substances

•Low school achievement •Disruption of family •Peer drug use

•Young among peer cohort structure •Single parenting
•Social networks that use
•Poorer relationships with •Homelessness
alcohol
their family •Poor educational
•Recent immigration
•Low household income attainment
•Small-area deprivation •Neighborhood
disadvantage
•Unemployment

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 7. The sociology of institutions
Goffman described a ‘total institution’ as one ‘whose character is symbolized by the barrier
to social intercourse with the outside’. Total institutions share the following characteristics:

1. All aspects of life are conducted in the same premises and under the same unitary
authority.

2. Each member’s daily activities are carried on in the immediate proximity of a large
batch of others, who are also required to do the same set of activities.

3. All parts of a single day’s activities are strictly scheduled with one leading into the
next.

4. The different enforced activities are based on a single plan whose purpose is the
fulfilment of the proposed official (or statutory) aims of the institution.

Goffman also described the ‘moral career’ of a mentally ill patient i.e. the process whereby a
person with social ties, friends, and family in the community is institutionalized and
converted into an inmate whose world is limited to his immediate hospital ambience (Peele
et al. 1977). See the figure below for more details.

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 •BETRAYAL FUNNEL: People we trust most – family and friends – conspire
against us when we are unwell, reporting our actions to doctors and mental health
professionals (called the ‘circuit of agents’) who run the decision-making process.
Step 1

•ROLE STRIPPING: The institutionalization process begins with a series of assaults

on the recruit’s self. The process of stripping inmates of their identity involves such
initiation rituals as trading personal clothes and belongings for hospital issue
Step 2

•MORTIFICATION: Mortification procedures that consist of a series of assaults on

the inmate's self-image. At the end of mortification one becomes a ‘full member’ of
the institution. Private, personal activities go on public display; he must request
permission for even the most minor activities that were purely volitional on the
Step 3 “outside,” such as smoking, shaving, or going to the toilet. This is termed as civil
death.

•PREVILEGE SYSTEM: The patient is then inserted into the lowest rung of an all-
embracing privilege system. This system is based on the house rules. The
privileges are usually reductions in the institution’s control over the patient’s life.
Step 4 Freedom is a token of reward.

According to Goffman although the stripping process and privilege system are offered in the
disguise of being in the patient’s best interests and on therapeutic grounds, the real purpose
is to break his spirit and make him more manageable. The stripping process and privilege
system introduce him to a therapeutic milieu and offer him a new identity – the patient
identity.

Batch-living: This refers to the pattern in which all inmates did ‘the same thing’ and led a
very similar life inside institutions. Binary living: Lives of the staff are in stark contrast as
they have power, connection with the outside world and could change their lives in the way
they choose. A binary division exists between staff and inmates.

Goffman considered ‘secondary adjustments’ as a direct result of institutionalization and as

a hallmark of institutionalism. Secondary adjustments refer to the habitual arrangements
used by patients who now act as if their major concern is to escape the pervasive control of
the institution. These were usually unauthorized activities leading to obtaining of
unauthorized ends.

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Russell Barton (1976) described 'institutional neurosis', characterized by apathy, lack of
initiative, loss of interest and submissiveness. The proposed causes of institutional neurosis
include loss of contact with the outside world, enforced idleness, brutality and
authoritativeness of staff, loss of friends and personal possessions, poor ward atmosphere
and loss of prospects outside the institution.

Social reactivity and schizophrenia: Wing & Brown explored social etiology of negative
symptoms of schizophrenia. They surveyed asylums (Mapperley Hospital at Nottingham,
Netherne in south London and Severalls in Essex) that existed in the late fifties and
concluded that social poverty and lack of stimulation were very much related to the severity
of blunted affect, poverty of speech, and social withdrawal – these were termed as ‘clinical
poverty’. But such relationship was found to be weak in a reappraisal in 1990. (Curson et al.,
1992). It was also feared that too much stimulation could provoke positive symptoms in these
patients. Thus, social reactivity is considered to be an important phenomenon in the
phenomenology of schizophrenia.

Morgan (1979) coined the term malignant alienation to describe a process characterised by a
progressive deterioration in the relationship between carers (staff in a ward) and a patient,
including loss of sympathy and support from members of staff, who tended to construe these
patients' behaviour as provocative, unreasonable, or overdependent. In some instances, such
alienation may precede suicide / attempted suicide of the patient

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 8. Criminology and penology
In simple terms, criminology is the study of crime, its origin and effects; in a broader sense
criminology is said to include the study of:

i) Attributes of a criminal.
ii) Characteristics and extent of crimes.
iii) Effects of crime on victims and society.
iv) Methods of crime prevention.
v) Types of crimes.

3 levels of explanation are often discussed with respect to the origin of criminal behavior-
Individual level (personal characteristics of the criminal), Situational or contextual level
(immediate circumstances or situations), Social-structural level (social relationships, milieu
and institutions). Different theories of criminology tend to construct their primary
explanation for criminal behaviour at one of the above levels.

Penology comes from the Latin word poena (punishment). Penology deals with the societal
response and treatment of crime and criminals and thus focuses on the characteristics and
workings of the Criminal Justice System. Also known as penal science, the broad goal of
penology is to aid society repress criminality. In this sense, it mostly deals with the
punishment of the offender but in the context of mental health issues, penology also covers
medical treatment and education that aims at rehabilitation and social inclusion of the
offender.

Relationship between crime and mental health: It is difficult to have a clear-cut

understanding of the relationship between crime and mental health. By definition, crime is
understood in a social context; what is a crime in one setting may not be a crime in another
time or place. So acquiring data relating crime and mental health is very difficult. Also,
convictions are not same as crimes. Most data available pertains to conviction rates; non-
convicted or unregistered crimes are far too many. Also, it is not easy to study if the mental
illness was directly related to an offence. A mentally ill person can commit a crime as
everyone else could, but whether it is related to his mental illness is the most important but
often unanswerable question.

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 9. Stigma and prejudice
Stigma is an attribute, trait or behaviour that that is considered shameful; that symbolically
marks the possessor as unacceptable and inferior or dangerous. (Goffman)

STIGMA TYPES
Enacted stigma refers to a patient’s actual experience of discrimination
Felt stigma refers to a patient’s fear of experiencing a discriminated act; it is more
prevalent and more disabling than enacted stigma.
Public stigma is the reaction that the general population has to people with mental illness.
Self-stigma is the prejudice which people with mental illness hold against themselves; this
internalized stigma develops from the prolonged societal response.
Courtesy stigma refers to the stigmatization unaffected person experiences due to his or
her relationship with a person who bears a stigma e.g. parents of children with psychiatric
conditions.

Not In My Back Yard or NIMBY opposition refers to the vehement disapproval by local
authorities, and social groups for localization of a community mental health facility in a
geographic area due to the fear and stigma against the mentally ill. Mind (National
Association for Mental health) organized a survey to measure NIMBY opposition wherein
more than 2/3rd of mental health services faced such opposition in England and Wales. Fear
of children’s safety, falling house prices and violence were the main concerns for the
opposers.

Themes of stigma
Hayward & Bright described 4 major recurring themes or beliefs behind the stigma against
mental illness. These include:

1. Dangerousness
2. Attribution of responsibility
3. Poor prognosis
4. Disruption of social interaction
These 4 themes formed the basis of an Office of National statistics survey in the UK
measuring public attitudes towards mental illness. Schizophrenia and addictions were
regarded most negatively; approximately 60% respondents thought addicted individuals
have only themselves to blame for their problems. Most individuals knew the difference
between various disorders and most felt that depression and anxiety are treatable. Little
change was recorded over 10 years, with over 80% endorsing the statement that “most
people are embarrassed by mentally ill people”, and about 30% agreeing, “I am embarrassed
by mentally ill persons” (Huxley, 1993).

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Surveys (e.g. Jorm et al., 1997) carried out on health professionals and the public with a case
vignette show that:

1. Professionals give much higher rating than the public for the helpfulness of
antidepressants for depression, and of antipsychotics and admission to a psychiatric
ward for schizophrenia.
2. Public give much more favourable ratings to vitamins and minerals and special
diets for both depression and schizophrenia, and to reading self-help books for
schizophrenia
3. The beliefs that health practitioners hold about mental disorders differ greatly
from those of the general public.

Hagighat proposed a unifying theory of stigma, which states that stigma serves the self-
interest of the stigmatisers in different ways as follows:

 Constitutional origins: Quick and easy stereotypes at the expense of

sophistication and depth. The human brain weights negative evaluations
preferentially to positive ones. Similarly, it is likely to interpret repeated episodes of
violence by a few as independent episodes of violence committed by the ‘mentally ill’.
It links negative (rarer than neutral or positive) events with rare objects (e.g. minority
groups).
 Psychological origins: Human tendency uses the example of the ‘unfortunate
other’ to feel happier about themselves e.g. those rewarded the same as others feel less
satisfaction than those in groups with others rewards less for the same work. Those
with low self-esteem derogate others to bolster their self-esteem and sense of well-
being. These psychological dividends benefit the stigmatisers in the presence of the
stigmatised.
 Economic origins: To increase one's access to resources, stigmatisation of rivals
is used as a weapon in the socio-economic competition. Stigmatisation is likely to be
more intense in more competitive, self-seeking societies.
 Evolutionary origins: Stigmatisation may have an evolutionary advantage in
some way. A strong discrimination includes avoiding such discriminated population
from being chosen as mates of sexual function.

How does stigma evolve? (Link and Phelan 2001)

1. Labelling: people distinguish and label human differences.

2. Stereotyping: dominant cultural beliefs are used to group and categorise
labelled persons to undesirable characteristics— to negative stereotypes.
3. Separation: the labelled persons are placed in distinct categories with an
observable degree of separation of "us" from "them."

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 4. Status loss and discrimination follow soon after.

According to Corrigan three different stigma components can be distinguished: stereotypes

(e.g. schizophrenics are violent), prejudice (endorse negative stereotypes result in emotional
reactions) which lead to social discrimination (the resulting behavioural reaction).

Dimensions of stigma (Jones et al., 2000)

1. Concealability - how obvious or detectable the characteristic is to others. Less

concealable problems are more stigmatised.
2. Course - whether the stigmatizing condition is reversible over time, with irreversible
conditions tending to elicit more negative attitudes from others.
3. Disruptiveness - the extent to which a mark strains or obstructs interpersonal
interactions. The degree of stigmatisation is directly proportional to the degree of
disruption in social interaction produced by the condition.
4. Aesthetics - the attractiveness or pleasing nature of a presentation to one's perceptions;
A disorder that elicits an instinctive, and strong reaction of disgust will be more
stigmatised.
5. Origin - one’s understanding of causal factors. A condition thought to be self-inflicted
will have a higher stigma.
6. Peril - feelings of danger or threat that a condition induces. Highly threatening
problems are highly stigmatised.

Interventions against stigma

MIND after NIMBY survey proposed 3 types of antistigma interventions:

 Rights based – legal methods

 Normalising approach – popularising the fact about how common mental illness are –
e.g. 1 in 4 film from Changing Minds campaign, improving contacts between mentally
ill and the neighbours, etc
 Educational media-based approach – highlighting the role of balanced reporting by
media.

Legislative intervention: Not much experimental evidence available to support that anti-
discrimination legislation would or would not change public stereo-types. Legislation may
reduce discriminatory acts but not the prejudice or stereotypes held. It may increase debate
and self-questioning about stigma. People may change behavior to avoid legal sanctions. But
there is a risk that suppressed discrimination will be shown in subtle, unpunishable forms.
This may suppress but not eliminate stigma.

Affective intervention: e.g. increasing contacts between local neighbourhood and the
mentally ill patients living in a hostel. The generalization from a few hostel inmates in a

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locality to the whole category of mentally ill cannot be drawn. It is also noted that when such
contacts were encouraged, the mobility of neighbours of such hostels was higher than that of
people in a control street. Such measures also have the risk of reinforcing a stereotype by sub
typing the better ones and differentiating them from the ‘dangerous’ ones.

Public education: had mixed results, but focussed interventions can increase socially
desirable responses around stigma in the post-campaign survey but no improvement in
behaviour. N.B. ignorance is not the only cause of stigma.

Liz Sayce (‘Psychiatric patient to citizen’) provides four different models for addressing
stigma and social exclusion. These are

A. Brain disease model - also known as ‘no fault’ approach – it’s an illness like any other.
This has the danger of lacking credibility, is too paternalistic and may make ill-person
‘a victim of fate’.
B. Individual growth model - considers a continuum or spectrum of mental health and
illness. In this model, good mental health, emotional distress triggered by bereavement
and enduring psychosis are related experiences (dimensional). The continuum
approach has been critiqued as advocating for the status quo rather than attitude shifts
involving cultural change though it is a popular approach particularly in mental health
promotion.
C. Libertarian model - advocates equal rights and equal criminal responsibility for mental
health service users. The biggest concern is that the net result will be a series of losses
for people with mental health problems rather than gains particularly in the courts and
workplace.
D. Disability inclusion model - the favoured approach that promotes the concept of social
inclusion on civil rights grounds and not just paternalistic ‘help’. Disability is the
impairment plus the effects of socially imposed barriers and prejudices faced by the
individual.

Changing Minds was a 5 years campaign spearheaded by Kendell and colleagues at the
Royal College of Psychiatrists. In the RCPsych 1998 survey, 70% believed that people with
schizophrenia are violent and unpredictable. Various anti-stigma measures were devised and
popularized. 1 in 4 is a short 2-minute film aimed at young adults aged 15-25 to challenge
preconceptions about mental illness. 1 in 4 refers to how common mental illnesses are. ‘Every
Family in the Land’ is a book on stigma published in conjunction. Various other methods
such as tube cards, press articles and videos and road shows were also conducted

Labelling and stigma: A survey of nearly 5000 German nationals revealed important
findings regarding the effect of diagnostic labeling on the stigma (Angermeyer et al. 2003).
Labeling as mental illness has an impact on public attitudes towards people with

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schizophrenia. Endorsing the stereotype of dangerousness has a strong negative effect and
increases the preference for social distance. By contrast, perceiving someone with
schizophrenia as being in need of help evokes mixed feelings and affects people's desire for
social distance both positively and negatively. Labeling has practically no effect on public
attitudes towards people with major depression.

Normalization is a concept that emerged in the context of the deinstitutionalization of people

with developmental disabilities. It focuses on providing disabled individuals with a life in
“normalized” settings in the community. It can be defined as “the utilization of means which
are as culturally normative as possible in order to establish and/or maintain personal
behaviours and characteristics which are as culturally normative as possible” (Wolfensberger
1972)

Social role valorisation was formulated in 1983 by Wolf Wolfensberger to expand the scope
of the principle of normalization. SRV aims to create social roles for devalued people to
enhance their competencies. In other words, SRV deals with the enablement, establishment,
enhancement, maintenance, and/or defense of valued social roles for people. SRV is primarily
a response to the historically universal phenomenon of social devaluation and especially
societal devaluation.

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 10. Culture and mental health

Comparative psychiatry refers to the study of mental illness in different sociocultural

settings; Kraepelin traveled to Southeast Asia and developed the concept of comparative
psychiatry. This is now referred to as transcultural psychiatry.

Two perspectives of cultural studies often discussed:

Emic perspective (emic view): Used to refer to the perspective of an individual from a
specific cultural group about his own group.
Etic perspective (etic view): Refers to the perspective of an individual outside a
specific cultural group about the studied group. The etic approach, for instance, involves
applying Western psychiatric concepts en bloc into a different culture and uses it for
diagnosis. This approach assumes

1. Universality of illnesses
2. Invariance of core symptoms
3. Validity of diagnostic constructs

Different views in etic / emic approaches:

ETIC approach EMIC approach
Diagnosis of mental Similar core symptoms in Linguistic and cultural
illness all cultures variations
acknowledged
Classification Common classificatory Locally derived systems
system systems endorsed endorsed
Preferred Identical rating scales and
measurement measures across nations
method
Preferred research Quantitative methods Qualitative methods
method emphasizing reliability are emphasizing cultural
preferred validity
Treatment methods Biomedically driven Local belief driven
Help seeking Provision of services most Individual health belief
behaviour important and explanatory models
most important

Ethnicity is often defined by a set of cultural patterns (values, beliefs, roles, affective and
cognitive styles, and norms), heritage, or ancestry shared by a social group of common
national or geographic origin.

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 Term Characters Determined by Perceived as
Race Physical Genetic Permanent
appearance
Culture Behaviour & Upbringing Changeable (see
attitudes (enculturation) acculturation)
and choice
Ethnicity Group identity Social; pressures, Partially
psychological changeable
need for
identification
(From Seminars in Gen Adult Psych 1e. Pg. 783)

Acculturation refers to the process of cultural change that takes place when an individual or
a group comes in continuous contact with a culturally distinct group. Acculturation can
result from immigration and can occur in either direction – hosts can get accultured; as
evident in certain places in times of Colonial rule. Four types are described according to the
degree of retention and adoption of the two cultures at ethnocultural group level:

Berry’s model of High degree of Low degree of retention of

acculturation retention of culture of culture of origin
origin
High degree of INTEGRATION ASSIMILATION
adoption of new
culture
Low degree of SEPARATION MARGINALISATION
adoption of new
culture

Assimilation: This refers to partial adaptation of a new culture (seen in migrants or

refugees) without retaining or giving up all of one’s culture of origin completely.
Integration refers to both high retention of one’s own cultural values and high
adoption of the practices of the new culture.
Separation refers to high retention of one’s own cultural values and low adoption of
the practices of the new culture.
Marginalisation refers to both low retention of one’s own cultural values and low
adoption of the practices of the new culture. These individuals get marginalized by
members of both culture of origin and culture of adoption.

When someone loses the identity of one’s culture of origin voluntarily e.g. upon immigration
but does not assimilate or integrate, then the risk of loss of cultural identity and subsequent
increase in mental illness are noted.
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Enculturation refers to culture being learnt through contact with family, friends, teachers
and the media. This happens to everyone irrespective of migration.

At a larger societal (as opposed to small group) level, Berry’s model is often mapped using
the terms given below:

Berry’s model of High degree of retention of Low degree of

acculturation individual culture retention of individual
identities culture identities

High degree of MULTICULTURALISM MELTING POT

relationship among
various cultures
Low degree of SEGREGATION EXCLUSION
relationship among
various cultures in the
society

Cultural bereavement refers to a self-limited grieving response developed by an individual

on leaving his own culture.

Cultural diffusion or syncretism refers to the spread of cultural traits (including psychiatric
syndromes, treatment methods) through contacts across societies. This leads to creating
innovations that are distinct from both groups.

Sojourning refers to voluntary but brief exposure to different culture e.g. tourists, Peace
Corps volunteers. Nostalgia or homesickness is common in sojourners and can be reduced by
shortening length of stay, keeping in touch with family and friends at home and learning
about a new culture before arrival.

Segregation: This refers to removal of people from communities and placing them in an
artificial community, which is more or less an institution. Goffman described 5 types of
segregation:

1. Incapable harmless – orphanages and old age homes

2. Ill but threat to society – mental hospitals
3. Not ill, threat to society with malice – prisons
4. Occupation related – military barracks, boarding schools
5. Retreat from the world – monasteries, convents.

What happens when a family emigrates?

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 1. The elderly often find difficult to adapt and change – rejection of new culture
happens
2. Complete assimilation is seen in young children
3. A bicultural pattern is seen among young adults in working age – at work they
adapt to new culture, but at home they remain attached to the culture of origin.

Function of culture in psychiatric practice

Culture as an explanatory tool: This allows description of non-pathological

behaviours in the context of one’s culture.
Culture as a pathoplastic agent: This allows description of psychopathology that
result from cultural practices.
Culture as a diagnostic factor: This allows culture-specific, unique diagnostic
framework e.g. culture-bound disorders
Culture as a service instrument: This allows utilization of cultural knowledge in
service delivery and resource distribution.
The five elements of cultural formulation (American Psychiatric Association, 2002)

1. The cultural identity of the individual

2. Cultural explanations of the individual’s illness
3. The influence of the patient’s psychosocial environment and level of functioning within
it
4. Cultural elements in the patient–professional relationship (this requires the psychiatrist
to be knowledgeable of her own cultural values and beliefs)
5. The use of cultural assessment in deciding diagnosis and care.
The concept of explanatory models

 Patients’ explanatory models are not fixed and are influenced by the circumstances of
their symptoms, age, gender, educational attainment, time point and context of
assessment and importantly their cultural beliefs.

 Explanatory models themselves can influence a physician’s assessments.

 The process of exploring patient’s identity and explanatory model ensures improved
understanding and informs the successful negotiation of different worldviews. This
exploration does not require psychiatrists to enter into another culture as a participant
observer.

Idioms of distress

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Idioms are well-structured and codified way expressing thoughts via language. Idioms in
one language cannot be translated as such to another – they lose their meaning out of context.
In cultural psychiatry, idioms of distress refer to somatic symptoms that serve as a code for
expressing one’s mental distress in some cultures.

Models of care in cultural psychiatry:

Culturally sensitive care could be delivered using various models. Some of these include

1. Ethnic minority services: Separate services are set up for the growing minority
population, but there is a risk of organizational marginalization in such models.

2. Cultural consultation model: This has been tested in Canada. It consists of a

specialized multidisciplinary team which provides consultations to other clinical
teams, sometimes to the families directly. They do not provide direct patient care.

3. Melting pot model: In this model, institutional factors promoting inequalities

are addressed. Culture is not perceived as a problem area that needs special resources.
Instead, mainstream services are commonly enriched by responding to all cultural
groups’ needs. This guarantees equality of access in care. (Melting pot refers to
regions or countries that accommodate other cultures in huge numbers, eventually
paving way for a high degree of admixture and cultural mosaicism, e.g., United
States).

4. A hedge-your-bets approach: Following both prescribed medication and ethnic,

spiritual therapy may be the best hope for securing adherence. This encourages
honest discussion with family and maintaining religious affiliations.

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 11. Culture-Bound Syndromes

Culture bound syndromes are identified in both ICD and DSM classification systems. Most of
these syndromes are merely locally flavoured varieties of illnesses found elsewhere. Most
actually occur in many unrelated cultures. More than the symptom profiles of the syndromes,
the explanatory mechanisms like witchcraft or humoral imbalances are the defining features.
Such illness beliefs can lead to behaviours that would seem to indicate disordered thought
processes outside their cultural context, which actually make sense within the context. For
example, consider the Chinese syndromes of pa-feng and pa-leng below.

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 Culture-Bound Syndromes
Amok Mostly dissociative not psychotic in nature. Starts with sullen period,
( F68 disorder of followed by outburst of violent, sometimes homicidal behaviour;
personality and A return to premorbid state occurs after the episode.
behaviour) Some instances of amok may occur during a brief psychotic episode or
constitute the onset or an exacerbation of a chronic psychotic process.
Seen in Malaysia, Laos, Philippines, Papua New Guinea, and Puerto Rico.
Ataque de An attack of distress wherein sudden shouting, crying, beating oneself on
nervios chest with dissociation and panic attacks can occur with a sense of being
(F45 somatoform) out of control. May have loss of consciousness or amnesia afterwards.
Related to acute stress (trauma or family conflict)
A sense of heat arising from chest into head may be present
Mechanism: dissociative trance.
Berdache North America
Term for a male who has assumed female gender role
Bouffee delirante Seen in French-speaking nations where a sudden outburst of agitated and
aggressive behaviour, confusion resembling an episode of brief psychotic
disorder.
West Africa and Haiti commonly.
Brain fag West Africa – seen in students with difficulties in concentrating,
remembering, and thinking.
A type of somatoform illness.
Dhat India/SE Asia
(F48 / F45: Refers to severe anxiety and hypochondriacal concerns associated with the
neurotic disorder seminal discharge accompanied by feeling weak and exhausted.
/ somatoform Called shenkui in China (fear of loss of yang from men: see below)
autonomic) According to old Hindu tradition, it takes forty drops of blood to create a
drop of bone marrow and forty drops of bone marrow to create a drop of
sperm
Frigophobia A morbid fear of feeling cold / wind due to presumed yin-yang imbalance.
(Pa-Leng : fear of Yin-yang refers to Oriental psychological notion of two opposing forces;
cold; Pa-Feng: yin is dark, female and negative force. Yang is bright, male and positive
fear of wind) force.
(F40 specific Excessive yin in males leads to pa-leng or pa-feng
phobias) Affected men typically bundle themselves in warm clothing, avoid wind or
drafts, and eat foods that are symbolically and calorically "hot' while
avoiding foods that are "cold"

Koro (Turtle Malaysia, SE Asia

Head) Refers to an episode of sudden and intense anxiety that the penis (or, in
(F48 / F45: women, the vulva and nipples) will recede into the body and possibly
neurotic disorder cause death.
/ somatoform Can occur as epidemics!
autonomic)
Latah Hypersensitivity to sudden fright, often with echopraxia, echolalia,
(F48 / F44: command obedience, and dissociative or trancelike behaviour seen in
neurotic disorder middle-aged women.
/ dissociative) Malaysia and south East Asia

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 Mal de ojo Mediterranean concept of evil eye affecting children with physical
symptoms mostly.
Nerfiza or Nevra Egypt, Greece and Central America
Common, often chronic, episodes of extreme sorrow or anxiety, inducing a
complex of somatic complaints such as head and muscle pain, diminished
reactivity, nausea, appetite loss, insomnia, fatigue and agitation. The
syndrome is more common in women than in men. Often treated with
traditional herbal teas
Piblokto Dissociative episode with excitement often followed by seizures and coma
(F44 dissociative) lasting up to 12 hours.
May be withdrawn before the attack and usually has amnesia for the
episode;
they may tear off clothing, shout obscenities, eat faeces, jump into ice cold
water naked etc.
Seen in Arctic Eskimo communities (Inuits)
Shinkeishitsu “Nervous traits’ in Japanese
A syndrome of obsessions, compulsive perfectionism, social withdrawal,
extreme sensitivity and neurasthenia.
Susto Attributed to a frightening event that causes the soul to leave the body and
(F48 / F45: results in unhappiness and sickness.
neurotic disorder
/ somatoform
autonomic)
Tajin-kyofu-shou Japanese psychiatric syndrome
(F40.1 / 40.8 Fear of losing good will of others due to imagined shortcomings of oneself
social phobia) Social anxiety, tremulousness, self-consciousness and a sense of physical
defect or deformity
Can develop into anthropophobia (fear of people) – a severe form of social
phobia
four subtypes: sekimen-kyofu (the phobia of blushing – closer to social
phobia), shubo-kyofu (the phobia of a deformed body- closer to body
dysmorphic disorder), jikoshisen-kyofu (the phobia of eye-to-eye contact),
and jikoshu-kyofu (the phobia of one’s own foul body odor).
Ufufuyane, Seen in Kenya, Southern Africa; Bantu, Zulu; and affiliated groups
(singular), Anxiety state attributed to the effects of magical potions (given to them by
Amafufunyane, rejected lovers) or spirit possession
(plural), Characteristic sobbing, repeated neologisms, paralysis, trance-like states, or
loss of consciousness in young, unmarried women, who may also
experience nightmares with sexual themes, and rarely episodes of
temporary blindness.
Windigo Involves an intense craving for human flesh and the fear that one will turn
(F68 personality into a cannibal.
and behaviour) Seen among Algonquian Indian cultures
(Adapted from American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders. 4th ed. Washington, DC.)

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 Piblokto

Windigo Pa-leng

Brain Fag

Tajin-kyofu-
shou,
Shinkeishitsu

Boufee
delirante
Amok, Koro, Latah

Mal-de-ojo,
Ataque de
Dhat
nervios,
susto

Ufufuyane

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What effect can culture have on psychopathology?

Tseng described 6 different effects:

1. Pathogenic: Culture is directly causative

2. Pathoselective: tendency to select certain culturally influenced reactions (e.g. culturally
sanctioned suicide of wife when husband dies prematurely)
3. Pathoplastic: Culture influences the manifestation e.g. delusional content. Acute onset of
schizophrenia was seen in 40.3% in developing nations compared to 10.9% of cases in
West. WHO conducted a collaborative study in 4 countries (Montreal, Tehran, Nagasaki,
Tokyo and Basel) using the Schedule for Standardised Assessment of Depression – this
study observed that there was a significant similarity in the core symptoms across various
nations, the differences were quantitative rather than qualitative in terms of depressive
symptoms.
4. Pathoelaborating: Universal behavioural reactions that are selectively reinforced by a
culture
5. Pathofacilitative: cultural beliefs affect the frequency of onset by facilitating risk factors.
6. Pathoreactive: culture affects the treatment, stigma and outcome. Interestingly, the
prognosis of schizophrenia seems much better in developing than developed nations. But
remission was achieved by 62.7% in developing countries compared to 36.8% in the West
(IPSS Data – WHO).

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 12. Philosophy in psychiatry
Philosophy concerns the framework of ideas within which we consider facts presented to us
rather than the facts themselves. William James asserted “philosophy is an unusually stubborn
effort to think clearly”.

Several streams of philosophical enquiries are often invoked to provide clarity and enquire the
concept psychiatric disorders. These include the issues of

1. Illness status of mental symptoms: Consider hypomania and its relationship with a
cheerful disposition. Various mental symptoms have questionable illness status that blurs
the clinical distinction of disease from normality.

2. Influence of morality, legality and mental health: In general psychiatric disorders are
more value-laden than physical disorders e.g. psychopathy and its relationship with
delinquency, alcoholism and its relationship with drunken behaviour, etc. Societal norms
regarding expected functions and roles profoundly influence the identification and
treatment of psychiatric disorders.

3. The issue of ownership or agency: This is especially relevant for symptoms of psychosis.

4. Variation of symptoms: The signs and symptoms of mental disorders are diverse with the
variation spanning across different dimensions e.g. organic-functional, mind-body, state-
trait, etc.

5. Similarities and differences with physical disorders: This has been a crucial issue in the
debate between pro-psychiatry and anti-psychiatry groups.

Anti-psychiatry movement
David Cooper coined the term ‘anti-psychiatry’ in 1960s. The term refers to a confederation of
psychiatrists, psychologists, nurses, social and welfare workers, lay people and patients who
oppose the traditional mental health practice and treatment. The central contentions of the anti-
psychiatry movement are about the diagnostic labels used, lack of agreement and measurability
among practitioners with regard to diagnosis, stigma carried by labeling and the problems with
current treatments which are seen as more damaging than being useful. Invoking various
streams of philosophical enquiries (see the list above) to study the concept of psychiatric
disorders, we can identify five major themes of arguments in the pro- vs. antipsychiatry debate.

 The psychological model: Mental disorders are learned abnormalities of behaviour; hence
the disease model is inappropriate (Eysenck, 1968).

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  The labelling model: The features of ‘so called’ mental disorders are, in fact, the response
of an individual labelled as deviant (see the section on sociology above).

 Hidden meaning model: Apparently irrational behaviours deemed as ‘symptoms‘ are

indeed meaningful for the patient; thus they do not characterise a disorder at all.

 Unconscious mind model: Apparently irrational behaviours representing ‘symptoms’ are

indeed products of an unconscious process and thus can be made comprehensible
(psychoanalytic view).

 Political control models: The medical model of insanity is a socio-political scheme devised
for the purpose of legitimizing the control of the ‘deviant, dangerous, or the undesirable’
(Also known as Foucault stance).

Three major pioneers are 1. R.D. Laing, 2. Thomas Szasz and 3. Foucault. R.D.Laing wrote ‘The
Divided Self’ (1959), ‘Sanity, Madness and the Family’ (1964). Thomas Szasz wrote ‘The Myth of
Mental Illness’ (1961) and ‘The Manufacture of Madness’ (1971). Foucault wrote Madness and
Civilization (1965). R.D. Laing famously said, “insanity need not always be a breakdown; it can
also be a breakthrough”. He also said, “insanity sometimes is the sane response to an insane
society.”

Philosophical basis of psychopathology

Human experience is varied and wide. In order to study the details of human experiences, a
student of psychiatry must initially reduce such broad human experience into a simpler subject
matter. Phenomenology is a method to define more clearly that which we seek to reduce, namely,
the subjective essence of the given experience. (Broome, 2007)

Karl Jasper: Karl Jaspers is widely considered a major figure in philosophy and psychiatry.
Jaspers method of philosophical enquiry into symptoms of psychiatry has laid the foundation for
descriptive psychopathology that we use today. He introduced phenomenology, a long regarded
as a method of philosophic enquiry, to psychiatry. He also distinguished the difference between
causal explanation (aetiology) and meaningful understanding (description) in psychiatry. In fact,
he provided what Ghaemi (2007) regards as the first scientific foundation to psychiatry.

The Understanding/Explanation Distinction: This dichotomy was clearly explained by Jaspers.

By understanding (Verstehen), Jaspers referred to the psychological intuition that an individual
could have about the meaning of a psychological state or event for another individual. By
explanation (Erklären), Jaspers referred to the observable influence of one event or process on
another that could be tested objectively. One can understand this distinction if one considers the

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fact that ‘explanation’ applies best to natural sciences (physics, chemistry, biology) and
understanding applies best to human sciences (like history and art). Psychiatry requires both
understanding and explanation for further study.

Descriptive psychopathology differs from explanatory psychopathology in that it does not

attempt to explain causality; it restricts itself to ‘understanding’ human experience through the
description of what is observed. For this to be practiced, one needs a common language or
terminology. By studying the glossary of psychopathology, one can prepare oneself for further
enquiries in psychiatry. Hence, it is clear that there are two components in descriptive
psychopathology. The initial process is one of observation of behaviour; this is accompanied by
an empathic assessment of subjective experience. The latter is referred to by Jaspers as
phenomenology. To describe a phenomenon, it is important to appreciate the phenomenon from
the beholder’s position. This attempt to ‘feel like how your patient might feel’ is very different
from feeling sorry or pitiful for your patient. The former is called empathy while the latter is
called sympathy. Empathy is an essential component of learning further about the pathological
processes taking place in a patient.

Phenomenology purports to employ various philosophical approaches to defining the symptoms

of psychiatric disorders.

1. Ostensive: illustrating a concept by clinical experience; defining by examples

2. Conventional: defining a concept using conventional description e.g. legal definitions
3. Persuasive: deliberate employment of a term to persuade users to employ it in a specific
manner
4. Declarative: formal explanation of the significance of a word or its constituent parts, as
used in the dictionaries
5. Contextual: defining a concept by the contexts in which it generally occurs e.g. lack of
energy is related to depression
6. Essential: defining the nature of an object
7. Semantic: defining what a word means using other words

Explanatory psychopathology assumes causative factors based on theoretical constructs. Such

explanations may be derived from experiments e.g. behaviourism or derived from arbitrary
hypothetical theories e.g. psychoanalysis.

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 13. Ethics in psychiatry
Ethics provides guidance on decisions that we make in clinical practice. The first written book on
medical ethics was authored by Ishaq bin Ali Rahawi. This book called Adab al-Tabib (Conduct
of a Physician), is thought to be first published in 9th century

Hammurabi code is the first attempt in history to codify medical competence and legal liability
for negligence. It is mostly concerned with surgical negligence and imposes eye-for-eye sentences
for assaults on noblemen though slaves can be ‘replaced if accidentally damaged’! Hammurabi
cannot be regarded as a code of ethics.

Charaka, an ancient Indian physician, proposed what seems to be the earliest of medical ethics
relevant to modern medicine. This clearly outlined four ethical principles of a doctor:

 Friendship
 Sympathy towards the sick (Caring attitude)
 Interest in cases according to one's capabilities and
 No attachment to the patient after his recovery.
Charaka also emphasised the personal values central to the nobility of the profession, thus: 'Those
who trade their medical skills for personal livelihood can be considered as collecting a pile of dust, leaving
aside the heap of real gold'. Furthermore, 'He who regards kindness to humanity as his supreme religion
and treats his patients accordingly, succeeds best in achieving his aims of life and obtains the greatest
pleasures'. Charaka also advised his fellow practitioners to “always strive to acquire knowledge”
(i.e. Continuous Professional Development in modern terms) and highlighted the importance of
confidentiality.

Present day ethical principles:

1. Higher order principles: Deontology and teleology are two alternative higher-order ethical
principles concerning current medical practice.

The term Deontology derives from the Greek ‘Deon’ for ‘duty’ indicating the centrality of rules
in governing medical practice. Accordingly, rights and duties determine action and so it is also
called as absolutism. According to Ross, some duties are right because of their very nature (such
as the duty to tell the truth); these are called prima facie duties. Others are right in particular
circumstances, called duty proper. Whilst this approach (duty-based approach) provides security
and clarity, there may be conflicts in managing particular problems and meeting the individual
patient’s wishes and needs. Examples of rules include GMC Good medical Practice and the
RCPsych code of ethics.

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The term Teleology derives its name from the Greek ‘Teleon’, meaning ‘purpose’ and the central
concept is that rather than rights, people have interests, whether these are concerns, desires or
needs. Accordingly, the broad judgment of benefits and harm determine medical practice. It
assumes that the right action is the one that has the best foreseeable consequences. It is also called
as consequentialism or utilitarianism. Utilitarianism takes two forms:

 Act utilitarianism deals with a specific act only (situational ethics).

 Rule utilitarianism deals with general practices (for which rules can be established).

Evaluation of utilitarianism: The strengths of utilitarianism lies in its practicality and clarity. It
approximates the principle of ‘beneficence’ (see below) and fits well with approaches to public
policy. Two factors extraneous to psychiatry influence utilitarianism's position in psychiatric
ethics. First, legislated responsibilities of psychiatrists, particularly in relation to issues of public
safety (e.g., when applying Mental Health Act). Such legal imperatives are invariably utilitarian
in nature and have usually emerged in the context of social and political responses to issues such
as public safety especially in relation to forensic patients. The other factor promoting utilitarian
thinking in psychiatric ethics has been the profound changes to healthcare systems in the face of
globalization and financial pressures (managed care settings).

2. Prima facie principles: American philosophers Tom Beauchamp and James Childress and
British doctor & philosopher Raanon Gillon pioneered the following prima facie principles:

 autonomy—respecting patients' wishes and freedom of choice

 beneficence—acting in patients' best interests

 Non-maleficence—avoiding harm – primum non nocere.

 Justice—treating problems equally, with equitable distribution of resources to the needy.

These four principles are the main guiding aspects of current practice, and most other related
ethical discussions relevant to clinical practice can be brought under these topics.

3. Models of doctor – patient interaction:

 The paternalistic model. It is assumed that the doctor knows best. It is an autocratic model
where treatments are prescriptive. May be desirable in emergency situations. But often this
approach results in a clash of values.

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  The informative model. The doctor is seen as a dispenser of information. Here the choice
is left wholly up to the patient. May be useful in one-off consultations, but may not work
well if strictly followed on long-term professional relationship.

 The interpretive model. Here the doctor will be treating the patient for a long time and
might know his/her patient well and understand the circumstances of their micro-
environment. Here shared decision-making is established.

 The deliberative model. The doctor here may act as a friend or counselor to the patient,
where information dispensing is coupled with advice on a course of action. This is
commonly used to enable lifestyle modification and to address maladaptive coping.

4. Other terms used:

 Direct Ethics is about the action taken. To determine what ethical behaviour is, we
should assess the act -- what has been done.
 Indirect Ethics is about the actor -- the nature of the individual choosing those actions.
The main concern here is the formation of character by a moral agent (a person).
 Pragmatic ethics: Emphasis is on achieving success, on reaching a goal with relatively
little concern for how that success is achieved.
 Humanistic ethics: Emphasis is on doing what's best for society. This dominates ethical
theory overwhelmingly; according to humanism, ethics is held as a virtue, with its goal
being social improvement rather than personal success.

Although some actions are always wrong (murder, for instance), in most cases, ethical behaviour
lies between extremes, along a range between excess and deficiency. This is the idea of the
golden mean of Aristotle.

Landmark publications relevant for critique on ethics

 Nuremberg Code 1974: Code of ethics following the Nuremberg Trials (post-World War II
Trial concerning doctors experimenting on people detained in concentration camps).
According to Nuremberg Code, human experimentation can be carried out only if
 Voluntary consent is given
 Research is intended for common good of the society
 Avoidance of unnecessary pain and suffering is guaranteed for the subjects
 Subject has liberty to withdraw at any point
 Qualified researchers undertake research
 Scientist must terminate a study if more harm is being caused than expected to the
subjects
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  Declaration of Geneva 1948: Reaffirmation of humanitarian aims of medicine by World
Medical Association. The Declaration of Geneva is a modification of Hippocratic Oath,
intended to highlight the dedication of medical profession for the cause of humanitarian
goals.
 Declaration of Helsinki 1964: This was adopted by The 18th World Medical Association
General Assembly in 1964 and has been amended five times since, most recently in 2000.
Notes of clarification were added in 2002 and 2004. The current (2004) version is the only
official one. The Declaration specifically addresses clinical research, reflecting changes in
medical practice from the term 'Human Experimentation' used in the Nuremberg Code.

Landmark studies relevant for critique on ethics

Tuskegee Syphilis Study (1932-1972): Between 1932 and 1972, US public health service followed
up nearly six hundred low-income African-American males, 400 of whom were infected with
syphilis. All diseased subjects were periodically examined but were not informed of the disease
that they were diagnosed with and the implications of such diagnosis, even after the introduction
of penicillin in 1950s. In some cases, when other physicians diagnosed subjects as having syphilis,
researchers intervened to prevent treatment, in order to study the natural course of syphilis.
Many subjects died of syphilis during the study. The study was strongly criticized, and US
government issued a public apology in 1997. As a result of this Belmont Report was produced.
Important principles outlined:

1. Respect for persons i.e. Individuals should be treated as autonomous agents and those
with diminished autonomy should be adequately protected for research purposes.

2. Informed consent should be obtained by providing full information, ensuring

comprehension and maintaining voluntariness (can withdraw at any time).

3. During a research, beneficial effects must outweigh any harms caused, with a systematic
assessment of benefits and risks carried out beforehand.

Willowbrook School Study (1963 - 1966): Mentally handicapped children at Willowbrook State
School were deliberately infected with hepatitis after parents gave consent for what they thought
to be vaccinations. The study was looking at the course of hepatitis and effectiveness of viral
inoculation. There is evidence to suggest only consenting families were admitted to the school.

Jewish Chronic Disease Hospital: Studies to develop information about the nature of human
transplant rejection. Chronically ill patients who did not have cancer where unknowingly
injected with cancerous human liver cells. The defense argued that the administration did not
want to scare patients and expected the cells to be rejected.
© SPMM Course 48
Tearoom Trade Study: During 1960s, a sociologist called Laud Humphries followed up many
men who had anonymous sex in public places by tracing their number plates after falsely
befriending them. The research was conducted without explicit informed consent and became a
matter of debate, highlighting the important of ethics in scientific research in non-medical fields
of enquiry.

DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgments have not been possible for every passage/fact that is common knowledge in
psychiatry. We do not check the accuracy of drug-related information using external sources; no
part of these notes should be used as prescribing information

© SPMM Course 49
Notes prepared using excerpts from:

 Angermeyer MC, Matschinger H. The stigma of mental illness: effects of labelling on public attitudes towards
people with mental disorder. Acta Psychiatr Scand 2003; 108:304–309.
 Bebbington & Kuipers, 2003. Schizophrenia and psychosocial stresses. In Schizophrenia, Hirsch & Weinberger
(Ed). Blackwell; Oxford.
 Benbow, A. (2007) Mental Illness, stigma and the media. Journal of clinical psychiatry, 6; supp 2: 31 – 35
 Bhugra & Gupta: Medical professionalism in psychiatry. Advances in Psychiatric Treatment (2010) 16: 10-13
http://apt.rcpsych.org/content/16/1/10.full
 Bhui, K & Bhugra D. Communication with patients from other cultures: the place of explanatory models.
Advances in Psychiatric Treatment 2004, 10 (6) 474-478;
 Boyer, BA. & Paharia, MI. (Ed) Comprehensive Handbook of Clinical Health Psychology. 2008. John Wiley &
Sons; NewYork
 Chapter on Sociology and Psychiatry. Companion to psychiatric studies. 6 th ed.
 Cooper, B. Immigration and schizophrenia; the social causation hypothesis revisited. British Journal of
Psychiatry (2005) 186: 361-36
 Corrigan PW, Watson AC. Understanding the impact of stigma on people with mental illness. World Psychiatry
2002; 1: 6– 20.
 Crisp, A. H., et al (2004) The College’s Anti-Stigma Campaign, 1998–2003: a shortened version of the
concluding report. Psychiatric Bulletin, 28, 133 –136.
 Curson DA, et al. Institutionalism and schizophrenia 30 years on. Clinical poverty and the social environment
in three British mental hospitals in 1960 compared with a fourth in 1990. British Journal of Psychiatry 1992; 160:
230-241.
 Galea et al. The Social Epidemiology of Substance Use. Epidemiol Rev 2004;26:36–52
 Hashemi, A. H. & Cochrane, R. (1999) Expressed emotion and schizophrenia: a review of studies across
cultures. International Review of Psychiatry, 11, 219–224
 http://www.medschools.ac.uk/
 Jorm AF, Korten AE, et al. Helpfulness of interventions for mental disorders: beliefs of health professionals
compared with the general public. Br J Psychiatry 1997; 171: 233-237
 Kendler, KS et al. Life Event Dimensions of Loss, Humiliation, Entrapment, and Danger in the Prediction of
Onsets of Major Depression and Generalized Anxiety. Arch Gen Psychiatry. 2003; 60(8):789-796.
 Kendler, KS et al. Stressful life events and genetic liability to major depression: genetic control of exposure to
the environment? Psychological Medicine (1997), 27: 539-547
 Link et al. Measuring Mental Illness Stigma Schizophrenia Bulletin, Vol. 30, No. 3, 2004. 30 (3): 511. (2004)
 Morriss & Morriss. Contextual evaluation of social adversity in management of depressive disorder. Advances
in Psychiatric treatment. 2000, 6, pp. 423–431
 Muntaner C et al. Socioeconomic Position and Major Mental Disorders. Epidemiol Rev (2004) 26 (1): 53-62.
 Peele et al. (1977). Asylums revisited. American Journal of Psychiatry, 134: 1077-81.
 Weindling, P.J. (2005). Nazi Medicine and the Nuremberg Trials: From Medical War Crimes to Informed Consent.
Palgrave Macmillan.
 WMA Medical Ethics Manual. Last Accessed on 30 Jan 2015 at
http://www.wma.net/en/70education/30print/10medical_ethics/
© SPMM Course 50
  

   

Neuroanatomy  
Paper  A   Syllabic  content  3.1  
 
© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
©  SPMM  Course   1  
1. General anatomy of the brain
A. Cortical structures
The  cerebrum  has  four  major  lobes  (frontal,  temporal,  parietal  and  occipital  lobes).  The  lobar  surface  is  
heavily  folded  forming  sulci  (valleys)  and  gyri  (ridges).  Primary  (major)  sulci  are  more  invariant  in  their  
appearance  than  the  secondary  (minor)  sulci.    

The  central  sulcus  divides  frontal  lobe  from  the  parietal  lobe.  Precentral  gyrus  (part  of  the  frontal  lobe)  is  
the  primary  motor  cortex.  The  representation  of  different  body  parts  in  this  region  is  often  termed  as  a  
homunculus.  Postcentral  gyrus  (part  of  the  parietal  lobe)  is  the  primary  somatosensory  cortex  with  a  
similar  homunculus  representation.    

The  lateral  sulcus  (Sylvian  fissure)  divides  frontal  lobe  from  the  temporal  lobe.  The  insula,  a  structure  
that  is  sometimes  regarded  as  the  fifth  lobe  of  the  cerebrum,  is  located  deep  in  the  Sylvian  fissure.  Insula  is  
the  seat  of  the  primary  gustatory  cortex.    

Other  major  primary  sulci  include      

1. Superior  and  inferior  frontal  sulci:  In  between  these  sulci  is  the  middle  frontal  gyrus  constituting  
the  dorsolateral  prefrontal  cortex,  often  considered  to  be  responsible  for  executive  functions  of  the  
human  brain.      
2. Cingulate  sulcus  on  the  medial  side  of  the  frontal  lobe.  The  anterior  portion  of  the  adjoining  
cingulate  gyrus  is  considered  to  be  the  seat  of  motivation.      
3. Olfactory  and  orbital  sulci  on  the  inferior  surface  of  the  frontal  lobe.  The  orbitofrontal  cortex  is  
often  considered  to  be  the  seat  of  associative  learning  and  decision-­‐‑making.    
4. The  Superior  temporal  sulcus  is  forming  superior  temporal  gyrus,  the  seat  of  primary  auditory  
cortex.    
5. The  interparietal  sulcus  separates  superior  and  inferior  parietal  lobes.  The  inferior  parietal  lobe  is  
made  of  the  angular  gyrus  and  supramarginal  gyrus  and  is  considered  to  be  important  for  
visuospatial  attention.    
6. Calcarine  sulcus  in  the  medial  occipital  cortex,  the  seat  of  primary  visual  (striate)  cortex    

Hemispheric lateralisation
¬ Most  fundamental  brain  functions  are  represented  bilaterally.  Higher  levels  of  associative  
functions  usually  lateralize  to  one  or  other  hemisphere.  For  example,  language  comprehension  is  
localized  to  the  left  temporal  cortex  while  prosody  (tonal  modulation  of  speech)  seems  limited  to  
the  right  hemisphere.  
¬ The  hemisphere  contralateral  to  the  dominant  hand  is  the  dominant  hemisphere,  and  it  mediates  
language  and  speech  functions.    
¬ Dominance  can  be  tested  using  Annette’s  handedness  scale  or  Edinburgh  handedness  inventory.  
But  handedness  is  not  always  same  as  dominance.  

©  SPMM  Course   2  
 ¬ In  right-­‐‑handed  people,  the  left  hemisphere  is  mostly  dominant.  In  10%  of  right-­‐‑handed  people,  
the  right  hemisphere  is  dominant.  Among  left-­‐‑handed  people  only  about  20%  are  right  
hemisphere  dominant,  with  64%  left  hemisphere  dominant  and  16%  showing  bilateral  dominance.  
¬ Size  asymmetry:  The  planum  temporale  is  a  
Left  Hemisphere   Right  Hemisphere  lesions  
triangular  region  on  the  upper  surface  of  the  
lesions  
superior  temporal  gyrus.  It  is  important  for   Aphasia   Visuospatial  deficits  
language  processing  and  is  larger  on  the  left  
Right-­‐‑left   Anosognosia  
than  the  right  hemisphere  in  65%  brains.  It  is   disorientation  
probably  the  most  asymmetrical  structure  in   Finger  agnosia   Neglect  
the  human  brain,  with  some  individuals   Dysgraphia  (aphasic)   Dysgraphia  (spatial,  neglect)  
Dyscalculia  (number   Dyscalculia  (spatial)  
having  a  five  times  larger  planum  temporale  
alexia)  
on  the  left  than  on  the  right.  This  asymmetry   Limb  apraxia   Constructional  apraxia    
is  reportedly  reduced  or  reversed  (right>left)   Dressing  apraxia  
 
in  schizophrenia.    
Face  recognition  (bilateral)  
 

B. Subcortical structures
Limbic system/ Papez circuit
¬ Broca  first  described  the  limbic  lobe.  Papez  and  later  Maclean  assigned  the  function  of  emotional  
processing  to  limbic  structures  though  this  view  is  challenged  in  recent  times.    
¬ The  Papez  circuit  consists  of  the  hippocampus  →  fornix  →  mammillary  bodies  →  
mammillothalamic  tract  →  anterior  thalamic  nucleus  →  genu  of  the  internal  capsule  →  cingulate  
gyrus  →    parahippocampal  gyrus  →  entorhinal  cortex  →  perforant  pathway  →  back  to  
hippocampus  
¬ The  boundaries  of  the  limbic  system  were  subsequently  expanded  outside  of  the  Papez  circuit  to  
include  the  amygdala,  septum,  basal  forebrain,  nucleus  accumbens,  and  orbitofrontal  cortex.  
¬ The  limbic  system  is  thought  to  be  involved  in  various  functions  such  as  mediation  of  emotional  
responses  (through  amygdala),  influencing  neuroendocrine  responses  (via  hypothalamus)  and  
reward  system  regulation  (via  nucleus  accumbens).  
¬ The  limbic  system  is  often  considered  to  be  evolutionarily  older  than  the  higher  cortical  centres.    

Medial temporal structures

¬ Include  the  hippocampus,  amygdala,  entorhinal  and  parahippocampal  cortex.    
¬ Hippocampus  appears  to  play  an  important  role  in  memory  processes.  It  is  one  of  the  few  brain  
regions  where  the  continuous  production  of  new  neurons  is  noted  even  in  adult  life.  
¬ Amygdala  appears  crucial  for  fear  conditioning  and  emotional  regulation  

Basal Ganglia
¬ The  basal  ganglia  are  a  group  of  gray  matter  nuclei  forming  the  largest  subcortical  structure  in  the  
brain.  They  are  involved  in  the  planning  and  programming  of  movement,  and  also  have  a  role  in  
the  processes  by  which  an  abstract  thought  is  converted  into  voluntary  action  

©  SPMM  Course   3  
 ¬ They  include  striatum  made  of  the  caudate  nucleus  and  putamen  and  pallidum  made  of  globus  
pallidus.  Putamen  and  globus  pallidus  are  sometimes  called  lenticular/lentiform  nucleus.  
¬ The  subthalamic  nuclei  and  the  substantia  nigra  are  both  functionally  related  to  the  basal  ganglia  
but  are  not  considered  to  be  a  part  of  this  structure.    
¬ Basal  ganglia  receive  crucial  inputs  from  glutamatergic  corticostriatal  projection.  Alexander  
described  five  important  circuits  involving  the  basal  ganglia.  These  are  
• Motor  circuit  
• Oculomotor  circuit  
• Dorsolateral  prefrontal  circuit  (executive)  
• Anterior  cingulate  circuit  (motivation)  
• Lateral  orbitofrontal  circuit  (social  intelligence)  
 

Disorder     Nature  of  basal  ganglia  dysfunction    

OCD     Volumetric  changes  and  higher  blood  flow  to  the  caudate  nuclei.  Increased  caudate  
metabolism  in  untreated  subjects  reduces  after  effective  treatment.    
Tourette’s  syndrome   Striatal  dopaminergic  dysfunction  
Huntington  chorea   Degeneration  of  the  striatum  (mainly  caudate  nucleus)  &  selective  loss  of  GABAergic  
neurons  
Wilson  disease   Copper  deposits  in  the  lenticular  nuclei    
CO  poisoning   Acute  bilateral  anoxic  damage  to  basal  ganglia  
Hemiballismus   Subthalamic  nucleus  damage  (especially  infarction)  
Parkinsonism     Depigmentation  of  Substantia  Nigra;  Lewy  bodies  are  seen.  Striatal  overactivity  
associated  with  bradykinesia  
Fahr'ʹs  disease   Progressive  calcium  deposition  in  the  basal  ganglia.  (early  onset  cases  present  with  
schizophreniform  psychoses  and  catatonia;  later  onset  cases  exhibit  dementia  and  
choreoathetosis)  
Thalamus
¬ A  large  oval  mass  of  grey  matter  nuclei  in  the  subcortical  region,  relaying  all  types  of  sensory  
information  onto  cortex  (except  olfaction).  
¬ It  also  relays  cerebellar  and  basal  ganglia  inputs  to  the  cerebral  cortex.  
¬ The  thalamus  is  said  to  play  a  crucial  role  of  filtering  sensory  information  in  preparation  for  
cortical  processing.  
¬ The  anterior  thalamus  is  a  part  of  the  limbic  system.  It  receives  the  mamillothalamic  tract  and  
fornix  and  connects  to  the  cingulate  cortex.  Thus,  it  relays  information  from  hypothalamus  and  
hippocampus  onto  the  frontal  cortex.  
¬ Pulvinar  is  associated  with  visual  attention.  Sleep  spindles  are  generated  in  the  reticular  nucleus  of  
the  thalamus.  

©  SPMM  Course   4  
Hypothalamus
¬ The  hypothalamus  regulates  physiological  
INFERIOR  OLIVARY  NUCLEUS  
functions  such  as  eating,  drinking,  sleeping,  
and  temperature  regulation.   Inferior  olivary  nucleus  is  located  in  the  
¬ The  hypothalamus  has  chemoreceptors  that   brainstem  and  aids  in  motor  coordination  by  
respond  to  variations  in  glucose  levels,   projecting  climbing  fibers  to  the  contralateral  
cerebellar  cortex  via  inferior  cerebellar  
osmolarity,  acid  balance,  etc.  It  also  plays  a  
peduncle.  
major  role  in  neuroendocrine  control.  
Inferior  olivary  lesions  lead  to  appendicular  
¬ The  ventromedial  hypothalamus  acts  as  the  satiety   ataxia  due  to  motor  incoordination  of  the  
centre  while  the  lateral  hypothalamus  is  the   contralateral  arm  and  leg.    Patients  with  
feeding  centre.  In  animals  with  a  lesion  of   inferior  olivary  lesions  will  fail  the  finger-­‐‑nose  
ventromedial  hypothalamus  hyperphagia  and   test,  mimicking  cerebellar  lesion.    But  unlike  
obesity  are  noted.   cerebellar  lesions  that  result  in  ipsilateral  motor  
incoordination,  the  contralateral  side  is  affected  
C. Cerebellum in  olivary  lesions.  

The  cerebellum  has  the  important  role  of  preparing  a  

motor  plan  and  predicting  balance  needed  between  
muscle  groups  to  carry  out  the  intended  action  smoothly.  Cerebellar  lesions  produce  ataxia  and  coarse  
intentional  tremors,  along  with  hypotonia,  past  pointing  and  pendular  knee  jerk.    
 
Increasingly  the  role  of  the  cerebellum  in  cognitive  processes  has  been  appreciated.  The  term  cognitive  
dysmetria  (Andreasen)  refers  to  the  difficulty  in  coordinating  and  monitoring  the  process  of  receiving,  
processing,  and  expressing  information  that  could  result  from  disrupted  cortico-­‐‑cerebellar  circuitry  in  
schizophrenia.  
 

D. Brain stem and cranial nerves

The  brain  stem  is  made  of  the  midbrain,  pons  and  the  medulla.    Most  of  the  cranial  nerves  (9  out  of  12)  
enter  or  exit  the  brain  from  the  brainstem.  
 
The  midbrain  consists  of  superior  (conjugate  gaze  control)  and  inferior  colliculi  (auditory  source  
localization).  The  substantia  nigra  is  also  located  in  the  midbrain  along  with  periaqueductal  grey  matter  
that  plays  an  important  role  in  vocalization  and  freezing  response  to  threat  and  in  pain  suppression.    
Pons  is  positioned  beneath  the  cerebellum  and  surrounds  the  upper  half  of  the  4th  ventricle  
Medulla  surrounds  inferior  part  of  the  4th  ventricle  and  is  continuous  with  the  spinal  cord.    
No. Name Anatomical features
I Olfactory Runs on the basal surface of frontal cortex without passing through the thalamus. Formed as
an outgrowth of forebrain
II Optic Also an outgrowth of the forebrain. Relays via thalamus (geniculate body)
III Oculomotor Purely motor function. Supplies four of the six ocular muscles
IV Trochlear Purely motor function. Supplies superior oblique (ocular muscle)
V Trigeminal Both sensory and motor. Transmits facial sensation and controls jaw muscles
VI Abducens Purely motor function. Supplies lateral abducens (ocular muscle)
©  SPMM  Course   5  
 VII Facial Both sensory and motor. Transmits taste sensation and controls facial muscles
VIII Vestibular Transmits auditory sensation
Cochlear Transmits balance sensation
IX Glossopharyngeal Motor control of pharynx; parasympathetic control of the parotid gland; taste from the back of
the tongue.
X Vagus Motor control of larynx and pharynx; parasympathetic control of the viscera; visceral
sensations.
XI Accessory Motor control of neck muscles
XII Hypoglossal Motor control of tongue muscles
 

E. Spinal Cord
Unlike  cerebrum  where  grey  matter  is  on  the  outer  surface,  in  spinal  cord  grey  matter  occupies  the  deeper  
aspect  forming  an  H  shaped  column  surrounding  the  CSF.  The  white  matter  bundles  form  anterior,  lateral  
and  dorsal  columns  around  the  grey  matter  zone.  The  dorsal  column  carries  proprioceptive  sensory  fibres;  
the  anterior  and  lateral  columns  are  made  of  ascending  spinothalamic  tracts  carrying  touch,  pressure,  
pain  and  temperature  sensations.    

F. Cerebrospinal fluid
CSF  is  secreted  by  the  choroid  plexus  in  the  lateral,  third  and  fourth  ventricles  and  at  a  rate  of  300  ml/day,  
which  is  almost  protein  free.  

Route:    From  lateral  ventricle  to  3rd  ventricle  via  interventricular  foramina  of  Monroe;  From  3rd  to  4th  
ventricle  via  cerebral  aqueduct  of  Sylvius;  From  4th  ventricle  to  subarachnoid  space  via  foramen  of  
Magendie  (single)  and  foramina  of  Luschka  (two  lateral).    

The  body  of  the  lateral  ventricle  lies  immediately  below  the  corpus  callosum,  and  the  two  lateral  ventricles  
are  separated  by  septum  pellucidum.  The  third  ventricle  lies  between  thalamus  and  hypothalamus.  The  
fourth  ventricle  lies  above  the  pons  and  just  below  the  cerebellum.  

Obstruction  to  CSF  circulation  commonly  occurs  within  third  or  fourth  ventricle  (foramen  of  Monroe),  
leading  to  non-­‐‑communicating  hydrocephalus.  Impairment  of  CSF  reabsorption  in  the  subarachnoid  
space  due  to  partial  occlusion  of  the  arachnoid  villi  leads  to  communicating  hydrocephalus.    

©  SPMM  Course   6  
2. Blood supply to the brain
A. Major branches
The  internal  carotid  artery  enters  the  circle  of  Willis  and  divides  to  form  the  anterior  cerebral  and  middle  
cerebral  arteries.    
The  anterior  cerebral  artery  supplies  the  medial  and  superior  strip  of  the  lateral  aspect  of  the  cerebral  
cortex  up  to  the  parietal/occipital  border.  
The  middle  cerebral  artery  supplies  most  of  the  lateral  aspect  of  the  cerebral  cortex.  This  includes  the  
Broca’s  and  Wernicke’s  areas  in  the  dominant  hemispheres.    
The  posterior  cerebral  artery  arises  
from  basilar  artery  and  supplies  the   Carotid  system   Vertebrobasilar  
inferomedial  temporal  lobe  and  the   TIA TIA
occipital  lobe.  
The  medulla  is  supplied  by  posterior   •Amaurosis  fugax  (due  to   •Diplopia,  vertigo,  vomiting
blockade  of  retinal  arteries) •Choking  and  dysarthria
inferior  cerebellar  arteries  and  anterior   •Aphasia •Ataxia
spinal  branches  of  vertebral  arteries.   •Hemiparesis •Alexia  without  agraphia
Pons  is  supplied  by  the  basilar  artery   •Hemisensory  loss •Hemisensory  loss
•Hemianopic  visual  loss •Hemianopic  visual  loss
that  runs  along  the  midline  of  the  pons.  
•Transient  global  amnesia
 
•Tetraparesis
  •Loss  of  consciousness  (rare)

B. Effect of lesions
 
Artery   Supply   Lesion  effects  
Anterior  Cerebral  Artery   Medial  surface  (ventromedial   Bilateral  infarct  produces  quadriparesis  (legs  weaker  
(ACA)   frontal  lobe,  the  cingulum,  the   than  arms)  and  akinetic  mutism  (ventromedial  or  
premotor  cortex,  and  medial   cingulate  syndrome)  
motor  strip)  

Recurrent  artery  of   Head  of  the  caudate  nucleus   Initially  an  agitated,  confused  state;  evolves  to  
Huebner  (branch  of  ACA)   akinesia,  abulia,  with  mutism  and  personality  changes  

Anterior  branches  of  the   Lateral  prefrontal  cortex   Planning  deficits,  impairment  of  working  memory,  
upper  division  of  the   and  apathy.  (DLPFC  dysfunction)  
Middle  Cerebral  Artery    

Anterior  communicating   Basal  forebrain   Akinesia  and  personality  change  (orbitofrontal  

artery   dysfunction)  with  a  confabulatory  amnesia  
resembling  Wernicke-­‐‑Korsakoff  syndrome.  

Posterior  inferior   Lateral  medulla   Wallenberg'ʹs  lateral  medullary  syndrome.  Acute  

cerebellar  artery  (PICA)   vertigo  with  cerebellar  signs.  Ipsilateral  face  
thrombosis   numbness,  diplopia,  nystagmus,  Horner’s  syndrome  
and  IX/X  nerve  palsy  with  contralateral  spinothalamic  
sensory  loss  and  mild  hemiparesis.    

©  SPMM  Course   7  
3. White matter pathways
There  are  3  major  types  of  white  matter  pathways.  Projection  fibers  run  vertically  connecting  higher  and  
lower  centres  of  the  brain.        Association  fibers  interconnect  different  regions  within  the  same  hemisphere  
of  the  brain.    Commissural  fibers  interconnect  similar  regions  in    the  opposite  hemisphere.    

Corpus  callosum  is  the  largest  bundle  of  fibres  that  connect  the  two  cerebral  hemispheres;  the  other  such  
bundles  are  anterior  commissure  (interconnects  olfactory  bulbs),  posterior  commissure  (interconnects  
midbrain  pretectal  nuclei),  hippocampal  commissure  and  habenular  commissure  (interconnects  posterior  
dorsal  thalamic  nuclei).    

The  pericallosal  artery  derived  from  the  anterior  cerebral  artery  provides  blood  supply  to  the  anterior  
aspect  and  most  of  the  body  of  the  corpus  callosum.  Left  sided  apraxia  and  agnosia  may  be  seen  in  cases  
of  vascular  disruption.    

Posterior  cerebral  artery  territory  supplies  splenium  (posterior  aspect  of  the  corpus  callosum)  and  
disrupted  supply  here  prevents  right  visual  cortex  accessing  the  dominant  hemispheric  processes  such  as  
language  resulting  in  alexia  and  color  anomia  but  with  preserved  ability  to  copy  words  as  motor  
information  is  relayed  via  anterior  corpus  callosum    

Fornix  is  an  important  white  mater  tract  that  connects  hippocampus  to  the  hypothalamus  via  mammillary  
bodies.  Thus,  it  relays  cortical  input  to  regulate  neuroendocrine  and  autonomic  systems.    

Arcuate  fasciculus  connects  Broca’s  and  Wernicke’s  areas.  Damage  results  in  conduction  aphasia.    

Uncinate  fasciculus  is  a  major  frontotemporal  tract  that  connects  orbitofrontal  cortex  to  the  anterior  
temporal  lobes.  It  plays  an  important  role  in  social  cognition  and  language.    

©  SPMM  Course   8  
4. Cell types in the nervous system
A. Cortical layers
The  human  brain  contains  approximately  1011  neurons  (nerve  cells)  and  approximately  1012  glial  cells.  

According  to  the  distribution  of  the  various  types  of  neurons  (i.e.  the  cytoarchitecture),  Brodmann  divided  
the  cortex  into  47  ‘specialised’  areas.      

The  neocortex  (most  of  the  cerebrum)  is  made  up  of  six  layers,  with  pial  surface  above  layer  1  to  the  white  
matter  below  layer  6.    Layers  2  and  4  are  mainly  afferent  (receiving  inputs)  while  5  and  6  are  mainly  
efferent  (sending  outputs).  

The  pyramidal  neurons  with  their  triangular-­‐‑shaped  cell  bodies  make  up  nearly  75%  of  the  cortical  
neurons.  Stellate  cells  (25%)  are  present  in  all  the  layers  except  layer  1.  

Layer   Name   Predominant  cells  

1   Molecular/agranular   Glial  cells,  dendrites  from  neurons  of  deeper  layers  and  the  
horizontal  cells  of  Cajal.  
2   External  Granular  layer   Granule  cells  and  small  pyramidal  cells  (these  get  larger  as  you  
move  down)  
3   External  Pyramidal  layer     Small  and  medium  sized  pyramidal  cells.  

4   Internal  Granular  layer   Some  pyramidal  cells,  mostly  granule  cells.  Receives  
  thalamocortical  inputs.    
5   Internal  Pyramidal  layer   Largest  pyramidal  cells  (esp.  in  motor  cortex:  Betz  cells)  
6   Multiform  layer   A  mixture  of  all  cells,  spindle  cells,  Martinotti  cells.  The  major  
source  of  corticothalamic  fibres.  Gives  rise  to  
association/commissural  and  projection  fibres.    
 

The  cerebellar  cortex  is  three  layered.    The  molecular  layer  consisting  of  basket  cells  and  stellate  cells,  
Purkinje  layer  consisting  of  Purkinje  cells  and  a  Granular  layer  consisting  of  granule  and  Golgi  cells.  

B. Special neuronal cell types

Purkinje  cells  are  a  class  of  GABAergic  neurons  located  in  the  cerebellar  cortex  only.  Purkinje  cells  form    
the  sole  output  of  all  motor  coordination  in  the  cerebellum  they  connect  to  the  deep  cerebellar  nuclei  via    
inhibitory  projections.    

Granule  cells  are  found  within  the  granular  layer  of  the  cerebellum,  layer  4  of  the  cerebral  cortex,  the  
dentate  gyrus  of  the  hippocampus,  and  in  the  olfactory  bulb.    

Large  pyramidal  cells  called  Betz  cells  are  seen  in  the  primary  motor  cortex.  Betz  cells  are  pyramidal  cell  
neurons  located  within  the  fifth  layer  of  the  grey  matter  in  the  primary  motor  cortex.  These  neurons  are  

©  SPMM  Course   9  
the  largest  in  the  central  nervous  system,  sometimes  reaching  100  µμm  in  diameter.  Betz  cells  represent  
about  10%  of  the  total  pyramidal  cell  population  in  layer  V  of  the  human  primary  motor  cortex.  

Stellate  cells  are  found  in  layer  IV  of  the  cerebral  cortex  (from  thalamus  feeding  forward  to  pyramidal  
cells)  and  also  in  the  cerebellum.    

C. Glial cells
BLOOD  BRAIN  BARRIER  
These  are  cells  with  supportive  metabolic  functions;  
 
they  also  participate  in  modulating  neuronal   The  blood-­‐‑  brain  barrier  is  located  in  endothelial  cells  
functions  e.g.  via  the  production  of  neurosteroids.   of  capillaries  of  the  brain.  Unlike  the  endothelial  cells  
There  are  3  types  of  glial  cells:   found  elsewhere,  brain’s  endothelial  cells  have  tight  
junctions  with  high  electrical  resistance  providing  an  
1. Astrocytes  are  the  most  numerous  of  the   effective  barrier  against  molecules.    In  addition,  brain  
three  types.  These  are  star-­‐‑shaped  cells  that   capillaries  are  in  contact  with  foot  processes  of  
enable  nutrition  of  neurons,  breakdown  of   astrocytes  that  separate  the  capillaries  from  the  
some  neurotransmitters,  and  maintaining  the   neurons.  
 
blood-­‐‑brain  barrier.    
Lipid  soluble  molecules  (ethanol  and  caffeine)  can  
2. Oligodendrocytes  are  seen  in  CNS  (not  in  
penetrate  the  barrier  relatively  easily  via  the  lipid  
peripheral  nerves,  where  Schwann  cells   membranes  of  the  cells.  In  contrast,  water-­‐‑soluble  
replace  them).  They  produce  myelin  sheaths   molecules  such  as  sodium  and  potassium  ions  are  unable  
that  help  in  saltatory  conduction  (pole  to  pole   to  transverse  the  barrier  without  using  specialized  
jumping),  which  quicken  the  process  of  signal   carrier-­‐‑mediated  transport  mechanisms.  
transmission.      
Inflammation  such  as  meningitis  weakens  the  blood  
3. The  microglia  are  descendants  of  
brain  barrier.  
macrophages.  They  are  scavenger  cells  that  
 
clear  neuronal  debris  following  cell  death.   There  are  some  areas  of  the  brain  that  do  not  have  a  
4. Ependymal  cells  are  a  special  type  of  glia  that   blood-­‐‑  brain  barrier.  These  are  so  called  circum-­‐‑
cover  the  ventricles  and  facilitate  CSF   ventricular  organs  e.g.  subfornical  organ,  area  
circulation  via  their  ciliary  processes.   postrema  (chemo  receptor  trigger  zone),  median  
eminence  and  posterior  pituitary.    
   

©  SPMM  Course   10  
5. Major neurochemical pathways
A. Dopaminergic pathways
Depending  on  the  length  of  the  projections,  dopaminergic  pathways  can  be  classified  into  

1. Long  paths:  Nigrostriatal,  mesocortical  and  mesolimbic  pathways.    

2. Short  paths:  Tuberoinfundibular  and  incertohypothalamic  pathway.    
3. Ultrashort  paths:  These  are  found  in  the  amacrine  cells  in  the  retina  and  in  the  olfactory  system.  

The  nigrostriatal  pathway  is  the  extrapyramidal  pathway  that  is  crucial  for  motor  control;  this  accounts  for  
most  of  the  brain’s  dopamine.    

Pathway   Origin  and  destination   Effect  of  dopamine  (DA)  blockade  

Nigrostriatal   Substantia  Nigra  to  striatum  and   DA  deficiency  (e.g  Parkinson’s)  or  blockade  due  
amygdala  via  medial  forebrain  bundle   to  antipsychotics  can  cause  extrapyramidal  side  
effects    
Mesolimbic   Ventral  tegmental  area  (VTA)  to   Blockade  of  DA  in  this  tract  produces  the  
Nucleus  accumbens  and  hippocampus   desirable  antipsychotic  effect  by  controlling  
via  medial  forebrain  bundle   positive  psychotic  symptoms  
Mesocortical   Ventral  tegmental  area  (VTA)  to   Low  levels  of  DA  or  DA  blockade  in  this  tract  is  
cingulate  cortex  and  prefrontal  regions     associated  with  negative  symptoms  (alogia,  
via  medial  forebrain  bundle   anhedonia,  amotivation  and  apathy)  
Tuberoinfundibular   Hypothalamus  to  the  pituitary  via   Dopamine  acts  as  PIH  –  prolactin  inhibitory  
portal  vessels     hormone.  DA  blockade  will  serve  to  increase  
  prolactin  levels.  
Incertohypothalamic   Internal  connections  within   Disturbed  thermoregulation  and  possibly  
hypothalamus   weight  gain  
 

B. Cholinergic pathways
The  two  major  cholinergic  pathways  are  

1. Brainstem  pathway:  This  forms  a  part  of  the  ARAS    -­‐‑  ascending  reticular  activating  system  that  is  
important  to  maintain  wakefulness  and  REM  sleep  state.    It  originates  from  pedunculopontine  
and  laterodorsal  tegmental  nuclei  and  innervates  thalamic  relay  neurons  and  reticular  nuclei.    
2. Basal  forebrain  pathway:  Originates  at  the  Nucleus  Basalis  of  Meynert  in  basal  forebrain  and  
projects  to  the  hippocampus,  frontal  cortex  and  amygdala.  Degeneration  of  this  pathway  is  
implicated  in  Alzheimer'ʹs  disease.  

©  SPMM  Course   11  
 C. Serotonergic pathways
Most  of  the  brain’s  serotonergic  neurons  originate  in  the  midbrain  dorsal  and  median  raphe  nuclei  and  
ascend  to  innervate  the  entire  cortex,  basal  ganglia,  thalamus,  and  also  descend  to  the  spinal  cord.  

D. Noradrenergic pathways
Noradrenergic  projection  originates  at  the  locus  coeruleus  (pons)  and  ascends  to  most  of  the  cortex  via  
medial  forebrain  bundle.  Similar  to  the  serotonin  system,  noradrenergic  projections  also  descend  to  the  
spinal  cord.      

E. Glutamatergic system
Glutamate  is  the  most  common  excitatory  neurotransmitter  in  the  brain.  As  a  result,  almost  all  cortical  
descending  tracts  (from  pyramidal  cells)  rely  on  glutamate  for  neurotransmission.  This  large  output  of  
corticofugal  fibres  makes  up  most  of  the  corona  radiata.  All  of  the  association  and  commissural  fibres  
also  use  glutamatergic  transmission.  Many  thalamic  neurons  are  also  glutamatergic.  Thus  thalamocortical  
projections  are  also  glutamatergic.  In  addition  cerebellar  output  from  deep  nuclei,  subthalamic  nuclei  to  
globus  pallidus  projections,  and  brainstem  to  spinal  cord  projections  are  also  predominantly  
glutamatergic.  

F. GABAergic system
GABA  is  the  primary  inhibitory  neurotransmitter  in  the  brain.    Unlike  other  neurotransmitters,  there  are  
no  specific  neurochemical  pathways  where  GABA  is  dominant.  Instead,  GABA  is  the  major  transmitter  for  
cerebral  interneurons  that  are  ubiquitous  throughout  the  cortex.  

Interneurons  are  usually  short  neurons  that  serve  to  connect  two  other  neurons,  thus  forming  an  essential  
part  of  the  complex  wiring  pattern  of  the  cortex.  They  carry  neither  motor  nor  sensory  information  but  
serve  to  modulate  local  neural  circuitry.    

2  major  cortical  interneuron  subtypes  are  noted:  parvalbumin  (PV)-­‐‑expressing  interneurons  (~40%  of  all  
interneurons)  and  somatostatin  (SST)-­‐‑expressing  interneurons  (30%  of  interneurons,  also  called  
Martinotti  cells).    

A  reduction  in  the  expression  of  PV-­‐‑interneurons  in  the  frontal  cortex  is  now  a  well-­‐‑replicated  feature  of  
schizophrenia.  PV-­‐‑interneurons  are  of  2  subtypes:  Basket  cells  and  Chandelier  cells.  

Basket  cells  receive  direct  input  from  thalamocortical  projections.  They  form  synapses  with  the  soma  or  
dendrites  of  the  pyramidal  neurons  and  serve  to  provide  the  excitatory-­‐‑inhibitory  balance  to  the  cortex.  

Chandelier  cells  form  synapses  with  the  proximal  axonal  hillock  of  pyramidal  neurons.  They  may  have  
an  overall  excitatory  role  by  serving  to  short-­‐‑circuit  the  action  potential  propagation  though  their  role  is  
still  unclear.  

 
©  SPMM  Course   12  
  

DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug related information using external sources;
no part of these notes should be used as prescribing information.

Notes prepared using excerpts from:

! Heide  et  al.  Dissecting  the  uncinate  fasciculus:  disorders,  controversies  and  a  hypothesis.  Brain.  
2013  Jun;136(Pt  6):1692-­‐‑707.    
! Ruigrok  TJ.  Cerebellar  nuclei:  the  olivary  connection.  Prog  Brain  Res.  1997;114:167-­‐‑92.  
! Lewis  DA  et  al.  Cortical  parvalbumin  interneurons  and  cognitive  dysfunction  in  schizophrenia.  
Trends  in  Neurosciences  2012  Jan;35(1):57-­‐‑67.    
! Andreasen  NC  et  al.  "ʺCognitive  dysmetria"ʺ  as  an  integrative  theory  of  schizophrenia:  a  
dysfunction  in  cortical-­‐‑subcortical-­‐‑cerebellar  circuitry?  Schizophr  Bull.  1998;24(2):203-­‐‑18.  

©  SPMM  Course   13  
  

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1. Physiology of Neuronal Activity
A. Action Potentials
An  action  potential  is  initiated  at  the  axonal  hillock  when  the  synaptic  signals  received  by  the  dendrites  
and  soma  are  sufficient  to  raise  the  intracellular  resting  membrane  potential  from  -­‐‑70  mV  to  the  threshold  
potential   of   -­‐‑   55mV.   At   -­‐‑55mV,   the   Na+   channels   present   at   the   axon’s   initial   segment   will   open.   The  
subsequent   Na+   influx   causes   rapid   reversal   of   the   membrane   potential   from   the   negative   values   to   +40  
mV.   When   the   membrane   potential   reaches   +40mV,   the   Na+   channels   close   and   the   voltage-­‐‑gated   K+  
channels  open.  As  K+  ions  move  out  of  the  axon,  the  cell  membrane  gets  “repolarized”.    

B. Synaptic activity
A  synapse  is  a  junction  between  2  nerve  cells.  Three  types  of  synapses  are  noted  in  the  nervous  system.  

¬ Chemical  synapses:  Presynaptic  neuron  releases  a  chemical  molecule  on  stimulation.  This  molecule  
acts  on  the  next  neuron  to  bring  on  a  molecular  effect  or  to  propagate  the  impulse  further  downstream.    
o Depending  on  the  effects  noted  on  the  postsynaptic  neuron,  a  chemical  synapse  could  be  
classified  as  either  excitatory  or  inhibitory.  Postsynaptic  neurons  are  depolarized  by  activity  at  
the  excitatory  synapses;  inhibitory  synaptic  activity  serves  to  hyperpolarize  them.    
o In  some  instance  the  postsynaptic  changes  induced  by  an  excitatory  synapse  may  be  sufficient  to  
induce  an  action  potential,  but  may  serve  to  facilitate  the  likelihood  of  generating  an  action  
potential  with  further  stimulation.  This  process  is  called  facilitation.  Due  to  this,  additional  
input  from  several  other  presynaptic  cells  through  other  synapses  may  result  in  a  spatial  
summation  effect  leading  to  an  action  potential.  Similarly  recurrent  stimulation  by  the  same  
synapse  can  result  in  temporal  summation  that  leads  to  an  action  potential.      
¬ Electrical  synapses:  They  bring  on  the  response  by  electrical  communication  without  chemical  
exchange.  
¬ Conjoint  synapses:  These  have  both  electrical  and  chemical  properties.  

©  SPMM  Course   2  
2. Neural basis of physiological functions
A. Eating
The  hypothalamus  has  2  centers  that  control  feeding  behaviour.  Ventromedial  hypothalamus  acts  as  the  
satiety  centre  while  lateral  hypothalamus  acts  as  the  feeding  centre.    

Neurochemical  substances  such  as  ghrelin  and  neuropeptide  Y  act  as  mediators  of  increased  appetite  
(orexigenic).  Leptin,  cholecystokinin  and  serotonin  act  as  mediators  of  satiety  (anorexigenic).  

Ghrelin  is  the  only  orexigenic  substance  produced  outside  of  the  CNS  –  it  is  synthesized  in  the  gastric  
mucosa;  adipose  cells  synthesize  leptin.    

Food  and  food  cues  increase  dopaminergic  activity  in  nucleus  accumbens  (reward  centre).  Destruction  of  
dopamine  pathways  reduces  eating  behaviour.  In  obesity,  D2  receptors  are  reduced  in  the  striatum.  

B. Temperature
The  hypothalamus  has  2  centers  that  control  body  temperature.  Preoptic  anterior  hypothalamus  acts  as  a  
hypothermic  centre  while  posterior  hypothalamus  acts  as  a  hyperthermic  centre.    

Stimulating  preoptic  anterior  hypothalamus  results  in  parasympathetic-­‐‑mediated  sweating  and  

vasodilation,  resulting  in  hypothermia.  Stimulating  posterior  hypothalamus  results  in  sympathetic  drive,  
shivers  and  vasoconstriction,  leading  to  hyperthermia.    

Body  temperature  varies  diurnally;  Lesions  in  the  median  eminence  reduces  the  diurnal  temperature  
variation.  

Certain  drugs  can  induce  malignant  hyperthermia,  but  not  through  hypothalamic  mechanism.  An  
abnormal  excitation-­‐‑contraction  coupling  in  skeletal  muscles  is  responsible  for  this  defect.  

Hyperthermia  is  also  seen  in  Neuroleptic  Malignant  Syndrome  (NMS)  induced  by  neuroleptic  use  or  
levodopa  withdrawal.    

C. Pain
Thalamus  plays  a  crucial  role  in  pain  perception  while  higher  cortical  centres  are  central  to  the  
localization  and  interpretation  of  pain  signal.    

Thin  unmyelinated  C  fibres  or  sparsely  myelinated  A-­‐‑delta  fibres  carry  pain  sensation  to  dorsal  horn  of  
the  spinal  cord.  Fast  transmission  takes  place  along  lateral  spinothalamic  route  to  aid  localization  while  
slow  transmission  takes  place  through  reticulothalamic  tract  to  aid  subjective  sensation.    

Opioid  receptors  in  dorsal  horn  and  possibly  those  in  brain  stem  (periaqueductal  grey  mater)  modulate  
pain  intensity.  Descending  fibres  from  serotonergic  raphe  nuclei  also  modulate  pain  perception;  this  may  
explain  the  role  of  tricyclic  drugs  in  reducing  chronic  pain.  

©  SPMM  Course   3  
Thalamic  pain  syndrome  can  occur  in  cases  of  stroke  involving  thalamoperforating  branches  of  posterior  
cerebral  artery.  Patients  have  contralateral  loss  of  sensation  with  burning  or  aching  pain  triggered  by  light  
cutaneous  stimulation.  

D. Thirst
Subfornical  organ  (SFO)  and  organum  vasculosum  of  the  lamina  terminalis  (OVLT)  are  
circumventricular  organs  playing  a  crucial  role  in  the  perception  of  thirst.  The  hypothalamic  
paraventricular  nucleus  is  also  involved  in  the  regulation  of  thirst.  

Angiotensin  II  acts  as  a  neurotransmitter  to  propagate  thirst  signals  to  hypothalamus.  Hypotension  also  
stimulates  thirst  through  pathways  originating  from  the  baroreceptors  on  aorta  and  carotid.    

Anti  diuretic  hormone  (ADH)  increases  water  reabsorption  at  renal  tubules  and  thus  helps  maintain  
body’s  fluid  balance.  The  syndrome  of  inappropriate  secretion  of  ADH  (SIADH)  may  result  from  
damage  to  paraventricular  and  supraoptic  hypothalamic  nuclei,  or  due  to  the  use  of  drugs  such  as  
carbamazepine  or  chlorpromazine.  Some  tumours  such  as  carcinoma  of  lung  can  also  produce  excess  
ADH.  Low  sodium  and  reduced  osmolarity  is  noted  in  the  presence  of  normal  renal  excretion  of  sodium  
and  high  urine  osmolality.  

E. Abnormalities in physiological drives

Disorder     Clinical  features  

Kluver-­‐‑Bucy   Bilateral  lesions  of  amygdala  and  hippocampus  results  in  placidity  with  decreased  aggressive  
syndrome     behaviour.  Prominent  oral  exploratory  behaviour  and  hypersexuality.  Hypermetamorphosis  
(objects  are  repeatedly  examined  as  if  they  were  novel)  is  also  seen.    
L a u r e n c e -­‐‑ Obesity  and  hypogonadism  along  with  low  IQ,  retinitis  pigmentosa,  and  polydactyly.  Diabetes  
M o o n -­‐‑ B i e d l   insipidus  is  also  seen.  Autosomal  recessive  with  genetic  locus  at  11q13  in  most  cases.  No  
S y n d r o m e   hypothalamic  lesions  have  been  found.  
Prader-­‐‑Willi   Hypotonia,  obesity  with  hyperphagia,  hypogenitalism,  mental  retardation,  short  stature,  
Syndrome   impaired  glucose  tolerance.  Abnormal  control  of  body  temperature  and  daytime  
hypersomnolence  is  related  to  hypothalamic  disturbances.  A  reduction  in  oxytocin  neurons  and  
satiety  neurons  is  noted.  Associated  with  paternal  deletion  (genomic  imprinting)  at  15q11-­‐‑q13  
Kleine-­‐‑Levin   Compulsive  eating  behaviour  with  hyperphagia,  hypersomnolence,  hyperactivity,  
Syndrome   hypersexuality  and  exhibitionism.  A  hypothalamic  abnormality  sometimes  preceded  by  a  viral  
illness;  often  resolves  by  the  third  decade  of  life.    
Psychogenic   Excessive  water  consumption  in  the  absence  of  hypovolemia  or  hypernatremia.  May  lead  to  
polydipsia   water  intoxication  and  serious  electrolyte  imbalance.    
 

©  SPMM  Course   4  
3. Neurodevelopment
A. Neurogenesis
Early  fetal  life  is  a  prolific  period  of  neurogenesis.  An  active  zone  of  nerve  cell  production  is  seen  
immediately  around  the  ventricles  of  the  neural  tube.  This  is  called  a  subventricular  zone.  Neurons  
produced  here  migrate  outwards  to  the  cortical  plate.    

Thalamic  axons  that  project  to  the  cortical  plate  initially  synapse  on  a  transient  layer  of  neurons  called  the  
subplate  neurons.  In  normal  development,  the  axons  subsequently  detach  from  the  subplate  neurons  and  
proceed  superficially  to  synapse  on  the  true  cortical  cells.  The  subplate  neurons  then  degenerate.  In  some  
patients  with  schizophrenia  an  abnormal  persistence  of  subplate  neurons  has  been  noted,  suggesting  a  
failure  of  axonal  path-­‐‑finding.  

It  is  now  known  that  continuous  neurogenesis  takes  place  in  certain  brain  regions  (particularly  the  dentate  
gyrus  of  the  hippocampus  and  olfactory  bulb)  in  adults.  Stress  reduces  hippocampal  neurogenesis;  
enriched  environments,  exercise  and  antidepressants  promote  hippocampal  neurogenesis.  There  is  some  
controversy  around  whether  adult  neurogenesis  is  observed  in  other  brain  regions.  

B. Neuronal Migration/Myelination
Neuronal  migration  takes  place  in  the  first  6  months  of  gestation.    

Two  types  of  migration  are  noted:  radial  and  tangential.  Radial  migration  is  the  primary  mechanism  by  
which  excitatory  neurons  reach  the  cortex.  Radial  glial  cells  form  scaffolding  through  their  foot  processes  
to  guide  the  migrating  neuronal  cells.  Successive  populations  of  migrating  neurons  travel  past  the  
previously  settled  neurons  (inside  out  pattern)  to  form  radial  stacks  of  cells  (Rakic’s  cortical  columns).  
Most  inhibitory  interneurons  in  the  external  and  internal  granular  layers  are  tangentially  migrated  
neurons.  

Abnormalities  in  neuronal  migration  result  in  neurons  failing  to  reach  the  cortex  and  residing  in  ectopic  
positions.  This  is  called  heterotopia.  

Myelination  begins  prenatally  at  around  4th  gestational  month;  it  is  largely  complete  in  early  childhood  
(by  2  years),  but  does  not  reach  its  full  extent  especially  in  association  cortices  until  late  in  the  third  decade  
of  life.  

C. Synaptic pruning
Synaptogenesis  occurs  very  rapidly  from  the  second  trimester  through  the  first  ten  years  of  life.  The  peak  
of  synaptogenesis  occurs  within  the  first  2  postnatal  years.  By  mid-­‐‑childhood,  more  neurons  and  cellular  
processes   are   established   than   required   for   adult'ʹs   brains.   Thereafter   a   process   of   pruning   or   synaptic  
elimination  takes  place  to  select  and  preserve  the  most  useful  while  eliminating  the  unnecessary  neuronal  
connections  in  the  adult'ʹs  brain.  This  synaptic  pruning  continues  through  the  early  teen  years.    

Neuronal  numbers  can  be  studied  using  a  wide  variety  of  markers  including  the  density  of  D2  receptors.  
Before  5  years  of  age,  D2  receptor  density  is  greater  than  adult  levels  but  regresses  during  the  second  

©  SPMM  Course   5  
decade.  Dopamine  receptors  continue  to  decrease  in  adult  years,  but  at  a  considerably  slower  rate  of  2.2%  
reduction  per  decade.  This  rate  is  faster  in  males  than  in  females.  In  schizophrenia,  the  rate  of  D2  receptor  
loss  is  faster  (6.0%  loss  per  decade)  than  in  healthy  men.    

While  excessive  or  prolonged  pruning  is  associated  with  schizophrenia,  relative  under-­‐‑pruning  is  
implicated  in  autism,  wherein  the  size  of  certain  brain  regions  may  be  larger  than  in  healthy  controls.  

D. Cerebral plasticity
Cerebral  plasticity  refers  to  the  capability  of  the  brain  to  be  molded.  Cortical  sensory  maps  change  with  
variations  in  sensory  input.  Patients  with  phantom  limb  also  show  reorganization  of  sensory  maps  after  
amputation  so  that  the  representation  of  the  amputated  limb  may  occur  on  the  cortical  face  area.  Repeated  
practice  also  leads  to  a  reorganization  of  brain’s  functional  regions.  Such  an  effect  is  seen  in  musicians,  
jugglers  and  other  professionals  who  repeatedly  undertake  a  learned  motor  task.    

©  SPMM  Course   6  
4. Neuroendocrinology
A. Pituitary gland
The  pituitary  gland  has  an  anterior  and  posterior  lobe.  The  anterior  lobe  secretes  many  hormones  that  are  
regulated  by  regulatory  neurohormones  produced  by  parvocellular  neurons  of  the  hypothalamus.  The  
posterior  lobe  releases  2  hormones  that  are  synthesized  in  the  magnocellular  cells  of  supraoptic  nuclei  and  
paraventricular  nuclei  of  the  hypothalamus.    

¬ Growth  hormone  excess  causes  acromegaly  in  adults  or  gigantism  in  children;  low  levels  are  
associated  with  dwarfism.  Exercise,  sleep  and  stress  increase  GH  release.  The  GH  response  to  
GHRH  and  the  normal  sleep-­‐‑associated  release  of  GH  are  altered  in  depression  and  anorexia  
nervosa.  

¬ Prolactin  release  is  inhibited  by  dopamine  from  the  hypothalamus;  TRH,  on  the  other  hand,  may  
facilitate  the  release  of  prolactin.  Prolactin  levels  are  increased  during  pregnancy,  nursing  and  
during  sleep  and  exercise.  Antipsychotics  remove  the  inhibitory  control  of  dopamine  by  blocking  
D2  receptors  in  the  tuberoinfundibular  tract.  This  leads  to  hyperprolactinaemia,  gynecomastia  in  
males  and  galactorrhea  in  females.    Long  standing  prolactin  increase  may  lead  to  osteoporosis.  

¬ Vasopressin  (ADH)  and  oxytocin  are  peptides  differing  from  each  other  in  only  two  amino  acids  
in  their  sequences.    Vasopressin  is  thought  to  play  a  role  in  attention,  memory,  and  learning.  
Release  of  vasopressin  is  increased  by  pain,  stress,  exercise,  morphine,  nicotine,  and  barbiturates  
and  is  decreased  by  alcohol.    Oxytocin  is  implicated  in  mammalian  bonding  behavior,  
particularly  in  the  initiation  and  maintenance  of  maternal  behavior,  social  bonding,  and  sexual  
receptivity.  

Region   Hormonal  output  

Anterior  pituitary   o GH  -­‐‑  growth  hormone  
o LH  -­‐‑  luteinizing  hormone  (a  gonadotrophin)  
o FSH  -­‐‑  follicle  stimulating  hormone  (a  gonadotrophin)  
o ACTH  -­‐‑  adreno  corticotrophic  hormone  (corticotrophin)  
o TSH  -­‐‑  thyroid  stimulating  hormone  (thyrotropin)  
o Prolactin  

Posterior  pituitary   o Vasopressin  (ADH  –  antidiuretic  hormone)    

o Oxytocin    

Hypothalamus   o CRH  -­‐‑  corticotrophin  releasing  hormone  

o GHRH  -­‐‑  growth  hormone  releasing  hormone  
o GnRH  -­‐‑  gonadotrophin  releasing  hormone  
o TRH  -­‐‑  thyrotrophin  releasing  hormone  
o SST  –  somatostatin  (inhibits  GH)  
o PIF  -­‐‑  prolactin  inhibitory  factor  (dopamine)  

 
©  SPMM  Course   7  
 B. Thyroid gland
TRH  from  the  hypothalamus  stimulates  the  secretion  of  TSH  from  the  pituitary.  TSH  in  turn  stimulates  
the  thyroid  gland  to  synthesize  and  release  thyroxine  T4  and  triiodothyronine  T3.  T4  is  the  predominant  
form  of  thyroid  hormone,  but  T3  is  biologically  more  potent.  T4  is  converted  into  T3  by  target  organs  as  
well  as  the  brain.  

Exogenous  administration  of  TRH  produces  a  brisk  response  by  increasing  TSH  concentration.  In  patients  
with  depression,  a  blunted  response  to  TRH  administration  is  seen.  Mania,  alcohol  withdrawal  and  
anorexia  can  also  cause  blunted  TRH  response.  

The  addition  of  T3  and  T4  as  supplements  to  antidepressant  treatment  has  been  shown  to  accelerate  
response  in  some  patients,  particularly  women.  Exogenous  administration  of  thyroid  hormones  (e.g.  in  
resistant  depression)  increases  serotonergic  transmission  with  decreased  5-­‐‑HT1A  sensitivity  and  increased  
5-­‐‑HT2A  sensitivity  

Nerve  growth  factor  genes  are  activated  by  T3  during  early  development  but  not  in  the  adult'ʹs  brain.    

Lithium  produces  hypothyroidism  especially  in  middle-­‐‑aged  women  who  are  predisposed  to  carry  
antithyroid  autoantibodies.    

Hypothyroidism  is  sometimes  implicated  in  rapid  cycling  mood  pattern  in  previously  stable  bipolar  
patients.  Hyperthyroidism  is  associated  with  symptoms  of  generalized  anxiety  disorder.    

Hyperthyroidism   Hypothyroidism  
Physical  symptoms:  Tachycardia,  weight  loss,  heat   Physical  symptoms:  Fatigue,  weight  gain,  cold  intolerance,  
intolerance,  sweating   dry  skin  

Mental  symptoms:  Anxiety,  irritability,  poor   Mental  symptoms:  Depression,  reduced  activity  
concentration,  agitation,  emotional  lability.     (psychomotor  retardation),  reduced  libido  and  poor  memory  

C. Adrenal Cortex
CRH  from  the  hypothalamus  stimulates  ACTH  release  from  the  anterior  pituitary.  ACTH  in  turn  
stimulates  the  release  of  cortisol  from  the  adrenal  cortex.  Cortisol  thus  produced  in  turn  inhibits  both  CRH  
and  ACTH  in  a  negative  feedback  loop  to  maintain  homeostasis.  This  is  called  Hypothalamic-­‐‑Pituitary-­‐‑
Adrenal  (HPA)  axis.  

HPA  axis  is  involved  in  regulation  of  stress  response.  With  chronic  stress  the  HPA  feedback  fails  and  
continuous  excess  of  cortisol  is  produced  with  deleterious  consequences  to  the  hippocampus  where  
glucocorticoid  receptors  are  abundant.    Decreased  hippocampal  neurogenesis  with  atrophy  of  
hippocampal  dendrites  results  in  shrinkage  of  the  hippocampus.  This  disrupts  long-­‐‑term  potentiation  
(LTP)  and  leads  to  impaired  memory  performance.  A  compensatory  increase  in  dendritic  arborization  of  

©  SPMM  Course   8  
neurons  in  the  basolateral  amygdala  may  occur,  contributing  to  a  memory  bias  towards  negative  events  in  
chronic  stress.  

Hypercortisolism  (Addison'ʹs  disease)   Hypocortisolism  (Cushing'ʹs  syndrome)  

Physical  symptoms:  Apathy,  fatigue,  and   Physical  symptoms:  Fatigue,  weight  gain,  cold  intolerance,  
depression   dry  skin  

Mental  symptoms:  Anxiety,  irritability,  poor   Mental  symptoms:  Depression,  mania,  confusion,  and  
concentration,  agitation,  emotional  lability.     psychotic  symptoms.  

A  diurnal  variation  in  cortisol  levels  occurs  in  humans,  with  peak  cortisol  levels  occurring  around  6:00-­‐‑
7:00  AM.  Hypercortisolemia  with  the  loss  of  the  normal  diurnal  variation  have  been  reported  in  
depression  (especially  in  melancholic  depression  with  the  somatic  syndrome),  in  some  patients  with  
mania  (especially  psychotic),  obsessive-­‐‑compulsive  disorder  and  schizoaffective  disorder.  In  PTSD  
hypocortisolemia  is  seen  in  a  subgroup  of  patients;  this  may  be  due  to  aberrant  feedback  to  the  pituitary  
due  to  excessive  glucocorticoid  receptors  –  probably  a  genetic  vulnerability.  Low  cortisol  is  also  seen  in  
chronic  fatigue  and  fibromyalgia.  

Dexamethasone suppression test (DST)

o Exogenous  corticosteroids  such  as  dexamethasone  will  suppress  endogenous  cortisol  production  if  
the  HPA  axis  is  intact.    
o In   DST,   1mg   dexamethasone   is   given   at   11PM   with   baseline   cortisol   sampling;   on   the   next   day   at  
8AM,  4PM  and  11PM  cortisol  levels  are  measured  again.  If  any  one  sample  has  >5mcg/L  of  cortisol,  
this   indicates   DST   non-­‐‑suppression.   This   demonstrates   the   failure   of   feedback   suppression   of  
ACTH/CRH   and   continuous   production   of   endogenous   cortisol   despite   administration   of  
exogenous  steroid  (dexamethasone).    
o DST  non-­‐‑suppression  is  seen  in  depression  and  other  psychiatric  hyper  cortisol  emic  states  (also  in  
organic  hyper  cortisol  emic  states  such  as  Cushing’s).  
o The  sensitivity  of  the  DST  for  detecting  major  depression  is  modest  (about  40%-­‐‑   50%)  but  is  higher  
(about  60%-­‐‑70%)  in  very  severe  depression  with  psychotic  as  well  as  melancholic  features.    
o DST   non-­‐‑suppression   is   non-­‐‑specific   to   depression   and   is   also   seen   in  mania   and   schizoaffective  
disorder.     In   addition,   a   number   of   major   medical   conditions,   pregnancy,   severe   weight   loss   and  
use   of   alcohol   and   certain   other   drugs   (hepatic   enzyme   inducers   that   reduce   dexamethasone  
availability  -­‐‑  barbiturates,  anticonvulsants,  and  others)  can  also  produce  DST  non-­‐‑suppression.    
o Despite   the   presence   of   depression,   DST   may   suppress   cortisol   if   the   patient   has   Addison’s   or  
hypopituitarism  or  taking  steroids,  high-­‐‑dose  benzodiazepines  or  indomethacin.  
o DST  non-­‐‑suppression  does  not  increase  the  likelihood  of  antidepressant  response.  A  negative  test  
is  not  an  indication  for  withholding  antidepressant  treatment.    
o Some  data   suggest   that  patients   with   DST   non-­‐‑suppression   are   less   likely  to   respond  to   a   placebo  
than  those  who  show  a  suppression  response.    

©  SPMM  Course   9  
 o Continued  failure  to  suppress  cortisol  despite  the  apparent  recovery  from  depression  suggests  an  
increased  risk  for  relapse,  poor  prognosis  and  possibly  later  suicidal  behaviour.    
 

D. Pineal gland
The  pineal  gland  is  also  called  epiphysis.  It  contains  pinealocytes  that  secrete  both  serotonin  (in  the  day)  
and  melatonin  (in  the  night).  The  gland  also  contains  calcium  deposits  that  become  more  prominent  with  
age  (corpora  arenacea  or  brain  sand).    

The  pineal  gland  contains  the  highest  concentration  of  serotonin  in  the  body.  Melatonin  is  synthesized  
from  serotonin  by  the  action  of  serotonin-­‐‑N-­‐‑acetylase  and  5-­‐‑hydroxyindole-­‐‑O-­‐‑methyltransferase.    

The  major  regulator  of  melatonin  synthesis  is  the  light-­‐‑dark  cycle,  with  synthesis  increased  during  
darkness.  The  pineal  gland  is  regulated  by  a  major  β-­‐‑adrenergic  mechanism,  and  β-­‐‑antagonists  such  as  
propranolol  decrease  melatonin  synthesis.  

Melatonin  regulates  circadian  rhythms.  It  has  both   ENDOCRINE  CHANGES  &  SLEEP  
synchronizing  and  phase-­‐‑shifting  properties  in  the    
regulation  of  biological  rhythms.   Start  of  sleep  –  increased  testosterone    
Slow  wave  sleep  –  increased  GH  &  SST;  reduced  
  cortisol  
  REM  sleep  –  reduced  melatonin  
Early  morning  sleep  –  increased  prolactin.  
   
Circadian  rhythm  development  in  the  first  1  
  month  involves  the  emergence  of  the  24-­‐‑hour  
core  body  temperature  cycle;  by  2  months  
 
progression  of  nocturnal  sleeping  is  noted  and  in  
3  months,  melatonin  and  cortisol  rhythms  are  
 
established.  
   

 
©  SPMM  Course   10  
5. Physiology of sleep
A. Measurement
¬ Actigraphy:  This  is  used  to  quantify  circadian  
sleep-­‐‑wake  patterns  and  to  detect  movement  
DREAMS  
disorders  during  sleep;  it  uses  a  motion  sensor.  
¬ Polysomnography  (PSG):  This  includes  EEG,   Dreaming  occurs  at  all  stages  of  sleep,  but  the  
content  varies.  In  non-­‐‑REM  sleep  the  dreams  
electromyogram  (EMG),  electrooculogram  
are  thought-­‐‑like  as  though  the  person  is  solving  
EOG.  ECG,  oximetry  and  respiratory  monitor  
a  problem.  In  REM  sleep  the  dreams  may  be  
can  also  be  added.  PSG  helps  in  the  diagnosis   illogical  and  bizarre.  
and  monitoring  of  sleep  apnoea,  narcolepsy,  
restless  legs  &  REM  behavioural  disorder.  Some  
of  the  terms  used  in  PSG  are  
o Sleep  latency:  time  from  ‘lights  out’  to  sleep  onset.  
o REM  latency:  Time  from  sleep  onset  to  first  REM  episode.  Normally  ~90  minutes  in  adults.  
o Non-­‐‑REM  latency:  Time  from  sleep  onset  to  first  Non-­‐‑REM  episode.  
o Sleep  efficiency:  (Total  sleep  time/total  time  in  bed)  X  100.  
o Multiple  sleep  latency  test:  This  is  used  to  assess  daytime  somnolence  and  daytime  REM  
onset  in  narcolepsy.  

B. Architecture
The  average  length  of  sleep  is  approximately  7.5  hours  per  night.    Sleep  is  made  up  of  non-­‐‑rapid  eye  
movement  (NREM)  and  rapid  eye  movement  (REM)  phases.    

NREM sleep: Stage  1  NREM  sleep

o 75%  of  adult  sleep  is  NREM.  Most  
•  5%  of  sleep
physiological  functions  are  markedly   •  Drowsy  period.  When  awoken  from  this  stage  one  
lower  in  NREM  than  in  wakefulness   denies  being  asleep.
•  Shows  low  voltage  theta  activity,  sharp  V  waves.
(decreased  muscle  tone,  respiration,  
Stage  2  NREM  sleep
temperature  and  heart  rate).    
•45%  of  sleep
o NREM  is  classified  as  stages  1  to  4  with   •Shows  the  development  of  sleep  spindles  and  K  
increasing  amplitude  and  decreasing   complexes.
frequency  of  EEG  activity.  Stages  3  &  4   Stage  3  NREM  sleep
together  constitute  slow  wave  sleep   •12%  of  sleep
(SWS).  SWS  dominates  initial  part  of  the   •Shows  <50%  delta  waves.  

sleep.     Stage  4    NREM  sleep

o Features  of  non-­‐‑REM  sleep  includes   •13%  of  sleep
•Shows  >50%  delta  waves.
§ Increased  parasympathetic  activity  
•Physiological  functions  are  at  the  lowest
(decreased  heart  rate,  systolic  blood  
pressure,  respiratory  rate,  cerebral  blood  flow)  
§ Abolition  of  tendon  reflexes  
§ The  upward  ocular  deviation  with  few  or  no  movements.  
©  SPMM  Course   11  
 § Reduced  recall  of  dreams  if  awaken.  (Sleep  terror  is  an  NREM  disorder.  When  awake  after  
sleep  terror  episodes,  children  appear  confused  and  do  not  recall  what  terrified  them).  

REM sleep
o 25%  of  adult  sleep  is  REM.    Darting  eye  movements  are  noted  in  REM  despite  other  muscles  being  
paralysed.    REM  sleep  is  characterized  by  a  high  level  of  brain  activity  and  physiological  activity  
similar  to  those  in  wakefulness.    
o In  REM  sleep  behavioural  disorder,  muscular  paralysis  does  not  occur  resulting  in  violent  
movements  coinciding  with  brain  activity.  
o EEG  shows  low-­‐‑voltage,  mixed-­‐‑frequency  (theta  and  slow  alpha)  activity  similar  to  an  awake  state.  
Sawtooth  waves  are  also  seen.    
o In  a  typical  night,  a  person  cycles  through  five  episodes  of  non-­‐‑REM/REM  activity.  The  REM  
episodes  increase  in  length  as  the  night  unfolds.  
o Features  of  REM  sleep:  
§ Increased  sympathetic  activity  (increased  heart  rate,  systolic  blood  pressure,  respiratory  
rate,  cerebral  blood  flow)  
§ Autonomic  functions  are  active  with  penile  erection  or  increased  vaginal  blood  flow  
§ Increased  protein  synthesis  
§ Maximal  loss  of  muscle  tone  with  occasional  myoclonic  jerks  
§ Vivid  recall  of  dream  if  awaken.  (Nightmares  occur  in  REM  sleep  –  hence  they  are  well  
recollected).  

C. Brain activity
Apart  from  various  oscillatory  patterns,  some  specific  patterns  of  electrical  activity  are  also  noted  during  
sleep.    

¬ Sleep  spindles  
• Waves   with   upper   alpha   or   lower   beta   frequency,   seen   in   many   stages   but   especially   in   stage   2.  
The  waveform  resembles  a  spindle  with  an  initial  increase  in  amplitude  that  decreases  slowly  
• Duration  usually  <1second.    
• They  usually  are  symmetric  and  are  most  obvious  in  the  parasagittal  regions.  
¬ K  complex:  
• K  complex  waves  are  large-­‐‑amplitude  delta  frequency  waves,  sometimes  with  a  sharp  apex.  
• They  can  occur  throughout  the  brain  but  more  prominent  in  the  bifrontal  regions.  
• These  may  be  mediated  by  thalamocortical  circuitry.  
• Usually  symmetric,  they  occur  each  time  the  patient  is  aroused  partially  from  sleep.  
• Semiarousal  often  follows  brief  noises;  with  longer  sounds,  repeated  K  complexes  can  occur.  
• Runs  of  generalized  rhythmic  theta  waves  sometimes  follow  K-­‐‑complexes;  this  pattern  is  termed  
an  arousal  burst.  
¬ V  waves:  
• V  waves  are  sharp  waves  that  occur  during  sleep.  They  are  largest  and  most  evident  at  the  vertex  
bilaterally  and  are  usually  symmetrical.    
• Multiple  V  waves  tend  to  occur  especially  during  stage  2  sleep.    

©  SPMM  Course   12  
 • Often   they   occur   after   sleep   disturbances   (e.g.,   brief   sounds)   and,   like   K   complexes,   may   occur  
during  brief  semiarousals.    
 

D. Regulation
Hypothalamic controls
¬ The  master  clock  of  the  brain  is  the  
suprachiasmatic  nucleus  (SCN)  located  in  the   SLEEP  &  AGEING  
anterior  hypothalamus  -­‐‑  this  orchestrates    
Newborns  sleep  about  16  hours  a  day.  They  spend  >50%  
circadian  rhythms  and  is  synchronized  by  signals  
of  sleep  time  in  REM  sleep.  Sleep  onset  REM  is  also  seen  
from  the  retina.  
in  neonates.    
¬ SCN  is  reset  each  day  by  signals  of  light  from  the  
retina.  Specialized  melanopsin-­‐‑containing  retinal   By  3-­‐‑4  months  of  age,  the  pattern  shifts  so  that  the  total  
ganglion  cells  project  via  retinohypothalamic   percentage  of  REM  sleep  drops  to  less  than  40,  and  entry  
tract  to  the  SCN.  This  provides  light  input   into  sleep  occurs  with  an  initial  period  of  NREM  sleep.  
By  late  teens  adult  pattern  of  sleep  is  established.    
independent  of  vision.  
¬ In  the  absence  of  solar  guidance,  the  24-­‐‑hour   This  distribution  remains  relatively  constant  until  old  
sleep-­‐‑wake  cycle  will  gradually  increase  to   age.  Absolute  reduction  occurs  in  both  slow-­‐‑wave  sleep  
approximately  26  hours  –this  is  called  free-­‐‑ and  REM  sleep  in  older  persons.  An  increase  in  
running.   frequency  of  awakenings  after  sleep  onset  also  occurs  
¬ Pineal  melatonin  secreted  during  darkness  can   with  age.  
 
also  reset  the  SCN.  Thus,  melatonin  promotes  
sleep  in  those  with  delayed  sleep  onset  or  jet  lag.  
¬ The  ventrolateral  preoptic  nucleus  (VLPO)  is  called  the  sleep  switch  nucleus.  It  has  projections  to  the  
main  components  of  the  ascending  arousal  system.  The  VLPO  induces  sleep  by  putting  the  brakes  on  
the  arousal  nuclei.  People  with  damage  to  their  VLPO  have  chronic  insomnia.  
¬ The  VLPO  must  be  inhibited  so  that  people  can  wake  up.  This  is  brought  about  by  a  negative  feedback  
from  the  monoaminergic  system.  The  switching  to  arousal  is  then  stabilised  by  orexin  (also  called  
hypocretin)  neurons  in  the  hypothalamus.  Orexin  neurons  are  mainly  active  during  wakefulness  and  
reinforce  the  arousal  system.  Patients  with  narcolepsy  have  reduced  number  of  orexin  neurons,  
leading  to  repeated  somnolence  during  the  day.    

Ascending Reticular Activating System - Neurotransmitters

 

Neurotransmitter   Cell  Bodies   Function  

Cholinergic   Midbrain-­‐‑pons  nuclei   REM  on  neurons.  Activation  brings  on  REM  sleep  
Noradrenergic   Locus  coeruleus   REM  off  neurons.  Activation  reduces  REM  sleep.  
Dopaminergic   Periaqueductal  gray  matter   D2  possibly  enhances  REM  sleep  
Serotoninergic   Raphe  nuclei   5HT2  stimulation  possibly  maintains  arousal  
Histaminergic   Tuberomammillary  nucleus   H1  stimulation  possibly  maintains  arousal  
 

©  SPMM  Course   13  
 E. Drugs and Disorders
Disorder  /  drugs   Changes  
Alcohol     § Increase  SWS  (chronic  use  –  loss  of  SWS)  
§ Reduce  initial  REM  but  increase  second  half  REM  

Alcohol   § Loss  of  SWS  

withdrawal   § Increased  REM  
§ Intense  REM  rebound  

Anxiety   § Increased  stage  1  sleep  (light  sleep)  

disorders   § Reduced  REM,  normal  REM  latency  
§ Reduced  slow  wave  sleep  

Benzodiazepines   § Decrease  sleep  latency  

§ Increase  sleep  time  
§ Reduce  stage  1  sleep  
§ Increase  stage  2  sleep  
§ Reduce  REM  and  SWS  
§ REM  rebound  on  cessation  
§ Prevent  the  transition  from  lighter  stage  2  sleep  into  deep,  restorative  (stages  3  and  4)  sleep.  

Cannabis   § Increase  SWS  

§ Suppress  REM  

Carbamazepine   § Suppresses  REM  and  increases  REM  latency  

§ Increases  SWS  

Dementia   § Increased  sleep  latency  &  fragmentation  

§ Reduced  sleep  time  

Depression   § Loss  of  SWS  slow  wave  sleep  (first  half)  

§ Increased  REM  (leading  on  to  Early  awakening)  
§ Reduced  REM  latency  

Lithium     § Suppresses  REM  and  increases  REM  latency  

§ Increases  SWS  

Opiates   § Decrease  SWS  &  REM  

§ Withdrawal  REM  rebound  

Schizophrenia   § Inconsistent  reduction  in  REM  latency  and  slow  wave  sleep.  
§ N.B.:  Antipsychotics  have  variable  effects  

SSRIs   § Alerting  due  to  5HT2  stimulation  

§ May  reduce  REM  latency  
§ Variable  effects  of  REM  suppression  

Stimulants   § Reduce  sleep  time  by  decreasing  both  REM  sleep  and  SWS  
§ REM  rebound  on  cessation  (except  modafinil)  

Tricyclics   § REM  suppression  (especially  Clomipramine)  

§ Increased  SWS  and  stage  1  sleep  

Z  hypnotics   § Less  effect  on  sleep  architecture;  Zopiclone  may  increase  SWS  

©  SPMM  Course   14  
6. Neurophysiological measurements
A. EEG
¬ EEG  records  the  electrical  activity  of  the  brain.  In  psychiatric  practice,  it  is  primarily  used  to  rule  
out  seizures,  monitor  ECT  and  in  polysomnogram  for  sleep  disorders.  
¬ Standard  EEG  uses  21  electrodes  placed  on  the  scalp.  Placement  of  the  electrodes  is  based  on  the  
10/20   International   System   of   Electrode   Placement.   This   system   measures   the   distance   between  
readily  identifiable  landmarks  on  the  head  and  then  locates  electrode  positions  at  10  percent  or  
20  percent  of  that  distance  in  an  anterior-­‐‑posterior  or  transverse  direction.    
¬ Activation  procedures  could  be  used  to  bring  up  abnormal  discharges.    
⇒ Strenuous  hyperventilation  (most  common,  safe)  
⇒ Photic  stimulation  using  an  intense  strobe  light    
⇒ 24  hours  of  sleep  deprivation  can  lead  to  the  activation  of  paroxysmal  EEG  discharges  in  
some  cases  
¬ EEG   recording   during   sleep   (natural   or   sedative   induced)   can   also   be   used   when   the   wake  
tracing  is  normal.  
Wave forms noted in EEG
 
Waves   Frequency   Notes    
Beta     >13Hz   Some  seen  at  frontal,  central  position  in  the  normal  waking  EEG    

Alpha     8  to  13  Hz   Dominant   brain   wave   frequency   when   eyes   are   closed   and   relaxing;   occipitoparietal  
predilection.   Disappears   with   anxiety,   arousal,   eye   opening   or   focused   attention.  
Dominance  reduces  with  age.  

Theta   4  to  8  Hz   A   Small   amount   of   sporadic   theta   seen   in   waking   EEG   at   frontotemporal   area;  
prominent   in   drowsy   or   sleep   EEG.   Excessive   theta   in   awake   EEG   is   a   sign   of  
pathology.  
Delta   <4  Hz   Not   seen   in   waking   EEG.   Common   in   deeper   stages   of   sleep;   the   presence   of  
focal/generalized  delta  in  awake  EEG  is  a  sign  of  pathology.  
Mu     7-­‐‑11  Hz   Occurs  over  the  motor  cortex.  It  is  related  to  motor  activity,  characterized  by  arch  like  
waves;  gets  attenuated  by  movement  of  the  contralateral  limb  
Lambda   Single   A   single   occipital   triangular,   symmetrical   sharp   wave   produced   by   visual   scanning  
waves   when  awake  (e.g.  reading)  or  in  light  sleep  

 
¬ Beta  and  alpha  are  called  fast  waves;  theta  and  delta  are  slow  waves.  

Early   Mid-­‐‑
Newborns Infants childhood adolescence Adults

•Dominant   •Irregular   •Alpha  range   •EEG   •Normal  

delta  and  theta   medium-­‐‑  to   develops  in   essentially  has   dominant  
waves high-­‐‑voltage   posterior  areas the  appearance   alpha  rhythm
delta  activity of  an  adult  
tracing  by  
12-­‐‑14  years.

©  SPMM  Course   15  
Abnormalities in EEG
EEG  in  various  disorders  
Absence  seizures  (petit-­‐‑mal)   Regular  3  Hz  Complexes  
Alzheimer’s  dementia   Rarely  normal  in  advanced  dementia;  may  be  helpful  in  differentiating  
pseudodementia  from  dementia  
Angelman’s  syndrome   1. EEG  changes  are  notable  by  the  age  of  2.    
2. Prolonged  runs  of  high  amplitude  2–3  Hz  frontal  activity  with  
superimposed  interictal  epileptiform  discharges  –  all  ages    
3. 3.  Occipital  high  amplitude  rhythmic  4–6  Hz  activity  facilitated  by  
eye  closure,  is  seen  under  the  age  of  12  years.    
4. 4.  There  is  no  difference  in  EEG  findings  in  AS  patients  with  or  
without  seizures  
Antisocial  personality  disorder   Increased  incidence  of  EEG  abnormalities  in  those  with  aggressive  behaviour  
 ADHD   Up  to  60%  have  EEG  abnormalities  (spike/spike-­‐‑waves)    
Borderline  personality  disorder   Positive  spikes:  14-­‐‑  and  6  per  second  seen  in  25%  of  patients  
CJD   Generalised  periodic  1-­‐‑2  Hz  sharp  waves  are  seen  in  nearly  90%  patients  with  
sporadic  CJD.  Less  often  in  familial  /  hormonal  transplant-­‐‑related  forms.  NOT  
seen  in  a  variant  form.  

Closed  head  injuries   Focal  slowing  (sharply  focal  head  trauma)  

Focal  delta  slowing  (subdural  hematomas)  

Diffuse  atherosclerosis   Slowed  alpha  frequency  and  increased  generalized  theta  slowing  
Herpes  simplex  encephalitis   Episodic  discharges  are  recurring  every  1-­‐‑3  seconds  with  variable  focal  waves  
over  the  temporal  areas.  

Huntington’s  dementia   Initial  loss  of  alpha;  later  flattened  trace  

Infantile  spasms  (seen  in   Hypsarrhythmia  [diffuse  giant  waves  (high  voltage,  >400  microvolts)  with  a  
tuberous  sclerosis)   chaotic  background  of  irregular,  asynchronous  multifocal  spikes  and  sharp  
waves].  Clinical  seizures  are  associated  with  a  marked  suppression  of  the  
background  -­‐‑  called  the  electrodecremental  response  
Infectious  disorders   Diffuse,  often  synchronous,  high  voltage  slowing  (acute  phase  of  encephalitis)  
Metabolic  and  endocrine   Diffuse  generalized  slowing.  Triphasic  waves:  1.5  to  3.0  per  second  high-­‐‑
disorders   voltage  slow-­‐‑waves  especially  in  hepatic  encephalopathy.  

Neurosyphilis   The  non-­‐‑specific  increase  in  slow  waves  occurring  diffusely  over  the  scalp.  

Panic  disorder   Paroxysmal  EEG  changes  consistent  with  partial  seizure  activity  in  one-­‐‑third;  
focal  slowing  in  about  25%  of  patients  
Seizures   Generalized,  hemispheric,  or  focal  spike/  spike-­‐‑wave  discharge.  
Stroke   Focal  or  regional  delta  activity  
Structural  lesions   Focal  slowing  /  focal  spike  activity  
 

©  SPMM  Course   16  
 ¬ Diffuse   slowing   of   background   is   the   most   common   EEG   abnormality;   it   is   nonspecific   and  
signifies  the  presence  of  encephalopathy.  Focal  slowing  suggests  local  mass  lesions;  e.g.  edema,  
haematoma  or  focal  seizure.  
¬ Epileptiform   discharges   when   seen   interictally,   can   be   considered   as   hallmark   of   seizure  
disorder.  But  this  is  not  a  common  finding.  If  this  is  lateralized  and  periodic,  it  may  suggest  an  
acute  destructive  brain  lesion.  

Effect of drugs on EEG

  Psychotropics  
Antipsychotics   Slowing  of  beta  activity  with  increase  in  alpha,  theta  and  delta  activity  
 
Antidepressants   Slowing  of  beta  activity  with  increase  in  alpha,  theta  and  delta  activity  
Lithium   Slowing  of  alpha  or  paroxysmal  activity  
 
Anticonvulsants   No  effect  on  awake  EEG  
  Primarily  sedating  drugs  –  decrease  alpha  
Barbiturates   Effects  are  opposite  to  that  of  alcohol.  Increased  beta  activity  upon  intoxication;  
  generalized   paroxysmal   activity   and   spike   discharges   (even   without   overt   fits)  
in  withdrawal  states.  
 
Benzodiazepines   Increased  beta;  decreased  alpha.  Overdose  leads  to  diffuse  slowing  
Opioids   Decreased   alpha   activity;   increased   voltage   of   theta   and   delta   waves;   in  
 
overdose,  slow  waves  are  seen.  

  Primarily  recreational  drugs  –  increase  alpha    

Alcohol   Increased   alpha   activity;   increased   theta   activity.   Withdrawal   increases   beta.  
  Delirium  tremens  has  beta  (fast)  wave  activity  –  other  deliria  have  increased  slow  
waves.  
  Marijuana   Increased  alpha  activity  in  frontal  area  of  brain;  overall  slow  alpha  activity  

  Cocaine   Same  as  marijuana;  longer  lasting.  

Nicotine   Increased  alpha  activity;  in  withdrawal,  marked  decrease  in  alpha  activity  
  Caffeine   In  withdrawal,  increase  in  amplitude  or  voltage  of  theta  activity  

B. MEG
¬ Magnetoencephalography  (MEG)  is  used  to  measure  the  magnetic  fields  produced  by  electrical  
activity  in  the  brain    
¬ In  contrast  to  electric  fields,  magnetic  fields  are  less  distorted/impeded  by  the  skull  and  scalp.    
¬ The  scalp  EEG  is  sensitive  to  both  tangential  and  radial  components  of  a  current  source  in  a  spherical  
volume  conductor,  MEG  detects  only  its  tangential  components.  Thus,  MEG  may  selectively  measure  
the  activity  in  the  sulci,  whereas  scalp  EEG  measures  activity  both  in  the  sulci  and  at  the  top  of  the  
cortical  gyri.  

C. ERP
¬ An  ERP  is  a  change  in  electrical  brain  activity  stereotyped  and  time-­‐‑locked  to  an  event  (e.g.,  stimulus),  
although  it  can  also  occur  for  the  omission  of  an  expected  stimulus.  ERPs  allow  the  investigation  of  
specific  types  of  information  processing  by  the  brain.    
¬ ERPs  are  small  relative  to  the  spontaneous  brain  activity  (background  EEG)  that  is  they  have  a  low  
signal-­‐‑to-­‐‑noise  ratio.  To  increase  the  signal-­‐‑to-­‐‑noise  ratio,  an  often-­‐‑used  method  is  ERP  averaging  
©  SPMM  Course   17  
¬ ERPs  have  polarity  (positive  [P]  or  negative  [N])  and  latency  (the  moment  of  peak  occurrence  after  
stimulus  presentation,  which  is  often  indicated  by  the  number  attached  to  the  labels  of  ERP  activity).  
¬ The  temporal  resolution  of  EEG,  MEG  and  ERP  analysis  is  much  higher  than  that  of  other  
neuroimaging  methods  like  functional  MRI,  SPECT  and  PET,  but  these  techniques  lack  the  high  spatial  
resolution  of  the  MR  techniques.    
¬ According  to  the  time  of  occurrence  ERPs,  can  be  classified  as  early,  mid  latency  and  late.    
¬ The  P300,  a  positive  late  ERP  component  around  
Early  ERPs
300  ms  after  stimulus  presentation,  is  typically  
•Basic  sensory  pathways  can  be  studied  by  
generated  when  a  rare  target  stimulus  is   recording  early  ERPs.
imbedded  with  more  frequent  stimuli  e.g.   •These  are  also  called  ‘evoked  potentials’  (EPs)  or  
brain  stem  evoked  responses  (BAER)
(auditory  ‘oddball’  protocol).  The  P300  is  related  
•They  occur  in  response  to  sounds  (Auditory  EP,  
to  the  maintenance  of  working  memory.  Decrease   AEP),  flashes  (Visual  EP,  VEP)  or  electrical  
stimulation  (Somatosensory  EP,  SEP).
in  P300  amplitude  is  well  established  as  a  
biological  trait  marker  in  schizophrenia.     Midlatency  ERPs
¬ The  Mismatch  Negativity  or  MMN  is  a  negative  
•  These  occur  after  BAER.  
ERP  component  that  is  recorded  between  100-­‐‑200   •The  three  well  known  midlatency  ERPs  are  N100,  
ms  in  response  to  low-­‐‑probability  deviant  sounds   P50  and  P200.  
•Their  amplitudes  reduce  with  repetition  
(oddball)  in  a  sequence  of  standard  sound   (habituation  response  /  sensory  gating).
stimuli,  when  the  participant  is  not  actively  
attending  to  the  deviants.  The  MMN  is  best  seen   Late  ERPs

in  the  difference  wave  between  the  ERP  in   •Cognitive  pathways  can  be  studied  by  recording  of  
ERPs  related  to  the  execution  of  psychological  
response  to  the  standard  and  deviant  sounds.  The   events  such  as  ayention,  emotion  or  memory  tasks.
MMN  reflects  involuntary  information   •P300  and  MMN  are  late  ERPs  
processing  in  auditory  context,  i.e.  the  mnemonic  
comparison  of  a  given  stimulus  with  a  previous  one  that  has  already  built  up  a  trace  in  memory.  The  
violation  of  the  previously  formed  memory  trace  produces  the  MMN.  Decreased  MMN  amplitude  is  
noted  in  schizophrenia.  
¬ The  Contingent  Negative  Variation  (CNV)  is  a  slow  negative  shift  in  the  interval  between  two  paired  
stimuli  presented  one  after  the  other  (S1  being  the  cue,  S2  being  the  imperative  stimulus  prompting  to  
respond).  CNV  reduction  in  central  (midline)  electrodes  is  noted  in  schizophrenia  patients  especially  
with  long  duration  of  illness  with  positive  symptoms.  

©  SPMM  Course   18  
  

DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug related information using external sources;
no part of these notes should be used as prescribing information.

Notes prepared using excerpts from:

! Seeman  P.  Pruning  during  development.  Am  J  Psychiatry  1999’  156:168.  

! Martin   et   al.   Repetitive   transcranial   magnetic   stimulation   for   the   treatment   of   depression:  
systematic  review  and  meta-­‐‑analysis.  British  Journal  of  Psychiatry,  2003:  182,  480  -­‐‑491.  
! The  APA  Task  Force  on  Laboratory  Tests  in  Psychiatry.  The  dexamethasone  suppression  test:  an  
overview  of  its  current  status  in  psychiatry.  Am  J  Psychiatry  1987;  144:1253-­‐‑1262  
! http://www.emedicine.com/neuro/TOPIC275.HTM  
! http://emedicine.medscape.com/article/1139332-­‐‑overview  
! Kaplan  &  Sadock'ʹs  Synopsis  of  Psychiatry:  Behavioral  Sciences/Clinical  Psychiatry,  10th  Edition  
! George,   MS   et   al.   Vagus   nerve   stimulation:   a   new   tool   for   brain   research   and   therapy.   Biological  
Psychiatry,  2000:  47,  287  -­‐‑295  
! Kaplan  &  Sadock  Comprehensive  Textbook  of  Psychiatry  9th  ed  –  Pages  199-­‐‑200.  
! Boyd  et  al.  The  EEG  in  early  diagnosis  of  the  Angelman  (happy  puppet)  syndrome.  Eur  J  Pediatr  
1988:  147;  508–513  
! Ohayon   MM   et   al.   Meta-­‐‑analysis   of   quantitative   sleep   parameters   from   childhood   to   old   age   in  
healthy   individuals:   Developing   normative   sleep   values   across   the   human   lifespan.   Sleep.   2004;  
27[7]:  1255-­‐‑1273.  
! Walter  et  al.  Contingent  Negative  Variation:  An  Electric  Sign  of  Sensori-­‐‑Motor  Association  and  
Expectancy  in  the  Human  Brain.  Nature  1964:  203,  380  -­‐‑  384  

©  SPMM  Course   19  
 Neurochemistry
Paper A Syllabic content 3.3

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We claim copyright for our own text material, productions and

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license if they are used in this material.
1. Synaptic transmission
 The presynaptic neuron synthesises, transports and stores the chemical messenger
(neurotransmitter). Synthesis takes place in cell body / soma which contains the essential protein
synthesis machinery. From here axonal transport occurs, and the neurotransmitter reaches the
synaptic terminal. Before its eventual release, the neurotransmitter is stored within the synaptic
vesicle. The release takes place through the process of membrane fusion and exocytosis.
 Upon release, the neurotransmitter occupies receptors present on the surface of the postsynaptic
neuronal membrane. Some of the neurotransmitter molecules will also act on autoreceptors that
are present in the presynaptic neuronal membrane. Such autoreceptor activity is considered to be
crucuial for feedback inhibition of the neurotransmitter synthesis and release.
 Neurotransmitters exhibit specificity in receptor interaction. One neurotransmitter can have more
than one receptor types, but within a given receptor site only a particular chemical conformation
can be accommodated (lock and key).
 Receptors have a finite number and thus get saturated if there is an over secretion of
neurotransmitter.
 Receptor binding is often competitive; relative synaptic concentrations of competing molecules
decide the eventual degree of receptor activity. Most receptors are bound reversibly i.e. following
dissociation of the neurotransmitter; the receptor falls back to its physiological status quo. Some
molecules can act irreversibly producing structural alterations in the protein of receptor
complexes.
 After synaptic release and activity, cessation of neurotransmitter action takes place via

1. Reuptake back to presynaptic neuron via special transporters (e.g. monoamine transporters)
2. Enzymatic breakdown at the cleft (e.g. via COMT/MAO-A enzyme)
3. Removed by glia or plasma circulation (e.g. glutamate shuttle)

 Feedback control of a neurotransmitter may exist at various points

1. Control of presynaptic synthesis

2. Regulation of release
3. Reuptake regulation
4. Autoreceptor mediated presynaptic inhibition
5. Independent postsynaptic inhibition via a different neuronal network
Neurotransmitters
Monoamines Amino acids Peptides
Dopamine GABA Endorphins
Norepinephrine Glycine Cholecystokinin
Epinephrine Glutamate Neurotensin
Serotonin Neuropeptide Y
Acetylcholine Leptin
Histamine Ghrelin

© SPMM Course 2
2. Classification of receptors
Receptors may be categorized into three categories:

(1) Ligand-gated channels (ionotropic), in which binding of a chemical messenger alters the
probability of opening of transmembrane pores or channels;

(2) Those in which the receptor proteins are coupled to intracellular G proteins as transducing
elements (metabotropic);

(3) Those termed ligand-dependent regulators of nuclear transcription (nuclear receptors).

Ionotropic or ion channel receptors result in fast response (GABAA benzodiazepine); G protein coupling
(metabotropic) is comparatively a slower process (most antipsychotics, antidepressants).

Ion channel receptors are made up of four or five protein subunits making up a pore like structure. The
GABA-A receptor's structure is typical of most ligand-gated (ionotropic) receptors [‘doughnut with a hole
in the centre’ or ‘rosette’ shaped]. Each protein subunit is a string of amino acids which passes in and out
of the cell membrane four times. At the extracellular end of this string is a large N-terminal; this end-chain
is thought to mediate GABA-channel interactions. In the middle of the string is a large intracellular loop of
amino acids with four sites where phosphorylation occurs.

Inhibitory neurotransmitter action leads to the entry of Cl- while excitatory action results in the entry of
Ca2+ or other cations. Ionotropic receptors include GABAA, NMDA, the 5HT3 subtype of serotonin
receptors.

G-protein-coupled metabotropic receptors are proteins that span the cell membrane seven times
(serpentine receptors). G protein-coupled receptors act via cyclase mediated second messenger activation
(GTP, ATP, etc.). Gs-proteins are stimulatory; Gi-proteins inhibit the adenylate cyclase. A third variant of
G-protein receptors acts via phospholipase C. Metabotropic receptors influence protein synthesis
eventually thus producing longer lasting effects. Metabotropic receptors include DA receptors, most 5HT
receptors except 5HT-3, NEN and neuropeptides including opioid receptors are G coupled.

Nuclear receptors such as glucocorticoid receptors are part of a superfamily of receptors that have a
cysteine-rich DNA-binding domain, a ligand-binding domain, and a variable amino terminal region.
Upon appropriate ligand binding, a nuclear receptor becomes a transcription factor and binds in turn to
DNA via zinc fingers. Other nuclear receptors include the receptors for progesterone, androgen, and 1,25-
dihydroxycholecalciferol (Vitamin D). Many receptors of this family are orphan receptors, for which the
ligands are still unidentified.

The glucocorticoid receptor is located mainly in the cytoplasm but migrates to the nucleus as soon as it
binds its ligand. In contrast, the estrogen and the triiodothyronine (T3) receptors are retained in the
nucleus and bind hormones directly in the nucleus itself.

© SPMM Course 3
3. Dopamine
Source

•tyrosine l-dopa  dopamine

Rate limiting step

•tyrosine hydroxylase

Breakdown enzymes

•Monoamine oxidase (MAO) & Catechol-o-methyl transferase (COMT).

•MAO-A more selectively metabolizes norepinephrine and serotonin
•MAO-B more selectively metabolizes dopamine.

Breakdown product

•Homovanillic acid

Reuptake

•Dopamine transporter (cocaine inhibits this transported)

Function

•Motivation, novelty seeking, reward circuitry (addictions), arousal and motor

movement gating in basal ganglia

Receptors

•5 types; D1 to D5 . All are G protein coupled

•D1-like  D1 & D 5; increase adenylate cyclase (stimulatory). D1 exclusively
postsynaptic; resistant to antagonism. D5 more limbic in distribution; 10 times
higher dopamine affinity
•D2-like  D2,3 & 4 ; decrease adenylate cyclase (inhibitory). D4 is found primarily in
the frontal cortex and clozapine has a high affinity. D4-selective antagonists do not
have antipsychotic efficacy.

Disorders

•Levels low in Parkinson’s; high in psychosis especially at mesolimbic area; may be

low in anhedonia and negative symptoms in mesocortical area.

© SPMM Course 4
4. Noradrenaline
Source

•tyrosine l-dopa dopamine  norepinephrine  epinephrine

Rate limiting step

•tyrosine hydroxylase

Synthetic enzymes

•dopamine-b-hydroxylase modulates norepinephrine production;

phenylethanolamine-N-methyltransferase modulates conversion of NEN to
epinephrine.

Breakdown enzymes

•Monoamine oxidase (MAO – A especially) & Catechol-o-methyl transferase (COMT).

Breakdown product

•3-methoxy-4-hydroxyphenylglycol (MHPG) & VMA – vanillyl mandelic acid.

•MHPG is the major metabolite in CNS while VMA is major metabolite from
peripheral nervous system/endocrine system.

Reuptake

•noradrenaline reuptake channel (tricyclics, reboxetine inhibit this)

Function

•arousal, anxiety, mood regulation, autonomic mediation

Receptors

•2 major types; α and β.

•α divided into a1 and a2
•α1 receptors phospholipase C coupled; mostly postsynaptic
•α2 receptors Gi coupled ; mostly presynaptic autoreceptors
•β-receptors Gs coupled; predominate locus ceruleus – may regulate a
•β1-receptors – high affinity to norepinephrine and β2-receptors – high affinity to
epinephrine.

Disorders

•Levels low in depression and abnormal in panic/anxiety disorders.

© SPMM Course 5
5. Serotonin
Source
•tryptophan5 hydroxy l-tryptophan  serotonin

Rate limiting step

•availability of tryptophan (hence it is possible to conduct tryptophan depletion
studies and manipulate 5HT system)

Synthetic enzymes
•tryptophan hydroxylase

Breakdown enzymes
•MAO (preferentially MAO-A)

Breakdown product
•5-hydroxyindoleacetic acid (5-HIAA)

Reuptake
•Serotonin reuptake channel (tricyclics, SSRIs inhibit this)

Function
•mood, perception of pain, feeding, sleep-wake cycle, motor activity, sexual behaviour,
and temperature regulation.

Receptors
•14 known subtypes of serotonin receptors (5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-
HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A, 5-HT5B, 5-HT6, and 5-HT7)
•All except 5-HT3 are G-protein-coupled receptors; 5HT3 predominant in gut;
associated with motility.
•5-HT1A receptors – Gi coupled postsynaptic; antidepressant response; sexual
behaviour
•5-HT1B receptors – Gi coupled presynaptic;
•5-HT1D receptors – Gi coupled - both presynaptic and postsynaptic.
•5-HT2 receptors - phospholipase C coupled; postsynaptic; antagonism leads to
antipsychotic response (atypicals) and sedation; LSD causes 5-HT2 stimulation; down
regulation noted after antidepressant treatment / ECT.
•5-HT6 may be involved in antidepressant action
•5-HT7 - regulation of circadian rhythm

Disorders
•low serotonin levels  increased depression, aggression, suicide, and impulsivity;
regulate dopamine system – role in psychosis

© SPMM Course 6
Receptor Action

5HT1A Antidepressant (agonist), anxiolytics (partial agonist)

5HT1B Aggression

5HT1D Antimigraine (antagonist)

5HT2A Antipsychotic (antagonist); hallucinogens (agonist / partial agonist); implicated in working

memory; also seen in platelets and smooth muscles

5HT2B Stimulation may produce cardiac valvular fibrosis (dexfenfluramine)

5HT2C Anxiogenic and anorexic effect (agonists)

5HT3 Antiemetic (antagonist)

5HT6 Possible antipsychotic/antidepressant action (antagonism)

5HT7 Regulation of circadian rhythm

DOPA decarboxylase (DDC) “is an enzyme implicated in 2 metabolic pathways, synthesizing two
important neurotransmitters, dopamine and serotonin (Christenson et al., 1972). Following the
hydroxylation of tyrosine to form L-dihydroxyphenylalanine (L-DOPA), catalyzed by tyrosine
hydroxylase, DDC decarboxylates L-DOPA to form dopamine. This neurotransmitter is found in different
areas of the brain and is particularly abundant in basal ganglia. Dopamine is also produced by DDC in the
sympathetic nervous system and is the precursor of the catecholaminergic hormones, noradrenaline and
adrenaline in the adrenal medulla”. In the nervous system, tryptophan hydroxylase produces 5-OH
tryptophan, which is decarboxylated by DDC, giving rise to serotonin. DDC is a homodimeric, pyridoxal
phosphate-dependent enzyme. (Excerpt from www.omim.org)

© SPMM Course 7
6. Acetylcholine
Source
•choline and acetyl-coenzyme A

Rate limiting step

•availability of choline

Synthetic enzymes

•choline acetyltransferase

Breakdown enzymes

•acetylcholinesterase – rapid metabolism

Breakdown product

•Choline

Reuptake

•no reuptake. Degraded choline is re up-taken and recycled.

Function

•Modulate arousal, learning, memory, rapid eye movement sleep, pain perception, and
thirst and parasympathetic mediation.

Receptors

•Muscarinic receptors - G-protein-coupled.

•Five subtypes (M1, M2, M3, M4, and M5)
•Nicotinic receptors - ion channels;
•more in peripheral parasympathetic system;
•Less common than M receptors in CNS – mediates attention.

Disorders

•reduced cholinergic function in Alzheimer's dementia; dopamine balance affected in

Parkinson’s

© SPMM Course 8
7. GABA
Source
•Glutamic acid (glutamate)

Rate limiting step

•glutamic acid decarboxylase (GAD) catalysis

Synthetic enzymes

•glutamic acid decarboxylase (GAD)

Breakdown enzymes

•GABA transaminase

Breakdown product

•Broken down to glutamate, and then eventually to succinic acid

Reuptake

•reuptake into both presynaptic nerve terminals and surrounding glial cells; uptake
system is bidirectional and both temperature- and ion-dependent process; (inhibited
by tiagabine)

Function

•Mediates anxiety, seizure cessation, and actions of benzodiazepines, barbiturates, and

alcohol.

Receptors

•GABAA and GABAB

•GABAA – opens chloride channel; inhibitory – leads to hyperpolarization; made of
five subunits and at least 14 subunit subtypes
•GABAB receptor is G-protein-coupled; baclofen is selective agonist

Disorders

•Role in anxiety disorders and alcoholism; may have a role in many other disorders
including epilepsy and Huntington’s.

© SPMM Course 9
8. Glutamate
Source
•1. from 2-oxoglutarate and aspartate by aspartate aminotransferase,
•2. from glutamine by glutaminase, or
•3. from 2-oxoglutarate by ornithine aminotransferase

Regulation

•accumulation of precursors such as glutamine or by end-product inhibition

Synthetic enzymes

•glutaminase

Breakdown enzymes

•Glutamate dehydrogenase, glutamine synthetase

Breakdown product

•Broken down to glutamine or alpha-ketoglutarate

Reuptake

•Largely glial uptake with conversion to glutamine

Function

•Important metabolic role – intermediary in oxidation pathway (malate shuttle),

immediate precursor of all GABA in CNS, intermediary in ammonia cycle; NMDA -
memory acquisition, developmental plasticity, epilepsy, and ischemic brain injury.
NMDA receptor mediates long-term potentiation

Receptors

•metabotropic - 8 in total; 3 groups. Group I - mGluR1& mGluR5 – linked to

phospholipase C
•Ionotropic: NMDA and non-NMDA
•NMDA - made up of subunits with distinct binding sites for glutamate, glycine,
phencyclidine (PCP), magnesium, and zinc.
•Non NMDA – kainate binding or AMPA type.

Disorders

•excitotoxic glutamate toxicity in stroke/schizophrenia/seizures suspected. NMDA

antagonists can cause hallucinations – e.g. PCP, ketamine

© SPMM Course 10
9. Glycine
 Glycine is the primary inhibitory neurotransmitter in the spinal cord
 It has the simplest structure of all aminoacids
 It is synthesized primarily from serine by serine trans-hydroxymethylase and glycerate
dehydrogenase, both of which are rate-limiting steps.
 Glycine acts as a ‘mandatory adjunctive neurotransmitter’ for glutamate receptors; the excitatory
glycine site on the NMDA receptor is called non-strychnine-sensitive glycine receptor.
 Strychnine-sensitive glycine receptor is an inhibitory receptor seen in the spinal cord where glycine
acts independently.
 Facilitating glycine transmission can help reduce negative symptoms of schizophrenia. An
experimental agent called bitopertin is a glycine reuptake inhibitor that has shown some early
promise in reducing negative symptoms.

10. Endocannabinoids
 Two endogenous cannabinoid substances - Anandamide (a weak ligand) and 2-
arachnidonylglycerol (a strong ligand) are formed from arachidonic acid and ethanolamine.
 The two types of cannabinoid receptors, central (CB1) and peripheral (CB2), both bind
tetrahydrocannabinol (THC), the active ingredient of marijuana.
 Anandamide lowers intraocular pressure, decreases activity level, and relieves pain.

11. Neurotrophins
These are substances that act as polypeptide growth factors influencing proliferation and differentiation
of neurons and glial cells. The best-characterised factors are Nerve growth factor (NGF); brain derived
neurotrophic factor (BDNF), neurotrophin 3 and neurotrophin 4.

According to neurotrophin hypothesis neurons compete during development for the limited resource of
growth factors in the target region. Those neurons that are highly responsive, e.g. via high affinity
binding sites, survive while others undergo programmed cell death. Incorrect targeting of axons may
also lead to apoptosis (programmed cell death).

BDNF may have a role in long-term potentiation (LTP) of memory. In animals, chronic stress leads to
down regulation of BDNF. BDNF has been shown to have trophic effects on serotonergic and
noradrenergic neurons. SSRIs and other antidepressants including ECT up regulate BDNF. The time
course of this up regulation coincides with observed therapeutic actions of antidepressant interventions.

A single nucleotide polymorphism in the BDNF gene on chromosome 11p13 results in an amino-acid
substitution of valine (val) with methionine (met) at codon 66 (Val66Met) reducing BDNF activity.
BDNF met/met mice demonstrate increased anxiety. Clinical studies in humans have demonstrated that
subjects with the Val66Met allele have impaired hippocampal activation and performance. It is
controversial if BDNF polymorphism increases the risk of clinical disorders or not.
© SPMM Course 11
12. Some clinical implications

Ach & LEWY BODY DEMENTIA β ADRENOCEPTOR

Brain acetylcholine levels are reduced in DLB Chronic antidepressant treatment induces a
similar to Alzheimer’s. Cortical choline acetyl reduction in β adrenoreceptor density around 2
transferase (ChAT) is reduced to a greater extent weeks after starting antidepressants; this correlates
(85%) in patients with hallucinations in Lewy with therapeutic effects.
body dementia than in those without
hallucinations (50%). Unmedicated suicide victims show higher density
This may partially explain the altered sleep-wake of β adrenoreceptors.
patterns seen in DLB and also the response of β blockade can reduce peripheral features of
hallucinations to acetylcholinesterase inhibitors anxiety driven by sympathetic overdrive.

ABERRANT SALIENCE 5HT & DEPRESSION

Kapur proposed that in the normal individual, the An increased density of 5HT2 binding sites has
role of mesolimbic dopamine is to attach been shown in post mortem studies of depressed /
significance or ‘salience’ to an external stimulus, suicidal patients. The increase in 5HT2A receptors
or an internal thought. This converts a neutral is most prominent in dorsolateral prefrontal cortex
piece of information into an attention grabbing one and in platelets of medication naïve patients. A
(Kapur, 2003). reduction in 5HT1A receptors has also been noted
in cortex
In acute psychosis where hyperdopaminergic state
is noted in mesolimbic system, insignificant events Long-term antidepressant treatment has been
and perceptions receive inappropriate salience shown to reduce 5HT2 receptors and increase
leading to delusional elaborations. 5HT1A function. But these changes may not be
causative of antidepressant action as they predate
Antipsychotics are claimed to "dampen the any clinical response to antidepressant therapy
salience" of these abnormal experiences - do not
erase the symptoms - but provide the platform for a Most directly acting 5HT1A agonists have poor
process of psychological resolution. antidepressant activity.

© SPMM Course 12
DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug related information using external sources;
no part of these notes should be used as prescribing information.

Notes prepared using excerpts from:

 http://omim.org/entry/107930
 Kapur, S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology,
and pharmacology in schizophrenia. Am J Psychiatry 2003; 160
 Angelucci et al. BDNF in schizophrenia, depression and corresponding animal models. Molecular
Psychiatry (2005) 10, 345–352
 Artigas F. Serotonin receptors involved in antidepressant effects. Pharmacology & Therapeutics,
2013; 119-31

© SPMM Course 13
  

Molecular  Genetics  
Paper  A   Syllabic  content  3.4  
 
© SPMM Course

   

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
©  SPMM  Course   1  
1. Cell cycle
Each  cell  undergoes  a  natural  cycle  in  terms  of  its  replication  and  nucleic  acid  synthetic  activity.  The  cell  
cycle  consists  of  four  separate  phases:  G1  phase,  S  phase,  G2  phase  and  M  phase.      

G1  stands  for  growth  phase  1,  S  for  the  synthetic  phase,  G2  for  growth  phase  2  and  M  phase  for  mitosis  
phase.  Cells  in  the  quiescent  G0  phase  of  the  cycle  are  stimulated  by  the  growth  factors  (e.g.  EGF,  
epithelial  growth  factor;  PDGF,  platelet-­‐‑derived  growth  factor;  IGF,  insulin-­‐‑like  growth  factor)  and  result  
in  activation  of  transcription  factors  and  lead  to  the  initiation  of  DNA  synthesis,  followed  by  mitosis  and  
cell  division.  Thus  from  G0  the  cell  moves  on  to  G1  when  the  chromosomes  are  prepared  for  replication.  
This  is  followed  by  the  synthetic  (S)  phase,  when  the  46  chromosomes  are  duplicated  into  chromatids,  
followed  by  another  gap  phase  (G2),  which  eventually  leads  to  mitosis  (M).  

Note  that  while  certain  cells  pause  or  freeze  the  cycle  temporarily  and  stay  in  G0,  e.g.  liver  cells,  neurons  
remain  in  G0  indefinitely.  

2. Cell division
Cell  division  is  a  process  by  which  cells  reproduce.  During  cell  division,  a  sequence  of  steps  enables  the  
replicated  genetic  material  in  a  parent  cell  to  be  equally  distributed  to  two  daughter  cells.    

Before  a  dividing  cell  enters  mitosis,  it  undergoes  a  period  of  growth  called  interphase.  Interphase  can  be  
termed  as  the  "ʺholding"ʺ  stage  occurring  between  two  consecutive  cell  divisions.  Replication  of  cellular  
genetic  material  and  organelles  occurs  during  interphase  in  preparation  for  the  next  division.  It  is  the  
longest  phase,  and  all  steps  in  the  cell  cycle  (i.e.  G0,  G1,  G2  and  S)  except  stage  (M)  constitute  interphase.  

Mitotic division  
Mitosis  is  composed  of  several  stages.  

¬ Prophase:  Condensation  of  chromatin  to  discrete  chromosomes,  accompanied  by  a  breakdown  of  the  
nuclear  envelope  and  the  formation  of  spindles  at  opposite  cellular  "ʺpoles”.    
¬ Metaphase:  Alignment  of  chromosomes  at  the  metaphase  plate  (a  plane  that  is  equidistant  from  the  
two  spindle  poles)  –  equatorial  alignment.  
¬ Anaphase:  Separation  of  paired  chromosomes  (sister  chromatids)  followed  by  migration  to  opposite  
ends  of  the  cell.  This  separation  of  chromatids  preserves  the  chromosomal  numbers  in  daughter  cells.  
¬ Telophase:  In  this  last  stage,  the  chromosomes  are  packed  into  distinct  new  nuclei  in  the  emerging  
daughter  cells.  Cytokinesis  (division  of  cytoplasm)  also  starts  at  this  time.  

Meiotic division
¬ Meiosis  is  divided  into  two  parts:  meiosis  I  and  meiosis  II.  At  the  end  of  the  meiotic  process,  four  
daughter  cells  are  produced  (only  two  are  produced  at  the  end  of  the  mitotic  process),  each  with  one-­‐‑
half  of  the  number  of  chromosomes  as  the  parent  cell,  unlike  mitosis  where  each  cell  has  the  same  
number  of  chromosomes  as  the  parent.  Meiosis  1  is  a  reduction  division.  

©  SPMM  Course   2  
¬ The  main  differences  are  the  occurrence  of  synapsis  (crossing  over)  in  the  prolonged  prophase  phase  
and  non-­‐‑separation  of  sister  chromatids  during  anaphase  1,  leading  to  reduced  (half)  chromosomal  
numbers  in  daughter  cells.  Meiosis  2  is  same  as  a  normal  mitosis.  

3. Chromosomal Numbers:
Chromosomes  are  intranuclear  structures  containing  one  linear  molecule  of  DNA.  Human  cells  are  called  
diploid  as  they  have  46  chromosomes,  23  inherited  from  each  parent;  thus  there  are  23  'ʹhomologous'ʹ  pairs  
of  chromosomes  (22  pairs  of  'ʹautosomes'ʹ  and  two  'ʹsex  chromosomes'ʹ).  The  sex  chromosomes,  called  X  and  
Y,  are  not  homologous  but  are  different  in  size  and  shape.  Males  have  an  X  and  a  Y  chromosome;  females  
have  two  X  chromosomes.    

During  the  mitotic  division,  each  chromosome  divides  into  two;  this  ensures  that  each  daughter  nucleus  
has  the  same  number  of  chromosomes  as  its  parent  cell.  During  gametogenesis,  the  number  of  
chromosomes  is  halved  with  meiosis  so  that  after  conception  the  number  of  chromosomes  remains  the  2  

same  and  not  doubled.  Hence,  gametes  are  haploid  cells.    

Chromosomes  can  be  classified  according  to  their  size  and  shape,  the  largest  being  chromosome  1.  The  
constriction  in  the  chromosome  is  the  centromere,  which  divides  the  chromosome  into  a  short  arm  and  a  
long  arm,  which  are  referred  to  as  the  p  arm  and  the  q  arm  respectively.    

o A  metacentric  chromosome  has  centromere  right  in  the  middle.  So  p  and  q  arms  are  of  equal  
length.    
o If  it  is  placed  at  one  end,  it  is  called  as  an  acrocentric  or  submetacentric  where  the  arms  are  of  
unequal  length.    
o If  centromere  is  at  the  tail  of  a  chromosome,  it  is  called  telocentric.  With  holocentric  chromosomes,  
the  entire  length  of  the  chromosome  acts  as  the  centromere.  These  latter  two  types  are  not  seen  in  
humans.      

When  cells  possess  chromosomal  numbers  different  from  normal  diploid  status,  they  are  called  aneuploid  
cells.  Aneuploidy  can  occur  in  single  numbers  e.g.  trisomy  21,  trisomy  18,  monosomy  of  Turner’s,  etc.  
Very  rarely,  the  entire  chromosome  set  will  be  present  in  more  than  two  copies,  so  the  individual  may  be  
triploid  rather  than  diploid  and  have  a  chromosome  number  of  69.  Triploidy  and  tetraploidy  (four  sets)  
result  in  spontaneous  abortion.      

These  aberrations  result  from  the  failure  of  chromosome  or  chromatids  to  separate  ('ʹnon-­‐‑disjunction'ʹ)  in  
meiosis,  with  one  gamete  receiving  two  copies  of  that  chromosome  and  one  another  with  no  copies  of  the  
chromosome.  This  can  produce  (i)  an  extra  chromosome,  so  resulting  in  a  fetus  that  is  'ʹtrisomic'ʹ  and  has  
three  instead  of  two  copies  of  the  chromosome;  or  (ii)  no  chromosome,  so  the  fetus  is  'ʹmonosomic'ʹ  and  has  
one  instead  of  two  copies  of  the  chromosome.  Nondisjunction  can  occur  with  autosomes  or  sex  
chromosomes.  However,  only  individuals  with  trisomy  13,  18  and  21  survive  to  birth,  and  most  children  
with  trisomy  13  and  trisomy  18  die  in  early  childhood.          

©  SPMM  Course   3  
Sometimes,  non-­‐‑disjunction  can  occur  during  mitosis  immediately  after  two  gametes  have  fused.  This  
leads  to  the  formation  of  two  cell  lineages,  each  with  a  different  chromosomal  make-­‐‑up.  This  occurs  more  
frequently  with  the  sex  chromosomes  and  results  in  a  'ʹmosaic'ʹ  individual.    Mosaics  exhibit  milder  
malformations  than  those  who  carry  complete  aneuploidies.  

Important trisomies/monosomies
¬ Down’s  syndrome:  Trisomy  21  is  the  most  common  chromosomal  disorder  that  occurs  at  a  rate  of  
1:700  causing  congenital  mental  retardation.  Prominent  findings  are  reduced  maternal  levels  of  α-­‐‑
fetoprotein,  increased  β-­‐‑hCG  and  increased  nuchal  fold  thickness  in  fetal  ultrasound.  The  child  shows  
mental  retardation,  flat  facial  profile,  prominent  epicanthal  folds,  simian  palmar  crease,  duodenal  
atresia,  hypothyroidism  and  heart  disease  (most  common  malformation  is  septum  primum–type  ASD  
due  to  endocardial  cushion  defects).  Alzheimer’s  disease  and  leukaemia  are  common  in  affected  adults  
who  survive  childhood  difficulties.  95%  of  Down’s  is  attributed  to  meiotic  nondisjunction  of  
homologous  chromosomes.  This  is  associated  with  an  advanced  maternal  age  (rates  are  1:1500  in  
women  <  20  but  1:25  in  women  >  45).  4%  of  cases  due  to  Robertsonian  translocation  and  1%  of  cases  
are  attributed  to  Down’s  mosaicism  (no  maternal  age  association  is  seen  in  these).  The  features  of  
mosaic  Down  syndrome  are  milder  but  similar  to  the  features  of  full  Down  syndrome.  However,  the  
clinical  phenotype  varies  according  to  the  level  and  distribution  of  trisomic  cells.  Thus,  the  affected  
individuals  may  range  from  completely  normal  to  presenting  the  full  expression  of  Down  syndrome.    
¬ Edwards’  syndrome  is  characterised  by  severe  mental  retardation  and  rocker  bottom  feet,  low-­‐‑set  ears,  

 
micrognathia  (small  jaw),  congenital  heart  disease,  clenched  hands,  the  a  prominent  occiput.  It  is  a  
result  of  trisomy  18.  It  occurs  at  a  frequency  of  1:8000  and  often  death  occurs  within  1  year  of  birth. It  
is  three  times  more  common  in  girls  than  boys.  
¬ Patau’s  syndrome  is  due  to  trisomy  13,  and  it  is  characterised  by  severe  mental  retardation,  
microphthalmia,  microcephaly,  cleft  lip/palate,  coloboma  eye,  abnormal  forebrain  structures,  
polydactyly,  and  congenital  heart  disease.  The  rate  of  occurrence  is  1:6000.  
¬ Metafemale  –  trisomy  X  

¬ Turner’s  syndrome:  Low  hairline,  broad  chest,  short  stature,  retrognathism  and  webbed  neck  are  
features  of  Turner’s  syndrome.  In  80%  
cases  the  origin  of  the  aneuploidy  is  from   Parental  origin  of  meiotic  error  leading  to  aneuploidy.  
Aneuploidy   Paternal  %   Maternal  %  
paternal  X  chromosome;  hence  the  single  
Patau  13   15   85  
X  chromosome  present  in  a  subject  with  
Edward’s  18   10   90  
Turner’s  is  of  maternal  origin.  The   Down’s  21   5   95  
incidence  of  Turner’s  syndrome  is   Turner’s  45X   80   20  
approximately  1  in  2000  live-­‐‑born  female   Klinefelter’s  47  XXY   45   55  
infants.  Random  inactivation  (see  below)  does  not  occur  in  cells  with  a    single  X  chromosome.  In  
general,  girls  with  Turner  show  a  disharmonic  IQ  profile.  The  full  scale  IQ  is  either  comparable  to  
general  population  or  lower  by  a  mean  of  10  points  (nearly  one  standard  deviation)  mostly  due  to  
reduced  performance  IQ  (at  least  20  points  or  1  standard  deviation  lower)  though  verbal  IQ  is  
preserved.  Specific  subtests  assessing  visuospatial  processing  such  as  ‘Block  Design’  and  ‘Object  

©  SPMM  Course   4  
 Assembly’  may  be  affected  more  than  others.  Mathematical  ability  may  also  be  lower  than  expected.  
This  specific  profile  persists  into  adulthood.  Females  with  a  45X  karyotype  (Turner  syndrome)  may  
have  higher  verbal  skills  if  their  only  X  chromosome  is  paternally  derived  instead  of  being  maternal  
origin  (most  commonly  it  is  maternal).  This  suggests  the  existence  of  an  imprinted  gene  that  is  inactive  
if  carried  on  a  maternally  derived  X  chromosome.  

4. DNA & RNA structure

Genetic  information  is  stored  in  the  form  of  double-­‐‑stranded  DNA.  DNA  and  RNA  are  the  most  
important  nucleic  acids  in  the  cellular  machinery.  These  nucleic  acids  are  composed  of  many  nucleotides.  
Nucleotides  are  phosphorylated  versions  of  nucleosides.  Each  nucleoside  consists  of  two  components:  A  
nitrogenous  base  and  a  pentose  sugar.  Each  strand  of  DNA  is  made  up  of  a  deoxyribose-­‐‑phosphate  
backbone  and  a  series  of  purine  (adenine  (A)  and  guanine  (G))  and  pyrimidine  (thymine  (T)  and  cytosine  
(C))  bases  of  the  nucleic  acid.  The  length  of  DNA  is  generally  measured  in  numbers  of  base-­‐‑pairs  (bp).    
Each  nucleotide  is  a  base  joined  to  a  sugar-­‐‑phosphate  unit.  The  two  strands  of  DNA  are  held  together  by  
hydrogen  bonds  between  the  bases.  There  are  only  four  possible  pairs  of  nucleotides  -­‐‑  TA,  AT,  GC  and  CG.  
The  two  strands  twist  to  form  a  double  helix  structure  for  DNA.  RNA  is  single  stranded  in  human  cells.  

A  gene  is  a  sub-­‐‑portion  of  DNA.  It  contains  codes  for  a  polypeptide  sequence.  The  length  of  each  gene  is  
variable  depending  on  the  size  of  the  polypeptide  coded.  A  set  of  three  adjacent  nucleotides  is  called  as  a  
codon;  each  codon  codes  for  a  specific  amino  acid.  There  are  only  20  amino  acids  of  which  around  10  are  
‘essential’  (i.e.  those  aminoacids  not  found  in  food  and  so  need  to  be  synthesized),  but  64  possible  codon  
combinations  that  make  up  the  genetic  code.  This  means  that  most  amino  acids  are  encoded  for  by  more  
than  one  triplet;  other  codons  are  used  as  signals  for  'ʹinitiating'ʹ  or  'ʹterminating'ʹ  polypeptide-­‐‑chain  
synthesis.    
EXON  
The  polypeptide  
coding  sequences  in  
a  DNA  are  called  
exons;  these  are  
interrupted  by  
INTRON  
intervening  

©  SPMM  Course   5  
sequences  that  are  non-­‐‑coding  (called  introns)  at  various  positions.  The  introns  contain  three  types  of  
sequences  (satellite,  mini  and  microsatellite:  see  the  graph  below).  All  introns  are  removed  from  the  
mRNA  before  it  leaves  the  nucleus  and  start  protein  synthesis.  Humans  have  3  ×  109  bp  of  total  
chromosomal  DNA  but  among  these  the  protein-­‐‑coding  genes  constitute  only  32  000  bp.  

5. Synthesis of DNA, RNA & Protein

Replication  refers  to  the  production  of  new  DNA  copies  from  template  copies  of  DNA.    

Synthesis  of  RNA  from  nuclear  DNA  is  called  transcription.  This  takes  place  in  the  nucleus  of  the  cell.    

Such  transcripted  RNA  initially  contains  the  ‘junk’  sequences  –  introns  –  that  do  not  code  for  polypeptides.  
This  unprepared  RNA  is  called  heterogeneous  nuclear  RNA  or  hnRNA.  This  hnRNA  then  undergoes  
splicing  aided  by  nucleosomes  in  the  nucleus  to  remove  non-­‐‑coding  sequences  and  results  in  messenger  
RNAs  (mRNA).  tRNAs  (transfer  RNAs)  are  also  synthesized  from  DNA  in  the  nucleus  in  a  separate  
process.  

Translation  refers  to  the  production  of  proteins  from  RNA.  This  takes  place  in  the  cytoplasm,  aided  by  
ribosomes.  Ribosomes  can  be  seen  attached  to  rough  endoplasmic  reticulum.    

§ As  tRNAs  that  are  synthesized  in  the  nucleus  enter  the  cytoplasm,  they  are  attached  to  specific  
amino  acids  according  to  the  codon  sequences.  This  energy  dependent  process  is  called  amino  acid  
activation,  catalyzed  by  a  specific  amino  acid  activating  enzyme  (aminoacyl-­‐‑tRNA  synthetase)  in  
the  presence  of  Mg2+.  There  is  a  separate  aminoacyl-­‐‑tRNA  synthetase  enzyme  for  each  kind  of  amino  
acid.  The  energy  stored  in  such  activated  amino  acids  is  used  in  making  peptide  bonds  during  
protein  translation.    
§ Translation  takes  place  in  the  cytoplasm  on  ribosomes  where  specific  mRNAs  are  involved.  tRNAs  
with  their  aminoacids,  sequentially  bind  to  various  sites  along  the  mRNA  in  a  zipper  like  fashion.  
§ Translation  includes  three  steps  –  initiation,  elongation  and  termination.  The  ribosome  contains  
two  sites  –  Peptidyl  P  site  where  methionine-­‐‑containing  tRNA  initially  binds  and  aminoacyl  A  site  
where  each  new  incoming  tRNAs  with  activated  amino  acids  can  bind.  In  elongation  step,  amino  
acids  are  added  one  by  one  in  a  sting  like  fashion  to  produce  proteins.  Chain  termination  is  
signaled  by  one  of  the  three  codons  UAA,  UGA  or  UAG.    

Modification  refers  to  posttranslational  changes  in  a  protein  molecule  before  it  becomes  functionally  
active.  Following  protein  synthesis  (sometimes  simultaneously  as  the  protein  is  being  synthesized)  
posttranslational  modifications  take  place  to  transport  the  synthesized  proteins  to  appropriate  cellular  
sites.  These  modifications  take  place  in  endoplasmic  reticulum  and  golgi  bodies.  The  Golgi  complex  is  a  
dynamic  system  acting  as  a  temporary  protein  repository  that  gives  off  vesicles  and  vacuoles  for  further  
processing  and  transport.  These  processes  include  covalent  modifications,  protein  folding  and  tagging  
with  signal  peptides  to  dispatch  to  appropriate  cellular  destinations.  Glycosylation,  proteolysis,  
phosphorylation,  gamma  carboxylation,  prenylation,  ubiquitation,  polyamination  and  nitration  are  some  
of  the  recognized  posttranslational  chemical  modifications.  This  process  is  essential  in  tagging  wrongly  

©  SPMM  Course   6  
folded  or  aberrant  proteins  to  enter  lysosomes  for  destruction.    Study  of  mRNAs  using  microchip  arrays  is  
called  transcriptomics.  

 
DNA  Sequences   EXONS  (coding)  

 
INTRONS  (non-­‐‑
coding)  

Tandem  Repeats   Interspersed  

 

 
Satellite                        (10-­‐‑15%   Telomeric  repeats  
large  series  of  simple  repeats)   (necessary  for  integrity  of  
chromosomes)   Long  Interspersed  
Nuclear  Elements  

Minisatellite    

Hypervariable  repeats  
(used  in  DNA  
  fingerprinting)  
Short  Interspersed  
Microsatellite    (single,  di   Nuclear  Elements  
or  tri  nucleotide  repeats)  

Note  that  microsatellite  tandem  repeats  give  rise  to  trinucleotide  sequences:  these  are  linked  to  a  
group  of  non-­‐‑Mendelian  disorders  called  trinucleotide  repeat  disorders.  

6. Types of mutations
 

¬ A  mutation  is  a  sudden,  permanent  and  heritable  change  in  the  DNA  sequence.  Such  changes  in  
DNA  will  be  transcripted  to  mRNA  and  can  get  translated  into  proteins  leading  to  disease  
expression.    
§ Point  mutation  refers  to  single-­‐‑base  alteration  in  DNA.  Point  mutations  are  usually  
substitutions  where  one  base  is  replaced  by  another.  It  could  be  termed  as  transition  if  a  purine  

©  SPMM  Course   7  
 is  replaced  by  another  purine  or  a  pyrimidine  replaced  by  another  pyrimidine  (e.g.  A  to  G).  It  is  
called  transversion  if  a  purine  is  replaced  by  a  pyrimidine  or  vice  versa  (e.g.  A  to  T).    
§ According  to  the  effect  on  triplet  sequence,  mutations  could  be  frame  shift  or  in-­‐‑frame.  In  frame  
shift  mutations,  the  deletion  or  insertion  is  not  in  multiples  of  three  codons  e.g.  a  segment  of  5  
bases  deletion  mutations.  This  leads  to  a  shift  in  triplet  reading  frame  with  variable  results.  In  
frame,  mutation  refers  to  changes  happening  in  multiples  of  3  bases,  with  no  disturbances  in  
actual  reading  frame.    
§ According  to  the  effect  of  a  mutation  on  protein  product,  mutations  could  be  silent,  mis-­‐‑sense  or  
nonsense.  A  silent  mutation  causes  no  change  in  protein  product  –  this  is  possible  because  a  
single  amino  acid  is  often  coded  by  more  than  one  triplet  sequence.  In  a  silent  mutation  one  
triplet  sequence  is  replaced  by  a  different  sequence  but  without  changing  amino  acid  product.  In  
mis-­‐‑sense  mutation,  the  new  mutant  codon  specifies  a  different  amino  acid  with  variable  effects  
on  final  protein  product.  For  example,  haemophilia,  sickle  cell  anaemia.  In  non-­‐‑sense  mutation  
the  new  codon  is  UUA  UGA  or  UAG,  which  signals  ‘stop’  to  the  amino  acid  sequence  resulting  
in  nonfunctional  protein.  Point  substitutions  do  not  shift  the  reading  frame;  they  often  occur  in  
non-­‐‑coding  regions  and  go  unnoticed.  Even  at  coding  regions  they  are  often  silent  or  mis-­‐‑sense  
mutations.  

¬ Translocation  refers  to  exchange  of  chunks  of  genetic  materials  from  one  chromosome  to  another.  
These  are  essentially  mutations  occurring  at  ‘larger’  dimensions.  

§ These  are  mostly  reciprocal  so  one  segment  is  exchanged  for  another  segment  among  
chromosomes.    

§ Robertsonian  translocation  is  a  non-­‐‑reciprocal  (i.e.  unequal  exchange)  that  results  in  a  single  
fused  chromosome  from  2  acrocentric  (non  homologous)  chromosomes.  Following  a  
Robertsonian  translocation,  the  small  'ʹp'ʹ  arms  are  discarded,  and  a  metacentric  fusion  
chromosome  results.  Thus  from  2  chromosomes  a  single  chromosome  is  formed  with  no  
significant  (only  trivial)  loss  of  genetic  material.  Hence,  these  are  viable  and  ‘balanced’  within  
the  individual  in  whom  they  occur.    

§ But  when  gametes  are  formed,  only  one  of  the  two  gametes  can  have  the  whole  translocated  
metacentric  fusion  chromosome,  effectively  resulting  in  monosomy  (unbalanced  translocation)  
for  one  gamete  if  fertilized  and  trisomy  for  the  gamete  with  fused  chromosome  (extra  load  of  
genes  now).  This  is  one  of  the  mechanisms  for  Down’s  syndrome.  Due  to  the  mother  being  a  
carrier  of  such  translocation,  the  recurrence  rate  of  Down’s  is  extremely  high  in  such  cases  
compared  to  sporadic  Down’s  due  to  non-­‐‑disjunction.  

Some deletion syndromes of psychiatric relevance

 

©  SPMM  Course   8  
Disorder   Location  and  mode  of   Features  
transmission  

DiGeorge   22q11.2  Autosomal  dominant,   Mild  to  moderate  learning  disability,  facial  deformities  
(Velocardiofacial)   50%  risk  to  offsprings,  5-­‐‑10%  risk   esp.  cleft  palate,  absent  or  malformed  parathyroids  
of  deletion  in  parents.  If  offspring   resulting  in  hypocalcemia,  broad  nasal  bridge,  
has  the  deletion,  then  25%  chance   articulatory  speech  and  swallowing  problems,  >25%  have  
of  schizophrenia,  if  not  then   psychosis  
general  population  risk  ~1%.    

Williams   7q11  microdeletion   Hypercalcemia  at  birth,  supra  valvular  aortic  stenosis,  
syndrome   moderate  learning  disability,  disinhibited  disposition,  
speech  that  appears  superficially  fluent,  hyperacusis.  

Smith  Magenis   17p11.2  microdeletion   Moderate  to  severe  learning  disability,  self  harming  
syndrome   behaviours  e.g.,  pulling  off  nails  (onychotillomania)  and  
inserting  foreign  bodies  into  body  orifices.  Sleep  
disturbances  and  self  hugging  are  also  noted.  

Angelman   Deletion  of  15q11-­‐‑13  maternally   Developmental  delay,  low  IQ,  jerky  movements  especially  
syndrome     inherited  (see  genomic  imprinting   hand-­‐‑flapping,  frequent  smiling,  and  seizures.  
below)  

Prader-­‐‑Willi   Deletion  of  15q11-­‐‑13  paternally   Obesity,  short  stature,  small  limbs,  decreased  IQ  with  
syndrome   inherited  (see  genomic  imprinting   hyperphagia  and  skin  picking.  
below)  

Cri-­‐‑du-­‐‑chat   Deletion  of  chromosome  5p  (the   Feeding  problems  due  to  difficulty  swallowing  and  
syndrome   locus  5p15.2  is  responsible  for  the   sucking,  cat-­‐‑like  cry  with  poorly  developed  facial  features.  
phenotype)  

7. Mendelian inheritance
 

Johann  Mendel  was  a  Catholic  priest  who  was  interested  in  horticulture  and  botany.  He  studied  garden  
peas  and  proposed  ‘laws’  of  inheritance.  The  first  law  is  the  law  of  uniformity.  According  to  this  law,  if  
two  plants  that  differ  in  just  one  trait  (black  and  white)  are  crossed,  then  the  resulting  hybrids  will  be  
uniform  in  the  chosen  trait  (either  black  or  white,  not  blue).  This  is  not  entirely  true  as  later  geneticists  
demonstrated  intermediate  phenotypes  resulting  from  co-­‐‑dominant  heterozygous  expression.    

The  second  law  is  called  the  principle  of  segregation.  It  states  that  “for  any  particular  trait,  the  pair  of  
alleles  of  each  parent  separate  and  only  one  allele  passes  from  each  parent  on  to  an  offspring.    Which  allele  
in  a  parent'ʹs  pair  of  alleles  is  inherited  is  a  matter  of  pure  chance”.  For  example  if  there  are  two  alleles  one  
determining  black  colour  and  the  other  determining  white  in  mother  and  two  alleles  with  one  

©  SPMM  Course   9  
determining  white  colour  and  one  determining  black  colour  in  the  father,  then  these  two  alleles  segregate  
and  only  one  of  them  could  be  passed  on  to  the  second  generation  from  each  parent.  This  will  produce  
three  possible  types  of  offsprings  as  shown  in  the  table.  This  was  later  proved  to  be  true  by  studying  
chromosomes  during  cell  division.    

The  third  principle  is  the  principle  of  independent  assortment.  It  states  that  “different  pairs  of  alleles  are  
passed  to  offspring  independently  of  each  other.    The  result  is  that  new  combinations  of  genes  present  in  
neither  parent  are  possible”.    As  a  very  simplistic  example,  if  a  man  with  blue  eyes  and  brown  hair  mates  
a  woman  with  brown  eyes  and  black  hair;  their  child  can  have  blue  eyes  and  black  hair.  The  inheritance  of  
blue  eyes  does  not  take  brown  hair  ‘with  it’;  these  traits  are  independently  assorted.  Thus  Mendelian  
principles  are  applicable  to  human  genetics  as  well.  Note  that  all  traits  studied  using  Mendelian  genetics  
refer  to  categorical,  all  or  none  traits  i.e.  black  vs.  brown,  blue  vs.  brown,  tall  vs.  short,  etc.  It  does  not  
apply  with  same  simplicity  to  dimensional  traits  such  as  IQ  or  blood  pressure.  

Mendel’s  Laws  (aide  memoir)   Explanations    

Law  of  uniformity:   Two  alternative  alleles  at  one  locus      

DD  X  dd    à  Dd   Two  homozygous  parents  (with  a  double  dose  of  either  one).  All  off  springs  
are  of  uniform  type  (all  Dds)  

Law  of  segregation   Two  heterozygous  parents    

Dd  X  Dd  à  DD  |  Dd  Dd    |  dd   Three  possible  types  of  offsprings  1DD.2Dd.1dd  

Law  of  independent  assortment   Two  loci  with  alleles  D,d  and  H,h.    

DdHh  (blue-­‐‑eye:brown  hair)  X   Double  heterozygote  X  Double  homozygote  parent  

ddhh  (brown  eye:  black  hair)  à  
Four  possible  types  of  offspring,  each  with  equal  probability  (blue  eye/brown  
DdHh  |  ddHh    |  Ddhh  |  ddhh  
hair,  blue  eye/black  hair,  brown  eye/black  hair,  brown  eye/brown  hair).  

Adapted  from  McGuffin  et  al.  (ed)  Psychiatric  genetics  and  genomics.  Oxford  Press:  P37  

A. Single gene inheritance (Mendelian) disorders

Autosomal dominant disorders
Each  cell  contains  two  copies  of  all  the  autosomes.  An  autosomal  dominant  disorder  occurs  when  one  of  
the  two  copies  has  a  mutation  and  the  protein  produced  by  the  normal  form  of  the  gene  cannot  
compensate.  So  the  mutant  allele  becomes  dominant  over  the  normal  allele  and  results  in  disease  
expression.  In  this  case,  a  heterozygous  individual  who  has  two  different  forms  (or  alleles)  of  the  same  
gene  will  manifest  the  disease.  The  offspring  of  heterozygotes  have  a  50%  chance  of  inheriting  the  
chromosome  carrying  the  disease  allele,  and  therefore  also  of  having  the  disease.  If  both  parents  are  
heterozygous,  the  recurrence  risk  is  75%.    

'ʹIncomplete  penetrance'ʹ  may  occur  if  patients  have  a  dominant  disorder  but  it  does  not  manifest  itself  
clinically  in  them.  This  gives  the  appearance  of  the  gene  having  'ʹskipped'ʹ  a  generation.  Having  incomplete  

©  SPMM  Course   10  
penetrance  increases  the  likelihood  of  having  an  unaffected  child.  The  variable  expression  refers  to  
differences  in  severity  of  the  disease  expressed.  A  mildly  affected  parent  may  have  a  severely  affected  
child.  

Spontaneous  disease-­‐‑causing  mutations  can  often  present    as  diseases  that  are  known  to  occur  in  
autosomal  dominant  fashion.  For  example,  achondroplasia  and  tuberous  sclerosis  are  commonly  due  to  
spontaneous  mutations,  but  families  show  AD  pattern.  Often  the  abnormal  gene  in  autosomal  dominant  
diseases  codes  for  structural  proteins  such  as  receptors  or  cytoskeleton  proteins.    

Sometimes  such  aberrant  production  of  an  autosomal  dominant  disorder  without  family  history  may  be  
due  to  a  phenotypically  indistinguishable  disorder  without  the  genotype  –  this  is  called  phenocopy.  
(Goldschedt,  1935)  e.g.,  anti-­‐‑psychotic  medication  causes  patients  to  manifest  the  same  symptoms  as  the  
genetically  determined  Parkinson’s  disease.  Another  example  is  genotypically  determined  Pendred  
syndrome  being  mimicked  by  endemic  cretinism.  

Autosomal recessive disorders

These  disorders  manifest  themselves  only  when  an  individual  is  homozygous  for  the  disease  allele;  i.e.  
both  chromosomes  carry  the  mutated  gene.  In  this  case,  the  parents  are  generally  unaffected,  healthy  but  
carriers  (heterozygous  for  the  disease  allele).  There  is  usually  no  family  history,  although  the  defective  
gene  may  be  passed  from  generation  to  generation  (skipping).  The  offsprings  of  an  affected  person  are  
healthy  heterozygotes  unless  the  other  parent  is  also  a  carrier.  If  carriers  marry  each  other,  the  offspring  
has  a  1  in  4  chance  of  being  homozygous  and  affected  and  a  1  in  2  chance  of  being  a  carrier,  and  a  1  in  4  
chance  of  being  genetically  normal.  Consanguinity  increases  the  risk.  Often  the  abnormal  gene  in  
autosomal  recessive  diseases  codes  for  enzymatic  proteins.  

Sex-linked disorders
Genes  carried  on  the  X  chromosome  are  said  to  be  'ʹX-­‐‑linked'ʹ,  and  can  be  dominant  or  recessive  in  the  same  
way  as  autosomal  genes.  Normally  males  inherit  an  X  chromosome  from  their  mother  and  a  Y  
chromosome  from  their  father,  whereas  normal  females  inherit  an  X  chromosome  from  each  parent.  The  Y  
chromosome  contributes  very  less  genetic  material  to  a  man’s  genetic  makeup.  Hence,  there  must  be  a  
mechanism  to  simulate  this  deficiency  in  females  too  to  preserve  natural  equality.  This  phenomenon  is  
now  known  to  be  ‘X  inactivation’.  This  occurs  very  early  in  the  development  of  female  embryos.  When  an  
X  chromosome  is  inactivated,  it  could  be  visualized  under  the  microscope  as  a  highly  condensed  Barr  
body  in  the  nuclei  of  interphase  cells.  An  inactivated  X  chromosome  does  not  get  transcripted  to  produce  
mRNA.  X  inactivation  is  random  process.  In  other  words,  some  cells  of  the  female  embryo  have  paternally  
inherited  X  inactivated  while  the  other  cells  have  maternally  inherited  X  inactivated.  It  is  an  irreversible,  
fixed  process  and  once  inactivated  these  chromosomes  do  not  get  reactivated  life  long.    The  entire  cell’s  
progeny  will  have  same  inactivation  replicated.  All  X  chromosomes  in  a  cell  are  inactivated  except  one,  
irrespective  of  original  number  of  X  chromosomes  in  a  cell.  Thus  females  with  trisomy  X  will  have  two  
Barr  bodies.  X  inactivation  occurs  via  DNA  methylation.    

©  SPMM  Course   11  
X-linked recessive disorders
If  a  recessive  disease-­‐‑causing  mutation  occurs  on  the  single  X  chromosome  of  a  man,  this  is  sufficient  to  
cause  disease,  as  another  X  chromosome  is  not  existent  to  compensate  any  deficiencies.  As  females  have  
two  copies  of  the  X  chromosome,  they  need  a  double  identical  mutation  for  disease  expression,  which  is  
extremely  rare.  But  during  random  X  inactivation  if  most  X  chromosomes  carrying  normal  alleles  are  
inactivated  (called  unfavourable  Lyonisation),  then  these  females  can  manifest  the  disease  phenotype  –
termed  as  manifesting  heterozygotes.  But  nevertheless  the  severity  of  expressed  disease  is  mild  and  can  
go  unnoticed  too.  Skipped  generations  are  commonly  seen  because  an  affected  male  can  transmit  the  
disease-­‐‑causing  mutation  to  a  heterozygous  daughter,  who  remains  normal  phenotypically  but  carries  and  
transmits  the  disease-­‐‑causing  allele  to  her  sons.    

Disorder   Location  and  mode  of  transmission   Features  

Tuberous  sclerosis   • 9q34  /  16p13     Adenoma  sebaceum,  normal  to  sever  MR,  
• Auto.dominant    (but  most  are   ash  leaf  macules,  brain  hamartomas,  heart  
spontaneous)   and  kidney  cysts  
• 1  in  30  000  

Treacher  Collins   • 5q31   Maxilla-­‐‑mandibular  hypoplasia,  malformed  

syndrome   • Auto.dominant   pinna,  down  slanting  palpebrae,  mild  to  
• 1  in  40  000   moderate  MR  

Apert  syndrome   • 10q   Variable  MR,  cranio  synostosis,  shallow  

• Auto  dominant   orbits,  trapezoid  mouth,  ‘mitten’  hands  and  
feet.  

Noonan  syndrome   • Chr  12   Mild  MR,  short  stature,  nuchal  

• Auto.dominant   edema/webbed  neck,  pulmonary  stenosis,  
• 1  in  1  500   cryptorchidism  

Hurler  syndrome   • 4p16   Deteriorating  IQ  after  age  2,  coarse  facies,  
• Auto.  recessive   clouded  cornea,  joint  stiffness.  
• 1  in  100  000  

Lesch-­‐‑Nyhan  syndrome   • Xq  26-­‐‑27   Poor  muscle  control,  and  moderate  mental  

• X  linked  recessive   retardation  –  year  1.  Self-­‐‑mutilating  
• Deficiency  of  the  enzyme   behaviors,  characterized  by  lip  and  finger  
hypoxanthine-­‐‑guanine  
biting  –  by  year  2.  Hyperuricemia  and  
phosphoribosyltransferase  (HGPRT)  
hyperuricosuria  -­‐‑severe  gout  and  kidney  
problems  –  can  present  anytime.  

From  McGuffin  et  al.  (ed)  Psychiatric  genetics  and  genomics.  Oxford  Press:  2002      

Male-­‐‑to-­‐‑male  transmission  is  not  seen  in  X-­‐‑linked  inheritance.  Affected  male  mates  with  a  homozygous  
normal  female,  all  of  the  daughters  will  be  heterozygous  carriers;  all  of  the  sons  will  be  homozygous  
normal.  If  a  carrier  female  mates  with  normal  male  (which  is  often  the  case  in  this  transmission),  then  half  

©  SPMM  Course   12  
of  the  sons  will  be  affected,  and  half  of  the  daughters  will  be  carriers.    e.g.  haemophilia  A/B,  Duchene  
muscular  dystrophy,  and  androgen  insensitivity  
syndrome.  
X-­‐‑LINKED  MENTAL  RETARDATION  
X-linked dominant disorders
(XLMR)    
These  are  rare.  Similar  to  X-­‐‑linked  recessive  pattern,  
Learning  disability  is  significantly  more  
male-­‐‑male  transmission  of  the  disease-­‐‑causing  
common  in  males  than  in  females.  So  X  linked  
mutation  is  not  seen.    Because  females  have  higher   genes  are  a  suspect  in  their  aetiology.    
gene  frequency  for  X  chromosomes  compared  to  males,    
females  have  twice  as  much  chance  than  males  to   XLMR  is  a  heterogenous  condition  -­‐‑  
inherit  an  X-­‐‑linked  disease-­‐‑causing  mutation.  Vitamin   subdivided  into  syndromic  (1/3rd)  and  non-­‐‑
D-­‐‑resistant  rickets  is  the  best-­‐‑known  example.  Females   syndromic  (2/3rd)    forms,  depending  on  the  
presence  of  further  abnormalities.  
who  are  heterozygous  for  the  mutant  gene  and  males  
 
who  have  one  copy  of  the  mutant  gene  on  their  single  
The  most  common  form  of  XLMR  is  the  
X  chromosome  will  manifest  the  disease.  As  in   Fragile  X  syndrome.  
autosomal  dominant  inheritance,  the  disease    
phenotype  is  seen  in  multiple  generations  making   Mutations  in  MECP2  gene  in  X  chromosome  
‘skipped  generations’  relatively  unusual.  If  the  affected   give  rise  to  a  wide  range  of  disorders,  
male  mates  with  homozygous  normal  female,  none  of   including  female-­‐‑specific  Rett  syndrome.  
MECP2  mutations  also  lead  to  other  
the  sons  will  be  affected  but  all  of  the  daughters  will  be  
phenotypes  such  as  severe  encephalopathy,  
affected.    Heterozygous  female  mating  a  normal  male  
progressive  spasticity,  Angelman  and  Prader-­‐‑
will  result  in  50%  of  sons  being  affected  and  50%  of   Willi  like  phenotypes  and  nonsyndromic  
daughters  being  affected.  An  atypical  pervasive   XLMR  in  males  
developmental  disorder  called  Rett’s  syndrome  is  
inherited  in  X-­‐‑linked  dominant  fashion.  

B. Non Mendelian inheritance

Mitochondrial  inheritance,  mosaicism,  trinucleotide  expansions  and  genomic  imprinting  do  not  follow  
normal  Mendelian  principles  and  so  are  called  non-­‐‑Mendelian  inheritance.  Polygenic  and  multifactorial  
disorders  too,  do  not  obey  Mendelian  principles  in  strict  sense.  

Mitochondrial inheritance
Mitochondrial  DNA  is  wholly  inherited  from  the  ovum.  The  sperm  has  no  mitochondria  in  its  ‘head’;  
‘head’  is  made  of  nuclear  material  and  acrosomal  cap.  The  ‘body’  of  sperm  has  many  mitochondria  that  
provide  energy  in  propelling  the  ‘tail’.  The  ‘body’  and  ‘tail’  are  shed  on  entry  of  sperm  into  the  ovum.  
Hence  the  mitochondria  of  an  embryo  are  completely  maternal-­‐‑derived.  The  mitochondrial  chromosome  
has  no  introns  in  the  genes.  Therefore  any  mutation  has  a  high  chance  of  having  an  effect.  Most  
mitochondrial  diseases  are  myopathies  and  neuropathies.  This  is  important  in  clinical  genetics  as  
mitochondrial  DNA  abnormalities  result  in  various  diseases  such  as  MELAS  (mitochondrial  myopathy,  
encephalopathy,  lactic  acidosis  and  recurrent  stroke  syndrome)  and  Leber  hereditary  optic  neuropathy.    

©  SPMM  Course   13  
Leber'ʹs  hereditary  optic  neuropathy  (LHON)  is  the  commonest  cause  of  blindness  in  young  men,  with  
bilateral  loss  of  central  vision  and  cardiac  arrhythmias.  These  diseases  are  purely  maternally  inherited.  
Mitochondrial  DNA  codes  for  13  proteins  involved  in  the  respiratory  chain  in  addition  to  22  tRNAs  and  2  
ribosomal  RNAs.  

Many  other  syndromes  have  been  described.  Myopathies  include  chronic  progressive  external  
ophthalmoplegia  (CPEO);  encephalomyopathies  include  myoclonic  epilepsy  with  ragged  red  fibres  
(MERRF)  and  mitochondrial  encephalomyopathy,  lactic  acidosis  and  stroke-­‐‑like  episodes  (MELAS).  
Kearus-­‐‑Sayre  syndrome  includes  ophthalmoplegia,  heart  block,  cerebellar  ataxia,  deafness  and  mental  
deficiency  due  to  long  deletions  and  rearrangements.    

Trinucleotide expansions
Trinucleotides  repeat  disorders  are  a  set  of  genetic  disorders  caused  by  trinucleotide  repeats  (codons  –  e.g.  
CGG,  CTG,  CAG,  etc.)  in  certain  genes  exceeding  the  normal  number  of  repeats.  The  mutation  results  in  
an  unstable  site,  which  is  often  fragile.    

Anticipation  refers  to  a  pattern  of  inheritance  in  which  individuals  in  the  most  recent  generations  of  an  
affected  family  develop  a  disease  at  an  earlier  age  and  with  greater  severity  than  those  in  previous  
generations.  This  is  mostly  due  to  the  gradual  expansion  of  trinucleotide  repeat  polymorphisms  (this  
instability  is  
Frag(g)ile  X   Friedreich   Huntington   MyoTonic  
called  a   syndrome AtaxiA ChoreA dysTrophy
dynamic  
•cGG •gAA •CAg •cTg
mutation).    

Fragile  X  genetics:  This  X-­‐‑linked  condition  accounts  for  more  cases  of  mental  retardation  in  males  than  
any  condition  except  Down  syndrome  with  the  frequency  of  1  in  4000.  It  can  affect  females  but  50%  less  
frequently  than  in  males.  A  fragile  site  near  the  tip  of  the  long  arm  of  the  X  chromosome  was  initially  
suspected.  Now  it  is  known  that  fragile  X  results  from  the  an  expansion  of  a  trinucleotide  repeat  (CGG)  
proximal  to  FMR1  gene.  If  the  number  of  CGG  repeats  in  this  location  increases  beyond  52,  this  
destabilizes  this  sequence  allowing  further  expansion  during  spermatogenesis  or  oogenesis.  Being  born  
with  one  FMR1  allele  with  200  or  more  repeats  results  in  lower  IQ  in  most  men  and  ~  60%  of  women.  The  
phenomenon  of  anticipation  is  seen.    Unlike  men,  heterozygous  women  usually  have  the  other  X  
chromosome  that  can  compensate  to  some  extent;  thus  they  show  no  physical  signs  other  than  early  
menopause,  mild  learning  difficulties  and  rarely  frank  retardation.  Affected  males  suffer  from  enlarged  
testes,  prominent  ear  lobes  and  a  protracting  jaw,  a  high-­‐‑pitched  voice,  and  mental  retardation.  Some  men  
carry  an  increased  number  of  CGG  repeats  in  the  FMR1  locus  but  do  not  show  a  full-­‐‑blown  clinical  
phenotype;  these  individuals  are  called  premutation  carriers.  Though  premutant  carriers  were  long  
thought  to  be  free  from  clinical  features,  it  is  now  known  that  they  are  at  increased  risk  for  developing  
intention  tremor  and  ataxia  especially  after  middle  age.  Women  who  are  premutation  carriers  (55–200  
CGG  repeats)  are  at  increased  risk  of  premature  ovarian  failure  and/or  mild  cognitive  or  behavioral  
abnormalities.  The  fragile  site  at  first  exon  of  FMR1  is  called  FRAXA,  a  second  site  at  Xq28  called  FRAXE  
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is  also  linked  to  mental  retardation.  FRAXF  is  the  third  fragile  site  sensitive  to  folate,  but  not  linked  to  MR.  
Similar  to  Myotonic  Dystrophy  (but  in  contrast  to  Huntington’s),  anticipation  rates  are  higher  in  maternal  
than  paternal  inheritance.  This  is  because  further  trinucleotide  expansion  occurs  during  oogenesis  rather  
than  spermatogenesis.  

Huntington’s  genetics:  Huntington'ʹs  disease  is  inherited  in  an  autosomal  dominant  manner  with  full  
penetrance  and  a  prevalence  rate  of  about  5  per  100,000.  The  gene  responsible  is  an  expanded  and  
unstable  CAG  trinucleotide  repeat  on  the  short  arm  of  chromosome  4  -­‐‑  4p16.3.  This  results  in  translation  
of  an  extended  glutamine  sequence  in  huntingtin,  the  protein  product  of  the  gene.  Huntingtin  is  expressed  
throughout  the  body.  Its  function  is  unclear.  Though  slightly  unusual  for  a  genetic  disease;  the  onset  is  
usually  between  30  and  50  years  of  age.  Most  adult-­‐‑onset  HD  cases  have  CAG  expansions  of  40-­‐‑55  repeats  
while  greater  expansions  (>70  repeats)  are  seen  in  childhood-­‐‑onset  HD.    The  phenomenon  of  anticipation  
is  seen  here  too.  But  unlike  other  X-­‐‑linked  disorders  (see  myotonic  dystrophy  below),  inheritance  of  HD  
from  the  father  is  associated  with  the  greater  repeat  expansion  and  earlier  age  of  onset.  Nearly  one-­‐‑third  
of  father-­‐‑to-­‐‑offspring  cases  show  an  expansion  resulting  in  juvenile-­‐‑onset  HD.  Characteristic  protein  
deposits  form  nuclear  inclusions  in  neurons  of  HD  patients.  

Myotonic  dystrophy  is  another  neurological  disease  with  trinucleotide  repeat  expansion.  Here  CTG  
repeats  are  expanded.  The  anticipation  resulting  from  trinucleotide  instability  is  higher  if  the  inherited  
expansion  comes  from  the  mother  than  the  father  in  MD.  This  is  because  oogenesis,  due  to  its  inherently  
long  dormancy  compared  to  spermatogenesis,  results  in  much  higher  instability.  As  a  result  anticipation  is  
more  prominent  in  maternal  transmissions.  

Genomic imprinting  
Though  no  structural  differences  exist  between  maternal  and  paternally  inherited  chromosomes  in  
humans,  there  are  some  subtle  functional  differences,  which  are  increasingly  being  appreciated.  For  
example,  a  deletion  of  part  of  the  long  arm  of  chromosome  15  (15q11-­‐‑q13)  will  give  rise  to  the  Prader-­‐‑Willi  
syndrome  (PWS)  if  it  is  paternally  inherited.  A  deletion  of  a  similar  region  of  the  chromosome  gives  rise  
to  Angelman'ʹs  syndrome  (AS)  if  it  is  maternally  inherited.  This  may  be  due  to  differential  regional  
expression  of  the  chromosomes.  Maternal  chromosome  15q11-­‐‑13  is  expressed  in  the  brain  and  
hypothalamus,  leading  to  neuronal  damage  in  its  absence.    This  phenomenon  is  called  genomic  
imprinting.  It  is  thought  to  be  due  to  DNA  methylation  effects.    
 
In  genomic  imprinting,  the  disease  phenotype  expressed  depends  on  whether  the  allele  is  of  maternal  or  
paternal  lineage.  This  parent-­‐‑of-­‐‑origin  phenomenon  is  an  important  exception  to  the  Mendelian  
inheritance  patterns.  Approximately  70%  of  patients  with  Prader  Willi  syndrome  have  a  deletion  in  their  
paternally  derived  15q11-­‐‑q13.  Maternal  uniparental  disomy  (inheriting  both  copies  from  mother  when  
embryo  is  formed)  occurs  in  most  of  the  remaining  patients  (25%).  Most  patients  with  Angelman’s  
syndrome  have  a  deletion  in  their  maternally  derived  15q11-­‐‑q13.  Paternal  uniparental  disomy  occurs  in  
about  4%  of  Angelman’s  syndrome.    

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Multifactorial inheritance
It  is  a  complex  inheritance  in  which  multiple  genes  are  involved  jointly  with  environmental  influences.    
Most  common  psychiatric  disorders  such  as  schizophrenia  do  not  show  a  Mendelian  pattern  of  
inheritance.  But  these  disorders  are  categorically  defined  as  present  or  absent  hence  cannot  be  regarded  as  
continuous  variables  too.  But  these  conditions  could  be  regarded  as  quasi-­‐‑continuous  in  that  those  who  
are  affected  can  be  graded  along  a  continuum  of  severity.  So  we  can  also  assume  that  there  is  an  
underlying  liability  to  develop  the  disorder,  which  is  continuously  distributed  in  the  population.  Those  
who  pass  a  certain  threshold  manifest  the  condition.  This  is  known  as  the  liability/threshold  model.  
If  the  underlying  liability  to  develop  the  disorder  is  inherited  in  a  multifactorial  fashion,  one  can  assume  
that  the  distribution  will  be  approximately  distributed  along  a  normal  distribution  curve.  But  compared  to  
the  normal  population,  the  genetic  liability  of  relatives  of  affected  individuals  will  be  increased,  and  their  
liability  distribution  will  be  shifted  to  the  right.  Thus,  the  proportion  of  relatives  above  the  disease  
threshold  will  be  greater  compared  with  the  general  population.  If  we  know  the  proportion  of  affected  
relatives  of  probands  and  the  proportion  of  those  affected  in  the  general  population,  it  is  possible  to  
calculate  the  correlation  in  liability  between  pairs  of  relatives  using  this  model.  Recurrence  risks  to  
relatives  for  multifactorial  disorders  are  influenced  by  the  disease  severity,  the  degree  of  relationship  to  
the  index  case,  the  number  of  affected  close  relatives  and,  if  there  is  a  higher  incidence  in  one  particular  
sex,  the  sex  of  the  index  case.  

Polygenic inheritance
Polygenic  inheritance  is  again  a  complex  inheritance  in  which  multiple  genes  but  no  environmental  factors  
are  involved.  Both  polygenic  and  multifactorial  inheritances  defy  normal  Mendelian  principles.  The  
additive  effects  of  many  genes,  i.e.  polygenic  inheritance,  probably  cause  characteristics  such  as  height  
and  intelligence,  which  show  a  normally  distributed  continuous  distribution  in  the  general  population.  

8. Polymorphisms
Polymorphism  refers  to  variations  in  genetic  make-­‐‑up  at  a  particular  locus  noted  in  general,  apparently  
healthy  population.  To  be  defined  as  polymorphism  the  variant  must  occur  in  at  least  1%  of  the  total  
population  and  must  be  associated  with  normal  but  varied  (not  disease  causing)  expression  of  final  
phenotype.  This  excludes  spontaneous  mutations  that  are  random  and  so  cannot  simultaneously  occur  in  
such  significant  (1%)  proportion  of  total  population.  ABO  blood  groups  are  good  examples  of  
polymorphism  expressed  in  protein  products  of  genes.    

• Restriction  fragment  length  polymorphisms  are  variations  that  change  the  sites  at  which  restriction  
enzymes  can  act  on  a  DNA  molecule,  rendering  differences  in  the  final  ‘restricted’  or  cleaved  DNA  
when  these  enzymes  are  applied  in  vitro  (Southern  Blotting).    

• If  polymorphisms  are  due  to  changes  in  single  nucleotide  in  a  sequence,  then  these  are  called  SNPs  
or  single  nucleotide  polymorphisms.  These  single-­‐‑base  polymorphisms  can  be  assayed  by  DNA  
sequencing  or  through  the  use  of  DNA  chips.  

• If  the  variations  are  due  to  changes  in  length  of    the  genetic  sequence,  these  are  termed  length  
polymorphisms.  
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 • VNTRs  (variable  number  of  tandem  repeats).  These  polymorphisms  are  the  result  of  varying  
numbers  of  repeats  in  a  specific  region  of  a  chromosome.  These  Polymorphisms  can  be  classified  
according  to  the  length  of  polymorphic  fragments;  Short  tandem  repeat  polymorphisms  (STRPs)  or  
microsatellites  range  in  size  from  2  to  6  bases.  The  minisatellites  vary  between  20  to  70  bases  each.  
Microsatellites  are  currently  preferred  as  genetic  markers  in  disease  mapping  because  they  can  be  
detected  using  the  polymerase  chain  reaction.    

• Polymorphisms  arise  out  of  mutations  originally  but  are  maintained  in  population  due  to  number  of  
factors  such  as  founder  effect,  genetic  drift  and  natural  selection.    

• Note  that  most  polymorphisms  occur  in  non-­‐‑coding  areas  (introns)  –  as  coding  sequences  or  exons  
on  mutation  often  produce  disease  phenotypes.  

• Serotonin  transporter  polymorphisms  are  noted  in  promoter  region,  which  is  a  non-­‐‑coding  part  of  
DNA  (5HTTLPR  –  5HT  transporter  linked  promoter  region).  5HTTLPR  can  be  of  a  short  variant  or  
long  variant  (length  polymorphism).  55%  of  Europeans  carry  the  long  allele.  In  those  with  short  
variant,  the  serotonin  transporter  expression  is  low;  short  variant  is  speculated  to  be  associated  with  
higher  incidence  of  affective  disorders,  neuroticism,  anxiety  and  PTSD.  But  the  evidence  is  
inconclusive  as  most  studies  are  case  control  design  with  significant  heterogeneity.  In  an  interesting  
study  of  environment-­‐‑gene  interaction,  Caspi  et  al  (2003)  noted  that  individuals  with  one  or  two  
copies  of  the  short  allele  of  the  5-­‐‑HT  T  promoter  polymorphism  exhibited  more  depressive  symptoms,  
diagnosable  depression,  and  suicidality  in  relation  to  stressful  life  events  than  individuals  
homozygous  for  the  long  allele.  

9. Cytogenetic techniques
 

¬ Blotting  techniques  
• Southern  blotting  is  a  widely  used  method  for  the  detection  of  a  specific  sequence  in  DNA.  This  
method  was  named  after  Dr.  E.  M.  Southern  who  introduced  this  method  in  1975.    
• Western  blotting  is  another  widely  used  method  for  the  detection  of  specific  protein  after  
electrophoresis.  The  sample  is  electrophoresed  on  a  polyacrylamide  gel,  then,  blotted  to  a  
membrane.  The  membrane  is  incubated  with  the  antibody  to  the  specific  protein.    
• Northern  blotting  is  a  detection  method  for  a  specific  RNA  after  electrophoresis.  

¬ Polymerase  chain  reaction  (PCR)  

Minute  amounts  of  DNA  can  be  amplified  over  a  million  times  using  an  in  vitro  technique  called  
polymerase  chain  reaction.  Using  this  technique,  minute  amount  of  DNA  such  as  those  from  buccal  cell  
scrapings,  blood  spots,  or  single  embryonic  cells  can  be  analysed.    The  DNA  is  amplified  between  two  
short  single-­‐‑stranded  DNA  fragments  called  oligonucleotide  primers,  which  are  complementary  to  the  
sequences  at  each  end  of  the  DNA  of  interest.  Hence  the  exact  DNA  sequence  to  be  amplified  needs  to  be  
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known  to  carry  out  PCR.    It  is  not  error  free  as  laboratory  contaminants  can  have  DNA  which  gets  
amplified  erroneously.    

The  technique  has  three  steps.  (1)  Double-­‐‑stranded  genomic  DNA  is  denatured  by  heat  into  single-­‐‑
stranded  DNA.  The  reaction  is  then  cooled  to  favour  DNA  annealing,  and  the  primers  bind  to  their  target  
DNA.  (2)  DNA  polymerase  is  used  to  extend  the  primers  in  opposite  directions  using  the  target  DNA  as  a  
template.  After  one  cycle  there  are  two  copies  of  double-­‐‑stranded  DNA,  after  two  cycles  there  are  four  
copies,  and  this  number  rises  exponentially  with  the  number  of  cycles.  (3)  The  cycling  is  set  to  produce  
necessary  number  of  amplifications.    

¬ FISH  –  Fluorescent  in  situ  hybridisation  

FISH  is  a  cytogenetic  technique  to  detect  and  localize  specific  DNA  sequences  on  chromosomes.  It  uses  
fluorescent  probes  that  bind  to  only  those  parts  of  the  chromosome  with  which  the  probes  have  high  
degree  of  sequence  similarity.  Fluorescence  microscopy  is  employed  to  detect  the  location  where  the  
fluorescent  probe  binds  to  the  chromosome.  FISH  is  often  employed  to  detect  specific  features  in  DNA.  

¬ DNA  Cloning  

Plasmid  is  a  bacterial  DNA,  which  is  extra  chromosomal,  and  independently  replicating  (similar  to  
mitochondrial  DNA  in  humans).  Any  particular  DNA  fragment  of  interest  can  be  isolated  and  inserted  
(using  a  DNA  ligase  enzyme)  into  the  genome  of  such  self-­‐‑replicating  plasmids.    When  used  for  such  a  
purpose  the  plasmids  are  called  vectors  (vehicles  for  DNA  replication).  Bacteriophages  and  other  viruses  
can  also  be  used  as  vectors.    Replication  by  the  millions  of  the  vectors  results  in  multiple  copies  or  clones  
of  the  inserted  sequence.  Removal  of  inserted  gene  sequences  from  the  host  vector  results  in  large  
quantities  of  the  required  genes.    

10. Heritability & concordance

 

Concordance:  A  twin  pair  is  said  to  be  concordant  when  both  co  twins  have  the  same  disease  expression  
(or  both  are  disease  free).  The  pair  can  be  discordant  if  one  of  them  harbours  a  disease  while  the  other  
does  not.  Due  to  higher  degree  of  genetic  sharing  among  homozygous  individuals,  one  would  expect  
higher  concordance  among  monozygotes  compared  to  dizygotes  if  the  disease  being  studied  has  a  
significant  genetic  component.  In  contrast,  a  trait  that  has  no  genetic  basis  should  have  equivalent  
concordance  rates  for  MZ  and  DZ  twins.  

Heritability  is  the  main  measure  of  genetic  variation  in  polygenic  (quantitative)  traits.  The  total  variation  
of  a  trait  in  a  population  can  depend  on  genetic  variation  or  environmental  variation,  so  heritability  is  the  
proportion  that  is  genetic,  not  environmental,  out  of  that  total.  The  relative  influence  of  genetic  factors  in  
defining  the  variance  in  a  trait  is  expressed  as  heritability.  If  this  is  defined  as  the  proportion  of  the  total  
phenotypic  variance  attributable  to  additive  genetic  variance,  then  it  is  known  as  narrow-­‐‑sense  
heritability.  Heritability  is  also  sometimes  used  to  describe  the  proportion  of  variance  explained  by  the  
total  genetic  variance  (additive  and  non-­‐‑additive  genetic  variance).  Here  it  is  called  broad-­‐‑sense  
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heritability.  Non-­‐‑additive  genetic  influences  include  phenomena  such  as  epistasis  –  gene-­‐‑gene  interaction,  
and  dominance  effects  where  presence  of  one  gene  mitigates  the  expression  of  other  gene.    

Heritability  can  be  calculated  from  concordance  rates  using  the  mathematical  formulae.  

Interpretation  of  heritability:  (from  Visscher  et  al.,  2008)  

STATEMENT   ACCURACY  

A  high  heritability  means  that  most  of  the   CORRECT.  So,  in  the  current  population,  the  phenotype  of  an  
variation  that  is  observed  in  the  present   individual  is  a  good  predictor  of  the  genotype  
population  is  caused  by  variation  in  genotypes.  

A  heritability  of  80%  means  that  80%  of  the   CORRECT.  It  does  not  mean  that  genes  account  for  80%  of  the  
variability  in  whether  an  individual  becomes   causative  factors  –  as  inheritance  is  not  same  as  genetic  
affected  is  inherited,  while  20%  is  not.     causation.  

High  heritability  implies  genetic  determination   FALSE.  It  does  not  mean  that  the  phenotype  is  determined  
once  we  know  the  genotype,  because  the  environment  can  
change  or  can  be  manipulated  to  alter  the  phenotype  

Heritability  is  the  proportion  of  a  phenotype   FALSE:  Phenotype  is  not  passed  on  –  only  the  genotype.  There  
that  is  passed  on  to  the  next  generation   are  many  modifiers  in  the  environment  and  cellular  machinery  
between  a  genotype  and  phenotype.  

Heritability  is  informative  about  the  nature  of   FALSE.  Heritability  is  measured  within  a  specified  population  
between-­‐‑group  differences   –  differences  among  groups  may  not  be  due  to  genetic  
differences  but  due  to  nature  of  studied  population  

A  large  heritability  implies  genes  of  large  effect   FALSE.  Not  true  for  polygenic  disorders.  There  is  no  strong  
relationship  between  heritability  and  the  number  or  size  of  
genes  affecting  the  trait.  An  exception  is  Mendelian  single  gene  
disorders  –  they  all  have  heritability  of  100%.    

Specific heritability factors

Some  common  and  highly  regarded  as  environmental  disorders  such  as  obesity  have  been  demonstrated  
to  have  high  familial  loading.  80%  of  offspring  with  both  parents  obese,  40%  of  offspring  with  one  parent  
obese  are  obese  themselves  compared  to  10%  obesity  in  children  with  both  lean  parents.  Reported  
estimates  of  heritability  for  IQ  from  twin  studies  are  remarkably  consistent  in  the  range  of  0.5–0.8,  with  
differing  estimates  for  the  various  components  of  cognitive  abilities.    

Disorder   Heritability  estimate*  

Schizophrenia   80  

©  SPMM  Course   19  
 Bipolar  disorder   >80  
Major  depression   40  
Generalized  anxiety   30  
Panic  disorder   40  
Phobia   35  
Alcohol  dependence   60  
*Based  on  DSM-­‐‑IIR  diagnosis.  The  estimates  must  be  treated  as  approximations  only.  Autism  and  Tourette’s  may  have  around  90%  
heritability.  (From  Owen,  MJ.,  Cardno,  AG.  &O’Donovan,  MC.  Psychiatric  genetics:  Back  to  the  future  Molecular  Psychiatry  
(2000)  5,  22–31)    

The  Big  Five  personality  traits  have  following  heritability:  Openness:  57%;  Extraversion:  54%;  
Conscientiousness:  49%;  Neuroticism:  48%;  Agreeableness:  42%  

11. Hardy Weinberg equilibrium

In  the  absence  of  mutation,  non-­‐‑random  mating,  selection  and  genetic  drift,  the  genetic  constitution  of  the  
population  remains  the  same  from  one  generation  to  the  next.      

This  principle  can  be  used  mathematically  to  

determine  frequency  of  an  abnormal  gene  or  genotype   GENOTYPE  FREQUENCY  
For  a  given  locus,  the  genotype  frequency  measures  the  
in  the  population.  If  p  is  the  frequency  of  the  normal  
proportion  of  each  genotype  in  a  population.    
gene  in  the  population,  q  is  the  frequency  of  the  
abnormal  gene,  p2  is  the  frequency  of  the  normal   In  a  population  of  100  individuals  assume  33  have  AA,  
homozygote,  q2  is  the  frequency  of  the  affected   45  have  AB  and  22  have  BB  genotypes.  The  genotype  

abnormal  homozygote,  2pq  is  the  carrier  frequency,   frequency  is  obtained  by  dividing  the  count  for  each  
genotype  by  the  total  number  of  individuals.  i.e  
and  p  +  q  =  1.      
genotype  frequency  for  AA  =  0.33,  AB  =  0.45  and  BB  =  
The  equation  can  be  used,  for  example,  to  find  the   0.22.    
frequency  of  heterozygous  carriers  in  an  autosomal  
The  term  gene  frequency  refers  to  the  proportion  of  
recessive  disease  XYZ.  If  the  incidence  of  disease  XYZ   chromosomes  in  a  population  that  contain  a  specific  
is  1  in  3600  live  births,  then  q2  =  1/3600,  and  therefore  q   single  allele.  In  the  above  example,  frequency  of  allele  A  
=  1/60.  Since  p  =  1  -­‐‑  q,  then  p  =  59/60.  The  carrier   =  2x33  (where  A  occurs  twice)  +  45  expressed  as  
frequency  is  represented  by  2pq,  which  in  this  case  is   percentage  =  111%  or  1.11.  Similarly  the  gene  
1/30.  Thus  1  in  30  individuals  in  the  whole  population   frequency  of  B  is  2X22  +  45  =  89%  or  0.89.  
is  a  heterozygous  carrier  for  disease  XYZ.  

Hardy  Weinberg  equilibrium  does  not  always  hold  true.  Consider  the  following  circumstances;  

• Natural  Selection:  Genes  which  hinder  survival  and  fertility  are  not  maintained  in  the  genetic  pool  
of  a  population.  This  is  because  the  abnormal  genes  are  not  passed  on  to  next  generation  when  
reproductivity  is  low  or  if  the  patient  dies  at  very  young  age.  Similarly  some  mutations  that  offer  
survival  benefits  are  maintained  in  higher  than  expected  rates  in  the  population.  For  example,  

©  SPMM  Course   20  
 sickle  cell  carriers  are  protected  against  sever  falciparum  malaria,  cystic  fibrosis  carriers  may  have  
an  advantage  against  typhoid,  etc.  
• Genetic  Drift:  Genetic  drift  refers  to  gene  frequency  change  caused  by  limitations  in  population  
size.  Genetic  drift  explains  why  some  genetic  diseases  are  unusually  common  in  small,  isolated  
populations.  In  a  small  population,  the  chances  of  random  distribution  is  limited  as  probabilities  of  
the  combination  are  restricted.  This  is  very  close  to  what  is  termed  as  ‘founder  effect’.  
• Gene  Flow:  Gene  flow  refers  to  the  exchange  of  genes  between  populations.  Due  to  migration  or  
other  social  reasons,  the  populations  studied  are  not  ‘closed’  populations  anymore.    
• Consanguinity:  Non-­‐‑random  mating  occurs,  and  mutations  are  preserved  within  a  closed  
pedigree  due  to  consanguinity.  Autosomal  recessive  diseases  are  more  often  seen  in  
consanguineous  families.  
• High  frequency  of  mutations:  Environmental  exposure  can  provoke  mutations  at  a  higher  
frequency  than  expected  in  a  stable  population  
e.g.  living  near  a  nuclear  reactor  leak.   EPISTASIS,  HETEROGENEITY  &  
PLEIOTROPY  
 
Gene-­‐‑  gene  interaction  particularly  between  
  different  alleles  at  different  genes  is  called  
epistasis.  This  can  occur  at  the  same  step  or  at  
  different  stages  of  the  same  biochemical  pathway.  

  Locus  heterogeneity  exists  when  the  same  disease  

phenotype  can  be  caused  by  mutations  in  different  
 
loci.  It  becomes  especially  important  when  genetic  
  testing  is  performed  by  testing  for  mutations  at  
specific  loci.  For  example  early  onset  Alzheimer’s  
 
could  be  caused  by  mutations  in  chromosome  1,  14  
  or  21.  

  Allelic  heterogeneity  refers  to  the  same  disease  

phenotype  resulting  from  different  types  of  
 
mutations  at  the  same  loci.  Consider  cystic  

  fibrosis,  here  nearly  600  different  mutations  at  the  

same  site  of  chromosome  7  results  in  same  disease.  
 
Pleiotropy  exists  when  a  single  disease-­‐‑causing  
  mutation  affects  multiple  organ  systems.  
Pleiotropy  is  a  common  feature  of  genetic  diseases.  
 
For  example,  consider  Marfan’s  syndrome.  
  Cardiovascular  system,  connective  tissue,  skeletal  
system  etc.  are  affected  by  a  single  genetic  
 
aberration.  

©  SPMM  Course   21  
12. Types of genetic studies
Genetic  methods  can  be  classified  into  four  paradigms  
1. Basic  genetic  epidemiology:  to  quantify  degree  of  familial  aggregation  and  heritability  
estimates  
2. Advanced  genetic  epidemiology:  to  explore  the  mechanism  of  action  of  genetic  risk  factors  
3. Gene  finding:  to  determine  the  genomic  location  and  identity  of  offending  genes  
4. Molecular  genetics:  to  trace  biological  pathways  from  DNA  to  disorder.  
Gene  mapping  refers  to  any  strategy  that  permits  finding  the  chromosomal  location  of  one  or  more  genes,  
often  related  to  a  disease.  Genetic  mapping  of  disease  genes  is  a  very  useful  method  because  it  does  not  
require  any  knowledge  of  a  gene'ʹs  function  to  find  the  chromosomal  location  initially.  Once  located  then  
the  identity  of  the  disease  gene  could  be  dissected.  Not  all  genetic  studies  are  aimed  at  gene  mapping;  
certain  simpler  designs  are  primarily  aimed  at  demonstrating  the  presence  or  absence  of  a  genetic  
influence  in  the  aetiology  of  a  disease  or  trait.  These  include  family  studies,  twin  studies,  and  adoption  
studies.  Gene  mapping  studies  involve  linkage  analysis,  sib-­‐‑pair  analysis  and  to  some  extent  allelic  
association  studies.  

A. Classical genetic studies:

Twin Studies
Monozygotic  (MZ,  or  "ʺidentical"ʺ)  twins  are  formed  when  an  embryo  is  cleaved  during  early  development.  
The  result  is  two  genetically  identical  embryos  wherein  70%  sharing  even  the  same  chorion.  Dizygotic  (DZ,  
or  "ʺfraternal"ʺ)  twins  are  the  result  of  the  fertilization  of  two  different  ova  by  two  different  sperm  cells.  DZ  
twins  are  genetically  the  same  as  siblings,  sharing  50%  of  their  genes.  

A  pairwise  concordance  rate  is  estimated  as  the  number  of  twin  pairs  who  both  have  the  disorder  divided  
by  the  total  number  of  pairs.  However,  where  there  has  been  systematic  ascertainment,  one  can  report  a  
probandwise  concordance  rate,  which  is  calculated  as  the  number  of  affected  twins  divided  by  the  total  
number  of  co-­‐‑twins.  This  is  possible  if  a  twin  register  is  maintained;  it  is  also  more  useful  method  as  this  
allows  comparison  of  general  population  risk  with  the  rate  in  co-­‐‑twins  of  probands.  

Challenges  in  interpreting  twin  studies    

• Monozygotes  are  often  treated  more  closely  than  dizygotes  as  they  look  identical;  so  they  share  
more  environment  than  dizygotes.  So  a  higher  concordance  may  be  due  to  higher  environmental  
effect.  
• Zygosity  assignment  done  via  anatomical  similarity  is  far  from  perfect.  Somatic  mutations  may  
occur  in  MZ  twins  after  the  cleavage  event  that  forms  them,  causing  "ʺidentical"ʺ  twins  to  be  at  least  
somewhat  different  genetically.    
• Chorionicity  i.e.  how  many  amnions  and  chorions  are  present  for  both  foetuses  determines  shared  
uterine  environment.    
• Twin  studies  assume  that  the  risk  of  disorder  is  same  in  monozygotic  and  dizygotic  pairs,  and  in  
singletons  at  the  outset.  This  assumption  holds  good  for  most  major  psychiatric  disorders,  while  it  
may  not  be  the  case  for  some  physical  disorders.  
©  SPMM  Course   22  
Family studies
There  are  two  types  of  family  studies.  The  family  history  method  is  simple  but  unreliable;  here  
psychiatric  history  is  taken  from  the  probands  himself/herself.  A  comparison  can  be  then  made  as  to  how  
many  relatives  are  affected  in  one  group  compared  to  another.    A  more  thorough  but  more  time-­‐‑
consuming  approach  is  the  family  study  method.  Here  all  available  relatives  are  directly  interviewed.  

See  below  for  other  major  

Disorder   MZ  Concordance     DZ  concordance  
disorders.  From  McGue  M  &   Male  alcoholism   41%   22%  
Bouchard  TJ  Jr.  Genetic  and   Female  alcoholism   34%   31%  
environmental  influences  on  human   Panic  disorder   24%   11%  
behavioral  differences.  Annu  Rev  
Bulimia   23%   9%  
Neurosci.  1998;21:1-­‐‑24.  
ADHD   58%   31%  
Autism   64%   9%  
 
Tourette’s   53%   8%  
Complete  case  ascertainment  refers  to  the  identification  of  all  affected  individuals  in  a  given  population.  
This  is  rarely  possible.  In  multiple  incomplete  
   Advantages   Disadvantages   ascertainments  consecutive  referrals  are  
Family   Practical   Many  false  negatives   identified;  there  is  a  chance  that    more  than  one  
History   Few  false  positive    
probands  may  come  from  same  family.  Most  
Method    
Family   Few  false  positives   Expensive   genetic  studies  are  concerned  with  in  the  
Study   or  negatives   proportion  of  individuals  who  have  ever  had  
the  disorder  (lifetime  prevalence).  But  not  all  family  members  may  have  reached  the  age  of  risk  for  the  
disorder,  and  some  may  have  died  prematurely  before  the  age  of  risk.  Hence,  age  correction  is  important  
while  ascertaining  cases.  There  are  many  methods  of  age  correction;  Weinberg'ʹs  shorter  method  is  the  
often  used  as  it  is  simpler.  (note  that  such  standard  age  correction  methods  do  not  exist  for  twin  studies;  it  
is  a  problem  in  MZ  twins  with  psychiatric  disorders  as  there  is  a  high  correlation  between  age  of  onset;  
sometimes  survival  analysis  can  be  used  for  non-­‐‑psychiatric  phenotypes  in  twins)  

Relative  risk  of  common  psychiatric  conditions  derived  from  family  studies  

Adapted  from  Johnstone,  EC.  Et  al   Disorder   Relative  risk  

(Ed)Companion  to  Psychiatric  studies  Page  158   ADHD   55  times  
Autism   45  times  
 
Schizophrenia   10  times  
Bipolar  disorder   7-­‐‑  11  times  
 
Alcoholism   4  to  6  times  
  Anorexia     2-­‐‑4  
Somatisation   3  times  
  Unipolar  depression   1.5-­‐‑3  
Generalised  anxiety  disorder   2-­‐‑5  
  Alzheimer’s  (late  onset)   2  times  
Panic  disorder   3  -­‐‑8  (summarized  as  5  by  
  Hettema,  2001)  

©  SPMM  Course   23  
Adoption studies  

Adoption  studies  are  useful  

to  differentiate  the  effects  of  
genes  and  environment.  The  
basic  method  of  the  adoption  
study  lies  in  comparing  the  
rates  of  disorder  in  biological  
relatives  and  adoptive  
relatives.  There  are  many  
types  of  adoption  studies.  

Types   Compared  groups  

   Group1   Group2  
Parent  as   Adopted  away  children  of  ill  parents   Adopted  away  children  of  well  parents  (biological  or  
proband    (1   (biological  or  adoptive)   adoptive)  
and  2)  
Adoptee  as   Biological  relatives  of  (ill  and  well)   Adoptive  relatives  of  (ill  and  well)  adoptees  
proband  (3)     adoptees  
Cross-­‐‑ Children  with  ill  biological  parents  but   Children  with  well  biological  parents  but  raised  by  ill  
fostering  (4)   raised  by  well  adoptive  parents   adoptive  parents  
 

Adoption  studies  have  certain  potential  problems.  (1)  There  is  a  tendency  for  higher  rates  of  some  
psychiatric  difficulties  amongst  adopted  children  as  adoption  itself  occurs  due  to  various  difficult  social  
circumstances.  (2)  Adoptive  parents  are  more  likely  than  not  to  resemble  biological  parents  as  social  
agencies  attempt  to  match  the  families  of  origin  to  families  of  adoption.      

B. Molecular genetic studies

Linkage analysis
During  prophase  I  of  meiosis,  homologous  chromosomes  line  up  and  occasionally  exchange  portions  of  
their  DNA.  This  process  is  termed  crossover  or  synapsis.  When  a  crossover  event  occurs  between  two  loci,  
x  and  y,  the  resulting  chromosomes  may  contain  a  new  combination  of  alleles  at  loci  x  and  y.  This  new  
combination  is  called  a  recombination.  Because  crossover  events  occur  more  or  less  randomly  across  
chromosomes,  loci  that  are  located  farther  apart  are  more  likely  to  experience  an  intervening  crossover  
and  thus  a  recombination  of  alleles.  This  offers  a  means  of  assessing  the  distance  between  loci  on  
chromosomes.  Alleles  of  loci  that  are  close  together  on  the  same  chromosome  are  likely  to  be  inherited  
together;  these  loci  are  said  to  be  linked.  To  be  linked,  these  alleles  must  be  syntenic  i.e.  on  the  same  
chromosome.  If  two  loci  are  on  different  chromosomes,  or  if  they  are  far  apart  on  the  same  chromosome,  
their  alleles  will  be  transmitted  independently.  As  crossing  over  is  an  independent  event  for  each  locus,  if  
an  allele  at  one  locus  is  transmitted,  there  is  a  50%  chance  (as  in  coin  tossing)  that  a  given  allele  at  the  

©  SPMM  Course   24  
other  locus  will  also  be  transmitted  to  the  daughter  cell.  But  linked  loci  are  close  enough  together  so  that  
the  chance  of  a  recombination  is  less  than  50%.  Thus,  their  inheritance  is  not  independent.  

The  distance  between  two  loci  can  be  inferred  by  estimating  the  frequency  with  which  cross-­‐‑overs  occur  
among  them.  The  lesser  the  cross-­‐‑over,  the  closer  the  loci.  Because  this  is  done  by  looking  at  
recombination  in  families,  this  is  called  as  recombination  frequency.  The  recombination  frequency  
provides  a  measure  of  the  genetic  distance  between  any  pair  of  linked  loci.  Genetic  distances  are  often  
expressed  in  centiMorgans  (cM).  One  centiMorgan  is  equal  to  a  1%  recombination  frequency  between  two  
loci.  1  cM  is  approximately  equal  to  1  million  base  pairs  of  DNA  (1  Mb).  But  crossovers  occur  more  
commonly  at  telomeres  and  less  common  near  centromeres.  

LOD Scores
To  estimate  the  likelihood  that  two  loci  are  truly  linked  with  a  specific  recombination  frequency,  an  LOD  
score  is  used.  The  LOD  ("ʺlog  of  the  odds"ʺ)  is  estimated  using  the  following  expression    

LOD  =  log  10   (probability  that  recombination  frequency  is  the  observed  value  Ø)              (probability  that  the  
recombination  frequency  is  50%  i.e.  chance)  

A  logarithm  is  used  because  it  allows  LOD  scores  from  different  individual  families  studied  to  be  added  
together  later  to  obtain  an  overall  LOD  score.  An  LOD  score  greater  than  3  is  usually  interpreted  as  
statistical  evidence  of  linkage  (i.e.,  the  numerator  is  1,000  times  greater  than  the  denominator,  indicating  
that  linkage  is  1,000  times  more  likely  than  nonlinkage).  Conventionally  an  LOD  score  of  -­‐‑2  or  less  is  
taken  as  evidence  that  two  loci  are  not  linked  (i.e.,  nonlinkage  is  100  times  more  likely  than  linkage).  

Two  loci  are  said  to  be  in  linkage  disequilibrium  if  specific  combinations  of  alleles  at  the  loci  are  seen  
together  on  chromosomes  more  often  than  expected  by  chance.  Because  recombination  is  rare  for  very  
closely  linked  loci,  such  loci  are  more  likely  to  exhibit  linkage  disequilibrium.  Such  linkage  
disequilibrium  can  be  analysed  in  association  studies  too.  

Two  different  approaches  can  be  adopted  in  linkage  studies:  

1. Candidate  gene  approach:  A  protein  is  suspected  to  be  involved,  then  the  gene  is  traced  from  
this  pathogenetic  knowledge.  

2. Positional  cloning  approach:  Genes  are  identified  through  their  positions  in  the  genome  rather  
than  functions.  Supported  by  human  genome  project.  

A  prerequisite  for  successful  linkage  analysis  (see  below)  is  the  availability  of  a  large  number  of  highly  
polymorphic  markers  dispersed  throughout  the  genome.  

Sib pair analysis  

In  this  method  several  hundred  DNA  markers  roughly  evenly  spaced  along  the  23  pairs  of  human  
chromosomes  are  taken  and  genotyping  is  carried  out  in  a  series  of  concordant  sibling  pairs.  ‘The  
probability  that  siblings  share  0,  1,  or  2  alleles  at  any  marker  locus  is  respectively,  0.25,  0.5,  and  
0.25.  However,  if  a  marker  locus  is  close  to  (and  therefore  linked  with)  a  locus  conferring  susceptibility  to  
©  SPMM  Course   25  
the  disease  this  will  be  detectable  as  increased  allele  sharing  at  the  marker.  This  approach  has  been  
successful  in  identifying  susceptibility  loci  for  disorders  such  as  type  1  diabetes.  The  main  drawback  is  
that  susceptibility  loci  of  very  small  effect  (such  as  conferring  a  relative  risk  of  less  than  2)  may  require  
large  numbers  of  sib  pairs in  the  region  of  600  to  800 to  be  detected.  In  a  disorder  such  as  
schizophrenia  the  relative  risk  in  a  sibling  of  an  affected  individual  is  about  10;  thus,  if  several  additive  
genes  are  involved,  none  may  individually  have  a  relative  risk  of  more  than  2’.  (Excerpts  from  McGuffin  &  
Martin,  BMJ.  1999  Jul  3;  319(7201):  37–40)  

Whole genome scan

It  is  a  type  of  linkage  analysis  in  which  markers  placed  at  regular  intervals  covering  the  whole  genome  are  
typed.  It  is  tedious  but  often  the  first  approach  when  no  genetic  information  is  available  about  a  particular  
phenotype.  A  good  example  is  that  of  neuregulin.    Stefansson  et  al.  typed    950  microsatellite  markers  
covering  the  whole  genome  in  110  Icelandic  patients  with  reconstructed  genealogical  relationships,  and  
found  that  neuregulin-­‐‑1  is  a  candidate  gene  for  schizophrenia  (Malats  &  Calafell,  2003).  

Association studies
Association  studies  are  more  straightforward  to  carry  out  than  linkage  studies.  Here  a  case  control  design  
is  often  adapted,  and  a  sample  of  cases  affected  by  a  disorder  is  compared  with  controls.  The  frequency  of  
alleles  at  the  marker  locus  is  then  compared  in  the  two  groups.  This  method,  though  increasingly  used,  
cannot  make  strong  causal  inferences.  The  locus  chosen  for  study  must  predispose  to  illness.  Thus,  loci  
chosen  for  association  studies  are  often  known  as  candidate  genes.  If  the  locus  does  not  predispose  to  
illness,  then  the  results  of  an  association  study  should  be  negative.  However,  false  positive  results  can  
occur  if  the  two  populations  are  not  carefully  matched  for  ethnic  background.  One  alternative  control  
group  is  the  parents  or  relatives  of  affected  individuals  (the  alleles  not  transmitted  to  the  affected  child  
compose  the  "ʺcontrol  group"ʺ—this  is  known  as  the  Transmission  Disequilibrium  Test  or  TDT).  In  
Genome  Wide  Association  Studies  (GWAS),  ‘candidate  gene’  approach  is  not  used.  Instead,  several  
thousands  of  single  nucleotide  polymorphisms  are  assayed  in  thousands  of  individuals.  This  is  the  new  
‘hot’  study  technique  in  psychiatric  genetics.  

Questions     Most  appropriate  method    

Is  the  phenotype  familial?   Family  study  
What  is  the  relative  contribution  of   Twin  studies,  adoption  studies  
genetic  and  environmental  factors?  
(Heritability)  
What  is  the  mode  of  transmission?   Segregation  analysis  
Where  might  be  the  ‘culprit’  genes?   Linkage  analysis  (known  ancestries)  
What  are  the  actual  genes  responsible?   Association  analysis  (population  level)  
 

©  SPMM  Course   26  
Linkage vs. association
Linkage  studies   Association  studies  

Uses  families   Uses  cases  and  controls  or  families  with  ‘internal  controls’  

Detectable  over  large  distances  >10cM   Detectable  only  over  small  distances  <1cM  

Can  usually  only  detect  large  effects  i.e.  RR>2     Capable  of  detecting  small  effects  e.g.  OR<2  

From  McGuffin  et  al.  (ed)  Psychiatric  genetics  and  genomics.  Oxford  Press:  2002  

C. Alternative approaches in genetic studies

¬ Transgenic  studies:  Transgenesis  is  a  term  that  describes  the  transfer  of  a  gene  from  one  species  to  
another.  In  practice,  this  term  often  refers  to  the  insertion  of  a  modified  mouse  gene  into  the  mouse  
genome  to  study  gene  function.  Transgenesis  is  a  direct  and  powerful  approach  for  analysing  gene  
function.  
¬ Epigenetics:  A  discrepancy  exists  between  the  information  provided  by  the  DNA  sequence  (i.e.  
number  of  genes)  and  what  is  translated  and  produced  by  cellular  machinery  (messenger  RNA  and  
proteins).  Though  the  DNA  sequence  provides  a  blueprint  for  synthetic  activities  of  the  cell,  a  number  
of  ‘epigenetic’  modifications  occur  resulting  in  a  second,  equally  complex  layer  of  information.  
Waddington  coined  the  term  epigenetics  to  explain  such  mechanisms.  DNA  methylation  and  histone  
modification  explain  most  of  the  epigenetic  variations  discovered  to  date.  Crow  has  argued  for  long  
that  epigenetic  defects  explain  most  of  the  concordance  seen  in  schizophrenia;  according  to  Crow,  the  
hemispheric  laterality  and  language  specialisation  unique  to  human  brains  is  the  source  of  
schizophrenic  defect  and  it  can  be  ascertained  only  by  an  epigenetic  enquiry.  
¬ Position  effects:  gene  activity  can  be  dependent  upon  the  precise  chromosomal  location  of  the  gene  
and  its  ‘neighbourhood’.  Such  genes  will  show  altered  activity  during  translocation,  even  if  the  gene  
itself  is  not  disrupted  by  chromosomal  breakage.  
¬ Endophenotypes:  This  term  was  coined  by  Gottesman  and  Shields  in  1975.  An  endophenotype  is  an  
unseen  but  measurable  phenomenon  that  is  present  in  the  distal  genotype  to  disease  pathway.  It  can  
be  a  biochemical,  neuroimaging,  electrophysiological,  pathological,  neuropsychological  or  socio-­‐‑
functional  marker.  To  be  termed  as  an  endophenotype,  Gottesman  suggested  certain  criteria  to  be  
satisfied  by  an  identified  disease  marker.  These  are  as  follows:  

1. Must  be  associated  with  a  candidate  gene  or  region  

2. Must  be  present  with  a  high  relative  risk  in  relatives,  thus  cosegregating  with  actual  illness  
3. Must  be  a  parameter  associated  with  disease  with  biological  plausibility  
4. Must  be  independently  expressed  in  clinical  state  (i.e.  must  not  be  a  state  but  a  trait  marker)  
5. Must  be  heritable    
6. Must  be  present  in  relatives  more  often  than  general  population  
It  is  anticipated  that  the  genetics  of  a  complex  construct  such  as  schizophrenia  can  be  studied  easily  in  
more  or  less  Mendelian  fashion  if  the  constructs  are  broken  down  to  constituent  endophenotypes.  The  
simpler  a  construct  under  study,  the  less  number  of  genes  will  be  on  the  causal  pathway.  Working  

©  SPMM  Course   27  
memory  defects,  information  processing  defects  such  as  prepulse  inhibition,  smooth  pursuit  defects,  glial  
cell  changes  and  certain  other  putative  neurocognitive  markers  are  termed  as  probable  endophenotypes  
for  schizophrenia.  To  be  an  endophenotype,  a  character  must  be  observable  independent  of  clinical  state  
and  must  be  measurable  in  relatives  at  a  higher  degree  than  the  general  population.  

In  spite  of  their  simplicity,  there  are  some  important  problems  that  need  to  be  overcome  while  studying  
endophenotypes.    

§ The  endophenotypic  expression  could  be  well  under  the  influence  of  the  developmental  
environment.    
§ An  endophenotype  can  be  differentially  expressed  in  different  brain  regions.    
§ Often  patients  have  multiple  endophenotypic  deficits  with  significant  interaction  among  
these.    
§ In  spite  of  hard  toil,  researchers  are  unable  to  narrow  down  genetic  linkages  of  suspected  
endophenotypes  to  achieve  better  than  modest  LOD  (log  of  odds)  scores.    
 

13. Psychiatric genetics

A. Causal models
Several  notable  features  regarding  psychiatric  genetics  are  listed  here  (excerpted  from  Craddock  et  al.,  
BJPsych,  2007:190;3)  

1.  Families  with  clear  Mendelian  inheritance  patterns  are  rare:  There  are  no  clear  demonstrations  of  
Mendelian  pattern  of  inheritance  of  schizophrenia  or  other  psychiatric  disorders  in  families.    

2.  Single  genes  of  major  effect  have  not  been  found:  Even  in  extended  pedigrees  with  multiple  cases  of  
psychiatric  illnesses,  intensive  molecular  genetic  studies  have  not  demonstrated  mutations  of  major  effect  
(LOD  scores  are  meager).  The  odds  ratio  in  most  psychiatric  genetic  association  studies  are  in  the  order  of    
1  to  2;  median  being  1.3.  This  is  insufficient  to  prove  a  genetic  cause  for  most  disorders.  These  findings  are  
suggestive  of  multiple  risk  alleles  of  modest  effect.  

3.  Mathematical  modelling  of  familial  risk  is  inconsistent  with  single  genes  of  large  effect:  According  
to  Craddock  et  al.,  “for  both  schizophrenia  and  bipolar  disorder  there  is  a  very  rapid,  non-­‐‑linear  decrease  
of  risk  when  moving  from  a  genetically  identical  individual  (i.e.  monozygotic  co-­‐‑twin  where  the  risk  is  50–
60%),  to  an  individual  who  shares  half  the  genes  (e.g.  sibling,  parent,  dizygotic  co-­‐‑twin  where  risk  is  
around  10%)”.  This  rapid,  non-­‐‑linear  decrease  of  risk  is  compatible  with  multiple  interacting  risk  factors,  
albeit  of  unknown  frequency,  that  individually  have  modest  effects.    

4.    The  causal  pathway  from  an  identified  genetic  abnormality  to  actual  disease  expression  is  too  complex  
and  not  fully  explored  in  any  known  genetic  markers  of  psychiatric  diseases.  For  example  it  is  unclear  
how  mutant  dysbindin  gene  that  is  implicated  in  schizophrenia  can  lead  to  a  belief  that  aliens  are  
invading  earth.  The  association  between  genes  and  diseases  are  very  non-­‐‑specific  and  weak  with  respect  
to  psychiatric  diseases.  
©  SPMM  Course   28  
5.  Contingent  models  of  association:  Non-­‐‑contingent  gene–disorder  association  refers  to  the  fact  that  the  
relationship  is  not  influenced  by  other  factors  such  as  environment  or  presence  of  other  genes  i.e.  not  
polygenic  or  multifactorial.  But  most  psychiatric  disorders  do  not  follow  non-­‐‑contingent  association  
models.    

6.  Practical  difficulties  in  conducting  genetic  enquiries  in  psychiatry:  

a.  Wide  ethnic,  geographical  variations  are  seen  in  psychiatric  disorders.    

b.  Ascertainment  method.  The  spectrum  of  clinical  features  (symptoms,  severity,  functioning,  
illness  course,  etc.)  of  individuals  recruited  depends  upon  the  mode  of  ascertainment.  These  
variations  can  reduce  or  increase  the  modest  effect  sizes  noted.    
c.  Unknown  phenotypic  model.  Reliance  on  DSM–IV  or  ICD–10  categories  is  a  huge  challenge  for  
psychiatric  genetics.  These  are  arbitrary  classifications,  and  it  is  possible  that  we  have  been  missing  
many  etiological  factors  due  to  these  empirical  categories.  For  example,  the  distinct  DSM-­‐‑based  
categories  of  affective  disorders  may  not  breed  true  as  strong  overlap  exists  between  the  genetic  
risk  of  unipolar  and  bipolar  disorders.    
Two  views  exist  concerning  the  causal  modeling  of  genetic  factors  in  psychiatric  disorders  (Craddock  et  al.,  
2007):  

1. Common  disease–rare  variant  model:    Rarely  occurring  mutations  cause  diseases  such  as  
schizophrenia.  There  are  various  different  mutations  that  can  explain  the  disease  (locus  and  allelic  
heterogeneity).  But  each  mutation  is  sufficient  but  not  necessary  to  cause  the  disease.  Each  family  
inherits  one  such  mutation  explaining  higher  risk  in  the  relatives.  These  mutations  are  rare,  but  
when  present  they  commonly  cause  the  disease.  
2. Common  disease–common  variant  model:  Here  a  disease  such  as  schizophrenia  is  thought  to  be  a  
result  of  the  co-­‐‑action  of  multiple  (ranging  in  principle  from  a  few  to  many  thousand)  common  
variants  (`polymorphisms'ʹ),  each  of  which  has  a  small  effect  on  illness  susceptibility  –  see  table  
below.  When  an  individual  inherits  several,  or  many,  susceptibility  variants  together,  they  have  a  
sizable  influence  on  disease  risk.  Hence,  the  mutations  or  polymorphisms  are  not  sufficient  by  
themselves  to  cause  disease,  but  they  occur  very  commonly  so  they  can  interact  in  combinations  
and  produce  the  disease.  This  model  is  more  popular  currently  and  forms  the  basis  of  association  
and  linkage  studies  being  carried  out  widely.  
Characteristics   Mendelian  disorders   Most  psychiatric  disorders  

Diagnostic  boundaries   Clear   Vague  

Phenocopies   Absent   Multiple  
Penetrance   Usually  complete/  predictable   Incomplete  /  unpredictable  
Association   Non-­‐‑contingent  models   Contingent  models  
Modelling  familial  risk   Linear  change  in  risk   Non-­‐‑linear  changes  in  risk  
MZ  concordance   Nearly  100%   30-­‐‑70%  only  
Locus  heterogeneity   Never  within  families;  often  absent   Likely  
across  families  too  

©  SPMM  Course   29  
  

B. Genetics of Schizophrenia
 

How   important   is   the   genetic   contribution   to   Gene  suspected  in  schizophrenia   Locus    
schizophrenia?     The   relative   risks   for   first-­‐‑degree      
relatives   /   twins   of   probands   are   higher   than   relative   NRG1   8p12-­‐‑p21  
Neuregulin  
risks   due   to   any   individual   environmental   factors.  
DTNBP1   6p22  
Without   genetic   contribution,   schizophrenia   cannot   be   dysbindin  
explained.   G72   13q34  
DAAO  (interacts  with  G72)   12q24  
Risk  to  family  members:   D  amino  acid  oxidase  
RGS4   1q21-­‐‑22  
Regulator  of  G  protein  signalling  4  
COMT   22q11  
Catechol-­‐‑o-­‐‑methyl  transferase  
DISC1   1q42  
Disrupted  in  Schizophrenia    

In  the  attached  chart  ‘parents’  refer  to  one  parent  having  

schizophrenia,   where   the   risk   to   the   child   is   13%.   If   both  
parents  have  schizophrenia,  then  the  risk  is  46%  -­‐‑   close  to  
monozygotic   twin   risk.   The   risk   to   a   half   sibling   is   4%.  
Note  that  for  the  children  and  siblings  of  individuals  with  
schizophrenia,  the  increase  in  risk  is  around  10-­‐‑fold,  but  it  
is   somewhat   less   than   this   in   parents.   This   is   probably  
‘explained   by   a   reduction   in   the   reproductive  
opportunities,   drive,   and   possibly   fertility   of   affected  
individuals’  (Craddock  et  al.  2005).  

¬ Monozygotic  (MZ)  concordances  =  41–65%    

§ Dizygotic  (DZ)  concordances  =  0–28%  
§ Broad  heritability  =  80%  
¬ The  most  frequent  personality  disorder  in  relatives  of  schizophrenia  patients  is  schizotypal  personality  
disorder  (DSM)-­‐‑nearly  15%  can  be  diagnosed  with  it.    
¬ Twin  studies  had  shown  significantly  higher  MZ  concordance  rates  for  schizophrenia  when  probands  
had  hebephrenic  or  nonparanoid  subtypes  than  paranoid  subtypes.  
 

¬ Psychotic  symptom  dimensions  consistently  show  only  modest  familial  aggregation  in  affected  sibling  
pairs,   and   rather   weak   and   inconsistent   relationships   with   the   familial   risk   of   psychoses.   So   the  
severity  of  schizophrenia  is  not  directly  associated  with  a  family  history  or  genetic  loading.  

©  SPMM  Course   30  
¬ Murray   et   al.   (2002)   point   out   a   number   of   studies   that   have   shown   a   higher   familial   risk   to   be  
associated  with  earlier  age  of  onset.  Sham  et  al.  (1994)  showed  that  the  morbid  risk  of  schizophrenia  is  
greater  among  the  relatives  of  those  probands  who  had  an  onset  before  rather  than  after  age  21  years.  
¬ Most   case-­‐‑control   studies   have   not   provided   evidence   in   support   of   COMT   associations,   but  
association  studies  with  family  design  provide  greater  evidence  for  COMT  in  schizophrenia.  
¬ In  Down’s  syndrome,  the  risk  of  schizophrenia  is  same  as  or  lower  than  the  general  population.  The  
exact  figure  is  unknown,  but  an  estimate  of  less  than  0.6%  is  quoted.  
 

C. Genetics of Mood disorders

If  one  parent  has  a  mood  disorder,  a  child  will  have  a  risk  of  between  10  and  25  percent  for  mood  disorder.  
If  both  parents  are  affected,  this  risk  roughly  doubles.  The  presence  of  more  severe  mood  disorder  in  the  
family  conveys  a  greater  risk.  

Bipolar disorder
¬ A  family  history  of  bipolar  disorder  conveys  a  greater  risk  for  mood  disorders  in  general  and  bipolar  
disorder  in  particular.  This  may  be  due  to  common  genetic  underpinnings  between  these  two  forms  of  
mood  disorder.  Estimates  of  broad  heritability  are  high:  nearly  85-­‐‑90%.  The  lifetime  risk  in  relatives  
does  not  vary  according  to  the  sex  of  relative  or  sex  of  proband.  
¬ Because  of  its  higher  prevalence,  the  unipolar  disorder  is  typically  the  most  common  mood  disorder  in  
families  of  bipolar  probands.    
¬ According  to  Craddock  et  al.  (2005),  lifetime  risk  of  narrowly  defined  bipolar  disorder  in  relatives  of  a  
bipolar  proband  are:      

o unrelated  member  of  the  general  population:  0.5–1.5%;    

o first  degree  relative  5–10%  (relative  risk  =  8);    
o monozygotic  co-­‐‑twin  40–70%  (relative  risk  =  60);  
¬ Lifetime  risk  of  unipolar  disorder  in  relatives  of  a  bipolar  proband  are:      

o unrelated  member  of  the  general  population:  5-­‐‑10%;    

o first  degree  relative  10-­‐‑20%  (relative  risk  =  2-­‐‑3times);    
o monozygotic  co-­‐‑twin  15-­‐‑25%  (relative  risk  =  3-­‐‑5  times);  
o Note:  You  can  get  the  risk  of  major  mood  disorder  by  adding  the  absolute  risk  of  unipolar  
and  bipolar  from  the  above  data.  
 

Genes  suspected  in  Bipolar  Disorder   Locus    

   
BDNF   11p13  
(Brain-­‐‑derived  neurotrophic  factor)  
DAO  G72/G30   13q33  
D  aminoacid  oxidase  
COMT   22q11  
Catechol-­‐‑o-­‐‑methyl  transferase  
Breakpoint  cluster  region  (BCR)  gene    

©  SPMM  Course   31  
Other  implicated  chromosomes  –    
• Chr  18  -­‐‑  nearly  4  loci,  affective  disorders  in  general;?  parent  of  origin  effect)    
• Chr  21q  -­‐‑  both  in  scz  and  BPAD.  
• An  X-­‐‑chromosomal  locus  to  BPAD  has  been  suggested  on  the  basis  of  the  cosegregation  of  BPAD  in  some  
families   with   color   blindness,   the   glucose-­‐‑6-­‐‑phosphate   dehydrogenase   deficiency,   and   the   coagulation  
factor   IX   deficiency.   In   an   extended   Finnish   pedigree,   Xq24-­‐‑q27.1   was   demonstrated   to   segregate   with  
bipolar  disorder.  
• Low  activity  allele  in  COMT  gene  may  be  associated  with  rapid  cycling.  
• Serotonin   transporter   gene   (hSERT)   and   5HT2A   gene   may   be   associated   with   modest   statistical  
significance  in  Seasonal  Affective  Disorder.  
 
 

Unipolar depression (MDD)

¬ Age-­‐‑adjusted  risk  of  MDD  to  first-­‐‑degree  relatives:  5-­‐‑30%,  relative  risk  1.1-­‐‑4.0.    MZ  Twin  concordance  
for  MDD:  40%.  DZ  Twin  concordance  for  MDD:  11%.  Heritability:  Unclear  (~20-­‐‑80%);  meta-­‐‑analysis  
reports  31-­‐‑42%.  (Data  from  NCHPEG  Empric  Risk  Data:  Retrieved  from  www.nchpeg.org  )  
¬ Early  onset  and  recurrent  episodes  likely  increase  risks  to  first-­‐‑degree  relatives.    Recurrence  risks  for  
unipolar  depression  could  be  50  percent  or  higher  for  probands  with  early-­‐‑onset  and  recurrent  
episodes.    While  the  definition  of  “early  onset”  is  not  entirely  clear,  research  suggests  that  family  
members  of  probands  who  had  onset  before  age  25-­‐‑30  years  have  the  highest  risk;  relatives  of  
probands  with  onset  between  ages  25-­‐‑40  years  have  an  intermediate  risk;  and  relatives  of  probands  
with  onset  after  age  40  years  have  a  risk  that  is  only  slightly  increased  over  the  population  risk  

Schizoaffective disorder
¬ The  risk  to  first-­‐‑degree  relatives  for  ANY  psychiatric  disorder  is  higher  in  SA  disorder  than  any  other  
psychiatric  disorder.  The  extent  of  heritability  is  unclear,  although  likely  in  the  range  of  schizophrenia.  
¬ Relatives  have  a  higher  rate  of  schizoaffective  illness,  schizophrenia  and  bipolar  disorder.    
¬ The   rate   of   bipolar   disorder   is   high   if   proband   has   a   schizoaffective-­‐‑manic   presentation.   The   rate   of  
schizophrenia  is  high  if  proband  has  schizoaffective-­‐‑depressive  presentation.  In  depressive  subtype  no  
elevation  in  bipolar  risk  has  been  noted  in  a  large  cohort  (Andreasen  1987).  
  Shared  genes  –  BPAD  and  Schizophrenia  
DAO  &  BDNF  –  seen  more  in  mood  disorders  than  schizophrenia    
  DISC  1  &  NRG  –  shared  with  schizophrenia;  seen  in  schizoaffective  disorder  
Dysbindin  –  seen  more  in  schizophrenia  than  mood  disorders  
CREB1  (chr2)  –  unipolar  depression  

Molecular associations (Schizophrenia and Bipolar disorder)

¬ G72:    The  function  of  G72  (also  sometimes  referred  to  as  DAOA)  may  be  to,  oxidize  serine,  a  potent  
activator  of  glutamate  transmission  via  a  modulatory  site  on  the  NMDA  (n-­‐‑methyl-­‐‑d-­‐‑aspartate)  
receptor.  Inadequate  DAOA  function  might  be  hypothesized  to  lead  to  problems  in  modulating  the  
glutamate  signal  in  areas  of  the  brain  such  as  the  prefrontal  cortex.  A  new  suggestion  is  that  the  major  
role  of  G72  may  be  in  maintaining  neuronal  structure.  
¬ Brain-­‐‑Derived  Neurotrophic  Factor  (BDNF):    Several  studies  have  shown  that  antidepressant  
administration  is  associated  with  increased  central  BDNF  levels  in  experimental  animals,  and  
administration  of  BDNF  itself  has  been  associated  with  the  antidepressant-­‐‑like  activity.  Depression  has  

©  SPMM  Course   32  
 been  postulated  to  be  associated  with  decreased  neurogenesis  in  the  hippocampus,  which  is  
dependent  on  neurotrophic  factors,  including  BDNF.    
¬ Disrupted  in  Schizophrenia  1  (DISC1):    This  gene  on  chromosome  1q  was  identified  in  a  Scottish  
family  with  a  genetic  translocation  and  with  multiple  cases  of  psychiatric  disorders,  primarily  
schizophrenia.  This  gene  is  expressed  in  multiple  brain  regions,  including  the  hippocampus,  where  it  
is  differentially  expressed  in  neurons.  It  is  associated  with  microtubules;  in  mice,  disruption  of  DISC1  
leads  to  abnormal  neuronal  migration  and  dendritic  organization  in  the  developing  cerebral  cortex.  
DISC1  appears  to  interact  with  phosphodiesterase  4B,  which  may  play  a  role  in  mood  regulation.  
¬ 5HTT,  MAOA,  COMT:  These  three  genes  have  been  shown  in  meta-­‐‑analyses  to  be  associated  with  BP  
disorder.  The  effect  size  for  each  appears  to  be  in  the  range  of  10–20%  increase  in  risk.  Each  of  these  
genes  is  associated  with  other  behavioral  phenotypes,  and  each  has  been  reported  to  interact  with  the  
environment  to  increase  the  risk  of  specific  disorders  (major  depression,  antisocial  personality  
disorder,  and  schizophrenia  respectively).  Recent  data  in  BP  illness  are  more  positive  for  5HTT  than  
for  MAOA  or  COMT.  
¬ Dysbindin:  Also  known  as  dystrobrevin  binding  protein  1  -­‐‑  involved  in  the  formation  of  synaptic  
structures  
¬ Neuregulin:  Involved  in  neuronal  migration  and  in  the  genesis  of  glial  cells  and  subsequent  
myelination  of  neurons  by  these  cells  
¬ GRK3:  This  is  the  only  candidate  identified  using  animal  model  studies  (a  mouse  model  employing  
methamphetamine).  This  gene  participates  in  the  down-­‐‑regulation  of  G-­‐‑protein  coupled  receptors  and  
is  associated  with  Bipolar  disorder.  

D. Genetics of dementias
Alzheimer’s disease (AD)
¬ Mutations  in  the  amyloid  precursor  protein  (chr  21  )  and  presenilin  1  (chr  14)  and  2  (Chr  1)  genes  may  
be  responsible  for  as  much  as  50%  of  familial  (ie,  autosomal  dominant)  AD  beginning  before  60  years  
of  age  (presenile).  But  this  accounts  for  less  than  1%  of  patients  worldwide.  
¬ The  genetic  factor  with  the  highest  attributable  risk  for  AD  is  apolipoprotein  E  (APOE).  The  APOE  
gene  on  chromosome  19q  has  3  codominant  alleles,   2,   3,  and   4,  differing  by  single-­‐‑base  
substitutions  in  the  coding  region  of  the  gene.  The  ancestral  allele,   4,  is  overrepresented,  and   2  is  
underrepresented  in  AD  (from  Graff-­‐‑Radford  et  al.:  Arch  Neurol.  2002;59(4):594-­‐‑600).  In  Caucasian  
subjects,  the  odds  of  AD  for  those  homozygous  for   4  and  for   3/ 4  heterozygotes  are  14.9  and  3.2  
times,  respectively,  greater  than  the  odds  associated  with   3  homozygosity.  The  mean  age  of  onset  of  
AD  is  2  decades  earlier  in   4  homozygotes.  The  APOE   4  allele  has  also  been  found  to  increase  AD  
risk  in  nonwhite  populations,  including  Afro-­‐‑Caribbean,  Chinese  and  Japanese.  The  increased  risk  
associated  with  the   4  allele  is  greater  in  women  than  in  men  though  this  is  not  replicated  in  African  
Americans.  
¬ Chr  21  harbours  mutant  APP  (Amyloid  Precursor  Protein)  –  this  is  related  to  Down’s  syndrome  and  
explains  the  higher  prevalence  of  AD  in  patients  with  Down’s  syndrome  

  Male  Abs.  risk%   Female  Abs.  Risk  %   Relative  risk  (both  sexes)  

©  SPMM  Course   33  
ApoE   status   unknown   6.3%   12%   -­‐‑  
(general  population)  

No  Apo   4   4.6%   9.3%   0.75  times  (less)  

Apo   4  heterozygote   12%   23%   3.2   times   (up   to   5   times   in   some  

studies)  

Apo   4  homozygote   35%   53%   14.9  times  

Modified  from  McGuffin  et  al.  (ed)  Psychiatric  genetics  and  genomics.  Oxford  press:  2002  

¬ An  actually  predicted  risk  of  developing  Alzheimer'ʹs  disease  in  the  first-­‐‑degree  relatives  of  probands  
with  Alzheimer'ʹs  disease  is  15-­‐‑19%,  compared  with  5%  in  controls.  Thus,  the  risk  to  the  first-­‐‑degree  
relatives  of  patients  with  Alzheimer'ʹs  disease  who  developed  the  disorder  at  any  time  up  to  the  age  of  
85  years  is  increased  some  3  –  4  times  relative  to  the  risk  in  controls.  This  translates  to  a  risk  of  
developing  Alzheimer'ʹs  disease  of  between  one  in  five  and  one  in  six  (from  Liddell  et  al.,  2001).  
¬ In  the  case  of  patients  with  Alzheimer'ʹs  disease  who  became  demented  late  in  old  age,  say  by  their  80s,  
relatives  probably  run  the  same  30-­‐‑50%  risk  of  developing  dementia  as  anyone  else  who  live  to  the  age  
of  90  years  and  beyond  (from  Liddell  et  al.,  2001).    
¬ Like  other  disorders  that  reflect  the  combined  action  of  several  genes,  the  risk  to  relatives  drops  
rapidly  as  the  degree  of  genetic  relatedness  falls.  Data  
are  limited,  but  the  risk  to  second-­‐‑degree  relatives,  
CADASIL  
such  as  grandchildren,  is  probably  less  than  twice  the   CADASIL  is  a  form  of  amyloid  angiopathy  that  can  
population  levels  (from  Liddell  et  al.,  2001)   present  with  Alzheimer’s  like  features.  NOTCH3  is  the  
¬  Probandwise  concordance rates  of  about  40%  for  DZ  
  only  gene  currently  known  to  be  associated  with  
and  84%  for  MZ  twins  are  seen.     CADASIL.  Most  mutations  in  the  NOTCH3  gene  in  
individuals  with  CADASIL  are  located  in  exon  4.  The  
Frontotemporal dementia mutation  detection  rate  is  up  to  96%  in  individuals  
¬ Frontotemporal  lobar  degeneration  (FTLD)  refers  to  
with  well-­‐‑defined  or  biopsy-­‐‑proven  CADASIL.  The  
the  3  different  syndromes  of  frontotemporal  dementia   defective  gene  is  identified  as  NOTCH3  in  19p13.1-­‐‑13.2  
(FTD),  progressive  non-­‐‑fluent  aphasia  and  semantic  
dementia.    
¬ Some  patients  with  FTLD  show  tau  protein  based  pathological  changes.  In  familial  cases,  mutations  
have  been  identified  in  the  microtubule-­‐‑associated  protein  tau  gene  (MAPT)  on  chromosome  17q21.    
¬ Many  cases  are  tau-­‐‑negative  but  show  ubiquitin-­‐‑immunoreactive    neuronal  cytoplasmic  inclusions.  In  
some  of  these  tau  negative  cases  mutations  have  been  identified  in  progranulin  (PGRN)  gene,  also  on  
chromosome  17q21.  
¬ Progranulin  is  a  widely  expressed  growth  factor  that  plays  a  role  in  wound  repair  and  inflammation  
by  activating  signalling  cascades  in  cell  cycle.  Progranulin  has  also  been  linked  to  tumorigenesis  

©  SPMM  Course   34  
Lewy Body dementia
No  specific  genetic  associations  have  been  established  for  Lewy  Body  Dementia.  Certain  mutations  have  
been  reported  inconsistently  at  alpha-­‐‑synuclein  locus.  DLB  is  considered  as  a  part  of  ‘synucleinopathies’  
where   synuclein   molecules   aggregate   in   presynaptic   terminals   producing   Lewy   bodies.   Other   diseases  
included  are  Parkinson’s  and  Multisystem  atrophy.    

Parkinson’s disease
LOCUS   POSITION/Protein   Clinical  features/inheritance  
PARK1,  PARK4   4q21   Alpha-­‐‑synuclein   Dominant   inheritance;   not   seen   in  
gene   sporadic   cases.   Onset   in   40s.   nigral  
degeneration  with  Lewy-­‐‑bodies.  
PARK2     6q25              Parkin  gene   Recessive   inheritance;   nigral  
degeneration   without   Lewy-­‐‑bodies.  
Onset   40   –   60.   (most   early   onset  
cases,  l-­‐‑dopa  responsive)  
PARK8   12   cen   (pericentromeric)       Dominant.   Onset   around   60.    
LRRK2  gene   Variable   -­‐‑synuclein   and   tau  
pathology.  
PARK6   1p35-­‐‑37   PTEN-­‐‑INduced   Autosomal  recessive;  onset  30-­‐‑40  (1-­‐‑
Kinase   (PINK1)     in   2%   of   early-­‐‑onset   cases,   l-­‐‑dopa  
mitochondria     responsive)  
PARK7      1p38      DJ-­‐‑1   Autosomal  recessive;  onset  30-­‐‑40  
α-­‐‑synuclein  is  a  protein  that  is  expressed  throughout  the  brain  and  has  potential  roles  in  learning,  synaptic  
plasticity,  vesicle  dynamics  and  dopamine  synthesis.    

E. Other disorders
Autism
¬ The  recurrence  rate  in  siblings  of  autistic  children  is    2%  to  8%  (higher  than  the  rate  in  the  general  
population  but  lower  than  in  single-­‐‑gene  disorders).  This  translates  to  50  times  (range:  30  –  120)  
relative  risk  in  siblings.    
¬ Risk  of  autistic  disorder  in  a  sibling  of  2  autistic  children:  25-­‐‑30%  (nearly  300  times  higher)  
¬ Twin  studies  reported  60%  concordance  for  classic  autism  in  monozygotic  (MZ)  twins  versus  0  in  
dizygotic  (DZ)  twins.  If  a  broader  autistic  phenotype  that  included  communication,  and  social  
disorders  is  considered,  the  concordance  increased  remarkably  from  60%  to  92%  in  MZ  twins  and  
from  0%  to  10%  in  DZ  pairs.  This  translates  to  90%  heritability.  
¬ The  identity  and  number  of  genes  involved  remain  unknown.  Chromosomes  2,  7  and  15  are  
implicated.  A  segregation  analysis  in  a  series  of  multiplex  families  was  consistent  with  autosomal  
recessive  inheritance  with  sex-­‐‑specific  modifications  
¬ The  striking  feature  is  the  association  of  the  genetics  of  autism  with  multiple  single-­‐‑gene  disorders.  
The  most  clearly  documented  of  these  disorders  is  the  fragile  X  syndrome.  Perhaps  8%  of  autistic  
subjects  have  the  cytogenetic  fragile  X;  16%  of  fragile  X  males  are  autistic.  There  are  also  probable  
associations  between  autism  and  tuberous  sclerosis,  neurofibromatosis,  and  phenylketonuria    

©  SPMM  Course   35  
¬ There  appears  to  be  as  much  variability  in  the  phenotypic  symptom  expression  within  monozygotic  
twins  as  between  MZ  pairs.  This  suggests  non-­‐‑genetic  influences  play  an  important  role  in  
determining  the  pattern  of  phenotype  in  autism  (LeCouteur,  1996).  
¬ Risk  for  broader  phenotype  (delayed  speech,  reading/spelling  difficulties,  social  
reticence/awkwardness,  poor  social  language  abilities)  in  first-­‐‑degree  relatives  and  dizygotic  twins:  
30%.  In  monozygotic  twins,  the  spectrum  phenotype  has  82%  concordance.  (All  data  excerpted  from  
http://pediatrics.aappublications.org/content/113/5/e472)      
¬  

ADHD
¬ Risk  to  first-­‐‑degree  relatives:  15-­‐‑60%,  2-­‐‑6  relative  risk    
¬ Risk  to  second-­‐‑degree  relatives:  3-­‐‑9%,  0.5-­‐‑0.8  relative  risk    
¬ Heritability:  ~70-­‐‑80%    
¬ Risks  are  higher  for  male  relatives  and  lower  for  female.    It  is  unclear  if  recurrence  risks  are  higher  
when  the  proband  is  female.    Continuation  of  illness  into  adulthood  may  indicate  increased  risk  to  
relatives.  

Personality disorders
¬ The  largest  factor  accounting  for  nearly  50%  or  more  of  the  variation  in  most  personality  traits  is  
nonshared,  person-­‐‑specific  environmental  variation.    
¬ Among  personality  disorders,  antisocial  PD  has  the  highest  heritability  (60-­‐‑70%).    
¬ Emotional  dysregulation  has  high  heritability  among  various  features  of  borderline  PD.    
¬ A  variant  of  the  tryptophan  hydroxylase  gene  (which  codes  for  the  synthetic  enzyme  for  serotonin)  is  
associated  with  low  5-­‐‑hydroxyindoleacetic  acid  (5-­‐‑HIAA)  in  cerebrospinal  fluid  and  suicide  attempts  
in  violent  criminal  offenders.  

Panic disorder
¬ Lifetime  prevalence  of  panic  disorder  (+/-­‐‑agoraphobia)  is  around  4.7%.    
¬ In  a  metaanalysis  of  family  studies,  Hettema  et  al.  (2001)  found  OR  of  5  for  panic  disorder  in  first-­‐‑
degree  relatives  (absolute  risk  8-­‐‑31%).  Early  onset  panic  disorder  confers  increased  risk  than  later-­‐‑
onset  disease.  Nearly  17  fold  increase  in  risk  is  seen  if  the  onset  is  before  20  years  compared  to  the  only  
6-­‐‑fold  increase  in  relatives  of  probands  with  onset  after  20  years.  The  heritability  is  estimated  to  be  
around  0.43.        

Social phobia
¬ The  10-­‐‑fold  increase  in  risk  is  seen  in  first-­‐‑degree  relatives  of  probands  with  generalized  social  phobia.  
Non-­‐‑generalised  discrete  social  phobia  does  not  show  familial  transmission.    
¬ Specific  phobias  are  3-­‐‑4  times  more  common  in  1st  degree  relatives  of  probands  (OR  4).  Nevertheless,  
twin  data  suggest  that  individual-­‐‑specific  environmental  influences  are  more  important  in  the  
development  of  simple  phobias.  

Alcoholism
¬ Genetic  influences  play  an  important  role  in  alcoholism:  the  risk  in  families  may  be  4  to  6  times  higher  
than  in  the  general  population.    

©  SPMM  Course   36  
¬ Majority  of  adoption  studies  show  that  the  risk  of  alcoholism  in  adopted  children  is  strongly  
correlated  with  their  biological  parents  rather  than  adoptive  parents  (  3-­‐‑  4  times  higher);  no  protective  
effect  was  noted  in  being  raised  away  from  drinking  biological  parents  (Goodwin  1973).  The  genetic  
risk  is  clearly  higher  in  males  and  weak  in  females.  
¬ Variants  in  GABRA2  on  chromosome  4p  have  been  shown  to  be  associated  with  alcohol  dependence  -­‐‑  
particularly  strongly  related  to  problems  with  impulse  control;  the  risk  allele  is  also  seen  in  
adolescents  with  conduct  disorder  and  in  alcohol  dependent  persons  who  are  drug  dependent.    
¬ ADH  (alcohol  dehydrogenase)  is  the  major  metabolic  enzyme  for  alcohol,  catalyzing  its  breakdown  
into  acetaldehyde,  which  is  then  further  metabolized  by  aldehyde  dehydrogenase  (ALDH).  Both  ADH  
and  ALDH  have  variants  associated  with  the  "ʺflushing"ʺ  reaction  to  alcohol.  The  strongest  finding  with  
regard  to  alcoholism  is  in  ADH4,  which  appears  to  be  associated  with  the  early  onset  of  regular  
drinking.    
¬ A  meta-­‐‑analysis  of  21  studies  shows  an  increased  risk  of  alcoholism  of  50–100%  of  persons  carrying  
the  A1  allele  of  DRD2.  However,  recent  work  has  questioned  whether  this  polymorphism  may  
actually  be  reflecting  variation  in  a  gene  next  to  DRD2.  

OCD
¬ Early  onset  suggests  higher  genetic  risk  
Family  History   Increased  Risk  for   General  
for  family  members;  some  studies   Offspring   Population  Risk  
suggest  increased  risk  only  in  the  case  of   Unipolar  depression     Unipolar  2-­‐‑fold  (16%);   6%  
early  age  at  onset  (generally  defined  as   Bipolar  4-­‐‑fold  (4%)  
before  18  years)  [www.nchpeg.org].   Bipolar  depression     Unipolar  2-­‐‑3  fold  (16%);   1%  
¬ Fathers  were  three  times  as  likely  as   Bipolar  8  to  9-­‐‑fold  (9%)  
mothers  to  receive  a  diagnosis  of  OCD   Schizophrenia  (SZ)   Unipolar  -­‐‑  2-­‐‑fold  (16%);   1%  
Bipolar  -­‐‑4-­‐‑fold  (4%)  
for  probands  with  severe  childhood  
Alcoholism   5-­‐‑fold  (27%  for  males,   5%  males,  1%  
OCD.   5%  for  females)   females  
¬ Increased  severity  and  chronicity   Panic  disorder   12-­‐‑fold  (6%)   0.5%  
appear  to  increase  risk     Tourette'ʹs  syndrome   100-­‐‑fold  (25%)   0.25%  
¬ Risk  to  1st  degree  relatives:    
Alzheimer'ʹs  disease   5-­‐‑fold  (15%)  at  age  75   3%  
• Onset  before  age  18:  range  of   Attention-­‐‑ 5-­‐‑fold  (15%)   3%  
~10-­‐‑35%         deficit/hyperactivity  
• Onset  after  age  18:  no  increased   disorder  
Anorexia  nervosa   10-­‐‑fold  (5%)   0.5%  
risk  to  ~15%    
Adapted  from  Tsuang  D,  Faraone  SV,  Tsuang  MT.  Psychiatric  genetic  
• MZ  Twin  concordance:  53-­‐‑87%     counseling.  In:  Floyd  EB,  David  JK  (eds).  Psychopharmacology:  The  Fourth  
• DZ  Twin  concordance:  22-­‐‑47%   Generation  of  Progress.  New  York:  Raven  Press,  1995.    

 
©  SPMM  Course   37  
14. Clinical genetics
When  an  individual  approaches  a  genetic  clinic  for  genetic  testing,  2  approaches  can  be  employed.  

• Direct  testing:   This   is   very   much   like   any   other   lab   test.   A   sample   is   tested   for   the   presence   of   a  
certain  genotype.  Only  one  individual  is  tested,  and  the  abnormality  that  is  being  sought  is  already  
known  to  have  an  association  with  the  illness  studied.  

• Gene  tracking:  Many  family  members  are  tested  to  discover  whether  or  not  the  suspected  patient  
seeking   the   test   has   inherited   the   high-­‐‑risk   chromosome   from   a   heterozygous   parent.   The   test   is  
based   on   Mendelian   principles   and   seeks   information   about   the   segregation   of   a   chromosome  
within  a  family.  It  can  be  used  even  if  the  exact  genetic  locus  associated  with  a  disease  is  unknown.    

. Prenatal   identification:   Prenatal   test   is   the   test   of   a   fetus   to   identify   a   suspected   genotype.   It   is  
often   initiated   on   the   basis   of   family   history   or   maternal   factors   (e.g.   older   mothers   at   risk   of  
Down’s).  Maternal  serum  screening  to  identify  neural  tube  defects  and  Down’s  is  offered  routinely  
in  many  countries.  In  general,  adult-­‐‑onset  genetic  conditions  are  not  usually  tested  prenatally.    

. Genetic  counseling  is  routinely  offered  to  individuals  seeking  genetic  tests.  The  counseling  service  
provides  information  about  risks  and  probabilities  before  the  test  and  also  provides  support  (but  
not   psychological)   services   after   the   testing.   Within   the   NHS   Regional   Genetic   Centres   that  
incorporate  cytogenetic,  molecular  and  clinical  genetic  services  operate  and  offer  familial  (carrier)  
testing,  diagnostic  and  prenatal  (presymptomatic)  testing.    

. DNA   banks   provide   secure,   long-­‐‑term   storage   for   an   individual’s   genetic   material.   While   this   is  
seen  as  beneficial  for  biomedical  research  the  possibility  of  misuses  has  raised  several  ethical  issues.  

. DISCLAIMER: This material is developed from various revision notes assembled while
preparing for MRCPsych exams. The content is periodically updated with excerpts from
various published sources including peer-reviewed journals, websites, patient information
leaflets and books. These sources are cited and acknowledged wherever possible; due to
the structure of this material, acknowledgements have not been possible for every
passage/fact that is common knowledge in psychiatry. We do not check the accuracy of
drug related information using external sources; no part of these notes should be used as
prescribing information.

©  SPMM  Course   38  
 Notes prepared using excerpts from
• Bouchard  &  McGue,  2003.  "ʺGenetic  and  environmental  influences  on  human  psychological  differences."ʺ  Journal  
of  Neurobiology,  54,  4-­‐‑45.  
• Braff  DL,  et  al.  Deconstructing  schizophrenia:  an  overview  of  the  use  of  endophenotypes  in  order  to  
understand  a  complex  disorder.  Schizophr  Bull  2007;  33:21–32    
• Caspi  A,  Sugden  K,  Moffitt  TE,  et  al.  Influence  of  life  stress  on  depression:  moderation  by  a  polymorphism  in  
the  5-­‐‑HTT  gene.  Science.  2003;301:386–389.  
• Collins,  K  et  al.  The  cell  cycle  and  cancer.  Proceedings  of  the  National  Academy  of  Sciences  94:  2776-­‐‑2778.    
• Craddock  &  Jones  The  British  Journal  of  Psychiatry  (2001)  178:  s128-­‐‑s133  
• Craddock  N,  et  al  (2005)  The  genetics  of  schizophrenia  and  bipolar  disorder:  dissecting  psychosis.  J  Med  Genet,  
42,  193–204.  
• Craddock,  N  et  al.  British  Journal  of  Psychiatry  2007  190:  200-­‐‑203    
• Devlin  and  Morrison.  Mosaic  Down'ʹs  syndrome  prevalence  in  a  complete  population  study.  Arch  Dis  Child  
89,12  (2004):  1177-­‐‑1178.  
• DNA  figure  source:  Boundless.  “Chromosomes  in  Human  Cells.”  Boundless  Anatomy  and  Physiology.  Boundless,  
05  Dec.  2014.  Retrieved  14  Dec.  2014  https://www.boundless.com/physiology/textbooks/boundless-­‐‑anatomy-­‐‑
and-­‐‑physiology-­‐‑textbook/    
• European  Journal  of  Human  Genetics  (2003)  11,  2,  S8–S10.  
• Farrer  MJ.  Nat  Rev  Genet.  2006  Apr;7(4):306-­‐‑18.  
• Gottesman,  II.  &  Gould,  TD.  The  Endophenotype  Concept  in  Psychiatry:  Etymology  and  Strategic  Intentions.  
Am  J  Psychiatry  2003  160:  636-­‐‑645    
• Graff-­‐‑Radford  NR  et  al.  Association  between  apolipoprotein  E  genotype  and  Alzheimer  disease  in  African  
American  subjects.  Arch  Neurol.  2002;59:594-­‐‑600.  
• Hayes,  P.C.,  et  al.  Blotting  techniques  for  the  study  of  DNA,  RNA,  and  proteins.  BMJ.  1989,  299(6705):  965–968.    
• Kato,  T.  Molecular  genetics  of  bipolar  disorder  and  depression.  Psychiatry  and  Clinical  Neurosciences  2007  
61:3-­‐‑19.  
• Kendler,  K.  Psychiatric  Genetics:  A  Methodologic  Critique.  Am  J  Psychiatry  2005;  162:3–11  
• Kendler,  KS  (2005)  “A  Gene  for...”:  The  Nature  of  Gene  Action  in  Psychiatric  Disorders.  American  Journal  of  
Psychiatry;  162:  1243  -­‐‑  1252.  
• Leonard,  JV  &  Shapira,  AHV.  Mitochondrial  respiratory  chain  disorders  I:  mitochondrial  DNA  defects.  The  
Lancet,  2000.  355:  299-­‐‑304.  
• Liddell  et  al.  The  British  Journal  of  Psychiatry,  2001:178,  7-­‐‑11.  
• McGuffin  P  &  Martin  N.  Behaviour  and  genes.  BMJ  1999;  319,  37-­‐‑  40.  
• Muhle  R,  Trentacoste  SV,  Rapin  I.  The  genetics  of  autism.  Pediatrics  2004;  113(5):472-­‐‑486.  
• Murphy,  K.    Schizophrenia  and  velo-­‐‑cardio-­‐‑facial  syndrome  .    The  Lancet  ,    359,  426  -­‐‑  430    
• Murray  et  al  (ed).  The  epidemiology  of  Schizophrenia.  Cambridge  University  Press,  2003.  p212  
• Peter  M.  Visscher,  William  G.  Hill,  and  Naomi  R.  Wray,  “Heritability  in  the  genomics  era  -­‐‑  concepts  and  
misconceptions,”  Nat  Rev  Genet  9,  no.  4  (April  2008):  255-­‐‑266.      
• Psychiatric  genetics  data  from  National  Society  of  Genetic  Counselors  (www.nsgc.org)  and  American  
Association  of  Family  Physicians  ACF  Genomics  data.  
• Qiu  J  (2006)  Epigenetics:  unfinished  symphony.  Nature,  441,  143–145.  
• Ranke,  M  &  Saenger,  P.    Turner'ʹs  syndrome.    The  Lancet,  358,  309-­‐‑314.    
• Ropers,  H.  H.  &  Hamel,  B.  C.  J.  (2005)  X-­‐‑linked  mental  retardation.  Nat  Rev  Genet,  6,  46-­‐‑57.  
• Snowden  JS  et  al.  (2006)  Progranulin  gene  mutations  associated  with  frontotemporal  dementia  and  progressive  
non-­‐‑fluent  aphasia.  Brain  129:3091–102.  
• Strachan  &  Read.  Human  Molecular  Genetics,  2nd  ed.  New  York:  Wiley-­‐‑Liss;  1999  
• Therman,  E.    Susman,  B.  &  Denniston,  C.  The  nonrandom  participation  of  human  acrocentric  chromosomes  in  
Robertsonian  translocations.  Annals  of  Human  Genetics  1989;53:49-­‐‑65    
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 ©  SPMM  Course   39  
  

   

Neuropathology  
Paper  A   Syllabic  content  3.5  
 
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©  SPMM  Course   1  
1. Alzheimer’s Dementia (AD)
 

Gross  changes  include  diffuse  atrophy,  flattened  cortical  sulci  and  enlarged  cerebral  ventricles.    

Histological  changes  include  neuronal  loss  (particularly  in  the  cortex  and  the  hippocampus),  synaptic  loss,  
granulovascular  degeneration  (small  vacuoles  with  central  granules,  in  the  cytoplasm  of  neurons  
especially  in  the  temporal  lobes),  senile  plaques,  neurofibrillary  tangles  and  Hirano  bodies.  Astrocytic  
gliosis  and  microglial  activation  are  also  noted  in  some  cases.  

A. Senile plaques
¬ Plaques  are  insoluble  amyloid  peptide  deposits.  The  peptide  involved  is  called  Aß  (beta  A4)  peptide.  
¬ Amyloids  are  fibrils  of  multimeric  chains  of  peptides  deposited  extracellularly.  They  have  a  beta  
pleated  sheet  confirmation.    
¬ Aß  is  cleaved  from  a  larger  transmembrane  protein—amyloid-­‐‑ß  precursor  protein—by  the  action  of  ß-­‐‑  
and   -­‐‑secretases  and  its  formation  is  prevented  by  the  action  of   -­‐‑secretase.  
¬ Plaques  vary  in  appearance,  and  two  main  subtypes  are  recognised.  
¬ Neuritic  plaques:  

o They  contain  Aß  in  the  form  of  amyloid  fibrils,  among  which  are  irregularly  swollen  dystrophic  
neurites  (degenerated  neuronal  processes).  
o The  neurites  are  well  visualised  with  silver  stains;  they  may  be  seen  as  an  eosinophilic  mass  on  
haematoxylin  &  eosin  stains.    
o Neuritic  plaques  may  contain  a  dense  central  core  of  amyloid.  
o Microglia  and  astrocyte  processes  are  present  towards  the  periphery  of  neuritic  plaques.    
o Seen  in  Down  syndrome  and,  to  some  extent,  in  normal  aging  as  well.  
o Amyloid  sensitive  stain  Congo  red,  under  polarized  light,  demonstrates  the  "ʺapple  green"ʺ  
birefringence  of  the  stained  tissue  with  neuritic  plaques,  due  to  the  presence  of  beta-­‐‑pleated  
sheets.  
¬ Diffuse  plaques:  

o They  consist  largely  of  non-­‐‑fibrillar  extracellular  Aß.  

o They  are  not  related  to  the  degree  of  cognitive  decline  
o Diffuse  plaques  contain  the  same  peptides  as  those  responsible  for  amyloid  formation  in  the  
neuritic  plaques.  However,  these  peptides  are  not  polymerized  to  form  fibrils  and  lack  beta-­‐‑sheet  
configuration    
o Only  neuritic  plaques  are  counted  in  neuropathological  tests.  

B. Neurofibrillary tangles (NFT)

¬ NFT  are  composed  of  cytoskeletal  elements,  primarily  abnormally  phosphorylated  tau  protein.  AD  is  
one  of  the  several  degenerative  tauopathies.    
¬ Tau  is  a  peptide  required  for  microtubule  assembly.  Microtubules  are  essential  to  transport  of  
materials  down  the  axons.  
©  SPMM  Course   2  
¬ Beta  A4  peptide  interacts  with  cholinergic  receptors  and  this  interaction  stimulates  the  abnormal  
phosphorylation  of  tau.  The  hyperphosphorylated  tau  is  a  major  constituent  of  the  tangle.  It  is  also  
present  in  the  degenerated  neurites.  Hence  both  tangles  and  neuritic  plaques  can  be  identified  by  
staining  with  antibody  to  the  abnormal  tau.    
¬ Apart  from  Alzheimer’s,  NFT  occur  in  several  disorders  including  Down  syndrome,  dementia  
pugilistica  (punch-­‐‑drunk  syndrome),  Parkinson-­‐‑dementia  complex  of  Guam,  Hallervorden-­‐‑Spatz  
disease,  and  the  normal  elderly.  
¬ Most  tangles  are  faintly  basophilic.  Tau  immunostaining  and  silver  impregnation  can  be  used  to  
improve  the  chances  of  light  microscopic  detection.    
¬ Tangles  are  mostly  intraneuronal,  though  upon  neuronal  degenration,  they  may  appear  
extracellularly,  thus  losing  their  basophilia.    
¬ According  to  Love  (2005),  “the  earliest  pattern  of  involvement  is  usually  not  associated  with  clinical  
symptoms:  tangles  and  neuropil  threads  are  restricted  to  parts  of  the  entorhinal  cortex  and  the  CA1  
field  of  the  hippocampus.    As  dementia  develops,  
tangles  and  neuropil  threads  accumulate  in  
CEREBRAL  AMYLOID  ANGIOPATHY  
increasing  density  in  other  parts  of  the  hippocampus  
(CAA)  
and  medial  temporal  neocortex,  and  then  in  other   CAA  is  the  accumulation  of  Aß  in  the  walls  
cortical  regions  and  in  subcortical  grey  matter   of  blood  vessels  (particularly  arteries  and  
structures  such  as  the  hypothalamus  and  thalamus”.   arterioles)  in  the  cerebral  cortex  and  
¬ A  staging  scheme  devised  by  Braak  and  Braak  (1995)   overlying  leptomeninges.    
is  often  employed  to  describe  the  extent  of  tangle    
This  affects  about  30%  of  normal  elderly  
related  abnormalities  (distribution  from  entorhinal  
people  but  over  90%  of  patients  with  AD,  in  
cortex  to  isocortex)  in  AD  and  correlates  well  with  
whom  the  angiopathy  tends  also  to  be  much  
the  severity  of  dementia.  Stages  V-­‐‑VI  operationally   more  severe.    
define  AD.    
CAA  is  an  important  cause  of  strokes  in  the  
C. Hirano bodies elderly.  Most  of  these  are  haemorrhagic;  
¬ These  are  rod-­‐‑shaped  eosinophilic  bodies  in  the   CAA  is  confined  to  superficial  cerebral  blood  
cytoplasm  of  neurons.  Hirano  bodies  are  seen  in  the   vessels,  rupture  of  the  amyloid  laden  blood  
extracellular  space  when  the  neuron  dies.   vessels  usually  causes  relatively  superficial,  
¬ Hirano  bodies  are  intracellular  aggregates  of  actin   lobar  haemorrhages  that  may  extend  into  the  
subarachnoid  space.    
and  actin-­‐‑associated  proteins    
¬ They  are  frequently  seen  in  hippocampal  pyramidal  
cells  

Neuropathological correlate of cognitive decline

The  number  and  distribution  of  tangles  increases  as  cognitive  decline  increases.  When  both  neuritic  
plaques  and  tangles  are  present,  the  presence  of  even  a  few  tangles  in  a  single  field  in  the  neocortex  
suggests  a  significant  cognitive  decline.  There  is  also  an  association  between  the  numbers  of  neuritic  
plaques  and  the  degree  of  cognitive  decline.  However,  this  is  less  apparent  than  the  relationship  between  

©  SPMM  Course   3  
tangles  and  cognitive  decline.  The  best  
neuropathological  correlate  of  decline  is  the  number  of  
Binswanger'ʹs  disease    
synapses.  The  marker  for  synapses  has  been  antibody  to   This  is  also  known  as  subcortical    vascular  
synaptophysin,  a  protein  found  in  the  presynaptic   dementia  or  subcortical  arteriosclerotic  
endings.     encephalopathy  
Characterized  by  the  presence  of  many  small  
Hippocampal pathology infarctions  of  the  white  matter  that  spares  
The  specific  cellular  pattern  of  neuronal  loss  is  noted  in   the  cortical  regions  
the  subiculum  of  the  hippocampal  formation  and  layers   Often  coexists  with  AD-­‐‑type  changes  
II  and  IV  of  the  entorhinal  cortex.  The  affected  cells  
connect  hippocampal  formation  with  the  association  
cortices,  basal  forebrain,  thalamus,  and  hypothalamus,  structures  crucial  to  memory.    This  pattern  of  
neuronal  loss  isolates  the  hippocampal  formation  from  its  input  and  output,  contributing    to  the  memory  
disorder  in  Alzheimer  patients  

 
©  SPMM  Course   4  
  

2. Lewy Body Dementia (DLB)

 

¬ Lewy  bodies  are  weakly  eosinophilic,  spherical,  cytoplasmic  inclusions.    

¬ In  Parkinson’s  disease  they  are  confined  to  substantia  nigra;  in  DLB  they  are  also  present  in  many  
areas  of  the  cerebrum  including  the  temporal  lobe,  the  cingulate  gyrus  and  the  frontal  lobes.  They  may  
also  be  found  in  the  dorsal  motor  nucleus  of  the  vagus.    
¬ Cortical  Lewy  bodies  are  less  conspicuous,  less  eosinophilic  and  lack  clear  halo  compared  to  those  in  
the  substantia  nigra.  Cortical  Lewy  bodies  take  up  a  homogeneous  eosinophilic  staining  in  the  
cytoplasm,  along  with  a  peripheral  displacement  of  the  nucleus.    
¬ There  is  no  simple  correlation  between  number  of  Lewy  bodies  and  cognitive  decline.    
¬ Antibody  to  protease  ubiquitin  can  be  used  to  identify  Lewy  bodies.    
¬ Lewy  bodies-­‐‑-­‐‑in  Parkinson'ʹs  disease  and  DLB  contain  accumulations  of  alpha-­‐‑synuclein.    Staining  
with  alpha-­‐‑synuclein  antibodies  is  an  excellent  tool  for  detecting  both  Lewy  bodies.  DLB  is  one  of  the  
various  degenerative  synucleopathies.    
¬ Alpha-­‐‑synuclein  accelerates  reuptake  of  dopamine  in  neurons,  and  this  dopamine  overload  might  be  
toxic.    
¬ A  high  proportion  of  patients  with  DLB/PDD  (about  75%)  also  have  AD-­‐‑type  neuropathological  
abnormalities.  Here  the  
plaque/tangle  burden  associated  
with  dementia  is  less  than  that  
Tauopathies   Synucleopathies  
seen  in  Alzheimer'ʹs  disease.     (tau  deposits) (alpha  synuclein  deposits)
¬ Lewy  neurites—these  are  nerve  
•Alzheimer’s  dementia •Parkinson’s
cell  processes  that  contain  
•Pick’s  disease •DLB
aggregates  of   -­‐‑synuclein.   •Progressive  supranuclear   •Multisystem  atrophy
These  abnormal  structures  can   palsy
•Corticobasal  degenerations
occur  in  both  DLB/dementia  of  
•Frontotemporal  dementia  
Parkinson’s  disease  and   with  parkinsonism  (FTDP-­‐‑17)
idiopathic  Parkinson’s  disease  
and  are  most  numerous  in  the  
CA2/3  region  of  the  hippocampus  and  in  the  substantia  nigra.    
¬ Some  patients  with  DLB  show  microvacuolation  of  the  cerebral  cortex,  predominantly  in  the  medial  
temporal  regions.  This  can  mimic  a  prion  disease.    

 
©  SPMM  Course   5  
  

3. Frontotemporal Dementia (FTD)

 

FTD  is  associated  with  three  types  of  underlying  pathology:    

Frontal lobe degeneration type

¬ Most  common  type  
¬ Spongiform  degeneration  or  microvacuolation  of  the  superficial  neuropil  is  seen  chiefly  in  layers  III  
and  V  of  the  cortex.  
¬  Loss  of  large  cortical  nerve  cells  with  minimal  gliosis  

Pick’s type
¬ Pick'ʹs  disease  is  characterized  by  a  preponderance  of  atrophy  in  the  frontotemporal  regions.    
¬ These  regions  also  have  a  loss  of  large  cortical  nerve  cells,  abundant  gliosis,  and  neuronal  Pick'ʹs  
bodies,  which  are  masses  of  cytoskeletal  elements.    
¬ Abnormal  swollen  oval-­‐‑shaped  neuronal  cells  with  loss  of  Nissl’s  substance  and  peripherally  
displaced  nucleus  are  called  Pick  cells  
¬ Pick'ʹs  bodies  are  seen  in  some  postmortem  specimens  but  are  not  necessary  for  the  diagnosis.  These  
are  argentophilic,  tau  and  ubiquitin  reactive  filamentous  inclusions.  
¬ Hirano  bodies  may  also  be  seen  albeit  with  a  lesser  frequency  than  in  Alzheimer’s.  

Motor neurone disease (MND) type

¬ Cerebral  atrophy  is  less  marked;  limbic  areas  are   HUNTINGTON’S  DEMENTIA  
largely  preserved      
Pathologically  there  is  severe  loss  of  small  neurons  
¬ Loss  of  large  cortical  nerve  cells,  microvacuolation,  
in  the  caudate  and  putamen  with  subsequent  
and  mild  gliosis.    
astrocytosis.    
¬ Ubiquitinated  but  not  tau-­‐‑immunoreactive    
inclusions  are  present  within  the  frontal  cortex  and   Characteristic  protein  deposits  form  nuclear  
hippocampus   inclusions  in  neurons  of  HD  patients.  
¬ MND  pathology  is  also  seen  in  anterior  horn  cells.    
With  the  loss  of  cells,  the  head  of  the  caudate  
  becomes  shrunken  and  there  is  "ʺex  vacuo"ʺ  
dilatation  of  the  anterior  horns  of  the  lateral  
  ventricles.  
 
 
 
 

©  SPMM  Course   6  
4. Creutzfeldt-Jakob Disease (CJD)
 

¬ Three  forms  exist:  sporadic  (most  common),  familial  and  variant  CJD  (vCJD  -­‐‑  related  to  bovine  
spongiform  encephalopathy).  
¬ There  are  no  characteristic  gross  pathologic  features  of  CJD  because  of  the  typical  short  course  of  the  
disease.  Persons  living  beyond  6  months  to  a  year  may  have  some  degree  of  generalized  cerebral  
atrophy.  
¬ Microscopically  CJD  shows  a  spongiform  encephalopathy  secondary  to  neuropil  vacuolisation.  Many  
round  to  oval  vacuoles  are  seen  in  the  neuropil  of  cortical  gray  matter  -­‐‑  vacuoles  may  be  single  or  
multiloculated.  The  vacuoles  may  coalesce  to  microcysts.  Most  cases  of  CJD  also  demonstrate  
neuronal  loss  and  gliosis.  
¬ Prion  protein  (PrPc)  is  a  normal  neuronal  cell  surface  protein  encoded  by  a  gene  on  chromosome  20.  In  
CJD,  this  is  converted  via  a  conformational  change  to  an  abnormal  form  designated  as  PrPSc.  This  
abnormal  form  is  protease-­‐‑resistant  and  can  accumulate  in  the  central  nervous  system  of  affected  
persons.  This  accumulation  triggers  further  conversion  of  normal  PrPc  to  PrPSc  and  accounts  for  the  
degenerative  changes  in  the  cerebral  cortex.  
¬ The  PrP  can  be  identified  in  tissues  with  immunoperoxidase  staining.  
¬ These  abnormal  PrPSc  can  be  transmitted  from  one  person  with  spongiform  encephalopathy  to  another  
person  via  pituitary  extracts,  corneal  transplants,  dural  grafts,  and  contaminated  electrodes  from  
neurosurgical  procedures.    
¬ In  variant  CJD,  there  is  a  marked  accumulation  of  the  prion  protein,  and  the  plaques  are  florid.  
¬ An  abnormal  protein  called  14-­‐‑3-­‐‑3  can  be  found  in  the  CSF  by  immunoassay,  but  this  protein  is  non-­‐‑
specific  and  may  be  found  in  association  with  viral  encephalitis  and  stroke.  It  is  less  frequent  in  variant  
CJD.  
¬ In  familial  cases  of  CJD,  the  typical  EEG  changes  are  often  lacking,  and  the  14-­‐‑3-­‐‑3  proteins  are  absent  
in  CSF  in  more  than  50%  of  cases.  
¬ The  presence  of  particular  polymorphisms  at  codon  129  of  PrP  may  have  an  influence  on  susceptibility  
to  disease.  The  amino  acids  methionine  (M)  or  valine  (V)  may  be  present  at  this  locus.  In  37%  of  
healthy  persons,  both  inherited  PrP  genes  code  for  methionine  (M/M),  and  50%  have  M/V.  In  contrast,  
73%  of  persons  with  sporadic  CJD  have  the  M/M  phenotype,  and  100%  of  persons  with  variant  CJD  
have  this  phenotype.    
¬ MRI  is  the  most  useful  supportive  diagnostic  test  in  variant  CJD.    A  characteristic  abnormality  seen  in  
the  posterior  thalamic  region  (pulvinar  sign)  is  highly  sensitive  and  specific  for  variant  CJD.    The  
pulvinar  sign  has  been  found  in  more  than  90%  of  pathologically  proven  vCJD  cases.    FLAIR  
sequences  of  MRI  are  most  likely  to  show  the  abnormality.  

©  SPMM  Course   7  
Feature   Classic  CJD   Variant  CJD  

Age   Elderly  7th  or  8th  decade  of  life   Adults  in  3rd/4th  decade  of  life  

Course   Shorter  course  (5  months)   More  prolonged  (1  year)  

Symptoms   Early  neurological  signs  and  dementia     Early   psychiatric/behavioural   signs   with   delayed  
neurological  features  

EEG   Triphasic  sharp  waves  often  seen     Triphasic   waves   are   rare,   and   changes   are   often   non-­‐‑
specific    

MRI   Pulvinar  sign  is  not  seen   Pulvinar  sign  is  present  

Biopsy   Only  a  few  plaques  noted   Large  number  of  plaques  

Tonsils   Prion   protein   cannot   be   isolated   from   Tonsillar  tissue  carries  prion  agent  
lymphoid  tissue  

©  SPMM  Course   8  
5. HIV associated pathology
 

CNS entry
¬ The  major  HIV-­‐‑1  receptors  are  CD4  and  CD8;  various  chemokine  receptors  e.g.  CXCR4  and  CCR5  are  
considered  as  HIV-­‐‑1  co-­‐‑receptors.    
¬ CD4+  helper  T  lymphocytes  are  the  major  routes  of  multiplication  and  entry,  apart  from  monocytes.  
Infected  CD4+  T  cells  and  monocytes,  which  circulate  in  the  blood,  are  the  potential  source  of  CNS  
infection.  
¬ The  strains  of  HIV,  which  are  isolated  from  the  brain,  have  the  characteristic  of  infecting  macrophages  
rather  than  lymphocytes.  Macrophage-­‐‑tropism  is  related  to  a  mutation  in  a  specific  region  of  gp120,  
the  external  glycoprotein  of  the  virus.  In  the  late  stages  of  the  infection,  active  replication  of  the  virus  
generates  more  of  these  mutants  and  the  compromised  immune  system  permits  the  escape  of  these  
mutants,  leading  to  predominance  of  macrophage-­‐‑trophic  strains.  
¬ In  order  to  enter  the  brain,  HIV-­‐‑1  must  cross  the  BBB  using  mechanisms  that  remain  unclear.  The  
generally  accepted  model  is  the  "ʺTrojan  Horse  hypothesis"ʺ.  HIV  enters  the  CNS  as  a  passenger  in  cells  
trafficking  to  the  brain  via  CD4  T  cells  or  monocytes.  Virus  accumulation  in  perivascular  regions  has  
been  demonstrated  as  a  proof  for  the  above  model.    
¬ An  alternative  hypothesis  of  HIV-­‐‑1  neuro-­‐‑invasion  proposes  the  entry  of  free  HIV-­‐‑1  by  migration  
between  or,  transcytosis  of  endothelial  cells.  The  mechanism  of  endothelial  infection  remains  a  
controversial  issue  –  as  CD4  expression  in  endothelial  cells  is  unclear.  
¬ Theoretically  all  the  main  cell  types  of  the  CNS,  astrocytes,  oligodendrocytes,  neurons,  perivascular  
macrophage  and  microglia,  can  be  infected  by  HIV-­‐‑1  since  they  possess  the  receptors  and/or  co-­‐‑
receptors  for  HIV-­‐‑1  entry,  but  only  the  latter  two  are  the  most  commonly  infected  cells  by  HIV-­‐‑1.  Most  
studies  have  indicated  an  absence  of  in  vivo  infection  in  neurons  -­‐‑  It  is  unclear  whether  detection  of  
infected  neurons  is  complicated  by  the  loss  of  the  infected  neuronal  populations.  

Mechanism of neuropathogenesis
¬ Two  components  of  this  mechanism  are:  
1. The  direct  effect  of  the  HIV-­‐‑1  infection  
2. The  indirect  consequence  of  infection  comprising  the  secretion  of  cytokines  and  neurotoxins.  
¬ The  infected  macrophages  and  microglia  participate  actively  in  the  neurodegeneration  by:  1)  shedding  
viral  proteins  and  2)  releasing  significant  amount  of  cytokines  and  neurotoxins  into  the  CNS.  3)  Tat  
and  TNF-­‐‑α  contribute  to  the  disruption  of  the  blood-­‐‑brain  barrier,  which  in  turn  become  more  
permeable  to  infected  monocytes  and  cytokines  present  in  the  periphery.  
¬ The  secreted  pro-­‐‑inflammatory  cytokines  activate  microglia  and  astrocytes,  which  in  turn  secrete  
neurotoxins.  In  addition,  the  alteration  of  astrocyte  function  results  in  an  increase  in  the  level  of  
neurotoxicity  in  the  brain.  
¬ Neuronal  injury  via  apoptosis  is  currently  believed  to  be  produced  by  toxic  products  released  directly  
by  HIV-­‐‑infected  macrophages  and  microglia  or  by  activated  astrocytes.  Some  of  these  factors  have  
been  identified:  they  include  the  platelet  activating  factor,  quinolinic  acid,  nitric  oxide,  and  some  

©  SPMM  Course   9  
 metabolites  of  arachidonic  acid,  which  are  neurotoxic,  and  tumour  necrosis  factor,  which  is  toxic  for  
oligodendrocytes  and  can  cause  demyelination.  

Biopsy findings
The  following  can  be  seen  in  the  biopsy  of  an  HIV  infected  brain  tissue  

1. Infiltration  of  macrophages  into  the  CNS  

2. Formation  of  microglial  nodules   VIRAL  LOAD  
3. Multinucleated  giant  cells  from  virus-­‐‑induced  fusion   The  current  method  used  to  predict  stage  of  
of   microglia   and/or   macrophages   in   central   white   disease,  to  monitor  disease  progression,  and  
to  formulate  treatment  strategies  is  to  
and  deep  gray  matter;  
determine  viral  load  (actual  number  of  viral  
4. Astrocyte  activation  and  damage;   particles  found  in  a  cubic  millimeter  of  
5. Neuronal   loss   particularly   in   hippocampus,   basal   blood).    
ganglia  and  caudate  nucleus.    
6. A   variable   degree   of   white   matter   pathology   with   HIV-­‐‑1  can  also  be  detected  in  the  cerebral  
myelin  damage   spinal  fluid  (CSF).  But    
CSF  viral  load  is  not  established  as  an  
7. Accumulation  of  lipid  macrophages  in  extreme  cases  
accurate  indicator  of  CNS  disease  related  to  
Most   common   psychiatric   presentation   in   AIDS   is   HIV-­‐‑ HIV.      
related  dementia,  followed  by  depression.    Psychosis  is  seen    
only  in  10%  of  HIV-­‐‑infected  individuals.  

©  SPMM  Course   10  
6. Schizophrenia
 

Gross changes
¬ A  decrease  in  brain  weight,  brain  length  and  volume  of  the  cerebral  hemispheres  enlargement  of  the  
lateral  ventricles  (especially  temporal  horns)  
¬ Reduced  tissue  volume  in  the  thalamus,  in  temporolimbic  structures  including  hippocampus,  
amygdala,  parahippocampal  gyrus.    
¬ White-­‐‑matter  reductions  in  parahippocampal  gyrus  or  hippocampus  
¬ An  increased  incidence  of  a  cavum  septi  pellucidi  is  noted.  
¬ Basal  ganglia  volume  reduction  was  noted  especially  in  preneuroleptic  era,  in  the  catatonic  subgroup.  
Enlargement  of  basal  ganglia  is  now  more  common  in  schizophrenia  as  a  consequence  of  treatment  
with  classical  neuroleptics,  which  can  be  reversed  by  the  use  of  atypical  substances.  
¬ Schizophrenia-­‐‑like  psychosis  is  commoner  in  temporal  lobe  epilepsy  when  the  focus  is  in  the  left  
hemisphere.  
¬ The  planum  temporale,  the  posterior  superior  surface  of  the  superior  temporal  gyrus,  is  a  highly  
lateralized  brain  structure  involved  with  language.  In  schizophrenic  patients,  a  consistent  reversal  of  
the  normal  left-­‐‑larger-­‐‑than-­‐‑  right  asymmetry  of  planum  temporale  surface  area  is  noted.  Heschl'ʹs  
gyrus  (primary  auditory  cortex)  showed  no  differences  between  the  left  and  right  sides.  

Histological changes
¬ No  evidence  for  astrogliosis  in  schizophrenia    
¬ Reduced  cell  numbers  or  cell  size  has  been  described  especially  affecting  neurons  in  the  hippocampus  
and  DLPFC.  
¬ Increase  in  neuronal  density,  which  may  relate  to  the  observed  decrease  in  neuronal  size  (with  
decreased  dendritic  arborization  and  a  decreased  neuropil  compartment)  has  been  reported.  
¬ Subtle  cytoarchitectural  anomalies  were  described  in  the  hippocampal  formation,  frontal  cortex,  e.g.  a  
significant  cellular  disarray  in  the  CA3–CA4  interface  
¬ Synaptic  studies  in  the  hippocampus  and  DLPFC  in  schizophrenia  show  decrements  in  presynaptic  
markers.  These  changes  may  reflect  a  reduction  in  the  number  of  synaptic  contacts  formed  and  
received  in  these  areas  and  supports  the  hypothesis  of  excessive  synaptic  pruning  in  schizophrenia.    
¬ Glutamatergic  synapses  may  be  especially  vulnerable  in  the  hippocampus  and  perhaps  the  DLPFC,  
with  predominantly  GABAergic  involvement  in  the  cingulate  gyrus.  
¬ Antipsychotics  alter  synaptic  and  neuronal  morphology,  particularly  in  the  caudate–putamen  and  
may  increase  glial  density  in  the  prefrontal  cortex.  

©  SPMM  Course   11  
7. Mood disorders
¬ A  strong  association  between  mood  disorder  and  the  number  and  severity  of  focal  signal  
hyperintensities  on  T2-­‐‑weighted  images  has  been  established.  These  white  matter  hyperintensities  
(WMH)  occur  particularly  in  the  deep  subcortical  white  matter  and  to  a  lesser  extent  in  the  basal  
ganglia  and  periventricular  tissue.    They  are  seen  in  excess  in  both  bipolar  and  unipolar  mood  
disorder,  with  an  odds  ratio  of   3  to  7  when  compared  to  healthy  controls.  
¬ In  major  depression,  WMH  are  particularly  common  in  elderly  subjects,  where  they  are  linked  to  risk  
factors  for,  and  the  presence  of,  vascular  disease.  This  finding  is  consistent  with  a  robust  
epidemiological  association  between  the  two  conditions.  
¬ WMH  confer  a  poor  prognosis  in  major  depression  and  bipolar  disorder.  
¬ Lithium  treatment  increases  cortical  grey  matter  volume  suggesting  that  lithium  is  neurotrophic.  
Lithium  may  also  enhance  neurogenesis  and  inhibit  apoptosis    
¬ Antidepressants  may  affect  neuronal  morphology.  These  agents  help  regenerate  monoaminergic  axons,  
promote  hippocampal  neurogenesis  and  prevent  the  loss  of  dendritic  spines  in  animal  models.    

8. Alcoholic brain damage

¬ Wernicke'ʹs  encephalopathy  is  characterized  by  degenerative  changes  including  gliosis  and  small  
hemorrhages  in  structures  surrounding  the  third  ventricle  and  aqueduct  (i.e.  the  mamillary  bodies,  
hypothalamus,  mediodorsal  thalamic  nucleus,  colliculi,  and  midbrain  tegmentum),  as  well  as  
cerebellar  atrophy.  
¬ Brain  shrinkage  can  be  found  in  uncomplicated  alcoholism,  which  can  largely  be  accounted  for  by  the  
loss  of  white  matter.  Some  of  this  damage  appears  to  be  reversible.    
¬ Alcohol-­‐‑related  neuronal  loss  has  been  documented  in  specific  regions  of  the  cerebral  cortex  (superior  
frontal  association  cortex),  the  hypothalamus  (supraoptic  and  paraventricular  nuclei),  and  cerebellum.    

9. Autism
¬ Hypoplasia  of  cerebellar  vermis  and  to  some  extent  the  cerebellar  hemispheres  is  documented.  
¬ Purkinje  cell  count  in  the  cerebellum  is  significantly  lower.  
¬ Inconsistent  changes  noted  in  the  neocortex.  Some  suggest  increased  cortical  volume,  probably  related  
to  reduced  pruning.  

©  SPMM  Course   12  
  

DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug related information using external sources;
no part of these notes should be used as prescribing information.

Notes prepared using excerpts from:

! Belay  &  Schonberger.  Variant  Creutzfeldt  Jakob  disease  and  BSE.    Clin  Lab  Med  2002;22:849-­‐‑62  
! Harrison  PJ.  The  neuropathology  of  primary  mood  disorder.  Brain  2002;125:1428–49.    
! Harrison   PJ.   The   neuropathology   of   schizophrenia.   A   critical   review   of   the   data   and   their  
interpretation.  Brain  1999;  122:  593–624  
! Neary,   D   &   Snowden,   J.   Fronto-­‐‑temporal   Dementia:   Nosology,   Neuropsychology,   and  
Neuropathology.  Brain  &  Cognition  1996;31:176-­‐‑87  
! Love,   S.   Neuropathological   investigation   of   dementia:   a   guide   for   neurologists   Journal   of  
Neurology,  Neurosurgery,  and  Psychiatry  2005;76(Supplement  5  ):v8-­‐‑v14.  
! Ghafouri,  M.,  Amini,  S.,  Khalili,  K.,  &  Sawaya,  B.  E.  (2006).  HIV-­‐‑1  associated  dementia:  symptoms  
and  causes.  Retrovirology,  3(1),  28.  
 

©  SPMM  Course   13  
 Applied Neuroscience
Paper A Syllabic content : various

© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
1. Lobar functions
A. Tests for frontal and parietal lobes
Frontal tests Comments
Similarities Comparing two objects to test the ability of ‘categorisation’ and not a description of common
‘parts’. This is a test for abstract ability.
Lexical Naming items bought in a supermarket or animals (category fluency) or generation of words
fluency starting with alphabets FAS (word fluency). Tests not only the speed and accuracy but also the
ability to shift from one set of objects to the next. e.g., supermarket list must include not only fruits,
but also baked goods, drinks, cleaning items, etc.
Luria motor Fist palm edge – must not be verbally facilitated. Test for motor planning, execution and error
test correction.
Go/on go test Tests response inhibition, the absence of perseveration and resistance to interference.
Cognitive E.g. ‘How tall is an average English woman?’ Use questions that need abstract not mere factual
estimates test thinking.
Trail making Consists of two parts. In part, A simple number sequence is used to join the dots. Test B uses
test alternating numbers and letters and is thought to be more sensitive to frontal lobe dysfunction. Not
specific for frontal lobe; tests visuomotor tracing, attention, conceptualisation and set shifting.
Other tests Include alternate pyramids and squares drawing, proverb interpretation, and to some extent
frontal release signs and digit span (normal: 7±2 forwards, 5±1 backwards) reflect frontal
functions.

Parietal test Comments

Copying Ability to draw shapes and constructing geometrical patterns is a parietal (esp. nondominant)
shapes function.
Identifying Dominant parietal damage can cause finger agnosia as a part of Gerstmann syndrome. Test for the
fingers ability to recognise the touched finger when eyes are closed. Also test for the ability to correctly
show one’s index, middle and ring fingers. Interlocking fingers test (ability to copy examiner’s
interlocked fingers) is also a parietal test.
Calculation Dominant parietal damage can cause acalculia as a part of Gerstmann syndrome. Test for simple
ability mathematical functions. Mere recognition and use of numbers constitute arithmetic ability; this is
often intact.
Graphesthesia Ability to recognise what number or alphabet is scratched on one’s skin without seeing. Bilateral
parietal function (somatosensory cortices)
Right Left Dominant parietal damage can cause right-left disorientation as a part of Gerstmann syndrome.
orientation Test for the ability to touch right ear lobe with the left index finger when eyes are closed.
Stereognosis Ability to recognise objects by palpation, and without visual inspection. Bilateral parietal function
(somatosensory cortices)
Two point Cortical sensation; bilateral somatosensory cortical function
discrimination
Visual Hemineglect is a feature of parietal lesions. Letter or star cancellation task, line bisection task,
inattention draw-a-person or draw-a-tree tasks are useful to identify hemineglect.

© SPMM Course 2
 B. Lobar lesions
Frontal lobe lesions

Unilateral lesions Bilateral lesions

Contralateral spastic hemiplegia Bilateral hemiplegia

Slight elevation of mood, increased talkativeness, Spastic bulbar (pseudo bulbar) palsy
tendency to joke inappropriately (Witzelsucht)
Frontal release signs (grasp and suck reflexes) Abulia (indecisiveness, lack of drive)
Anosmia Decomposition of gait and sphincter incontinence
Motor speech disorder with agraphia, with or Varying combinations of grasping, sucking, obligate
without oro-buccal apraxia (left) imitative movements, utilization behavior.
Loss of verbal fluency with perseveration (left)

Specific frontal syndromes (pseudo depressive, dysexecutive and pseudo psychopathic)

GELASTIC SEIZURE

An epileptic fit of incessant ‘laughter’, not necessarily

euphoria, is called gelastic seizure. This occurs with
Parietal lobe lesions left prefrontal seizures.

Unilateral lesions Bilateral lesions

Corticosensory syndrome and sensory extinction Spatial disorientation & visual spatial defects
Mild hemiparesis Bilateral ideomotor and ideational apraxia (more prominent
with left-sided lesions)
Homonymous hemianopia or inferior Tactile agnosia (bimanual astereognosis) (more prominent
quadrantanopia (incongruent or congruent) with left sided lesions)
Neglect of the opposite side of external space Anosognosia, dressing and constructional apraxias (may
(right parietal lesions) occur with lesions of either hemisphere are more frequent
and severe with nondominant right lesions)
Gerstmann syndrome (dysgraphia, dyscalculia, Balint syndrome
finger agnosia, right-left confusion) (left)

© SPMM Course 3
Temporal lobe lesions
Unilateral lesions Bilateral lesions

Homonymous upper quadrantanopia Auditory, visual, olfactory, and gustatory hallucinations

Wernicke’s aphasia Dreamy states with uncinate seizures
Varying degrees of amusia and/or visual Emotional and behavioural changes
agnosia
Impairment auditory verbal learning Disturbances of time perception
Dysnomia Korsakoff amnesic defect (hippocampal formations)

Apathy and placidity

Hypermetamorphopsia (compulsion to attend to all visual stimuli),

hyperorality, hypersexuality, blunted emotional reactivity (Kluver-
Bucy syndrome; the full syndrome is rarely seen)

Psychopathology of the auras of Temporal lobe epilepsy

Autonomic sensations

•most common of auras, causing epigastric aura, salivation, sometimes vertigo etc.

Forced thinking

•The individual has a compulsion to think on a certain restricted topic.

Evocation of thought GESCHWIND SYNDROME

• Intrusion of stereotyped words or thoughts.
This is an uncommon type of
Sudden obstruction to thought flow
personality change reported in epilepsy
•Similar to schizophrenic thought block is also reported.
patients (esp. TLE).
Panoramic memory

•Recall of expansive memories in incredible detail, as if running a video show of past. Symptoms include hypergraphia,
Psychic seizures circumstantiality, interpersonal
•Isolated auras with hallucinations, depersonalisations, micropsia or macropsia, déjà vu viscosity, hyperreligiosity, and
or jamais vu (especially if right sided origin)
hyposexuality.
Uncinate crises

•Hallucinations of taste and smell associated with dream like reminiscence and altered It is thought to be result of lost
consciousness.
connectivity among cerebral areas. This
Transient dysphasia
may also explain the personality features
• Points to left hemisphere origin.
often seen in epilepsy (characterised by
Strong affective experiences
increased suspiciousness and paranoia)
•Fear and anxiety very common.

Dostoevsky’s epilepsy

•Ecstatic content in epileptic aura.

© SPMM Course 4
Occipital lobe lesions

Unilateral lesions Bilateral lesions

Contralateral (congruent) homonymous Cortical blindness (pupils reactive)

hemianopia which may be central (splitting the
macula) or peripheral; also homonymous
hemiachromatopsia
Elementary (unformed) hallucinations—usually Anton syndrome (visual anosognosia, denial of cortical
due to irritative lesions blindness)
If deep white matter or splenium of corpus Loss of perception of color (achromatopsia)
callosum is involved, alexia and color-naming
defect
Visual object agnosia Prosopagnosia (temporo-occipital), simultanagnosia
(parieto-occipital)
Visual illusions (metamorphopsias) and Balint syndrome (parieto-occipital)
hallucinations (more frequent with right sided
lesions)

C. Neuropsychological tests
The Wechsler Adult Intelligence Scale (WAIS)
 Most widely used intelligence test in clinical practice.
 The latest revision, the WAIS-III, is designed for persons 16 to 89 years of age. Wechsler Intelligence
Scale for Children-III [WISC-III] is used for <16. For ages, 4 to 61/2 years Wechsler Preschool and
Primary Scale of Intelligence-Revised [WPPSI-R] is used.
 The WAIS is composed of 11 subtests made up of six verbal subtests and five performance subtests,
which yield a verbal IQ, a performance IQ, and a combined or full-scale IQ.
 Verbal tests = similarities, arithmetic, digit span, vocabulary, information and comprehension
 Performance tests = picture arrangement, block design, picture completion, digit symbol, matrix
reasoning (replaces object assembly)
 Certain tests are called ‘hold tests’ as they are supposed to be resistant to age-related decline; these tests
may be sensitive for organic brain damage such as dementia. In WAIS, hold tests are vocabulary,
information, object assembly and picture completion. Non-hold tests are block design, digit span,
similarities and digit symbol. A deterioration quotient is derived from the difference between ‘don’t
hold’ and ‘hold’ test scores.

© SPMM Course 5
Other cognitive instruments
Raven’s progressive matrix is a test for IQ that is independent of education and cultural influences. It taps
on general intelligence with visuospatial problem-solving tasks (performance IQ).

Reading is an ability that is seemingly resistant to organic brain damage. NART – National adult reading
test taps on previous word knowledge before becoming ill. Hence, it is used to estimate premorbid IQ.

Stroop test measures set shifting abilities and response inhibition. It is a test of frontal function and the
ability to pay selective attention.

The Wisconsin Card Sorting Test (WCST) contains

stimulus cards of different colour, form, and number.
NEUROCOGNITIVE DEFICITS IN
These are presented to patients to sort into groups SCHIZOPHRENIA
according to a single principle (e.g., to sort by colour, Overall deterioration in IQ.
ignoring form and number). Persons with damage to Short-term memory disturbances.
the frontal lobes or to the caudate and some persons Deficits in higher order reasoning and perceptual
with schizophrenia give abnormal responses. difficulties.
Frontal test deficits: Patients perform far more
Trail Making Test (TMT - B), Wisconsin Card Sort poorly than controls on category test, Wisconsin
Test (WCST), Hayling test (Sentence completion), card sort test, paired associates verbal learning test,
Trail B of the Halstead-Reitan battery.
Brixton task, all test set-shifting ability, which is a
part of executive functioning.

The Wechsler Memory Scale-Revised (WMS-R) is the most widely used memory test battery for adults.
The scale yields a memory quotient (MQ), which is corrected for age and generally approximates the
WAIS IQ. In amnesic conditions, a disproportionately low MQ but a relatively preserved IQ is seen. WMS
consists of the following tests:
 verbal paired associate
 paragraph retention,
 visual memory for designs,
 orientation,
 digit span,
 rote recall of the alphabet, and
 counting backward.
Benton Visual Retention Test involves the presentation of a geometric figure for 10 seconds, after which
the patient attempts to draw the figure from memory. (Short-term visual memory test)

The Bender Visual Motor Gestalt Test is a test of visuomotor coordination that is useful for both children
and adults.

Halstead & Reitan developed a battery of tests that helps to determine the location of specific brain
lesions. It consists of Category test, Tactual performance test, Rhythm test, Finger-oscillation test, Speech-
sounds perception test, Trail making test A and B, Critical flicker frequency, Time sense test, Aphasia
screening test, Sensory-perceptual tests.

© SPMM Course 6
2. Consciousness
 Consciousness is a state characterised by an awareness of self and environment and an ability to
respond to environmental factors; it is made up of two components – arousal (wakefulness) and
awareness (attentional processing).
 Arousal depends on intact functioning of ARAS – Ascending Reticular activating System.
Thalamocortical connections generate rhythmical bursts of neuronal activity (20 – 40 Hz) which are
in desynchrony by default. ARAS acting via the thalamic intralaminar nuclei synchronises these
oscillations. Arousal is directly proportional to the degree of such synchrony achieved. The absence
of arousal produces stupor and coma.
 The maintenance of attention appears to require an intact right frontal lobe
 Small lesions of ARAS are enough to produce a stuporous state, but large bilateral lesions are
required at the cortical level to cause the same depression in alertness.
 Stupor: In this state the individual appears to be asleep and yet, when vigorously stimulated, may
become alert as manifest by eye opening and ocular movement (Cartlidge 2001). Most patients in
stupor have diffuse organic cerebral dysfunction. Caloric testing in organic stupor will usually
reveal tonic deviation whereas in a psychiatric stupor (catatonia/depression) ocular nystagmus will
be seen (Cartlidge 2001). This is because the following tonic deviation in a conscious subject, a fast
phase of correction appears resulting in nystagmus.
 Akinetic mutism: It is seen in patients with diencephalic or bilateral anterior cingulate damage. The
syndrome is characterised by immobility and eye closure with little or no vocalisation. Sleep/wake
cycles can be seen, as indicated by eye opening. There is little in the way of movement to painful
stimuli, and the hallmark is the absence of spasticity and rigidity (Cartlidge 2001). Akinetic mutism
can arise as a result of lesions that interfere with reticular/cortical integration but spare the
corticospinal pathways. There is some debate about whether or not the syndrome should be clearly
differentiated from the vegetative state. CJD can also present with akinetic mutism before death.
 Vegetative state: This results from the isolated actions of the ARAS and the thalamus in the
absence of higher cortical influence due to extensive cortical damage. A patient in the fully
established vegetative state will almost invariably show spasticity and rigidity of the limbs, which
are absent in patients with the syndrome of akinetic mutism. In the early stages of the vegetative
state, the two clinical syndromes are indistinguishable.
 Locked in syndrome: Acording to Cartlidge (2001), the ventral pontine or locked in syndrome
describes a condition of total paralysis below the level of the third nerve nuclei. Such patients can
open their eyes and elevate and depress their eyes to command. Horizontal eye movements are
usually lost, and no other voluntary movement is possible. The diagnosis of this state depends on the
recognition that the patient can open his eyes voluntarily rather than spontaneously in the vegetative
state. This generally results from infarction of the ventral pons, pontine tumours, pontine
haemorrhage, central pontine myelinolysis, head injury or brain stem encephalitis.

© SPMM Course 7
3. Attention and orientation
 Attention can be clinically tested using serial 7s, digit span, spelling ‘‘world’’ backwards, or asking to
recite the months of the year or days of the week in reverse order.
 Although serial 7s is commonly used, it is frequently performed incorrectly by the elderly, as well as
by patients with impaired attention.
 A reverse-order month of the year is a highly over-learned sequence and is a preferred measure of
sustained attention.
 Digit span is a relatively pure test of attention that depends on working memory. Digit span is
impaired in delirium, focal left frontal damage, aphasia, and moderate to severe dementia, but
preserved in the amnesic syndrome (for example, Korsakoff’s syndrome or medial temporal lobe
damage). Normal digit span of 7 +/- 2 varies with age and general intellectual ability. In the elderly,
or intellectually impaired, 5 can be considered normal. Reverse digit span is usually one less than
forward span.
 Orientation is usually assessed in time, place and person; it is worth noting that an intact orientation
does not exclude a memory disorder.
 Time orientation is the most helpful test and should include the time of day. Many apparently
healthy people do not know the exact date, and being inaccurate by two days or less is considered
normal.
 Time intervals are often poorly monitored by patients with delirium, moderate to severe dementia,
and in the amnesic syndrome, and are easily tested by asking about the length of time spent in
hospital.
 Person orientation includes name, age, and date of birth. Disorientation to one’s own name is
usually only seen in psychogenic amnesia.
 Orientation to place is affected in reduplicative paramnesia, seen in delirium.

© SPMM Course 8
4. Executive function
 This includes planning, initiation, sequencing, coordinating, error detection, error correction, set
shifting, and termination. It is closely allied to other frontal functions such as judgement, problem
solving, impulse control, and abstract reasoning.
 Executive function is generally believed to be a dorsolateral frontal lobe function and depends on
intact frontal-subcortical circuits.
 Impulsivity is thought to reflect failure of response inhibition, and is seen in inferior frontal
pathology. It can be assessed using the Go-No-Go task. The examiner instructs the patient to tap
once in response to a single tap, and to withhold a response for two taps. This test can be made more
difficult by changing the initial rule after several trials (for example, ‘‘tap once when I tap twice, and
not at all when I tap once’’).
 The ability to switch task, and the inhibition of inappropriate, or perseverative, responses can also be
assessed by asking the patient to copy a short sequence of alternating squares and triangles, and
then to continue across the page. Perseveration in drawing one or other of the shapes may be seen in
frontal lobe deficits, but the test is relatively insensitive.
 The cognitive estimates test may prompt bizarre or improbable responses in patients with frontal or
executive dysfunction. Although it is a formal test performed at the bedside by asking, for example,
the height of the Post Office Tower, the population of London, or the speed of a typical racehorse.
 Questions about the similarity between two conceptually similar objects can be used to assess
inferential reasoning, which may be impaired in the same way. Simple pairs such as ‘‘apples and
oranges’’ or ‘‘desk and chair’’ are tested first, followed by more abstract pairs such as ‘‘love and
hate’’ or ‘‘sculpture and symphony’’. Patients typically answer, quite concretely, that two objects are
‘‘different’’ or that they are ‘‘not similar’’ instead of forming an abstract concept to link the pair. This
often persists despite encouragement to consider other ways in which the items are alike.
 Testing of proverb meanings probably measures a similar skill, but it is highly dependent on
educational and cultural background.

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5. Visuospatial ability
 Information from the visual cortex is directed towards the temporal or parietal cortex via one of the
two streams. The dorsal (‘‘where’’) stream links visual information with spatial position and
orientation in the parietal lobe, whereas the ventral (‘‘what’’) stream links this information to the
store of semantic knowledge in the temporal lobes.
 The frontal eye fields are important in directing attention towards targets in the visual field.
 Neglect and constructional apraxia are disorders of visuospatial function.

Neglect
o Neglect of personal and extrapersonal space is usually due lesions to the right hemisphere—
usually the inferior parietal or prefrontal regions.
o Left side of personal and extrapersonal space is represented only on right parietal lobe, but right
personal and extrapersonal space gets bilateral representation. Hence, a left-sided lesion rarely
results in neglect, but right-sided lesion can result in left-sided neglect.
o Deficits can be uncovered by simultaneous bilateral sensory or visual stimulation, or having the
patient bisect lines of variable length. Letter and star cancellation tasks are similar, more formal
tasks.
o Visual neglect may produce a failure to groom one-half of body, or eat what is placed on one
side of a plate. In extreme cases, patients may have anosognosia and deny they are hemiplegic or
even that the affected limb belongs to them.
Dressing and constructional apraxia
o Although deficits in dressing and constructional ability are termed apraxias, they are best
considered as visuospatial, rather than motor impairments.
o Copying three-dimensional shapes such as a wire cube, interlocking pentagons (as in MMSE), or
constructing a clock-face with numbers are good tests of constructional ability and may also
highlight neglect if present.
o Dressing apraxia is easily tested by having the patient put on clothing that has been turned
inside out.

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6. Memory
Classification of memory
 According to duration:
 Immediate memory functions over a period of seconds; closely related to concept of working
memory
 Recent memory applies on the scale of minutes to days; and
 Remote memory encompasses months to years.
 According to the type of encoding memory, can be classified into explicit or declarative memory
and implicit or procedural memory.
 Explicit memory can be either semantic (meanings) or episodic (events). Episodic memory
depends on the hippocampal–diencephalic system. It is the time-locked memory for personal
events (‘when and where’ memory); it includes both anterograde and retrograde memory.
Semantic memory involves memory for word meaning and general knowledge.
 The implicit memory includes skills and procedures e.g. car driving.
 Working memory refers to the very limited capacity that allows us to retain information for a few
seconds.). It is made of a central executive system (attentional system, dorsolateral prefrontal) and at
least 2 important buffer systems – the visuospatial sketchpad (right hemisphere) and phonological loop
(left hemisphere).
 The term ‘‘short term’’ memory is applied, confusingly, to a number of different memory problems,
but has no convincing anatomical or psychological correlate

Brain structures involved in memory

 Hippocampus
 Left hippocampus for encoding declarative verbal and right hippocampus for encoding non-
verbal memories.
 Navigational memory and memory of object location in space are also served by the
hippocampus.
 Animal studies have defined a hippocampal place code, a pattern of cellular activation in the
hippocampus that corresponds to the animal's location in space.
 Unilateral hippocampal lesions are compensated well, and clinically significant amnesia does
not occur.
 Amygdala has been suggested to rate the emotional importance of experience and to regulate the
level of hippocampal activity accordingly. It is involved in emotional memory and emotional face
processing. It helps in memory consolidation, depending on emotional input for the content of the
memory. Amygdalar damage leads to loss of fear conditioning and in monkeys, loss of maternal
behaviour has also been noted. Despite the amygdalar damage, learning and consolidation of
memory can occur, especially in the absence of emotional valence and arousal.
 Diencephalic structures such as the dorsal medial nucleus of the thalamus and the mamillary
bodies are associated with new learning; their damage leads to diencephalic amnesia seen in
Korsakoff syndrome.

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  Other regions: In most cases of memory loss procedural memory is intact. A deficit in procedural
memory with preservation of declarative memory may be seen in persons with Parkinson's disease,
in whom dopaminergic neurons of the nigrostriatal tract degenerate. Though speculative,
cerebellum, striatum, amygdala and certain parts of the neocortex (including motor area) are
thought to be involved in non-declarative procedural memory storage. The anterior temporal
lobe is the key area for semantic memory.
 Long-term potentiation: Strengthening of the connection between two neurons on repeated
communication is called long-term potentiation - LTP. This may be the neuronal basis of memory.
It is mediated by NMDA mediated Ca2+ entry in glutamate neurons. Learning increases branching
and synapse formation and may also influence neurogenesis.

Disorders of memory
 Amnesia is a term used either for pure memory deficits (mostly episodic) or cognitive deficits
where memory loss is predominant and not congruent with the level of loss in other domains.
 Generally both anterograde and retrograde memory loss occur in parallel, such as in Alzheimer’s
disease or head injury.
Anterograde Forgetting newly encountered information from
 Relatively pure anterograde
amnesia the time of a lesion.
amnesia may be seen when
there is hippocampal damage, Presents as forgetfulness regarding appointments,
losing items around the home, inability to
e.g. herpes simplex remember conversation leading to repeated
encephalitis, focal temporal questions etc.
lobe tumours, or infarction.
Retrograde Loss of memory of past events that happened
 Confabulation—for example, in amnesia before the lesion was sustained.
Korsakoff’s syndrome—might
be grandiose or delusional, Presents as loss of memory of past events such as
but more often involves the jobs, holidays, not able to remember the
topography of a route and getting lost.
misordering and fusion of real
memories which end up being
retrieved out of context.
 A transient amnesic syndrome with pronounced anterograde, and variable retrograde, amnesia is
seen in transient global amnesia (TGA), while ‘‘memory lacunes’’, and repeated brief episodes of
memory loss suggest transient epileptic amnesia (TEA).
 Ribot's Law of retrograde amnesia: ‘The dissolution of memory is inversely related to the recency
of the event’. Recent memories are more likely to be lost than the more remote memories in organic
amnesia (not always the case though).
 Semantic dementia: It is a variant of frontotemporal dementia. Patients with semantic breakdown
typically complain of loss of words. Vocabulary diminishes, and patients use substitute words
such as ‘‘thing’’. There is a parallel impairment in appreciating the meaning of individual words,
which first involves infrequent or unusual words.
 A word finding difficulty is common in both anxiety and aging, but variable and not associated
with impaired comprehension. This is in stark contrast to the anomia in semantic dementia which
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 is relentlessly progressive and associated with atrophy of the anterior temporal lobe, usually on
the left.
 Working memory deficits can present as lapses in concentration and attention e.g. losing one’s
train of thought, inability to process a complex task as the components are not retained long
enough in memory to be processed. Basal ganglia and white matter diseases may present with
predominantly working memory deficits.
 Dissociative amnesia is not an organic syndrome, but centred on the loss of memory of important
recent events that is partial, patchy and selective. It can occur as a part of dissociative fugue. The
characters of dissociative amnesia are episodic memory loss (retrograde only with no anterograde
deficits) for events that happened in a discrete period of time from minutes to years. In dissociative
amnesia, the problem is not inefficient retrieval but the strikingly complete unavailability of
memories which were formed normally and were previously accessible. The forgotten events are
generally traumatic or stressful.

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7. Language
 Aphasia refers to a higher-level language defect despite intact hearing, sound production,
articulation mechanisms.
 Aphasia is almost always organic. Naming defects (anomia) accompanies any aphasia in various
degrees.
 To understand aphasia, consider the following facts
 Sound received by ears is transmitted to Wernicke’s area and auditory association cortex that
processes the language component.
 Arcuate fasciculus connects Wernicke’s area to Broca’s area. (NOTE: this is different from the
uncinate fasciculus that interconnects the anterior temporal and inferior frontal gyrus)
 Broca’s area is the higher motor area of language production. Signals from Broca’s area are
relied on onto the motor area to coordinate the delivery of language via the tongue, lips and
vocal cords.
 Three important components of language are
 Fluency depends on intact Broca’s area and its forward connections.
 Comprehension depends on intact Wernicke’s area and its connection with association cortex
and sensory input
 Repetition requires no high-level processing. Repetition can occur if Broca’s, Wernicke’s and
arcuate fasciculus are intact. Repetition does not need relay of signals from either Broca’s or
Wernicke’s areas to higher association areas.
Type of aphasia Fluency Repetition Comprehension Naming Adapted from Harrison’s
Textbook of internal
Wernicke’s sensory aphasia Intact Lost Lost Lost
medicine; 15 e
Broca’s motor aphasia Lost Lost Intact Lost
Conduction aphasia Intact Lost Intact Lost
Transcortical sensory aphasia Intact Intact Lost Lost
Transcortical motor aphasia Lost Intact Intact Lost

 In Broca's aphasia the speech is nonfluent; it often appears laboured with any interruptions and
pauses. Function words (propositions, conjunctions) are most affected though the good degree of
meaning-appropriate nouns and verbs are still produced. Abnormal word order and a
characteristic agrammatism are noted. Speech is telegraphic. Harrison’s Textbook of Medicine
quotes the following example: "I see...the dotor, dotor sent me...Bosson. Go to hospital. Dotor...kept
me beside. Two, tee days, doctor send me home”.
 In Wernicke's aphasia, the comprehension is impaired for both spoken and written language.
Language output is fluent but is highly paraphasic, sometimes with string of neologisms and
circumlocutions. Hence, it is also termed as "jargon aphasia." The speech contains large numbers
of function words (e.g., prepositions, conjunctions) but few substantive nouns or verbs that refer to
specific actions. The output is, therefore, voluminous but uninformative, mimicking schizophrenic
speech disturbance at times.

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  Pure word deafness: Patient can speak read & write fluently, but comprehension is impaired only
for spoken language. Bilateral (or left sided with disrupted connections to non-dominant circuit)
damage to the superior temporal pole is suspected.
 Pure word blindness (alexia no agraphia): Here the patient can speak normally and comprehend
what is spoken; he can also write spontaneously and to dictation, but reading comprehension is
impaired. It almost always involves an infarct to the left posterior cerebral artery affecting
splenium of the corpus callosum and left visual cortex. So the affected person, who is still able to
see with the right visual cortex, cannot undertake lexical word processing making him unable to
read.
 Pure word dumbness: Spoken language cannot be produced clearly, but the patient can
comprehend language well, can read and write.
 Pure agraphia: This is an isolated inability to write while other faculties of language are preserved.

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8. Apraxia
 Damasio and Geschwind (1985) defined apraxia as a condition with varying combinations of the
following disturbances in order of progressive dysfunction:
o A failure to produce the correct movement in response to a verbal command,
o A failure to correctly imitate a movement performed by the examiner,
o A failure to perform a movement correctly in response to a seen object and
o A failure to handle an object correctly
 Although a number of categories, such as limb kinetic, ideomotor, and ideational, exist, these labels
are seldom useful in clinical practice. It is more helpful to describe the apraxia by region (orobuccal
or limb), and to provide a description of impaired performance, recording both spatial and
sequencing errors on several different types of task.
 Apraxia is of limited localizing ability, but the left parietal and frontal lobes appear to be of greatest
importance.
 Progressive, isolated limb apraxia is virtually diagnostic of corticobasal degeneration.

Types of apraxia
Functional classification:

Apraxia type Definition Localization

Constructional Inability to construct elements into a meaningful Right cerebral hemisphere, often
apraxia whole. e.g., inability to draw or copy simple diagrams parietal lobe.
or figures.
Ideational/concept Impairment in carrying out sequences of actions Left parieto-occipital and
ual (multiple-step task) requiring the use of various parietotemporal regions
objects in the correct order to achieve an intended
purpose. The patient does not know ‘what’ to do.
Ideomotor The disorder of goal-directed movement. The patient Mainly in the left hemisphere; frontal
(most common knows what to do but not how to do it. Impairment of and parietal association areas.
type among all pantomiming ability to use tool. Abnormalities include Unilateral lesions of the left
apraxias) the use of body-part-as-object substitution, e.g. the hemisphere in right-handed patients
patient uses his own finger to represent a toothbrush produce bilateral deficits, usually less
when asked to brush his teeth and abnormal severe in the left than in the right
orientation of body part performing the action. limb
Improves on imitation and with the use of the actual
tool. Tool use is more affected than gestures.
Regional classification:

Buccofacial Inability to coordinate and carry out facial and The most frequent type of all focal brain lesion
apraxia (aka lip movements such as whistling, winking, related apraxia syndromes. Associated with
facial-oral coughing, etc. on command. left inferior frontal lobe and the insula, and
apraxia) commonly accompanies the aphasia caused by
lesions of Broca’s area.
Limb-kinetic Loss of hand and finger dexterity resulting Dominant frontoparietal or primary motor
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 from the inability to connect or isolate cortex
individual movements. Affects use of tools,
gestures, especially distal fingers movements.
Can be either ideomotor or ideational type.
Other variants Apraxia of speech, apraxia of eyelid opening
and apraxia of gait.

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9. Agnosias
Visual agnosia
o Visual object agnosia refers to a failure of object recognition despite adequate perception.
o Patients with apperceptive visual agnosia have normal vision, but cannot identify and name
objects. But these subjects have preserved semantic representation of the object, as evidenced by
their ability to name objects in description or touch. This is seen in patients with bilateral
occipitotemporal infarction.
o In associative visual agnosia, the stored semantic knowledge is affected. Lesions of the anterior
left temporal lobe are often seen.
o To test for visual agnosia, it is important to assess visual object naming/description and tactile
naming, naming described objects, and providing semantic information about unnamed items.
Prosopagnosia
 The ability to recognise familiar faces is affected in prosopagnosia. But clues such as voice, gait,
etc. can aid identification.
 The deficit is often not just restricted to faces; fine-grained identification within categories may
also be impaired (e.g. types of fruits and flowers).
 The underlying semantic knowledge associated with a particular person is not disrupted; so
when asked to describe the facial features of a named person, the patient can usually describe
this well.
 Face processing is a bilateral function; more key areas may be present on the right hemisphere.
 Acquired prosopagnosia is usually associated with bilateral or right-sided lesions of the occipital
- temporal junction (FUSIFORM GYRUS). In rare cases of prosopagnosia after left-sided lesions
in left-handed subjects, it is attributed to a reversed hemispheric specialization for face
processing.

Colour deficits
Achromatopsia Colour agnosia Colour anomia

Loss of ability to discriminate colours. Loss of the ability to Disorder of colour naming
(Often associated with pure alexia) retrieve colour despite intact perception and
information stored in colour knowledge
semantic knowledge base (‘‘What colour is this?’’)
(E.g. ‘‘What colour is a
banana?’’)
Medial occipitotemporal damage due to Left occipito-temporal Disconnection of the language
left posterior cerebral artery infarction damage structures in the temporal lobe
from the visual cortex

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10. Other neurological deficits
Acalculia refers to the inability to read, write, and comprehend numbers. It is NOT the same as
anarithmetrica, which is the inability to perform arithmetical calculations. Acalculia can be tested using
the simple calculation, writing numbers to dictation, copy numbers and read them aloud, and give
reasons for calculated answers.

Balint’s syndrome results from bilateral superior-parietooccipital damage (disruption to the dorsal
‘‘where” stream linking visual and parietal association areas). The triad of symptoms is shown in the
attached figure. Possible causes include carbon monoxide poisoning, infarction, and Alzheimer’s disease.

Gerstmann syndrome is characterized by four

simultanagnosia
primary symptoms: dysgraphia/agraphia,
dyscalculia/acalculia, finger agnosia and left-right
•inability to attend to more than one item of a
disorientation. The full presentation of tetrad is complex scene at a time
rare but occurs with lesions in the dominant
angular and supramarginal gyri (parietal lobe).
optic ataxia

Anton’s syndrome occurs in bilateral occipital

•inability to guide reaching or pointing despite
damage. The patient denies any deficit and may
adequate vision
even attempt to walk and navigate without success.

Marchiafava-Bignami disease is due to oculomotor apraxia

symmetrical demyelination and necrosis of corpus
callosum and adjacent anterior commissure. It is •inability to voluntarily direct saccades to a
visual target
mostly seen in alcoholics using red wine
excessively (not clear whether some impurities are implicated). Patients present with sudden onset of
stupor or coma and seizures. A chronic onset of dementia and/or gait problems with spasticity is also
reported.

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11. Cranial nerves
Olfactory nerve CN I
 Only sensory nerve to have no thalamic relay
 Unilateral anosmia should raise the suspicion of a lesion affecting the olfactory nerve filaments,
bulb, tract, or stria.
 Because the cortical representation for the smell in the piriform cortex is bilateral, a unilateral
lesion distal to the decussation of the olfactory fibers (i.e. temporal/ uncinate) causes no olfactory
impairment.
 Frontal meningiomas can cause unilateral anosmia.
 Head injury is probably the most common cause of disruption of the olfactory fibers Hyposmia is
an early feature of Parkinson’s disease and Alzheimer’s dementia and may precede motor and
cognitive signs respectively.
 Impaired sense of smell is seen in some patients at 50% risk of Parkinsonism.
Optic nerve CN II
Syndrome Lesion
Unilateral one eye blindness Lesion anterior to optic chiasm e.g. optic nerve itself or retina

Bitemporal hemianopia Optic chiasmatic lesion e.g. cranipharyngioma, pineal tumors

Homonymous hemianopia – left Lesions of the right sided optic tract, lateral geniculate body, optic
radiations and striate cortex (any retro chiasmatic structure)
Homonymous hemianopia – right Lesions of the left retro chiasmatic structures
Enlargement of the blind spot Any process causing disc swelling

Superior quadrantanopia Optic irradiation lesion at temporal lobes of contralateral side

Inferior quadrantanopia Optic irradiation lesion at parietal lobes of contralateral side

Cortical blindness Occipital cortex lesions

 Hemianopia is a field defect covering roughly half of the field. Vertical hemianopia can be nasal or
temporal. Horizontal or altitudinal hemianopia can be superior or inferior. If only one-fourth of
the field is affected, this is called quadrantanopia.
 Bilateral field defects are homonymous when they affect the identical portion of vision in both
visual fields
 Funnel vision: In patients with organic visual system defect, the visual field projected at 2 metre
distance is larger than the field at 1 m. This is seen in glaucoma, retinitis pigmentosa, post
papilledema optic atrophy, bilateral occipital infarcts with macular sparing.
 Tunnel vision refers to the absence of disparity between 2m and 1m fields on confrontation test.
The presence of patchy spirals of field loss is seen in hysteria or malingering.
 Cortical blindness often results from simultaneous bilateral posterior cerebral artery occlusion.
Patients often have a bilateral homonymous hemianopia with the small central field around the
point of fixation (macular sparing or keyhole vision) or complete blindness. Occasionally, patients
with cortical blindness deny their visual defect (Anton's syndrome).
 The following testing is appropriate for optic nerve:

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 1. Acuity using the Snellen chart (near and distant vision)
2. Visual fields using confrontation test or perimetry
3. Colour vision using Ishihara chart
4. Fundoscopy

Pupillary light reflex

Afferent fibres in each optic nerve (some crossing in the chiasm) pass to both lateral geniculate bodies and
relay to the Edinger-Westphal nuclei (midbrain) via the pretectal nucleus. Efferent (parasympathetic)
fibres from each Edinger-Westphal nucleus pass via the third nerve to the ciliary ganglion and thence to
the pupil. Light constricts the pupil being illuminated (direct reflex) and, by the consensual reflex, the
contralateral pupil.

The convergence / accommodation reflex

Fixation on a near object requires convergence and is accompanied by pupillary constriction. Afferent
fibres in each optic nerve, which pass through both lateral geniculate bodies, also relay to the convergence
centre. This centre receives muscle spindle afferent fibres from the extraocular muscles - principally
medial recti - which are innervated by the third nerve. The efferent route is from the convergence centre
to the Edinger-Westphal nucleus, ciliary ganglion and pupils.

Pupils that accommodate but do not react are said to show light-near dissociation. Two important types
are Argyll Robertson pupil, seen in neurosyphilis and diabetes (more common these days), and Adie pupil
due to peripheral pupillary defect producing a tonic pupil. ARP (note: Accommodation Reflex Present –
light reflex absent) is due to an afferent defect in pupillary reflex pathway – possibly pretectal.

Oculomotor nerve - CN III

 The oculomotor nucleus of the nerve is located in the midbrain
 Supplies the levator palpebrae superioris; the superior, inferior, and medial recti; and the inferior
oblique muscles.
 Lesions of CN III result in paralysis of the ipsilateral upper eyelid and pupil, leaving the patient
unable to adduct and look up or down. The eye is frequently turned out (exotropia).
 Lesions of the nucleus of the third nerve cause bilateral ptosis, in addition to the findings
mentioned above.
 Paralysis of CN III is the only ocular motor nerve lesion that results in diplopia in more than 1
direction.
 Pupillary involvement is an additional clue to the involvement of CN III.
 Pupil-sparing CN III paralysis occurs in diabetes mellitus, vasculitides of various etiologies, and
certain brainstem lesions such as due to multiple sclerosis.
Trochlear nerve - CN IV
The nucleus of the nerve is located in the midbrain. It innervates the superior oblique muscle. Trochlear
nerve typically allows a person to view the tip of his or her nose.

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Trigeminal nerve - CN V
 The nucleus of the nerve stretches from the midbrain (i.e. mesencephalic nerve) through the pons
(main sensory nucleus and motor nucleus) to the cervical region ( a spinal tract of the trigeminal
nerve).
 It provides sensory innervation for the face and supplies the muscles of mastication.
 Divisions: ophthalmic; V1, maxillary; V2, mandibular; V3.
 Corneal reflex:
 Afferent – V nerve
 Efferent – facial nerve
 Complete paralysis of CN V results in sensory loss over the ipsilateral face and weakness of the
muscles of mastication. Attempted opening of the mouth results in deviation of the jaw to the
paralyzed side.
 Acoustic neuroma can press on 5th nerve leading to loss of the corneal reflex.
Abducens nerve - CN VI
The nucleus of the nerve is located in the paramedian pontine region on the floor of the fourth ventricle. It
innervates the lateral rectus, which abducts the eye. Patients complain of double vision on horizontal gaze
only. This finding is referred to as horizontal homonymous diplopia. Paralysis of CN VI is a false
localising sign as it may result from increased intra cranial pressure.

Facial nerve - CN VII

 Motor supply to facial muscles from the motor nucleus.
 Though it is considered a predominantly motor nerve, it also innervates a small strip of the skin of
the posteromedial aspect of the pinna and around the external auditory canal. It serves to conduct
taste sensation from the anterior two-thirds of the tongue and relay to sensory nucleus tractus
solitarius.
 Secrotomotor functions include parasympathetic relay to lacrimal, lingual and submandibular
glands.
 A lower-motor-neuron lesion of the nerve, results in complete ipsilateral facial paralysis; the face
draws to the opposite side as the patient smiles. Eye closure is impaired, and the ipsilateral
palpebral fissure is wider. This is called Bell ’s palsy where the cause is idiopathic.
 In an upper motor neuron lesion, only the lower half of the face is paralyzed. Eye closure is usually
preserved.
Vestibulocochlear nerve - CN VIII
 2 components – vestibular for balance; cochlear for hearing.
 Auditory part tested using 512 Hz – Weber’s test and Rinne’s test.
 The Weber test involves holding a vibrating tuning fork against the forehead in the midline. The
vibrations are normally perceived equally in both ears because bone conduction is equal. In
conductive hearing loss, the sound is louder in the abnormal ear than in the normal ear. In
sensorineural hearing loss, lateralization occurs to the normal ear.
 In the Rinne test, the vibrating tuning fork is placed over the mastoid region until the sound is no
longer heard. It is then held at the opening of the ear canal on the same side. A patient with normal

© SPMM Course 22
 hearing should continue to hear the sound. In conductive hearing loss, the patient does not
continue to hear the sound since bone conduction, in that case, is better than air conduction. In
sensorineural hearing loss, both air conduction and bone conduction are decreased to a similar
extent.
 The vestibular portion transmits information about linear and angular accelerations of the head
from the utricle, saccule, and semicircular canals of the membranous labyrinth to the vestibular
nucleus.
 The Romberg test is performed to evaluate vestibular control of balance and movement. When
standing with feet placed together, and eyes closed, the patient tends to fall toward the side of
vestibular hypofunction. Results of the Romberg test may also be positive in patients with
polyneuropathies, and diseases of the dorsal columns, but these individuals do not fall consistently
to one side as do patients with vestibular dysfunction.
 Provocative tests include caloric testing. Normally on cold water testing, nystagmus is noted to the
opposite side; warm water elicits nystagmus towards the same side. (Remember the mnemonic
COWS)
Glossopharyngeal nerve - CN IX
 The nucleus of the CN IX is anatomically indistinguishable from the CN X, therefore, known as
nucleus ambiguous. Its main function is the sensory innervation of the posterior third of the
tongue and the pharynx. It also innervates the pharyngeal musculature, particularly the
stylopharyngeus, in concert with the vagus nerve.
 Vascular stretch afferents from the aortic arch and carotid sinus travel via glossopharyngeal nerve
to the nucleus solitarius – important for neural control of blood pressure.
 Lesions are affecting the glossopharyngeal nerve result in loss of taste in the posterior third of the
tongue and loss of pain and touch sensations in the same area, soft palate and pharyngeal walls.
 CN IX and CN X travel together, and their clinical testing is not entirely separable.
Vagus nerve - CN X
 Starting in the nucleus ambiguous, the vagus nerve has the longest peripheral course of all cranial
nerves – it stretches up to splenic flexure of the colon.
 Provides motor supply to the pharyngeal muscles (except the stylopharyngeus and the tensor veli
palati), palatoglossus, and larynx.
 It innervates the smooth muscles of the tracheobronchial tree, esophagus, and GI tract up to the
junction between the middle and distal third of the transverse colon.
 The somatic sensation is carried on the back of the ear, the external auditory canal, and parts of the
tympanic membrane, pharynx, larynx, and the dura of the posterior fossa.
 The pharyngeal gag reflex (ie, tongue retraction and elevation and constriction of the pharyngeal
musculature in response to touching the posterior wall of the pharynx, tonsillar area, or base of the
tongue) and the palatal reflex (ie, elevation of the soft palate and ipsilateral deviation of the uvula
on stimulation of the soft palate) are decreased in paralysis of CN IX and CN X.
 In unilateral CN IX and CN X paralysis, touching these areas results in deviation of the uvula to
the normal side.

© SPMM Course 23
Spinal accessory nerve - CN XI
 Spinal root supplies trapezius and sternocleidomastoid.
Hypoglossal nerve - CN XII
 It provides motor innervation for all the extrinsic and intrinsic muscles of the tongue. To test the
hypoglossal nerve, have the patient protrude the tongue; when paralyzed on 1 side, the tongue
deviates to the side of paralysis on protrusion.

12. Traumatic brain injury

 Traumatic brain injury is the result of mechanical forces applied to the skull and transmitted to the
brain. This may lead to focal and/or diffuse brain damage.
 Focal lesions often result from a direct blow to the head and include brain laceration, contusion,
intracerebral hemorrhage, subarachnoid or subdural hemorrhage, and ischemic infarct.
 Concussion causes transient coma for hours followed by apparent complete clinical recovery. Brain
contusion leads to prolonged coma, focal signs and lasting brain damage. Pathological support for
the distinction between concussion vs. contusion is poor.
 Contusion occurs directly beneath (coup injury) or contralateral (contrecoup injury) to the site of
impact. Contre-coup is most common in the orbital–frontal area and the temporal tips, where
acceleration/deceleration forces cause the brain to impact on the bony protuberances of the skull. A
frontal behavioural dyscontrol syndrome occurs in cases of bilateral orbitofrontal injury.
 Mechanisms of TBI include axonal and neuronal damage from direct trauma, shearing and rotational
stresses on decelerating brain, brain oedema and raised intracranial pressure, brain hypoxia and
ischaemia.
 The differential motion of the brain within the skull can cause shearing and stretching of the axons
resulting in diffuse axonal injury (DAI). DAI related damage occurs over a more widespread area
with extensive lesions in white matter tracts than in focal brain injury. DAI is more often associated
with persistent vegetative state and coma.
 Two types of amnesia can occur after head injury:
 Post-traumatic amnesia (PTA) includes anterograde amnesia for the period of injury and the
period following injury until normal memory resumes.
 Retrograde amnesia includes dense amnesia for the period between the last clearly recalled
memory prior to the injury and the injury itself. The duration of PTA is mostly in minutes, and
with increasing time after the injury, the duration of PTA reduces gradually.
 GCS (Glasgow coma scale) at 24 hours after injury is widely used to assess severity. Apart from GCS
other indices of TBI severity include the length of coma (LOC), duration of post-traumatic amnesia
(PTA), and the Abbreviated Injury Scale (AIS) scores. LOC and PTA have been used exclusively to
predict the functional outcome, but the AIS has been used to predict survival. Most investigations
have found LOC or PTA to be more predictive of functional status than GCS.
 Poor prognostic factors with respect to psychiatric morbidity following head injury includes long
duration of loss of consciousness, long PTA, elderly, chronic alcohol use, diffuse brain damage, new
onset seizures and focal damage to dominant lobe.

© SPMM Course 24
 Duration of PTA Classification Functional outcome

PTA less than 60 minutes Mild injury May return to work in <1 month

PTA between 1-24 hours Moderate injury May return to work in 2 months

PTA between 1-7 days Severe injury May return to work in 4months

PTA greater than 7 days Very severe injury May require > 1 year for return to work

 Late sequelae
o Cognitive impairment is common especially after closed head injuries with PTA lasting >24
hours.
o Personality changes are most likely after a head injury to the orbitofrontal lobe or anterior
temporal lobe.
o Depression (most common sequelae) and anxiety occur in roughly 1/4 of head injury survivors.
Suicide risk is also higher post head injury.
o Post-concussional syndrome is characterized by headache; dizziness; insomnia; irritability;
emotional lability; increased sensitivity to noise, light, etc.; fatigue; poor concentration; anxiety;
and depression.
o A schizophrenia-like psychosis with prominent paranoia is associated with left temporal injury
while affective psychoses (esp. mania in 9% patients) are associated with right temporal or
orbitofrontal injury. There is also an increased prevalence of schizophrenia post head injury (-2.5%
develop the disorder).
o Post-traumatic epilepsy is seen in 5% closed and 30% open head injuries (usually during the
first year) and worsens the prognosis.
o Less psychopathology in children after head injury due to increased brain plasticity.

© SPMM Course 25
DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug related information using external sources;
no part of these notes should be used as prescribing information.

Notes prepared using excerpts from:

 Barton, JJS. Prosopagnosia associated with a left occipitotemporal lesion. Neuropsychologia. 2008 46(8):2214-
24
 Cartlidge, N. States related to or confused with coma. Neurol Neurosurg Psychiatry 2001; 71(Suppl 1):i18-i19
 Higgins, E S.& George, MS. Neuroscience of Clinical Psychiatry, The: The Pathophysiology of Behavior and
Mental Illness, 1st Edition. Lippincott Williams & Wilkins 2007. Page 16
 http://www.emedicine.com/neuro/TOPIC632.HTM
 http://emedicine.medscape.com/article/1147993-overview
 Katz DI, Alexander MP. Traumatic brain injury: predicting course of recovery and outcome for patients
admitted to rehabilitation. Arch Neurol 1994; 51: 661–70
 Kipps & Hodges. J. Neurol. Neurosurg. Psychiatry 2005;76;22-30
 Koyama T, Tamai K, Togashi K (2006) Current status of body MR imaging : fast MR imaging and diffusion-
weighted imaging. Int J Clin Oncol 11:278-285.
 Lewis DA. Structure of the human prefrontal cortex. Am J Psychiatry. 2004; 161[8]: 1366
 Moo et al. J Neurol Neurosurg Psychiatry 2003;74:530-532
 Semple et al (Ed). The Oxford Handbook of Psychiatry 1 st edition. Oxford University Press 2005.
 Zadikoff C and Lang AE. (2005) Apraxia in movement disorders. Brain 128:1480–97

© SPMM Course 26
 Basic Pharmacology
Paper A Syllabic content 4.1
© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
1. Historical overview

 In 1915, Macht and Mora coined the term "psychopharmacology" when studying opioid
alkaloids on rat behavior in a circular maze.

 In 1931 Sen & Bose, Indian physicians from Calcutta, reported on the antipsychotic
properties of the plant Rauwolfia serpentine. Reserpine was rediscovered by Kline in 1954.

 In 1949, Cade in Australia discovered the use of lithium compounds in mania, initially on
the basis of a presumed relationship between urate metabolism and mania. Lithium urate
was prescribed to promote the solubility of uric acid. Later he noted that lithium ion itself
had calming properties even in healthy controls.

 Between 1950 & 1952 presurgical antihistamine chlorpromazine was shown to have
antipsychotic effects independently by Delay and Deniker’s team, and Charpentier from
Rhône-Poulenc in France. In 1955 Delay coined the term neuroleptic.

 The first true antidepressant was discovered in 1952. Mood lifting properties of Iproniazid,
an anti-tuberculosis treatment, led to the discovery of the antidepressant class. But
hypertensive reactions precluded the large-scale use of iproniazid. Imipramine, which was
manufactured as chlorpromazine derivative, came to market soon after.

 The first benzodiazepine, chlordiazepoxide (Librium) was discovered serendipitously by

the Austrian scientist Leo Sternbach in 1954.

 Kuhn (1958) discovered that among the various different psychiatric disturbances
‘endogenous’ depression responded best to imipramine. In 1961, second TCA
amitriptyline was introduced.

 In 1958, Janssen synthesised butyrophenone haloperidol from pethidine. Wide scale use of
antipsychotics started from this time. Antipsychotics came to be known as major
tranquilizers while barbiturates and benzodiazepines were called minor tranquilizers.
Large scale hospital discharges and deinstitutionalization started.

 1963 Cheese reaction was proposed to be the mechanism for MAOI associated
hypertension by Blackwell.
© SPMM Course 2
  Janssen synthesized an atypical agent risperidone in 1989.

 Carlssen synthesized purpose made SSRI Zimeldine – but this was withdrawn due to the
incidence of hypersensitivity syndrome and demyelinating disease that followed its use.

 In 1970s, Fluoxetine was tested as a noradrenaline reuptake inhibitor but was discarded as
it had a poor activity in this regard. Later it was rediscovered as serotonin reuptake
inhibitor, reaching the market in 1987.

 Kane et al. 1988 rediscovered clozapine via a multicentre randomized design comparing
chlorpromazine vs. clozapine in ‘treatment resistant’ schizophrenia. 4% showed response
to chlorpromazine while 30% showed response to clozapine.

 1990s ‘Prozac era’ – widescale antidepressant prescription started

 Reappraisal of suicides associated with antidepressant treatment – ‘black box warning’

issued for prescribing antidepressants to adolescents and children.

 CATIE study results published in 2005 – reappraisal of the usefulness of atypical and
typical antipsychotics. CuTLASS study from UK follows with a demonstration of no
apparent economic gain from atypicals.

© SPMM Course 3
2. Classification of psychotropics

Chemical structure Psychotropics

ANTIPSYCHOTICS
Aliphatic phenothiazines Chlorpromazine, Promazine, Triflupromazine
Piperidine derivatives Thioridazine
Piperazine derivatives Trifluoperazine, Fluphenazine, Perphenazine, Thioridazine
Butyrophenones Haloperidol, Droperidol
Thioxanthenes Thiothixene, Flupenthixol, Zuclopenthixol
Dihydroindoles Molindone
Diphenylbutylpiperidine Pimozide (long t1/2)
Dibenzoxapine Loxapine
Benzisoxazole derivative Risperidone
Substituted benzamides Amisulpride, Sulpiride
Dibenzodiazepine Clozapine
Dibenzothiazepine Quetiapine
Thienobenzodiazepine Olanzapine
Benzisothiazole Ziprasidone
Arylpiperidylindole (quinolone) Aripiprazole
ANTIDEPRESSANTS
Tertiary amines Imipramine, Amitriptyline, Clomipramine, Dosulepin,
Trimipramine (also Venlafaxine)
Secondary amines Desipramine, Amoxapine, Nortriptyline and Protriptyline
[more potent; less sedating; more (also Duloxetine)
noradrenergic, less antihistaminic
or anticholinergic than tertiary]
Hydrazine derivatives Phenelzine, Isocarboxazid (greater hepatotoxicity than
Tranylcypromine, a non hydrazine compound)
Aminoketone Bupropion (amphetamine-like)

OTHER PSYCHOTROPICS
Azaspironedecanedione Buspirone
Triazolopyridine Trazodone, Nefazodone.
Imidazopyridine Zolpidem
Pyrazolopyrimidine Zaleplon
Cyclopyrrolone Zopiclone
Benzothiazolyl piperazine Ziprasidone

© SPMM Course 4
Classification by mechanisms of action
SSRIs NaSSA – Noradrenergic and specific
Citalopram, Paroxetine, Fluoxetine, Sertraline serotonergic antagonist – Mirtazapine and
and Fluvoxamine, S enantiomer of citalopram Mianserin
- Escitalopram DARI – Dopamine reuptake inhibitor -
SNRIs – serotonin and noradrenaline Bupropion
reuptake inhibitor RIMA – reversible inhibitor of Monoamine A
Venlafaxine, Milnacipran, Duloxetine, oxidase - Moclobemide
Sibutramine SARI – serotonin antagonist and reuptake
NARI – Noradrenaline reuptake inhibitor – inhibitors – Nefazodone, Trazodone.
Reboxetine
NDDI – Noradrenaline Dopamine Dis-
Inhibitor - Agomelatine

Novel agents in the making

Xanomeline underwent phase 3 trials as a treatment option for schizophrenia. It acts via M1/M4
agonism Xanomeline showed a trend toward improving cognitive function in Alzheimer’s, and
produced robust and dose-dependent reductions in psychotic symptoms in AD. In schizophrenia,
early trials showed efficacy in both the positive and the negative symptoms along with
improvements in verbal learning and short-term memory but, a high degree of gastrointestinal
side effects were observed.

Ketamine is a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist that has shown

rapid antidepressant effects in treatment-resistant depression. Large scale trials are being
undertaken currently.

Pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate receptor 2/3

agonist, appeared to be a promising agent for sometime as initial phase 2 studies showed
promising efficacy against positive and negative symptoms when used as an add-on therapy in
schizophrenia. But this result was not replicated in a later study, mostly due to high placebo
response. It is devoid of affinity for dopamine receptors.

© SPMM Course 5
3. The principles of rational prescribing of psychotropics
Watchful waiting: When treating conditions such as depression and anxiety, NICE recommends
watchful waiting before pharmacological interventions.

Start-low go slow: Psychotropic medications should be prescribed at the lowest possible dose
and for the minimum duration possible. If the expected improvement does not occur, the
formulation and the management plan must be
revised. CHEMISTRY & STORAGE

Therapeutic monitoring: Many psychotropics Drugs exposed to moisture and light can gain
have dose-dependent therapeutic and side effects. moisture quickly – reducing the availability of
Plasma monitoring can be useful in some active excipients. This is termed as
hygrophilicity.
circumstances (see therapeutic window
Some drugs are extremely sensitive to
phenomenon discussed later) environmental moisture to such an extent that
they will turn from crystalline states into pastes or
Metabolic monitoring: Metabolic side-effects liquids if left in contact with moist air even for a
arguably contribute to more days of life lost than short period of time. A good example of this type of
any other adverse effects when taking deliquescent material is Sodium Valproate. This
property is called as deliquescence.
psychotropics. Various classes of psychotropics
have specific recommendations as to the
frequency and extent of metabolic monitoring.

Response assessment: A good follow-up schedule is essential to monitor the effect of prescribed
psychotropics. Without this, the purpose of pharmacological treatment will fail.

Avoiding polypharmacy: Most national guidelines explicitly recommend avoiding the

combination of psychotropic agents, especially antipsychotics.

Informed consent: When prescribing, it is imperative that pros and cons of a treatment are
discussed in advance to enable the patient to make an informed decision regarding the
treatments offered.

Patient choice: Guidelines such as NICE recommends that patients must be supported to make
the final choice of a specific psychotropic drug for an indication (e.g. antipsychotics for psychosis)
from various options provided by the psychiatrist.

Off-label use: While off-label use of psychotropics for uncommon, non-specific indications is not
recommended; this practice is not illegal per se in most countries. Such practices often have only
flimsy or no evidence-based support. The prescriber must explain to the patient if the medication
is being used outside its licensed indications and provide the available evidence to demonstrate
its effectiveness.
© SPMM Course 6
Long-term prescriptions: When treating chronic illnesses, relevant local & national guidelines
should be followed. Information about which medications worked before and which did not
should be noted, in addition to noting the adverse effects produced by each of them.

© SPMM Course 7
4. Placebo effect
 Placebo is any intervention deliberately used for non-specific psychological or
psychophysiological treatment effect. Placebo effect, as defined in research trials, includes
any difference in outcome between a placebo-treated group and an untreated control group
in an unbiased experiment (Ernst 2001).
 Placebos could be pharmacologically active or inert substances, most commonly the latter.
 An ‘active placebo’ has some activity inherently, but not against the treated condition.
 The term placebo literally translates in Latin meaning ‘to please’. It was coined by an
anaesthetist Beecher in 1955.
 When a substance administered for placebo effects produces prominent side-effects, it is
known as a ‘nocebo’. The term ‘nocebo effect’ (Latin: ‘I shall harm’) refers to the negative
consequences, adverse reactions and intolerance resulting from the administration of a
placebo. Nocebo effects are usually non-specific e.g. headache and nausea.
 Placebo sag is a term used to refer to decrease in placebo effect with repeated or chronic
administration of placebo drugs.
 The placebo effect may be disproportionately large for non-blinded therapies potentially
resulting in what has been called the efficacy paradox.
 Placebos work best for pain, disorders of autonomic sensation, and disorders of factors
under neurohumoral control e.g. nausea, blood pressure, and bronchial asthma.
 Psychiatric disorders such as depression, anxiety and phobias show good placebo response.
In depressive illness, the response rate varies from 25 to 60%, in mania it is as high as 25%
and in schizophrenia it may vary from 25 to 50%, depending upon the criterion of
improvement that is used and other factors. In panic disorder, placebo response rates of up
to 70% are seen. More chronically ill patients show lower placebo response rates.
 Placebos fail in hereditary degenerative disorders, toxic and metabolic syndromes or
vascular events.
 Placebo effects are not unique to placebo preparations; they are seen with active drugs too.
e.g. a substantial proportion of patients responding to analgesics or antidepressants do so
due to the placebo effect. Hence, the net effect of a given drug is thus the sum of the drug's
pharmacological effects and the placebo effect.
 Physiological changes in opioids and GABA have been proposed to explain some aspects
of placebo action; this neuropeptide hypothesis holds good for placebo analgesia, but not
proven to operate in other conditions e.g. depression.
 Three factors are necessary for placebo action: the nature of the disease treated and the
nature of the dynamic relationship between patient and doctor, patients’ expectations and
experience with treatment in the past. Gender, suggestibility scores, and IQ do not affect
placebo effect consistently.
© SPMM Course 8
  Placebos are more effective for clinical than experimentally induced conditions.
 Placebos work better for severe than mild pain, but mildly depressed patients respond well
than severely depressed ones.
 In studies of depression and schizophrenia the difference in improvement in the group of
patients on active treatment compared with the group on placebo increases gradually, with
little difference until about 2 weeks of treatment and the full difference developing by 6
weeks and it increases progressively for several months.
 Those who respond to a placebo for one condition, when treated by one doctor, will not
show same placebo response for another condition or another doctor. Hence, there are no
homogeneous placebo reactors in the population. This view is furthered by the
demonstration that the use of placebo ‘run-in’ approach in antidepressant trials, wherein
‘placebo reactors’ are eliminated before the trial commences, does not actually lower the
placebo response rate or increase the drug–placebo difference to a great extent. But such
procedures reduce generalisability and pragmatic nature of these trials as placebo
responders may be most likely to benefit from a biologically active treatment, and their
exclusion makes any estimate too conservative.
 A placebo can be a procedure and not a medication e.g. sham ECT, and sham surgeries
with the only skin incision.
 The placebo response is higher in trials with more than 2 arms compared to those with two
arms only (placebo vs. active arms). In a three-armed trial, participants are aware that they
have 2 /3 chance of receiving active treatment compared to ½ chance in 2 armed study –
hence there is a higher placebo response.
 People have individual traits that predispose them to be more or less responsive to certain
stimuli; the interaction between the learned associations of the clinical situation and the
person’s particular biology produces a response.
 Placebo analgesia may be associated with decreased beta-adrenergic activity of the heart as
measured by decreased heart rate and low-frequency heart rate variability
 Capsules are perceived to be stronger than tablets, producing more placebo effects. Larger
pills have stronger placebo effect than smaller pills. The number of pills also influences
the perception of pill strength. Multiple pills have stronger placebo effect than single pills.
 Anxiety symptoms responded better to green tablets and depressive symptoms responded
better to yellow tablets. These are examples of the relative potency of medication varying
with pill colour (Schapira et al. 1970).
 Injections elicit a stronger placebo effect than oral medications. Surgery is likely better
than the others in terms of eliciting placebo effects.
Why does a placebo work?

© SPMM Course 9
 1. Natural remission theory states that the disorders for which placebo works are inherently
episodic (i.e. natural cycles show periods of remission and relapse). Hence even without
treatment an improvement would have occurred, and placebo use is merely coincident.
2. Measurement regression: When a continuous variable is measured repeatedly in a sample,
with each subsequent measurement the mean of the sample will move from extreme values
and become closer to the population mean, the central value. This might explain why there
is an apparent placebo response in control groups.
3. Conditioning theory: Placebo is in a way a behavioural intervention. Patients, who have
learnt that receiving a medication will improve symptoms, will be showing a conditioned
response of improvement when a placebo is administered. Learned associations producing
placebo effects can be acquired through conditioning, especially for immune or endocrine
conditions.
 According to classical conditioning models of placebo effects active medications are
Unconditioned Stimuli and the vehicles in which they are delivered (i.e., the pills,
capsules, syringes, etc.) are Conditioned Stimuli. The medical treatments that people
experience during their lives constitute conditioning trials, during which the vehicles are
paired with their active ingredients leading to the unconditioned response of therapeutic
benefits initially. These repeated pairings endow the pills, capsules, and injections with
the capacity to evoke therapeutic effects as Conditioned Responses later on.
 During placebo treatment, the belief of the patient in being treated may result in
selective attention to symptom improvement and expectation. The momentary
experience of symptom improvement may then act as a reward and positively reinforce
preceding changes of autonomic function. Thus, visceral learning due to a mechanism
similar to operant conditioning may occur, in which the reward is internally provided
 Placebo responses are mediated by conditioning when unconscious physiological
functions, such as hormonal secretion, are involved, whereas they are mediated by
expectation when conscious physiological processes, such as pain and motor
performance, come into play, although a conditioning procedure is performed.
4. The role of endogenous opioids: Endogenous opioids (e.g. endorphins) play a significant
role in mediating placebo-induced analgesia. Interestingly, placebo-induced analgesia is
partially reversed by administering the opioid antagonist naloxone. Dopamine reward
system is being increasingly implicated in placebo effects in psychotropic research.

The nature of placebo response in depression is compared with the antidepressant-induced

response in depression. Placebo response starts abruptly, occurs early in treatment and is less
likely to persist (Quitkin et al., 1991). But the antidepressant response is often gradual, occurs later
and is more likely to persist. But the neurobiological correlates of the responses may not be truly

© SPMM Course 10
different as shown by Mayberg et al. (2002). Mayberg et al. (2002) observed that the patients in
their study whose depression relented after treatment with either fluoxetine or placebo had
nearly identical positron emission tomography (PET) brain scans. The ACC is an important
anatomical component of the dopaminergic as well as an opioid system and has been activated
during placebo analgesia.

© SPMM Course 11
5. Drug approval
Any drug must undergo the following steps before approval is granted by regulatory agencies
such as FDA in the US and MHRA in the UK.

1. Preclinical Animal Studies: The pathway a drug must undergo before approval and
marketing start with animal studies where the molecule is demonstrated to have specific actions.
These extensive preclinical animal studies must be carried out at least on two different animal
species. Mutagenicity, carcinogenicity and organ system toxicity are studies at this phase.

2. Human trials – volunteers phase 1: (safety) An investigational new drug then enters human
trials. The first phase consists of determining if the drug is safe for human subjects. It is
administered to a small group of volunteers and safety; tolerability and pharmacokinetics of the
drug are ascertained. They are usually open or uncontrolled studies.

3. Human trials – patients phase 2: (effectiveness) In phase 2 effectiveness is studied in hundreds

of patients with target disease in comparison to placebo to see if it works at all against the disease.
The main methods are controlled trails or small randomized controlled trials.

4. Human trials – patients phase 3: (superiority or equivalence to standard looking for

comparative efficacy) and tolerance profile) In phase 3 the drug undergoes extensive double-
blind RCT to determine how well does it work and what are the common side effects.

5. Human trials – post-marketing surveillance phase 4: Phase 4 takes place if all the previous
phases are successfully crossed – the drug undergoes an approval process by regulatory bodies
and post-marketing surveillance ensues. Less common side effects, which sometimes could lead
to drug withdrawal, can be picked up when large scale prescribing takes place during post-
marketing surveillance observations.

Psychotropic Drugs Adverse effects detected by post marketing surveillance

1. Nefazadone Hepatotoxicity
2. Droperidol, Thioridazine QT prolongation on ECG
3. Sertindole Sudden cardiac death
4. Thalidomide (analgesic) Phocomelia
5. Nomifensine Hepatotoxicity
6. Zimeldine Hypersensitivity reactions and Guillain-Barre syndrome
7. Remoxipiride(sulpiride group) Aplastic Anaemia
8. Mianserin Blood dyscrasias
9. MAOIs Cheese reactions
10. Clozapine Agranulocytosis

© SPMM Course 12
6. Medication adherence
 Compliance is defined as the extent to which a person’s behaviour coincides with medical
advice.
o Implies sole patient’s responsibility
o Criticized as paternalistic.
 Adherence includes the concept of patient choice: both clinician and patient share the
responsibility for adherence.
o In most research, definitions for adherence are usually dichotomous, but adherence
is rarely an all-or-nothing phenomenon.
 Concordance is based on the notion that the therapeutic alliance between the prescriber and
patient is a negotiation process, with equal respect for both the patient’s and clinician’s
agenda

Adherence measurement tools

 Self-report methods:
 For example, using the Tablet Routines Questionnaire, which assess the daily
routines for taking medication and the proportion of drug an individual has missed
in the previous week and last month (Scott and Pope, 2002)
 Pill counts
 Adherence (%) can be calculated as (number of pills taken ÷ number of pills
prescribed) × 100 (Azrin and Teichner, 1998)
 Electronic methods
 Electronic devices have been developed which can be attached to the tablet bottle.
They record the time and date on every occasion that the bottle is opened
 Prescription monitoring
 The frequency of prescription dispensing for an individual can be monitored as a
proxy measure of adherence
 Saliva, plasma and urine assay tests
 Most objective measures
 Not available for all psychiatric drugs – expensive, invasive and have limited value
in assessing partial adherence, leading to overestimate of adherence to long half-life
drugs.
Non-adherence rates are reported as 40–60% for antipsychotics, 18–56% for mood stabilizers and
30–97% (median 63%) for antidepressants. Nonadherent patients with schizophrenia are 3.5 times
more likely than adherent patients to relapse within 2 years.

© SPMM Course 13
 Factors affecting adherence

Factors with no influence on adherence Factors that reduce adherence: Factors that increase adherence

•Age at illness onse •Asymptomatic stage of illness •Presence of family support

•Age at first hospitalization •Cognitive deficits •Liquid or sublingual forms
•Sex •Comorbidity – alcohol and substance •High enthusiasm fromclinican
misuse •Good patient-clinician relationship
•Socioeconomic status,
•Devaluation of medication effects by •Continued access to clincians
•Marital status
the physician
•Ethnicity
•Fear of side-effects.
•High frequency of daily doses
•Homelessness
•Lack of insight (most common cause)
•Long duration of illness (chronic
diseases)
•Oral formulations have poorer
adherence than depots
•Past history of non-adherence
•Polypharmacy
•Prophylactic or maintenance treatments
•Psychopathology of hostility,
suspiciousness and disorganization

 Patients with poor insight may still take medications – accepting label is less important than
enhancing awareness of drug effects
 Dose strength – the relationship between dose strength and adherence is probably
curvilinear, with very low doses being associated with poor efficacy and very high doses
with excessive side-effects
 The health belief model of adherence outlines four main belief categories that a patient
considers before making a decision regarding prescribed medications:
1. Benefits
2. Costs
3. Susceptibility
4. Secondary benefits of medication and adherence.

Improving adherence
Adherence enhancement is possible if the patient’s perceptions are altered. Most patient/family
directed psychoeducational programmes focus primarily on imparting knowledge without
focusing on attitudinal and behavioural change; hence they are largely ineffective in enhancing
adherence.
© SPMM Course 14
  Cognitive-based interventions target the patient’s attitudes and beliefs towards
medication to influence the personal construction of the meaning of medication and illness
(Zygmunt et al., 2002).
 Behaviour-modification interventions assume that behaviour is learnt and can be
modified. Patients are provided with instructions and strategies (e.g. reminders, self-
monitoring tools, cues and reinforcements) to improve adherence (Zygmunt et al., 2002).
 Motivational interviewing enables the patient to express personal reasons for and against
improving their treatment adherence.
 Compliance therapy is a brief intervention based on motivational interviewing and
cognitive approaches. In compliance therapy, a patient’s ambivalence towards medication
is explored initially, followed by a discussion of the consequences of medication cessation.
Analogies with chronic physical illness are made, and the pros and cons of medication are
considered during the course of treatment.

© SPMM Course 15
 DISCLAIMER: This material is developed from various revision notes assembled while preparing
for MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books.
These sources are cited and acknowledged wherever possible; due to the structure of this
material, acknowledgements have not been possible for every passage/fact that is common
knowledge in psychiatry. We do not check the accuracy of drug related information using
external sources; no part of these notes should be used as prescribing information.

Notes prepared using excerpts from:

 Deb, S et a (2008). International guide to prescribing psychotropic medication for the management
of problem behaviours in adults with intellectual disabilities. World Psychiatry; 8(3); 181-86
 Ernst, E. (2001) Towards a scientific understanding of placebo effects. In Understanding the Placebo
Effect in Complementary Medicine. Theory, Practice and Research (ed. D. Peters), pp. 17–30. London:
Churchill Livingstone.
 Ian M Anderson & Ian C Reid. Fundamentals of clinical Psychopharmacology (2nd edition)
 Kaur H, Mariappan TT, Singh S. Behavior of uptake of moisture by drugs and excipients under
accelerated conditions of temperature and humidity in the absence and presence of light Part-III,
Various drug substances and excipients. Pharma Technology 2003:52-56
 Mayberg HS, Silva JA, Brannan SK, Tekell JL, Mahurin RK, McGinnis S, Jerabek PA: The
functional neuroanatomy of the placebo effect. Am J Psychiatry 2002; 159:728-737
 Oken BS . Placebo effects: clinical aspects and neurobiology (2008), 131, 2812^2823
 Patel, M & David, A. Medication adherence: predictive factors and enhancement strategies
Psychiatry, 3, 10:41-44.
 Quitkin, FM et al (1991) Heterogeneity of clinical response during placebo treatment. American
Journal of Psychiatry, 148, 193 -196
 Rajagopal, S. The placebo effect. Psychiatr Bull 2006 30: 185-188
 Sadock, BA & Sadock, VA (ed). Kaplan & Sadock's Comprehensive Textbook of Psychiatry.
Lippincott Williams & Wilkins; 8th edition
 Ter Riet et al (1998) Is placebo analgesia mediated by endogenous opioids? A systematic review.
Pain, 76, 273 -275
 The use of drugs in Psychiatry; John Cookson, David Taylor and Cornelius Katona. (5th edition)
 Vallance, AK. Something out of nothing: the placebo effect. Advan. Psychiatr. Treat., July 1, 2006;
12(4): 287 - 296.

© SPMM Course 16
 Pharmacokinetics
Paper A Syllabic content 4.2

© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
 1. Principles of pharmacokinetics
Pharmacokinetics refers to the time course and disposition of drugs in the body (what the body
does to the drug). The pharmacokinetics for the same drug will differ to some extent on the basis
of the route of administration of the drug. Commonly utilized routes of administration of
psychotropic drugs include oral, intramuscular, intravenous and rectal routes. Other possible
routes include inhalation, topical, subcutaneous, sublingual and intra-arterial but are not
generally used in psychiatric practice

Pharmacokinetics involves the processes of (ADME); Absorption, Distribution, Metabolism,

and Elimination. We will consider each of the above processes in further detail below.

A. Absorption
The route of administration and chemical properties of a drug influences its absorption. The
various factors that affect rate of absorption include

 The form of the drug (e.g. enteric coating of a tablet slows down its disintegration in the
stomach)
 The rate of blood flow at the site of administration (higher the blood flow, greater will be
the rate of absorption)
 Solubility of the drug which depends on the pH of the drug, size of particles in the
formulation and the pKa of the drug (pKa is the pH at which precisely half of the drug is
in its ionized form)

Oral administration
This is one of the most common routes of drug administration. It leads to a variable plasma
concentration, as the absorption may be erratic and subject to metabolism by liver and gut
mucosa (first-pass effect). Drugs absorbed from the gut undergo extensive metabolism before
entering the systemic circulation.

The main mechanisms of absorption of drugs from the GI tract are 1. Active transport 2. Passive
diffusion (most common mechanism) 3. Pore filtration

Factors influencing absorption of drugs from GI tract include

 Intestinal motility
 Gastric emptying
 Gastric and intestinal pH
 Intestinal microflora
 Area available for absorption

© SPMM Course 2
  Integrity of blood flow
 Presence or absence of food
P-GLYCOPROTEIN

Poor oral absorption leads to lower Presence of reverse transporters such as P-

bioavailability of the drug in plasma compared glycoprotein can affect drug absorption. P
to intravenous administrations. This is mainly glycoprotein pumps certain drug molecules
actively out into gut lumen from the gut cells.
due to lack of absorption from the intestine
related to the presence of inhibitory factors like Inhibition of P-glycoprotein (e.g. by grapefruit
food or gastric acid or due to changes in juice) can increase absorption of certain
intestinal motility e.g. having diarrhea or medications. The “grapefruit juice effect” is due
to components of grapefruit juice - bergamottin,
vomiting can affect drug absorption. The
6,7-dihydroxybergamottin, and naringenin –
presence of food delays gastric emptying. The that significantly increase drug oral
anticholinergic activity of some psychotropic bioavailability by selectively and rapidly down-
drugs like tricyclic antidepressants, opiates, etc. regulating intestinal (but not liver) CYP3A4
and to a lesser extent, CYP1A2.
can lead to delayed gastric emptying. The
intestinal flora or intestinal wall enzymes can This effect is greatest for drugs with high first
have drug-metabolizing activity, which could pass metabolism such as calcium antagonists
affect the rate of absorption. For e.g. felodipine and nimodipine, terfenadine,
carbamazepine, triazolam and midazolam (to
Chlorpromazine is sulfated in the gut; this
some extent diazepam), simvastatin and
reduces its absorption. methylprednisone. Grapefruit also significantly
affects buspirone and pimozide.
Site of absorption: The small intestine is less
acidic than the stomach and most absorption
takes place here. This is aided by a large surface area and long transit time via the small intestine.
Although oral administration occurs primarily in the small intestine, the absorption of many
‘slow or sustained release’ drugs occurs in the large bowel.

Special preparations: With oral administration, the rate and sometimes the extent, of absorption
are largely determined by disintegration and dissolution of the dosage form, both being
important for absorption. Tablets and capsules must disintegrate into smaller pieces to expose a
greater surface area for absorption. Enteric coating slows down the rate of disintegration.
Disintegration is often prolonged by hard compaction or by incorporating wax in a drug matrix.
As a result of this, such modified release preparations can prolong the effects of the drugs and
reduce peak plasma concentrations and therefore may reduce side effects (E.g. lithium,
carbamazepine, sodium valproate, quetiapine XL)

Liquids or syrups are more quickly absorbed than tablets because disintegration and dissolution
are not required. Dissolution rate is dependent on

© SPMM Course 3
 1. Size of drug particle
2. Solubility of the drug
3. Properties of intestinal fluid (e.g. p H)

Intramuscular administration
With IM administration, absorption occurs over 10-30 minutes. It avoids most of the first pass
metabolism. This route could be used in an emergency (acute disturbance, sedation etc.) or for
maintenance medications (depot injections).

The rate of absorption of drugs administered intramuscularly is dependent on blood flow and
aqueous solubility. Lipid soluble drugs are rapidly absorbed; drugs with a relative low molecular
weight are better absorbed. Increased muscle blood flow e.g. after muscular exercise increases the
rate of absorption.

Depot preparations of solutions of drugs in inert oil allowing delay absorption.

Intravenous routes
IV administration is the most rapid method of absorption and quickest route for achieving
therapeutic concentration. It is used mainly in emergency situations. IV administered drug enters
systemic circulation rapidly with no first-pass metabolism (100% bioavailability).

IV route also carries the higher risk of sudden and life-threatening adverse effects.

© SPMM Course 4
 B. Permeation:
Permeation of a drug is defined as the lipid membrane permeability of the drug molecule. After
oral administration, a drug may be incompletely absorbed e.g. only 40% of a dose of
chlorpromazine reaches the systemic circulation. This is mainly due to lack of absorption from
the gut.

Lipophilicity: Inherent properties of certain drugs can also affect their absorption e.g. highly
hydrophilic drugs cannot cross the lipid cell membrane while highly lipophilic drugs will
struggle to cross the water layer in the extracellular space. Drugs such as atenolol are too
hydrophilic to be absorbed easily, and have a low bioavailability as a result.

Apart from lipid solubility, concentration gradient affects permeation. Only free drug forms
contribute to the concentration gradient. Hence, protein binding indirectly affects permeation.

Permeation can take place either via simple diffusion i.e. along concentration gradient without
any specific transport mechanism or facilitated diffusion i.e. along concentration gradient but
‘facilitated’ by the presence of carrier specific mechanisms. Active transport refers to transport
against concentration gradient where ATP dependent energy expenditure takes place.

Surface area and vascularity of the gut mucosa are important with regard to absorption of drugs
into the systemic circulation.

Only the nonionized form of a drug can cross lipid membranes of a cell. Many drugs are either
weak acids or weak bases. These substances exist in either nonionized or ionized forms in
equilibrium, in relation to the pH of the environment and their pKa (the pH at which the
molecule is split into 50% ionized and 50% nonionized forms).

The ionized form is more water-soluble than the nonionized form. As a consequence, ionized
drug is more or less trapped in the glomerular filtrate and does not get reabsorbed. Hence, renal
clearance is higher for ionized drugs. A weak base can be ionized by acidifying urine; a weak
acid by alkalinising urine. Hence for salicylate (aspirin) overdose, and barbiturate overdose,
alkalinization helps to reduce toxicity. Acidification may help in the elimination of
amphetamines and phencyclidine (but often complications associated with this procedure
overrides any benefits).

© SPMM Course 5
 C. Distribution:
Distribution of a drug refers to ‘where’ in the body it can be found. Drugs are not evenly
distributed throughout the body. Some drugs are confined to the body fluids only, but others
accumulate in particular tissues.

Drug distribution is influenced by various factors.

1. Hemodynamic factors like cardiac output, regional blood flow. Organs with the
highest blood perfusions such as the brain, kidneys, and liver receive the highest
distribution and redistribution is seen in the second distribution phase to tissues such
as skeletal muscles, adipose tissues and skin.
2. Plasma protein binding
3. Permeability factors- higher the lipid solubility of the drug, the greater its rate of entry
into cells.
4. Blood-brain barrier
5. Blood- CSF barrier

Distribution can be viewed as the drug achieving equilibrium between different compartments.
An approximation of this property is provided by the two compartment model; body is divided
into a central compartment made of the plasma and a peripheral compartment made up of fat
and other tissues, which vary with age, sex and weight. Distribution of a drug leads to a fall in
the plasma concentration (central to peripheral shift) and is most rapid after intravenous
administration.

Protein binding: The distribution of a drug depends on how protein bound it is. When in the
blood, many drugs are bound to circulating plasma proteins. It is the unbound fraction of the
drug (free fraction) that can be active i.e. bind to receptors, pass across blood brain barrier, etc.
Generally equilibrium exists between the fraction of bound and unbound molecules. Reduced
protein-binding increases the free drug fraction and, therefore, the effect of the drug.

Plasma protein binding is usually reversible (not covalent). Therefore, changes in protein binding
can have profound effects on the availability of the drugs. Drugs that are highly protein bound
(>90%), such as phenytoin, are most prone to interactions mediated by this mechanism. For
example, diazepam displaces phenytoin from plasma proteins, resulting in an increased plasma
concentration of free phenytoin and an increased risk of adverse effects. The effects of protein
displacement are usually not of clinical significance, as the metabolism of the affected drug
increases in parallel with the free drug concentration. The result is that, although the plasma level
of the free drug rises briefly, the increased metabolism rapidly restores the level to the previous
steady state. Therefore, any untoward effects of the interaction are normally short-lived
© SPMM Course 6
(Chadwick et al., 2005). Protein binding interactions become relevant in a renal disease where
proteinuria can occur.

The principle plasma protein responsible for binding to acidic drugs is albumin while α1-acid
glycoprotein is the primary binding protein for alkaline drugs. Most psychotropic drugs are
basic, and they may bind to, for example, alpha-1 acid glycoprotein and lipoproteins.

Protein binding is 95-99% for drugs like diazepam, chlorpromazine, amitriptyline and
imipramine. Protein binding is 90-95% for phenytoin, valproate, and clomipramine.

Volume of distribution: Vd =Q/Cp, where Vd-volume of distribution, Q-quantity of drug and

Cp-plasma concentration at the time of administration (‘zero time’).

Vd refers to an apparent (not true) volume in which an ingested drug is distributed in the body.
The higher the Vd, the lower the plasma concentration. Vd tells us about the characteristics of a
drug. When Vd is high, this indicates that the drug has a high affinity for tissues outside body
water such as brain and fat.

The Vd gives some idea of the whereabouts of the drug in the body. A low value (say 10 or 20
litres) suggests that the drug is concentrated in the blood itself. A high value (say 500 or 1000
litres) indicates that the drug is concentrated in the cells or fatty tissues and not the blood.
Increased lipid solubility is associated with increased volume of distribution. This is the case for
most psychotropic drugs at physiological pH.

If a drug is highly protein bound, its plasma concentration will be high (as proteins exist in
plasma), resulting in lower Vd. In other words, Vd is restricted by the total plasma volume for
highly protein bound drugs.

Tissue binding (e.g. fat or muscle) and accumulation of drugs results in low plasma
concentration and, as a result, a high Vd. Hence, competition for protein binding can alter Vd.

Blood-brain barrier
The distribution of a drug to the brain is governed by 3 factors

1. Brain’s regional blood flow

2. Blood-brain barrier
3. Drug’s affinity for receptors in the brain

Blood-brain barrier is a structural and functional barrier comprised of the capillary endothelium
of the brain, which possesses tight junctions, acting in unison as a single sheet or membrane.

© SPMM Course 7
This barrier prevents proteins and other molecules such as immunoglobulins from entering or
leaving the brain’s blood supply. It also protects the brain from the entry of bacteria, viruses and
maintains an osmotic gradient and maintains the cerebral glucose compartment differently from
the periphery.

Factors that could affect the permeability of the BBB include fever, head injury, hypoxia,
hypercapnia, retroviruses, inflammation, vasculitis, hypertension, cerebral irradiation, and aging.

The integrity of the BBB can be measured in different ways e.g. by measuring leakiness to labeled
IgG molecules or gadolinium.

The ability of a drug to pass blood brain barrier depends on its molecular size, lipid solubility
and ionic status. Unionized molecules that are freely available and less protein bound are
transported across the barrier easily. In general higher the lipid-water partition coefficient,
greater the ability to cross the barrier. Exceptionally there are few molecules that pass the barrier
effectively in spite of having a low lipid-water partition coefficient. These have specific carrier
mechanisms e.g. aminoacid transport system (this is stereospecific; so l- amino acids not d- amino
acids are easily transferred). L-dopa, l-tryptophan and valproate have specific carrier
mechanisms. Some small molecules diffuse readily into the brain and CSF from cerebral
circulation e.g. lithium ion.

Some areas of the brain around the ventricles (circumventricular organs) lack BBB; e.g.
subfornical organ, area postrema of the medulla and the median eminence. These
circumventricular organs allow the transfer of many compounds from blood to brain. This may
have a survival benefit as certain toxic substances stimulate area postrema and induce nausea
and vomiting.

There is no evidence that inhaled medications bypass the BBB. But to some extent, nasal sprays
can reach the brain via olfactory epithelium and bypass the barrier. Anaesthetic agents do not
increase the permeability of the blood-brain barrier.

In addition to BBB, a blood- cerebrospinal fluid barrier also exists. This is seen in the choroid
plexus. Here the tight junctions are located between adjacent epithelial cells, as opposed to
adjacent endothelial cells in the case of BBB.

© SPMM Course 8
 D. Bioavailability:
Bioavailability refers to how much of an administered drug reaches its target. It is the extent to
which the drug reaches the systemic circulation when taken by a patient orally or parenterally,
compared with the same quantity of drug given intravenously. In other words, it is the fraction
that circumvents the first pass effect and actually reaches the systemic circulation.

Plotting plasma concentration against time, for a given dose, provides oral bioavailability. The
area under the curve (AUC) after a single dose is proportional to the amount of drug in plasma
and allows determination of the fraction of the dose absorbed-the bioavailability. The area under
the curve obtained for orally administered drug divided by the area under the curve obtained for
intravenous administration of the same dose gives the bioavailability fraction. It is determined by
three factors:

1. Absorption
2. Distribution
3. Elimination (metabolism and or excretion).

When a drug is administered intravenously, the availability of the drug is 100%. In other words,
the amount of drug that enters systemic circulation following IV administration is 100%. This is
not the case with extravascular or non-parenteral administrations such as oral, per rectal,
inhalational, intramuscular or subcutaneous routes. The reduction in amount reaching circulation
is related to the degree of absorption and the effect of ‘first-pass’ metabolism, also called
presystemic metabolism. This metabolism is prominent in the gut mucosa, liver and to some
extent in the muscle tissue. This explains why higher doses are generally needed orally as
compared to intramuscularly. Certain examples of drugs that can undergo a high degree of first-
pass metabolism include imipramine (only 30-80% of the oral dose enters systemic circulation)
and fluphenazine (only 10% of oral dose enters systemic circulation).

Hepatic impairment can reduce first pass metabolism, requiring adjustment of dosages of drugs
that are metabolized by the liver.

Bioequivalence: It is a measure of comparability of plasma levels of two different formulations of

the same active compound when given at same dose and the same route of administration. Two
products are said to be bioequivalent when the graphical trace of their plasma level plot against
time are superimposable. For this to happen, the two compounds must have the same
bioavailability and rate of absorption. Bioequivalence is an important feature to be considered
when changing from one brand to another brand of the same compound e.g. camcolit vs. priadel

© SPMM Course 9
for lithium carbonate or Clozaril vs. zaponex for clozapine.

E. Metabolism of drugs:
Xenobiotics refer to the mechanism by which a foreign agent such as a drug molecule is
metabolized and eliminated from our body. The metabolism or biotransformation of a drug
renders it less lipid-soluble and more water-soluble. Therefore, the products of such metabolism
are more readily eliminated from the body.

The liver is the principal site of metabolism, but metabolism can occur in the gastrointestinal tract,
plasma, lungs, kidneys, suprarenal cortex, placenta, skin, and lymphocytes.

The four major metabolic routes are oxidation, reduction, hydrolysis, and conjugation.

There are 2 phases of drug metabolism.

 Phase 1 metabolism includes oxidation, reduction and hydrolysis (often mediated by CYP
system, see below), as a result of which a molecule (could be active or inactive) suitable for
conjugation is produced. It is not essential that a drug undergo phase 1 metabolism in
order to undergo phase 2 metabolism e.g. lorazepam, temazepam and oxazepam undergo
direct phase 2 reactions. (As a result, in patients with alcoholic liver disease, oxazepam is
favoured for alcohol detoxification instead of chlordiazepoxide which requires intact liver
enzymes for phase 1 clearance)
 Phase 2 metabolism involves conjugation reactions such as glucuronidation, as a result of
which polar compounds (mostly inactive) that are excretable in bile or urine are formed.
A drug or drug metabolite from a phase 1 reaction is conjugated to a polar (water soluble)
group by phase 2 metabolism. The result of this would be a water-soluble conjugate that
can undergo renal excretion easily if it has a relative molecular mass of less than 300. If the
relative molecular mass is more than 300, then the excretion would take place through bile.

Metabolism usually yields inactive metabolites that are more polar and are easily excreted.
Metabolism could also transfer some inactive pro-drugs into therapeutically active metabolites.

Cytochrome P450 enzymes: Most psychotherapeutic drugs are oxidized by the hepatic
cytochrome P-450 enzyme system. The human CYP enzymes comprise several distinct families
and subfamilies. The most studied is CYP2D6. Together with CYP3A4, this constitutes nearly 90%
of all psychotropic metabolism.

The CYP enzymes are responsible for the inactivation of most psychotherapeutic drugs. These
enzymes act primarily in the endoplasmic reticulum of the hepatocytes and cells of the intestine.
Therefore, any cellular pathophysiology caused by viral hepatitis or cirrhosis may affect the
© SPMM Course 10
efficiency of drug metabolism by the CYP enzymes.

There are 3 ways in which drug interactions may influence the CYP system. It includes induction,
non-competitive inhibition, and competitive inhibition.

Genetic variations in the hepatic enzymes affect the rate of metabolism. Between 5 and 10% of
Caucasians lack the enzyme CYP2D6 and are poor metabolizers of corresponding substrates. Up
to 15-20% of East Asians are poor metabolizers of CYP2C19 substrates.

The table below gives the list of some psychotropics with CYP-mediated drug interactions. Some
of the important pharmacokinetic drug interactions involving psychotropics include

 SSRIs especially fluvoxamine and fluoxetine inhibit CYP system. Fluoxetine increases
plasma tricyclic antidepressants via 2D6 and 2C19. Fluvoxamine increases plasma
clozapine concentrations. Clozapine levels may be increased 10-fold by the addition of
fluvoxamine, which can induce seizures.
 Carbamazepine decreases the plasma concentration of several drugs including
contraceptive pills.
 Most antidepressants can inhibit the metabolism of warfarin via a complex mechanism
resulting in potentially serious bleeding.
 Tricyclics and haloperidol compete with each other for same metabolic enzymes.
 Carbamazepine and phenobarbitone can induce their own metabolism.
 Alcohol, smoking and brussel sprouts are CYP inducers. Grapefruit juice and caffeine
inhibit CYP system

CYP enzyme Major psychotropics Effects of psychotropics

metabolized

CYP2D6 All TCAs, fluoxetine, Paroxetine, to some extent fluoxetine,

paroxetine, trazodone, neuroleptics, amitriptyline and
nefazodone, valproate, all clomipramine inhibit 2D6.
neuroleptics, risperidone.

CYP3A4 (Most prominent in Clomipramine, fluvoxamine, Stimulated by carbamazepine and

gut wall mucosa) mirtazapine, nefazodone, barbiturates. Inhibited by calcium
Carbamazepine, most channel blockers, fluoxetine, and
benzodiazepines. nefazodone. Smoking induces CYP1A2
via PAH.

© SPMM Course 11
Autoinduction: Carbamazepine is metabolized by the hepatic CYP2D6, synthesis of which in
turn is induced by carbamazepine. As a result of this autoinduction, the rate of metabolism of
carbamazepine (and other P450 substrates) gradually increases over the first several weeks of
treatment. The initial steady state may be attained within 4 to 5 days, but autoinduction may
delay final steady state until 3 to 4 weeks after treatment initiation. Hence, the level of
carbamazepine must be monitored, and its dose often needs to be raised during this early phase
of treatment. Chlorpromazine can also induce its own metabolism to some extent.

Effect of smoking and caffeine: Smoking and caffeine

affect glucuronidation reaction via UGT enzyme and
ALCOHOL BREAKDOWN
CYP1A2. Drugs which are not dependent on CYP1A2
or UGT for their metabolism are unaffected by smoking Four distinct pathways for ethanol
or caffeine consumption. For example, risperidone and degradation have been described - 3 oxidative
pathways and 1 non-oxidative pathway.
aripiprazole (metabolized by CYP2D6 and CYP3A),
quetiapine (mainly metabolized by CYP3A), and Each of the oxidative pathways starts with
ziprasidone (mainly metabolized by an aldehyde the oxidation of ethanol to acetaldehyde,
oxidase and CYP3A) are unaffected. But the metabolism which is then oxidized to acetate for
subsequent extra-hepatic activation to acetyl-
of clozapine and olanzapine is mainly dependent on
CoA. The first pathway which contributes for
CYP1A2 and UGTs. Because caffeine competitively >90% breakdown in Caucasians, utilizes
inhibits CYP1A2, it increases the levels of clozapine and cytoplasmic alcohol dehydrogenase, the
olanzapine while Polyaromatic Hydrocarbons (PAH) in second oxidative pathway uses the
endoplasmic reticulum Microsomal Ethanol
cigarettes induce the enzyme. The effects of inhibitors
Oxidizing System (MEOS or CYP450 2E1)
(caffeine) are seen sooner than those of inducers and the third pathway uses peroxisomal
(smoking), which require fresh synthesis of CYP1A2 catalase.
enzymes to produce an effect (de Leon, 2004).
The nonoxidative pathway for ethanol
metabolism is less well characterized but
produces fatty acid ethyl esters (FAEEs) as
primary end products.

© SPMM Course 12
 F. Excretion:
The major routes of drug excretion are via urine, faeces and bile. Psychotropic drugs are also
excreted in sweat, sebum, tears, saliva and breast milk. Both active forms and inactive
metabolites can be excreted.

Ionized and non-lipid soluble compounds are the most suited forms for renal excretion. The
factors influencing excretion include

 Increased age (decreases excretion)

 Reduction in renal blood flow e.g. dehydration
 Renal impairment leading to decreased renal function
 Alterations in re-absorption: urine pH. (Changes in the p H of the tubular filtrate can
alter the rate of elimination of the drugs. Normally urine is weakly acidic and good for
excretion of drugs such as tricyclics and amphetamines. Alkaline diuresis is required to
enhance elimination of drugs such as aspirin or phenobarbitone in overdose) and low
sodium (Low sodium increases lithium reabsorption and decreases excretion leading
to consequent toxicity)

Clearance: Clearance is the term used to describe the rate of elimination of a drug. Clearance is
defined as the volume of blood cleared of a particular drug in unit time. Total body clearance
depends on renal and nonrenal clearance such as sweat, bile, etc.

Clearance is directly proportional to the volume of distribution. Cl=k x Vd, Where the constant of
proportionality, k, is the first order elimination constant.

Clearance is specific for each drug and does not depend on drug concentration in plasma
(because if concentration increases, elimination will also increase under first order kinetics). It
represents the relationship between the rate of drug elimination (t1/2) and plasma level. For
drugs with first order kinetics, clearance is constant irrespective of dose consumed because the
rate of elimination is directly proportional to plasma level.

Renal elimination without significant liver breakdown is seen for drugs such as lithium,
amisulpride, sulpiride, gabapentin, acamprosate and amantadine. Both sulpride and amisulpride
have up to 90% elimination via renal route – a minor portion is excreted via the biliary system.
Amisulpride produces 2 weak metabolites following limited hepatic breakdown.

Half-life: The half-life of a drug refers to the time taken for the plasma concentration of a drug to
halve. It is represented by the expression ‘t1/2’. Following intravenous injection, there is a rapid
© SPMM Course 13
fall in the plasma drug concentration, which is caused by redistribution of the drug from the
blood circulation into other tissues. The time taken for this redistribution to halve the initial peak
concentration is the distribution half-life. Following this, the process of drug elimination occurs.
The time taken by this elimination process to halve the plasma drug concentration is the
elimination half-life. Most often, clinicians are interested in the elimination half-life.

G. Elimination kinetics:
Drugs can undergo two different types of clearance (similar to absorption) when administered.
When a constant fraction of drug is cleared per unit time, it is called as first order kinetics. This
means that when the amount of drug in plasma or dose of administered drug increases, the
clearance proportionately increases as a stable fraction of plasma concentration. In other words,
the higher the amounts of a drug present, the faster the elimination. When represented
graphically, first-order elimination follows an exponential decay versus time. Using this
exponential curve, the time to eliminate 50% of a given amount (or time to achieve a decrease in
plasma level to 50% of original) is the elimination half-life (t1/2). For example, if t1/2 is 2 hours for a
drug A then the plasma concentration changes as follows

100mg/ml (2hours) 50mg/ml (2hours)  25mg/ml (2hours) 12.5mg/ml

Most psychotropic drugs follow first order kinetics. In first order kinetics, the rate depends only
on the drug concentration. It is not dependent on any other rate-limiting step.

When the system facilitating such clearance of drugs gets saturated, drugs follow zero-order
kinetics. Here a constant amount, not a fraction, of the drug is cleared per unit time. This means
that irrespective of the amount of drug in plasma or dose of drug administered, the body clears
only a fixed unit of the drug. As such, increasing dose might result in serious toxicity in this case.
Certain drugs have propensity to undergo zero order kinetics even at therapeutic dose levels.
Here the concept of half-life does not hold true as ‘half life’ depends on the dose administered.

100mg (2hours) 80mg (2hours)  60mg (2hours) 40mg

In the above example, 20mg of the drug is metabolized in every 2 hours. The apparent ‘half-life’
of 100mg dose is about 5 hours, but the apparent ‘half-life’ of 80mg dose is only 4 hours. Slow
release preparations (e.g. lithium MR, depot preparations) follow zero-order absorption kinetics;
drugs that rapidly saturate enzymes such as alcohol and phenytoin follow zero-order elimination
kinetics. In very high supratherapeutic doses, saturation of enzymes can happen for drugs such
as fluoxetine, wherein first order elimination switches to become zero order. Note that in zero
order kinetics, the rate does NOT depend on the drug concentration; it depends on some other
rate limiting step e.g. availability of enzymes, slow release formula, etc.

© SPMM Course 14
Steady state: When a drug is administered episodically, the plasma values acutely rise
immediately after administration and then fall when the continuous input of drug does not take
place. But before the fall in levels reaches a flat trough, the next dose gets administered
(depending on t ½ of the specific drug, dosing interval varies). Hence, the actual plasma level
starts building up gradually with every subsequent dose. It is estimated that it takes 4-5 t½ for a
drug to reach the steady plasma level. When steady state is reached, fluctuations in plasma level
do not get eliminated. But the average plasma concentration between 2 successive doses remains
the same. Steady state is reached when for a given drug, rate in = rate out. The time to reach
steady state is dependent on the elimination t½ of a drug; the actual level of the steady state is
independent of the frequency of administration; instead it depends on the actual dose
administered. Loading doses can help achieving steady state more rapidly.

© SPMM Course 15
 2. Indices of safety and efficacy:
Quantal or dose-response curves: Quantal curves plot the percentage of a population showing a
specified, predefined categorical drug effect against the dose or log dose administered. The dose-
response curve plots the drug concentration against the continuous effects of the drug.

Using these curves, the median effective dose, or median toxic doses can be determined. The
median toxic dose is the dose at which 50% of patients experience a specific toxic effect, and the
median effective dose is the dose at which 50% of patients have a specified therapeutic effect.

In addition, using these curves the range of intersubject variability in drug response could be
studied. Steep D-R curves reflect little variability; flat D-R curves indicate great variability in
patient sensitivity to the effects of a drug. The therapeutic index can be determined using these
curves.

Therapeutic index: It is the relative measure of the toxicity or safety of a drug. It is defined as the
ratio of the median toxic dose to median effective dose. In other words, it is the ratio of the
minimum plasma concentration causing toxic effects to that causing a therapeutic effect. This can
vary according to the toxic symptom specified for a given drug. For example, the gastrointestinal
toxicity of lithium can occur at a lower plasma concentration than that for seizures. In the
laboratory this is usually determined using the median lethal (LD50) and median toxic dose
(TD50) in animal studies. In humans, this is identified using ‘minimal’ effective and ‘minimal’
toxic doses using trial data. Note that the term therapeutic index is only relevant when
considering dose-dependent side effects; it is not useful when studying idiosyncratic reactions.

Therapeutic index range: Certain drugs such as lithium, carbamazepine and phenytoin have a
narrow range of plasma levels within which the efficacy is optimum and toxicity is less evident;
crossing this range on higher side will increase toxicity while on the lower range will reduce
efficacy. Drugs with the low therapeutic index or narrow therapeutic range will require plasma
monitoring.

Therapeutic window: This term is often confused with therapeutic safety range. In fact, this term
is used to describe a specified plasma concentration value, only within which certain drugs
appear to have a therapeutic efficacy. This does not concern the side effects or toxicity.
Imipramine, nortriptyline, and desipramine have a curvilinear relationship when plasma levels
are plotted against the therapeutic response, i.e. very high or very low levels do not help the
patient.

© SPMM Course 16
 3. Variables affecting pharmacokinetics:
A. Changes in the elderly
Domains Change Effect

Body An increase in total body fat. A A larger volume of distribution and longer half-life of
composition decrease in total muscle mass (lean lipophilic chemicals because of their increased
body mass). A decrease in total body sequestration in fat. e.g. benzodiazepines excretion slower
water. in the elderly

Plasma Decrease in plasma protein binding Nearly 15-25% - due to higher proteinuria and to some
protein capacity in elderly individuals extent due to lesser plasma protein synthesis by the liver.
Albumin decreased; protein affinity decreased; acid
glycoprotein increased. Higher free drug plasma
concentration – increased metabolism and clearance of the
free drug. More frequent protein binding interactions.
Phenytoin is affected

Liver Hepatic metabolism not altered Liver withstands aging to considerable extent unless
much. Decreased hepatic blood flow associated physical frailty present. No changes noted up to
occurs. age 60 - 80. After 80, CYP system declines. Phase 2
(conjugation) metabolism is not affected (Hence lorazepam
better than diazepam for elderly). Decreased hepatic first
pass effect. Higher oral bioavailability of certain agents.

Kidney Decreases in renal blood flow have More frequent toxicity of renally eliminated agents (e.g.
been approximated at 10% per lithium).
decade beginning after the fourth
decade - leads to reduced creatinine
clearance and GFR.

GI tract Absorption is not greatly affected. GI Slower but nearly equal absorption of oral administered
blood flow is diminished. Gastric pH drugs. Decreased gastric first pass metabolism noted. A
is increased as acidity drops. reduction in the gastric wall content of dopa decarboxylase

Leads to a 3-fold increase in the concentration of levodopa

in the elderly.

Brain Decreased number of brain Some of these counterbalance each other. On the whole
receptors acetylcholine postsynaptic receptors; anticholinergic side effects more pronounced leading to
choline acetyltransferase is increased frequency of delirium on polypharmacy.
diminished, level of brain
acetylcholinesterase also decreased
during aging.

Kidney mass has been reported to be substantially reduced in old age, by approximately 20 to 25%
between the age of 30 and 80 years. Renal blood flow reduces with age even in those with normal
health. Renal blood flow decreases by about 10% per decade after the age of 20. By age 80, RBF

© SPMM Course 17
may be 600ml/min as compared to 1200ml/min in young adults.

Creatinine measurements can yield spurious results; hence GFR formulas must be used to correct
for age and other variables. Nearly 40% renal function is lost by the age 80. The average decline is
around 10mL/min/1.73m2 per decade after age 30. This takes an adult GFR from
130mL/min/1.73m2 to a value of 80mL/min/1.73m2 when the age is 80 (The Baltimore
Longitudinal Study).

B. Changes in neonates:
 Neonates have a higher proportion of total body water and extracellular body water
 Neonates have a lower proportion of adipose tissue.
 The glomerular filtration rate is lower in those aged less than 3-5 months
 Neonates have lower gastric acidity and have an increased gastric emptying time
 Neonates have a more permeable blood—brain barrier
 The microsomal enzyme activity in the liver is lower in those than 2 months
 Neonates have a lower plasma concentration of albumin

C. Changes in pregnancy:
Pregnancy is associated with several pharmacokinetic changes:

 Delayed gastric emptying,

 Decreased GIT motility,
 Increased volume of distribution (5%),
 Decreased drug-binding capacity,
 Decreased albumin level
 Induced liver metabolic pathway,
 Increased GFR & renal clearance.

Psychotropic medication usually passes from the maternal blood to the foetus due to lack of
strong barrier, but rate and amount of transfer are variable. Higher doses are associated with
higher serum level in the infant.

D. Changes with renal impairment:

 Benzodiazepines should be used with caution
 The half-life of diazepam remains unchanged in end-stage renal disease, but its metabolite,
desmethyldiazepam, may accumulate, causing excessive sedation.
 The half-life of lorazepam is increased from 8–25 hours in healthy adults to 32–72 hours in
end-stage renal disease
 At a low level of renal function, lorazepam dosage should be reduced by 50% to avoid

© SPMM Course 18
 excessive sedation.
 Imipramine and amitriptyline can be given at their usual dosage as renal impairment does not
increase their half-lives
 Half normal dose is used for citalopram in patients with renal impairment or in elderly
 The half-life of paroxetine is considerably increased with severe renal impairment, requiring
dosage reduction.
 The dosage of fluoxetine and fluvoxamine does not have to be reduced in the elderly or
patients with renal impairment
 Sertraline manufacturers do not recommend its use in renal impairment
 Haloperidol does not require a dose reduction in renal impairment unless excessive sedation
or hypotension occurs.
 Amisulpride is renally excreted almost exclusively. Hence, renal failure will be a relative
contraindication to use this drug. Product monograph suggests alternate day dosing or dose
reduction if no other alternatives are possible.
 Risperidone and its active metabolite 9-hydroxy-risperidone are substantially excreted in the
urine so that in renal impairment the elimination half-life is prolonged
 Lithium is best avoided or given at low dosages.

© SPMM Course 19
 4. Clinically relevant kinetics and interactions:
A. Tricyclic antidepressants:
 The tricyclics are orally well absorbed but have variable time to achieve peak plasma
concentration (1 to 12 h).
 Many of them have active metabolites – see table below.
 Nearly 7-9% Caucasians are slow metabolizers (measured by debrisoquin hydroxylation) of
tricyclics due to CYP2D6 polymorphism (Up to a 40 times difference in plasma TCA
concentrations can occur as a result).
 Children clear more tricyclics from their body whereas the elderly clear less.
 Most tricyclics have a long half-life (close to 24 h) that allows once-daily dosing. They readily
cross lipid barriers such as blood-brain barrier and placenta.
 They are extensively bound to plasma proteins e.g. Imipramine 80-95%.
 For TCAs plasma (not serum) levels are measured to assess therapeutic dosing. The levels are
determined after 5-7 days when steady state is reached, and 8-12hrs after last dose to avoid
false peaks earlier when absorption is occurring. A sigmoidal curve where proportional dose-
response plateaus at a particular dose is noted for imipramine and desipramine. For
nortriptyline a clear therapeutic window is seen between 50 to 150ng/ml. This inverted U is
not due to decreased responsivity secondary to side-effects.

Antidepressant Active metabolite

Imipramine desipramine

Amitriptyline nortriptyline

Trazodone, nefazodone mCPP

Fluoxetine norfluoxetine

Sertraline desmethylsertraline

 Amitriptyline and clomipramine decrease the metabolism of morphine and may

contribute to opioid toxicity through UDP glucuronyl transferase interaction. (Chadwick
2005)

© SPMM Course 20
Drugs Mechanism Effect

Quinidine, cimetidine, Inhibit TCA metabolism Increase plasma TCA levels

fluoxetine, paroxetine,
phenothiazines, disulfiram,
methylphenidate

Smoking, phenytoin, Induce metabolism Reduce TCA levels

carbamazepine, OC pills and
barbiturates

Phenothiazines Mutual inhibition of metabolism Both antipsychotic and TCA levels

increase

Anticoagulants TCAs increase warfarin levels High risk of bleeding

Clonidine TCAs reduce clonidine levels Hypertensive crisis

MAOIs Synergistic serotonergic Higher risk of serotonin syndrome

enhancement esp. clomipramine
Lower risk of cheese reaction
TCAs reduce tyramine entry via
monoamine reuptake channels

l-dopa TCAs reduce absorption of l-dopa Lowers l-dopa efficacy in Parkinsonism

Morphine Amitriptyline and clomipramine Increased opioid toxicity

decrease the metabolism through
UDP glucuronyl transferase
interaction

© SPMM Course 21
 B. SSRIs

Fluvoxamine

Sertraline

Escitalopram

Citalopram

Fluoxetine

Paroxetine

Lower end: Greatest nonlinearity of kinetics

Unpredictable side effects

Longest t1/2 of primary drug

 The SSRIs are rapidly

Longer time to stabilize
absorbed. treatment availability may be increased by the presence of
Sertraline
food. Higher dose dependent side effects
 Most are highly protein bound except escitalopram which is 56% bound.
 Fluoxetine is metabolized to norfluoxetine, which has similar activity on 5-HT reuptake as
fluoxetine. The half-life of norfluoxetine is 4–16 days while t1/2 of fluoxetine itself is 4–6
days.
 Similarly, sertraline metabolite has longer half-life but unlike norfluoxetine it is not a
potent reuptake inhibitor.
 Desmethylcitalopram is a potent noradrenaline uptake inhibitor but not produced
sufficiently and weakly crosses the blood–brain barrier.
 Fluvoxamine and paroxetine do not have active metabolites.
 Both fluoxetine and paroxetine are capable of inhibiting their own clearance at clinically
relevant doses. As such, they have nonlinear pharmacokinetics: changes in dose can
produce proportionately large plasma levels.
 The half-life is not related to time to onset of action, but it is relevant for discontinuation
reactions.

© SPMM Course 22
  Selectivity: Citalopram is the most selective (and escitalopram) while paroxetine is the
most potent. Fluoxetine weakly inhibits noradrenaline reuptake and binds to 5-HT2C
receptors; sertraline weakly inhibits noradrenaline and dopamine reuptake. Paroxetine has
significant anticholinergic activity at higher dosages and binds to nitric oxide synthase.
Fluoxetine & olanzapine when taken together increase brain concentrations of
noradrenaline.
 Dosing: Apart from depression and GAD, panic disorder, OCD, OCD spectrum disorders
and bulimia respond to SSRIs. OCD may need a higher dose for several months for the
effects to become evident. Fluoxetine treatment of bulimia is best given together with
psychotherapy. Again higher dosages are required. SSRIs are useful in premenstrual
dysphoria (PMDD) where sertraline or paroxetine used either daily or only during luteal
phase produces a positive effect. Intermittent dosing is usually as effective as continuous
administration. Beneficial effects are seen very quickly in one to two days, but proof of
efficacy is lacking.

 Fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-
desmethyldiazepam, there is a strong likelihood of substantial accumulation of both.
Accordingly, diazepam and fluvoxamine should not ordinarily be co-administered.

 Citalopram is metabolized by CYP2C19 initially and then by CYP2D6. CYP3A3 and

CYP3A4 are responsible for demethylation of sertraline.

Drug CYP450 Profile Interacting Effect Clinical notes

psychotropic drug
Fluoxetine Inhibits 2C19, 2D6. All TCAs especially Levels of these Potential TCA toxicity.
Partially Clomipramine drugs increase in Associated with therapeutic
metabolized by Imipramine (both plasma. benefit?
2D6. 2C19 & 2D6), Effect may last up to 2
Citalopram, weeks after stopping
Sertraline, fluoxetine.
Moclobemide,
Duloxetine,
Mirtazapine
Venlafaxine.
Paroxetine Predominantly All TCAs Levels of these Potential TCA toxicity,
metabolized by Citalopram, drugs increase in may be associated with
2D6. Inhibits 2D6 Fluoxetine, plasma. therapeutic benefit when
Fluvoxamine, combined.
Duloxetine, May have non-competitive
Mirtazapine, inhibition resulting in
Venlafaxine. unpredictable effect in
combinations.

© SPMM Course 23
Fluvoxamine Inhibits 1A2, 2C19, Clomipramine, Levels of these Potential TCA toxicity.
3A4 Doxepine, drugs increase in
Trimipramine plasma.
Duloxetine,
Mirtazapine
Citalopram,
Escitalopram,
Sertraline
Trazodone.
Duloxetine Inhibits 2D6, similar All TCAs Levels of these Potential TCA toxicity
to SSRIs. Citalopram, drugs increase in especially at higher dose -
Fluoxetine, plasma. may not be clinically
Paroxetine, meaningful at lower doses.
Fluvoxamine,
Mirtazapine,
Venlafaxine.
Desipramine, Inhibits 2D6 All TCAs Can increase levels Potential serotonin toxicity.
Clomipramine Citalopram, of these drugs
Fluoxetine
Fluvoxamine,
Duloxetine,
Mirtazapine
Venlafaxine.
 The autoinhibition of CYP2D6 is responsible for nonlinear pharmacokinetics of paroxetine
and at least partially for the nonlinear pharmacokinetics of fluoxetine.

 Fluvoxamine reduces the clearance of theophylline approximately 3-fold via CYP1A2

inhibition. Therefore, if theophylline is co-administered with fluvoxamine, its dose should
be reduced to one-third of the usual daily maintenance dose and plasma concentrations of
theophylline should be monitored. No dosage adjustment is required for fluvoxamine.

SSRI Plasma elimination half-life Linearity of

pharmacokinetics

Single dose Multiple dose

[active metabolite]
Paroxetine 10h. 21h. Nonlinear

Fluvoxamine 11h. 14h. Nonlinear

Sertraline 26h. 26h. [36h.] Linear

Citalopram 33h. 33h. Linear

Fluoxetine 1.9 days 5.6 days [7-15 days] Nonlinear

 When fluvoxamine is administered with warfarin, warfarin plasma concentrations

increases by 98% and prothrombin times are prolonged. Hence, anticoagulant dose must
be adjusted accordingly.

© SPMM Course 24
 C. Other antidepressants
The MAOIs are all rapidly absorbed. For the irreversible MAOIs the half-life does not correlate
with duration of action as the effects on the MAO enzyme are irreversible and new enzyme needs
to be synthesized for restoration of normal activity - a minimum of 5 to 7 days. Hence, it is
recommended that for drugs that can interact fatally with MAOIs (irreversible) - the safest
recommendation is to wait 2 weeks before starting.

The combination of MAOIs and pethidine (meperidine) can produce either a depressive
(pronounced sedation due to opioid toxicity) or excitatory reaction (related to serotonin excess:
agitation, hyperpyrexia and cardiovascular collapse, coma, and death). Pethidine, in particular,
has a serotonin releasing property and some reuptake inhibition property. Pethidine must never
be used in the presence of MAOIs because of the risk of this fatal excitatory interaction. Morphine
has fewer propensities to cause this interaction.

Amphetamine also induces serotonin release, while methylphenidate does not. The latter is
relatively safe in terms of serotonin toxicity with MAOIs.

Venlafaxine has low protein binding; it has t1/2 around 3.5 hours. Venlafaxine is well absorbed
per orally. An extended-release formulation of venlafaxine is available, facilitating once daily
administration. The metabolite O-desmethyl venlafaxine (ODV) has a half-life of 9 hours. It is
metabolized by hepatic cytochrome P450 (CYP) 2D6. Venlafaxine has no enzyme-inducing
properties.

Duloxetine has t1/2 of about 12 hours – it is extensively metabolized by hepatic enzymes CYP450
and highly protein bound.

Trazodone and nefazodone undergo extensive hepatic metabolism, and one major metabolite is
m-chlorophenylpiperazine which stimulates 5-HT receptors. Trazodone is readily absorbed and
has a half-life of 5 to 9 hours. Trazodone is a weak inhibitor of serotonin reuptake and antagonist
of serotonin 5-HT2A and 5-HT2C receptors. The active metabolite of trazodone is m-
chlorophenylpiperazine (mCPP) is 5-HT2C agonist with t1/2 around 14 hrs. mCPP can cause
migraine, anxiety, and weight loss. Trazodone has an acute sedative effect, which is useful in the
treatment of agitation, anxiety, and insomnia. Antianxiety effects of trazodone appear earlier than
antidepressant effects.

Trazodone can increase levels of digoxin and phenytoin and warfarin. CYP 3A4 inhibitors can
increase mCPP by reducing its breakdown leading to an increase in side effects.

Buspirone has a short half-life of 2-11 hours. Hence it is given three times daily. Buspirone has an
active metabolite called 1-pyrimidinylpiperazine (1-PP) – which has some degree of activity

© SPMM Course 25
compared to buspirone but achieves higher brain concentration in the brain. Buspirone acts as a
partial agonist on serotonin 5-HT1A receptors – presynaptic agonism leads to inhibition of release
of serotonin, with consequent antianxiety effects. Postsynaptic agonism leads to antidepressant
activity.

St John’s wort: It acts via multiple monoamine reuptake inhibition. It is a CYP inducer and can
interact with warfarin, OCPs and antiepileptics, decreasing their efficacy.

Terms used to describe therapeutic effects of antidepressants

non-response •minimal or <25% decrease in baseline severity of sx

partial response •25-50% reduction in baseline severity (sx still evident)

partial remission •>50% reduction, but still some sx evident

remission •no sx; returning to normal function (<6months from last episode)

relapse •return to fully sx state when in remission

recovery •extended remission sustained for longer than 6-12 months

recurrence •onset of a new episode of depression when in recovery

Mirtazapine reaches peak plasma concentrations within 2 hours; it binds to plasma proteins (85%)
and has a bioavailability is approximately 50%, owing to extant first-pass metabolism. It follows
first-order linear elimination kinetics over a dose range of 15 to 80mg. The elimination t ½ ranges
from 20 to 40 hours. Metabolism is mediated by the CYP2D6 and CYP3A4; thus paroxetine and
fluoxetine, which inhibit the CYP system, can increase plasma concentrations of mirtazapine by
1/5th to 1/3rd but usually there are no clinical consequences. Carbamazepine causes a 60% decrease
in plasma concentrations. Mirtazapine has no inhibitory effects on CYP isoenzymes.

Agomelatine undergoes extensive first-pass metabolism with a low bioavailability. It is

extensively protein bound (95%) and has a half-life of 2.3 hours. It is mostly metabolized by
CYP1A2 (90%) and CYP2C9 (10%).

© SPMM Course 26
 D. Mood stabilisers
Lithium is orally well absorbed but not metabolized in the liver; it is renally excreted. Lithium
carbonate and citrate are not bioequivalent preparations; hence the careful prescribing practice is
required. Lithium is rapidly and completely absorbed after oral administration. Lithium takes 4-
5 days to achieve a steady state in healthy young males. It is not protein bound. Lithium’s plasma
half-life is around 18 hours initially but later after 1 year of chronic use increases to 36 hours.

Lithium is excreted via the proximal tubules where sodium is also filtered. Hence, any loss of
body sodium can increase lithium reabsorption as compensation in error leading to toxicity.
Hence maintaining sodium homeostasis is important in patients on lithium therapy.

Agents increasing Agents decreasing lithium Toxicity with normal levels

lithium levels levels
ACE inhibitors Osmotic diuretics Carbamazepine – increased antithyroid
effect and neurotoxicity
Loop diuretics Caffeine Atracurium – increased neuromuscular
blockade
Fluoxetine Aminophylline Haloperidol, clozapine – increased
neurotoxic effects
NSAIDs Theobromine, Theophylline Calcium channel blockers – increased
neurotoxicity
Thiazides Carbonic anhydrase Metronidazole – increased
inhibitors neurotoxicity
Valproate is available as semisodium compound (divalproex) and as sodium salt of the valproic
acid. Divalproex consists of half valproic acid and half sodium valproate. Semisodium compound
is somewhat better tolerated. Valproate is well absorbed, with a bioavailability close to 100%. It
is quite hydrophilic, with a low volume of distribution.

Valproate has t1/2 of 9 to 16 hours and is highly (90%) protein bound. This binding is saturable so
that at higher doses a greater percentage of the drug may be in the free form. At higher doses, the
increased free fraction may remain in the plasma compartment (rather than escaping into the
tissues) and thus be cleared by the liver. This may yield ‘‘sublinear’’ kinetics so that with higher
plasma concentrations, greater increases in dose may be required to yield the desired increase in
plasma level (Graves, 1995). Binding interactions occur so that VPA can increase free diazepam.

Carbamazepine has a tricyclic structure and undergoes hepatic metabolism. It has an erratic
absorption and a bioavailability of about 80%. It is about 75% bound to plasma proteins.
Carbamazepine induces its own breakdown. Before autoinduction of the epoxide pathway (via
induction of CYP3A3/4), the half-life of CBZ is about 24 hr, and the clearance is about 25 mL/ min.
After autoinduction (2 to 4 weeks into therapy), the half-life falls to about 8 hr, and clearance rises

© SPMM Course 27
to about 75mL/min. The active CBZ-10,11-epoxide (CBZ-E) metabolite has a half-life of about 6 hr.
The conventional form needs to be given in multiple divided doses while extended release can be
given twice a day. A steady-state plasma concentration of 4 to 12 ng/ml is therapeutic.

Verapamil and diltiazem can increase carbamazepine levels and cause clinical toxicity, but this
does not occur with other calcium channel blockers nifedipine and nimodipine. Also,
carbamazepine decreases nimodipine and felodipine levels. Valproate inhibits epoxide hydrolase,
increasing the plasma carbamazepine-epoxide levels, often without altering total plasma
carbamazepine levels. Valproate also displaces carbamazepine from plasma proteins, increasing
free carbamazepine. Patients can have neurotoxicity due to elevated plasma carbamazepine -
epoxide levels in spite of normal plasma total carbamazepine levels. Carbamazepine reduces
warfarin efficacy. Erythromycin can produce carbamazepine toxicity.

Gabapentin has no significant mood stabilizing effects though it is useful to treat anxiety in
bipolar patients. It is not bound to plasma proteins, is not metabolized and is 100% excreted in
the urine. Gabapentin has a half-life of about 6 hrs (4 to 9) and a clearance similar to that of
creatinine (120 ml/min, similar to the glomerular filtration rate), so that increased physical
activity may increase GBP clearance. The bioavailability of gabapentin is not dose-proportional; it
decreases as the dose increases. When gabapentin is given in 3 divided doses, at 900 mg per day
the bioavailability is approximately 60%, but at 2400 mg per day it drops to 34% and at 4800 mg
per day it is only 27%. Gabapentin does not induce or inhibit hepatic metabolism. It is not bound
to plasma proteins and displays linear pharmacokinetics at usual dosages. Consequently, drug-
drug interactions are not an issue with gabapentin. It is usually given three times a day. In
patients with normal renal function, steady state is reached after 1 to 2 days of taking a stable
dose of gabapentin. The dose that a patient takes should not be increased until steady state has
been reached (or some time later) so that the effects of the previous dosage can be assessed.

Lamotrigine achieves peak concentrations within about 3 hours postdose with an oral
bioavailability of about 98%. It is 56% plasma protein bound with t½ of 24 to 36 hours. Enzyme-
inducing drugs (phenytoin, phenobarbital or carbamazepine) reduce the half-life of lamotrigine
whereas valproate increases the half-life. Lamotrigine itself does not affect CYP450 in most cases
but increases levels of carbamazepine-10,11-epoxide, the metabolite of carbamazepine.

E. Typical antipsychotics:
 Typical antipsychotics are well absorbed when administered both orally or parenterally. Peak
plasma levels are reached in 30 min after intramuscular injection and 1 to 4 h after oral
injection. Steady state is achieved in 3 to 5 days.
 The half-life for elimination is in the range of 10 to 30 h.

© SPMM Course 28
 Lipid storage and brain retention are significant; depot forms of haloperidol or fluphenazine
may persist for 1 to 3 months.
 Thioridazine has an active metabolite mesoridazine, and loxapine produces 7-
hydroxyloxapine.
 Typical antipsychotics are mainly substrates of CYP1A or CYP2D6, or both and can inhibit
2D6.
 Chlorpromazine has highly variable absorption rate (around 37% bioavailability) for different
persons and has nearly 100s of metabolites.
 Antacids can decrease absorption of phenothiazines; this leads to reduced plasma
concentration and therapeutic effect of phenothiazines

Interactions:

Enzyme Carbamazepine, phenytoin, ethambutol, barbiturates - reduce antipsychotic levels.

inducers
Clearance SSRIs, TCAs, cimetidine, erythromycin, ciprofloxacin, and ketoconazole can inhibit
inhibitors metabolism – increase antipsychotic levels.
Depot atypicals
Depot drug Preparation Kinetics
Flupenthixol decanoate Esterified in coconut oil Peak levels 3–7 days post IM.
Apparent half-life of 17 days

Fluphenazine decanoate Esterified in sesame oil Peak levels are 24h post-IM.
The apparent half-life of 7-14
days. Smoking reduces levels

Haloperidol decanoate Esterified in sesame oil Peak levels 7 days post IM.
The apparent half-life of 3 weeks.
Smoking reduces levels

Perphenazine decanoate Esterified in sesame oil Peak levels 1-7 days post IM.
Apparent half-life of 2 weeks

Pipotiazine palmitate Esterified in coconut oil Peak levels 1-2 weeks post IM.
Apparent half-life of 2 weeks

Zuclopenthixol decanoate Esterified in coconut oil. Contrast Peak levels 1 week post IM.
this depot from zuclopenthixol The apparent half-life of 7-20
acetate preparation used for days.
rapid tranquillisation

© SPMM Course 29
 F. Atypical antipsychotics:
All atypicals are orally well absorbed.

Drug Half life Chlorpromazine equivalents

(100mg/day CPZ or 2mg Haloperidol)

Risperidone 15hrs 2 mg/day

Clozapine 16hrs 50 mg/day
Quetiapine 6hrs 75 mg/day
Olanzapine 30 hrs 5mg/day
Aripiprazole 90hrs 7.5 mg/day
From Woods SW. J Clin Psychiatry. 2003 Jun;64(6):663-7.

 Risperidone undergoes extensive first-pass hepatic metabolism to 9-hydroxyrisperidone, an active

metabolite. CYP 2D6 catalyzes hydroxylation of risperidone to 9-hydroxyrisperidone. Risperidone is
90% protein bound; its metabolite is 77% bound.
 Paliperidone is the major active metabolite of risperidone (9-OH). It is a potent 5HT2 blocker apart
from partially blocking D2 receptors. Its efficacy and side effects are the same as risperidone. It comes
in a sustained release preparation similar to methylphenidate XL wherein gradual water absorption
delivers the drug molecules slowly. Once daily administration is sufficient; there is no need to titrate
the dose.
 Quetiapine has a shorter half-life of 6 to 12 hours, and multiple daily dosing is required; though with
longer use, as pharmacodynamic receptor action has longer duration once daily dosing may be
sufficient.
 Aripiprazole and its active metabolite dihydro
aripiprazole have exceptionally long half-lives of 75 DEPOT KINETICS
(nearly 3 days) and 94 hours respectively, and steady
state concentrations are achieved after 14 days. Some long-acting injections (such as
risperidone, pipotiazine) show delayed as
Aripiprazole is metabolized by CYP 3A4 and CYP
well as prolonged release. These require
2D6 enzymes. It is highly (99%) protein bound. adeqaute cover with oral antipsychotics after
first dose is administered.
 Atypical depots
o Aripiprazole depot: no need to refrigerate; once
Steady-state plasma levels are often delayed
monthly; gluteal administration only; only 2 for 2–3 months. During this time, plasma
weeks oral dose tapering needed. levels are likely to rise substantially even
o Paliperidone depot does not need oral tapering; when dosages are not increased, thus
once monthly; no need to refrigerate; primarily producing dose-dependent side effects.
renal excretion.
Dose–response relationships are not clearly
o Risperidone microspheres are used in depot
understood for most LAIs. Test doses are
preparations; they release the active drug at often used but may not be sufficient to assess
therapeutic levels only 3 weeks after gluteal or tolerability in longer-term use.
deltoid injection. Long-acting risperidone should

© SPMM Course 30
 be supplemented with oral risperidone for 3 weeks. Requires refrigeration as it is granular, not
ester-based.
o Olanzapine depot is a crystalline salt composed of olanzapine and pamoic acid with a half-life of
30 days and steady state reached at 12 weeks. Oral supplementation of olanzapine is not required.

G. Antidementia drugs:
 Tacrine is poorly absorbed with short t1/2. It is metabolized by CYP 1A2 hepatic enzymes.
 Donepezil has an oral bioavailability around 100%, with linear pharmacokinetics. The drug
reaches steady state in about two weeks. Its t1/2 is long - 70 hours, enabling once-daily dosing.
Donepezil is extensively bound to plasma proteins, and while a part is excreted unchanged
the other is extensively metabolized by CYP 2D6 and 3A4 hepatic enzymes to active and
inactive metabolites.
 The oral bioavailability of rivastigmine is about 40% up to a dose of 3 mg, after which this
increases non-linearly. The t1/2 of rivastigmine is just 1.5 hours. The drug undergoes
hydrolysis by cholinesterase itself, with minimal hepatic involvement. It is excreted almost
entirely in the urine as the sulfate of the decarbamylated metabolite.
 The oral bioavailability of galantamine is about 90%; it has low protein binding (18%). It
undergoes metabolism by CYP2D6 and CYP3A4 enzymes while one-third is excreted
unchanged in the urine.
 Memantine has low protein binding (45%) and a long half-life of 60–80 hours. Approximately
half the dose of memantine is excreted unchanged in the urine; the remainder undergoes
hepatic conversion to inactive metabolites. Drugs that alkalinize the urine (e.g., carbonic
anhydrase inhibitors) reduce the clearance of memantine.

H. Other drugs:
 Methylphenidate is absorbed well orally and achieves peak plasma levels in 1-2hrs with t1/2
2-3 hrs necessitating multiple daily dosing. This is obviated by sustained release preparation
that can be given once daily.
 Modafinil reaches peak plasma concentrations in 2 to 4 hours and has a half-life of 15 hours.
 Atomoxetine has a t1/2 5 hours and is metabolized by the CYP 2D6 pathway. SSRIs may raise
atomoxetine levels.

© SPMM Course 31
Benzodiazepines:
Drug Duration of action Effect
Diazepam, Long-acting Can have more than 200hrs t1/2 in genetically slow
chlordiazepoxide, metabolizers. Also, toxicity can take 1 – 2 weeks to be
clonazepam, evident when higher doses are given.
flurazepam
Lorazepam, oxazepam, Intermediate or Severe withdrawal phenomena but the lesser risk of
temazepam, short acting daytime impairment and daytime sedation. Rebound
Alprazolam insomnia and anterograde amnesia more often seen in
short t1/2. Lorazepam t1/2 15 hours; temazepam
somewhat shorter – 10 hours.
Triazolam Very short acting Used in anaesthesia
Diazepam is well absorbed orally - oral bioavailability nearly 100%. Peak plasma concentration is
reached in 15 - 90 minutes after oral administration; has a second peak at 6 - 12 hours due to
enterohepatic recirculation. Diazepam is widely distributed - highly lipophilic (so CSF
concentration more or less equals plasma concentration) with 95-99% plasma protein binding. It
has a slow elimination t½ 30 h (ranges between 20 - 100 h). It also takes a long time to reach
steady state (5 -6 days). It gets extensively metabolized in the liver with 3 active metabolites:
Nordiazepam or desmethyldiazepam (principal metabolite – could accumulate due to long t1/2),
Oxazepam and Temazepam.

“Z”-hypnotics
 Zolpidem, zaleplon, and eszopiclone are quickly and completely absorbed when given orally. Food
may delay absorption by an hour.
 Lack of active metabolites of zolpidem, zaleplon, and eszopiclone avoid the accumulation and hang
over effects.
 NICE's appraisal committee concluded that no compelling evidence of a clinically useful difference
exists between the Z-drugs and short-acting benzodiazepines in terms of effectiveness, adverse effects,
or potential for misuse or dependence. But this is controversial.

Z HYPNOTICS
Zopiclone / Onset within 45 mins; Benzodiazepine receptor selective for alpha 1 subunit;
Eszopiclone half-life 4 to 5 hours (acts eszopiclone is the only Z-hypnotic indicated for sleep
(enantiaomer) up to 8 hours) maintenance therapy (US FDA) – others are used for
initiation problems.
Zaleplon Onset within 30 mins; Shorter half-life and quick onset – makes it suitable for
half-life 1 to 2 hours (acts those with sleep initiation problems; not so helpful for
up to 4 hours). the maintenance of sleep.
Zolpidem Onset within 30 mins; Shorter half-life and quick onset – makes it suitable for
half-life 1 to 4 hours (acts those with sleep initiation problems; not so helpful for
up to 6 hours). the maintenance of sleep. Less hangover effect.

© SPMM Course 32
DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgments have not been possible for every passage/fact that is common knowledge in
psychiatry. We do not check the accuracy of drug-related information using external sources; no
part of these notes should be used as prescribing information

Notes prepared using excerpts from:

 Chadwick, B. et al. Potentially hazardous drug interactions with psychotropics. Advances in

Psychiatric Treatment (2005) 11: 440-449
 Davis, J et al (2006) Switch or stay? Am J Psychiatry 163:2032-2033,
 De Leon, J. (2004) Psychopharmacology: Atypical Antipsychotic Dosing: The Effect of Smoking
and Caffeine. Psychiatric Services. 55 (5): 491-493.
 Lieberman & Tasman, Handbook of Psychiatric Drugs.
 Mendelson WB, et al. The treatment of chronic insomnia: drug indications, chronic use and abuse
liability. Summary of a 2001 New Clinical Drug Evaluation Unit meeting symposium. Sleep Med
Rev. 2004;8:7-17.
 Palaniyappan, L., Insole, L. & Ferrier, IN. The safety and efficacy of antidepressant combinations:
A review. Adv Psych Treatment. In press.
 Puri, BK. Drugs in psychiatry- Oxford Medical Publications; ; 13-37
 Sandson NB, Armstrong SC, Cozza KL: Med-Psych Drug-Drug Interactions Update An Overview
of Psychotropic Drug-Drug Interactions. Psychosomatics 2005;46:464–494.
 Schrier, RW. Diseases of the Kidney & Urinary Tract: Clinicopathologic Foundations of Medicine.
Lippincott-Wilkins, 2007 Pg 301
 Tamminga, C & Davis, JM Schizophrenia Bulletin vol. 33 no. 4 pp. 937–946, 2007
 Taylor D. Psychopharmacology and adverse effects of antipsychotic long-acting injections: a
review. The British Journal of Psychiatry Nov 2009, 195 (52) S13-S19
 http://www.drugs.com/pro/fluvoxamine.html
 Phipps A & Turkington, D. Psychiatry in the renal unit. http://apt.rcpsych.org/content/7/6/426

© SPMM Course 33
 Pharmacodynamics
Paper A Syllabic content 4.3
© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
© SPMM Course 1
1. Introduction

The term pharmacodynamics refers to the study of the mechanism of action of drugs (the effect of
drugs on the body). Most psychotropics affect neurotransmitters of the brain. This effect can
occur at various levels.

Level of action in Examples

neurotransmission cycle
Synthesis L-tryptophan, l-dopa
Storage Reserpine depletes NA and DA.
Release from storage Amphetamine stimulates release of NA and DA

Reuptake SSRI, TCA, cocaine – dopamine reuptake, Bupropion –

dopamine & Noradrenaline reuptake
Degradation MAO inhibitors, Acetyl cholinesterase inhibitors e.g.
donepezil
Pre synaptic receptors Clonidine, lofexidine at alpha2.

Post synaptic receptors Most antipsychotics at D2

Partial agonism Aripiprazole – D2; Buspirone 5HT1A; Clonazepam –
BDZ receptor; Buprenorphine – opioid receptor mu
Antagonism Flumazenil for benzodiazepines, antipsychotics at D2
Full agonism Benzodiazepines at GABA-A complex, bromocriptine
for dopamine
Second messengers Lithium at inositol level.

Refer to Neurochemistry SPMM Notes for more details of different neurotransmitters, their
structure and receptor actions.

© SPMM Course 2
2. Receptor mechanisms

The ‘receptor’ of a drug can be defined generally as the cellular component to which the drug
binds and through which the drug initiates the pharmacodynamic effects on the body. There are
2 major superfamilies; Ionotropic or metabotropic receptors.

 Ionotropic: Theses are ligand-gated ionic channels. Their activation leads to a rapid
transient increase in membrane permeability to either positive cations like sodium or
calcium or negative anions like chloride. It causes excitation or inhibition of the
postsynaptic membrane. Examples are nicotinic acetylcholine receptors, GABA-A
receptors, glutamate receptors and serotonin 5HT 3.
 Metabotropic: These produce slower response involving so-called G-proteins which bind
to the intracellular portion of the receptor and activate a second messenger. Altered
second messenger levels result in changes in the phosphorylation state of key proteins
rendering them active or inactive. Examples are Dopamine (D1-5), Noradrenaline, and
Serotonin 5HT1-7 except 5-HT 3, muscarinic acetylcholine receptors and opioid receptors
(mu). Ionotropic receptors result in quick response (GABAA, a benzodiazepine); G protein
coupling (metabotropic) is a comparatively slower process (most antipsychotics,
antidepressants.

Kinetics of receptor binding: A drug can be an agonist for a receptor and can stimulate the
biological activity of the receptor or could be an antagonist that inhibits the biological activity.

 Full agonists produce a maximal response. The measure of the degree of response is
usually measured against physiological neurotransmitter efficiency for any given receptor.
 Partial agonists cannot elicit a maximal response and are less effective than full agonists.
Examples are Aripiprazole, buspirone and buprenorphine. Partial agonists have a ceiling
effect. The degree of response of a partial agonist depends on availability of physiological
neurotransmitter in the vicinity; i.e. when maximal dopamine is available, partial agonist
aripiprazole can actually inhibit the dopaminergic transmission as a less efficient molecule
competes with more efficient molecule. In dopamine deficient states, the same partial
agonist can enhance dopaminergic effects.
 An inverse agonist is an agent that binds to the same receptor but produces the opposite
pharmacological effect. No clinical drug acts via this mechanism but several have been
researched especially at GABA complex.
 Antagonists are drugs that interact with receptors to interfere with their activation by
neurotransmitter or other agonistic molecules.

© SPMM Course 3
Types of antagonism

 Competitive antagonism can be reversed completely by increasing the dose of the agonist
drug. Competitive antagonists reduce the potency (minimal dose needed to produce an
effect) but not the efficacy (maximal response produced) of agonists. Examples of
competitive antagonism include atropine at muscarinic receptors and propranolol at beta-
adrenergic receptors.
 Noncompetitive antagonists alter the receptor site in some way so increasing the dose of
the agonist drug can reverse the effects only partially. Non-competitive antagonism
reduces both the potency and the efficacy of agonists. Therefore, non-competitive
antagonists not only shift the curve to the right but also reduce the maximum effect. For
example, ketamine and phencyclidine are noncompetitive NMDA antagonists.
Irreversible antagonists bind irreversibly to the target site e.g. most traditional MAOIs.
 Pharmacological antagonism refers to the opposing action of two molecules by acting via
same receptors. Physiological antagonism refers to the opposing action of two molecules
by acting via different receptors e.g. acetylcholine vs. adrenergic actions.
 Chemical antagonism refers to the opposing action of two molecules by acting via
chemical reactions. This is not seen in psychotropics, but heparin and protamine reaction
is an example.

Most drugs bind reversibly to receptors, and the response is proportional to the fraction of
receptors occupied (law of mass action). As the concentration of drug increases, the responses
increases until all receptors are occupied giving a dose-response curve.

Receptors can be up-regulated or down-regulated by drugs. With therapeutic use, agonists may
cause down-regulation (desensitivity) or reduction in receptor numbers while antagonists may
have the opposite effect- upregulation (hypersensitivity) or increase in receptor numbers.

The potency of a drug with receptor binding action refers to the amount of the drug needed to
produce a particular effect compared to another standard drug with similar receptor profile
(‘vigor’). The potency of a drug is determined by;
a. The proportion of the drug reaching the receptor
b. The affinity for the receptor
c. Efficacy
Affinity refers to the ability of the drug to bind to its appropriate receptor (‘affection’). Drugs
that bind readily to a receptor are described as having high affinity for that receptor and, in
general, the higher the affinity and the more receptor a drug occupies, the more potent it is.

© SPMM Course 4
Efficacy refers to how well the drug produces the expected response i.e. the maximum clinical
response produced by a drug (‘productivity’). Efficacy depends on affinity, potency, duration of
receptor action in some cases and kinetic properties such as half-life, among other factors.

Haloperidol is more potent than chlorpromazine as approximately 5 mg of haloperidol is

required to achieve the same effect as 100 mg of chlorpromazine. These drugs, however, are
comparable in the maximal clinical response achievable using them i.e. equally efficacious but
not equipotent.

© SPMM Course 5
3. Modes of therapeutic action for psychotropics

Antipsychotic drugs
In general all antipsychotics act via varying degrees of D2 blockade. Aypical drugs show selectivity for D2
receptors and also show high 5HT2: D2 blocking ratio. Specific actions are listed below.

DRUG MECHANISM
Amisulpride Both D2 and D3 antagonism. Similar dose-dependent pre & postsynaptic profile to
sulpride. Some degree of limbic selectivity and 5HT7 activity also noted.
Aripiprazole Partial dopamine agonist at D2. Also 5HT2A antagonist. Exhibits a Goldilocks’
phenomenon -stabilising action wherein anatagonising DA at sites of excessive
dopamine such as mesolimbic zones while mimicking DA (agonism) at dopamine
deficient zones such as mesocortical areas that are linked negative symptoms. Does
not produce much change in tuberoinfundibulum where normal DA levels are
expected in schizophrenia. Aripiprazole acts on both postsynaptic D2 receptors and
presynaptic autoreceptors.
Asenapine D2 antagonist and serotonin 5HT2A blocker (similar to olanzapine). Has potent
alpha-2 blockade effect. Sublingual; allegedly weight and prolactin-neutral. Licensed
for use in mania.
Chlorpromazine, The moderate antimuscarinic effect in addition to D2 blockade. Highly sedative
promazine phenothiazine drugs.
Clozapine A High ratio of 5HT2 to D2 blockade; also blocks D4 and 5HT6 receptors. Has
notable alpha 1 antagonism and anticholinergic and antihistaminic properties. Weak
D1 and D2 affinity. Also binds 5HT3. Proposed to have a faster dissociation rate
(similar to quetiapine) hence a hit and run profile is noted.
Lurasidone D2 antagonist and serotonin 5HT2A blocker (similar to risperidone). Also has a high
affinity for serotonin 5HT7; partial agonist at 5HT1A receptors. Has minimal affinity
for alpha-1 (less orthostatic effect) and histamine receptors (thus may be weight
neutral)
Olanzapine Atypical antipsychotic. Has high 5HT2 / D2 blockade ratio. Potent D4 blockade and
5HT6 blockade also noted. It has significant anticholinergic and some antihistaminic
effects.
Paliperidone A metabolite of risperidone. Similar mechanism of action
Quetiapine Similar to clozapine – hit and run profile on D2. Compared to other atypicals it has
somewhat lesser 5HT2A blockade. Significant anticholinergic effects similar to
olanzapine.
Risperidone Serotonin-Dopamine Antagonist - Atypical Antipsychotic. Has high 5HT2A
antagonistic property. In higher therapeutic doses can bind to D2 in a similar fashion
to typicals and can lead to extrapyramidal and prolactin related side effects.
Sulpiride Pure D2 antagonist. At low doses presynaptic receptors blocked (helps negative
symptoms?); above 800mg/day doses, affects postsynaptic D2 – reducing positive
symptoms.
Thioridazine, D2 antagonists. Marked antimuscarinic effect. Less EPSEs than other typicals.
pericyazine,
© SPMM Course 6
pipotiazine
Thioxanthenes Exhibit stereoisomerism. D2 antagonists – typical antipsychotics.
Ziprasidone Atypical antipsychotic with 5-HT2A and D2 blockade. Antagonizes 5-HT1D, 5-HT2C,
D3, D4 receptors. Poor affinity for muscarinic effects; some antihistaminic property
noted. Agonistic at 5-HT1A; also some serotonin and norepinephrine reuptake
inhibition noted.
Zotepine Atypical antipsychotic with 5HT2A, 5HT2C, D1, D2, D3, D4 antagonism. Potent
noradrenaline reuptake inhibitor. Potent antihistaminic activity and some NMDA
antagonism.

© SPMM Course 7
 Antidepressant drugs
DRUG MECHANISM
Agomelatine Agomelatine enhances norepinephrine and dopamine neurotransmission through 5-
HT2C antagonism. It is also a direct agonist at melatonin (MT1 and MT2) receptors.
GABA interneurons tonically inhibit noradrenergic circuits (from locus coeruleus)
and dopaminergic circuits (from ventral tegmentum) projecting to the prefrontal
cortex. Serotonin via 5HT2C stimulation drives these GABA interneurons. Thus,
norepinephrine and dopamine circuits are inhibited by the normal tonic release of
serotonin onto 5-HT2C receptors (Stahl, 2007). Thus agomelatine, through 5HT2C
inhibition, acts as norepinephrine and dopamine disinhibitor (NDDI).
Antidepressant with possible sedative effects.
Amoxapine Tetracyclic with dibenzoxazepine structure. Has both dopamine antagonistic and
serotonin-noradrenaline reuptake inhibition effects. So claimed to have significant
antipsychotic properties in addition to antidepressant effects. Similarly,
extrapyramidal side effects are seen more often than other tricyclic.
Bupropion Dopamine and noradrenaline reuptake inhibitor. Used to help quit smoking and in
depression. It is noted to increase the efficiency of noradrenergic transmission and
reduce total norepinephrine turnover. It has no antimuscarinic activity. Some degree
of competitive nicotinic antagonism.
Buspirone Partial agonist on serotonin 5-HT1A receptors. At presynaptic levels, it is mostly a full
agonist, which inhibits the release of serotonin, with consequent antianxiety effects.
Partial agonist action at postsynaptic receptors appears to account for the
antidepressant activity.
Citalopram SSRI, most selective of all SSRIs for serotonin reuptake. Occurs in a racemic mixture
of which s isomer has pharmacological activity. But r- enantiomer inhibits the action
of s- enantiomer; hence if escitalopram is used (s- enantiomer) lesser dose is
sufficient.
Clomipramine Tricyclic – regarded as most potent; higher SRI selectivity than other TCAs but lesser
selectivity than SSRIs.
Desipramine Tricyclic with least anticholinergic action but lethal on overdose.
Duloxetine SNRI similar to venlafaxine. Said to have a better profile for psychosomatic pain and
neuropathic pain.
Levothyroxine & Levothyroxine is T4; liothyronine is T3 – both are thyroid hormones; suppress TSH
Liothyronine and acts as an adjuvant in resistant depression. The exact mechanism of
antidepressant effects unknown – possibly via neuroendocrine changes.
Lithium Lithium is thought to act via the second messenger system. It putatively enhances
serotonin transmission by
1. Increasing tryptophan uptake into neurons
2. Enhancing serotonin release
3. Downregulation of 5HT1A, 1B and 2 receptor subtypes is also noted on chronic
administration.
4. Directly inhibiting glycogen synthase kinase-3 (GSK-3) and also
5. Competing with magnesium directly at several important regulatory enzymes
such as inositol-monophosphatase (IMPase), which catalyzes inositol second
messenger system.

© SPMM Course 8
 According to the inositol depletion hypothesis, inhibition of IMPase by lithium
reduces myoinositol and phosphoinositide phosphate (PIP-2), leading to therapeutic
efficacy. Further, through an increase in intracellular sodium, it may also affect
Na+K+ pump and reducing dopamine synthesis in dose-dependent fashion.

Milnacipran SNRI similar to venlafaxine. New drug Levomilnacipran also acts similarly
Mirtazapine 5HT2A antagonism, alpha 2 antagonism, anti histaminic and anti 5HT3 properties
noted. Mianserin has similar profile, but it is not antihistaminic; instead it has
anticholinergic properties.
Moclobemide Reversible inhibitor of MAO-A selectively.
Nefazadone 5HT2 antagonist with some serotonin reuptake inhibition and mild norepinephrine
reuptake inhibition. Has some alpha 1 antagonistic effect. Produces mCPP as a
metabolite.
Paroxetine Selective Serotonin Reuptake Inhibitor – most potent of all SSRIs in serotonin
reuptake blockade, but not specific – has significant antimuscarinic action.
Phenelzine Monoamine Oxidase Inhibitor – increased availability of monoamines including
serotonin and noradrenaline may explain the mechanism of antidepressant action
though disputed.
Pindolol Beta blocker with intrinsic sympathomimetic activity. Also 5HT1A antagonism –
tipped to enhance the onset of action of SSRIs through this mechanism.
Reboxetine Noradrenergic specific reuptake inhibitor (NARI)
Selegiline Monoamine Oxidase Inhibitors – selective for B at normal therapeutic doses;
selectivity lost when a patch is applied at higher doses, leading to some
antidepressant action.
SSRIs Reuptake inhibition at somatodendritic areas takes place soon after administration –
this leads to down regulation of somatic autoreceptors for serotonin and as a
consequence inhibitory tone on serotonergic transmission is lost; the serotonergic
output is facilitated. (see below)
Tranylcypromine Monoamine Oxidase Inhibitors. Irreversible, non-selective. Positive enantiomer
better MAOI, negative enantiomer better reuptake inhibitor.
Trazodone 5HT2A/2c antagonism and some alpha 2 blockade. Alpha 1 blockade and
antihistaminic properties also noted. Feeble reuptake inhibition at serotonin
transporters.
Tricyclics Monoamine reuptake inhibition (see below). The varying degree of noradrenaline
and serotonin reuptake inhibition. Very minimal negligible effect on dopamine.
Clomipramine is the most serotonin specific. Secondary amines are more
noradrenergic.
Venlafaxine SNRI. Serotonin noradrenaline reuptake inhibitor. Acts as an SSRI in lower (<150mg)
doses.
Vilazodone Mechanism not fully understood but selective serotonin reuptake inhibition and also
a partial agonist action at serotonergic 5-HT1A receptors (the chemical structure is
close to trazodone and nefazodone)
Vortioxetine A structure similar to reboxetine but predominantly an SSRI-like effect. In addition,
also shows 5HT3 antagonism and 5HT-1A agonism.

© SPMM Course 9
Selectivity of antidepressants: The ratio of concentration required to produce equivalent inhibitions of
serotonin (5-HT) to Noradrenalin is shown below.

 Amitriptyline 1:1
 Clomipramine 1:7
 Fluoxetine 150:1
 Citalopram >2000:1

Inhibition of nerve terminal NE neuronal uptake system

Increase in synaptic concentrations of NE

Desensitization of inhibitory Alpha2-adrenoceptors in the terminal

Increase in neuronal NE release

Further increase in synaptic concentrations of NE

Desensitization of postsynaptic Beta adrenoceptors without affecting postsynaptic Alpha1-adrenoceptor

sensitivity

Mechanism of TCA Action

5HT Reuptake inhibition at somatodendritic areas

Increase in local concentrations of 5HT

Desensitisation of inhibitory 5HT1A autoreceptors in the soma

Increase in neuronal 5HT release

Increase in synaptic concentrations of 5HT

Desensitization of presynaptic 5HT1B receptors without affecting postsynaptic 5HT1A sensitivity

Mechanism of SSRI Action

© SPMM Course 10
 Mood stabilizers
DRUG MECHANISM
Carbamazepine Prolongs sodium channel inactivation. As a consequence, calcium channel
inactivation is prolonged. It also reduces glutamate neurotransmission, adenosine
A1 receptor antagonism and increase in brain catecholamine activity. It inhibits
peripheral benzodiazepine receptors and reduces limbic kindling. It interferes with
glial cell steroidogenesis.
GABApentin GABA analogue structurally - binds to the α2δ subunit of the voltage-dependent
calcium channel in the central nervous system. Acts on l-amino acid transport and
thus can increase GABA availability in the brain. It crosses BBB via this l-AA
transport. Has a high-affinity site in GABA-A complex; but no benzodiazepine-like
actions noted.
Lamotrigine Blockade of voltage-sensitive sodium channels leading to modulation of glutamate
and aspartate release; some effect on calcium channels. Some inhibition of serotonin
reuptake and weak inhibition of 5-HT3 receptors.
Levetiracetam Indirectly enhance GABA system. Anticonvulsant with weak evidence against
mania.
Oxcarbazepine A metabolite of carbamazepine; similar mechanisms proposed.
Pregabalin GABA analogue structurally (similar to gabapentin). Like gabapentin, pregabalin
binds to the α2δ subunit of the voltage-dependent calcium channel in the central
nervous system. This may subtly reduce the release of certain neurotransmitters. It
may as well influence GABergic neurotransmission. It has anti-epileptic, analgesic
(neuropathic pain) and anxiolytic effects. It is more potent than gabapentin hence
has a higher therapeutic index and fewer dose-related side effects.
Tiagabine Tiagabine is a potent and selective reuptake inhibitor of GABA. It also has mild
antihistaminic effects.
Topiramate Topiramate is a fructose derivative; it is a selective inhibitor of Glutamate AMPA
receptors, blocks Na+ receptors, and has indirect GABAergic activity by potentiating
the action of GABAA receptor.
Valproic acid Unknown- speculated to act via increased GABA release, decreased GABA
metabolism, increased neuronal responsiveness to GABA and increased GABA
receptor density, inhibition of phosphokinase C similar to lithium and functional
dopamine antagonism.
Vigabatrin VIGABATRIN expands as Vi- GABA- TR-transaminase IN- inhibitor. The name
explains the mode of action.

© SPMM Course 11
 Sedatives & Hypnotics
DRUG MECHANISM
Benzodiazepines Act via a particular site called omega site in GABA-A complex. All are agonists
except clonazepam, which is a partial agonist. They facilitate GABA action on
GABA-A complex – thus facilitating inhibitory neurotransmission via chloride ions.
They have no direct agonistic action in the absence of GABA. They do not increase
the number but the frequency and duration of chloride channel opening.
Chloral hydrate, Barbiturate like agents. Probably potentiate GABAergic neurotransmission.
paraldehyde and Paraldehyde is cyclic ether. They have a poor safety profile and hence none of these
meprobamate are in clinical use currently.
Flumazenil Benzodiazepine antagonist
Ramelteon Ramelteon is a melatonin receptor full agonist with high affinity and selectivity for
human melatonin receptors MT1 and MT2 over the MT3 receptor. It decreases sleep
latency and increases sleep time across all ages; the dose-response curve is flat with
no significant difference in efficacy between the 16-mg or 64-mg doses of ramelteon.
It may have lower abuse potential than other hypnotics
Thiopental Act directly on GABA-A complex and facilitate GABA transmission by opening
chloride channels and enhancing hyperpolarisation. At lower doses, barbiturates
enhance GABA by decreasing the rate of GABA dissociation and increasing the
duration (not a number) of GABA-activated chloride channel opening. At slightly
higher concentrations, barbiturates directly activate chloride channel opening even
in the absence of GABA, an action that is not shared by benzodiazepines.
Zolpidem, Z-drugs act via GABA A complex but act differently than benzodiazepines.
Zaleplon, Benzodiazepines occupy all 3 subunits of the ω receptor, but Z-drugs occupy only
Zopiclone, certain subunits. e.g,. zolpidem and zopiclone acts on ω1 receptors – hence no
eszopiclone muscle relaxant, anxiolytic and anticonvulsant effects noted. Also, slow wave sleep
is unaffected. Zaleplon occupies all 3 ω receptors. Zopiclone occurs as a racemic
mixture where only s-isomer is active (eszopiclone).

Z HYPNOTICS

Given their selectivity on BDZ-receptor subunits,

Z-drugs are less likely to impact sleep stages and
have a lower risk of tolerance and dependence
compared with benzodiazepine hypnotics

Zopiclone is the least selective of all Z-drugs

© SPMM Course 12
 Addiction pharmacology
DRUG MECHANISM
Alcohol Intercalates into the fluid cell membrane; decreases NMDA sensitivity; increases
GABA sensitivity; down-regulates calcium channels; up-regulates nicotine receptor
gated sodium channels.
Amphetamine Acts via releasing stored monoamines especially noradrenaline and dopamine.
Hence a central sympathomimetic.
Buprenorphine Partial opioid agonist. Lower doses – mild agonism; higher doses – antagonistic
effects.
Cannabis Acts via cannabinoid receptors. CB1 is central and activated by 11OH tetra hydro
cannabinoid. This inhibits GABA tone in the substantia nigra and other areas. May
be related to increased dopamine activity at reward centres. CB2 is peripheral
immune-related and seen in spleen and thymus. (Endogenous cannabinoids called
anandamides are derived from arachidonic acid; their function is unclear)
Clonidine, Presynaptic alpha 2 agonist – reduces central sympathetic tone. Opioid receptors on
lofexidine locus coeruleus projections reduce noradrenergic tone on long-term use. The cellular
machinery compensates via up-regulation of adenylate cyclase and maintains
sympathetic tone in a chronic user. Sudden withdrawal leads to increased adrenergic
firing rate (withdrawal symptoms); hence alpha 2 autoreceptor stimulation which
reduces central sympathetic tone helps in opioid withdrawal.
Dexfenfluramine Produce massive serotonin release from nerve endings. [Fen-Phen was an off-label
& Fenfluramine combination of fenfluramine and phentermine used for promoting weight loss but
fenfluramine (and dexfenfluramine) was withdrawn due to irreversible serotonergic
damage, valvular regurgitation and pulmonary fibrosis].
Disulfiram Inhibits aldehyde dehydrogenase. Leads to accumulation of acetaldehyde if alcohol
is consumed producing unpleasant reactions.
Levomethadyl Long-acting opioid agonist; potentially similar use as methadone. Withdrawn due to
acetate (LAAM) prolonged QT and torsades de pointes. Pure mu agonist.
LSD 5HT2A partial agonism producing hallucinogenic effect
MDMA Has 2 isomers  R(-) isomers produce LSD-like effects and the S(+) isomers have
amphetamine-like properties LSD-like action is mediated via serotonin release from
presynaptic neurons. In the long term, this can damage serotonergic tracts
irreversibly.
Methadone Opioid receptor agonist. Longer acting than heroin and orally available. Pure mu
agonist.
Naloxone Short-acting opioid mu antagonist
Naltrexone Longer acting opioid mu antagonist
Phencyclidine Noncompetitive NMDA antagonist similar to ketamine; also binds to sigma
receptors
Varenicline Varenicline (Champix) is a partial agonist at the α4β2 unit of nicotinic acetylcholine
receptor. It assists smoking cessation by relieving nicotine withdrawal symptoms
and reducing the rewarding properties of nicotine.

© SPMM Course 13
 Anti dementia drugs
DRUG MECHANISM
Donepezil, Cholinesterase Inhibitors. The act by inhibiting acetyl cholinesterase enzyme that
Galantamine, breaks down acetylcholine centrally. Rivastigmine inhibits both the acetyl and butyl-
Rivastigmine cholinesterase while donepezil and galantamine are acetyl specific. Galantamine also
has nicotine agonistic properties.
Memantine Blockade of N-methyl-d-aspartate (NMDA) glutamate receptors. Unlike ketamine,
which is a high-affinity noncompetitive blocker, memantine is a non-competitive
blocker with low affinity and binds only to actively open NMDA channels. Its
receptor dissociation rate is relatively fast, and so it does not accumulate and
interfere with normal NMDA activity.
 Acetylcholine is inactivated by both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
Cholinesterase inhibitors increase the amount of ACh available through inhibition of these enzymes.
 An acetylcholinesterase inhibitor can work at
either of two sites on AChE, an ionic subsite or
a catalytic esteratic subsite; Tacrine and RILUZOLE
donepezil act at the ionic while physostigmine
and rivastigmine act at the catalytic esteratic It is approved for use in Motor Neuron Disorder.
subsite. It is unclear whether this would help features of
 Tacrine, and to some extent rivastigmine are fronto-temporal dementia associated with MND. It
non-selective inhibitors of both AChE and prolongs survival by nearly 10% for more than a
BChE. year of treatment.
 CNS specific inhibition of AChE can occur with
Riluzole’s mechanism of action is via 1. Sodium
donepezil.
channel blockade 2. High-voltage calcium channel
 Binding to the AChE sites may be either
blockade 3. NMDA-glutamate receptor
reversible or irreversible, and may be
antagonism.
competitive or noncompetitive with
acetylcholine. It preferentially blocks the sodium channels in
 Galantamine is a competitive drug while damaged neurons, reducing calcium flow and
tacrine is a non-competitive inhibitor. indirectly preventing excitotoxic damage.
 AChE tetramer, G4, is located on the
presynaptic membranes while a monomer, G1,
is found on postsynaptic membranes. Although
G4 is decreased along with the neuronal loss in
AD, postsynaptic cholinergic receptor neurons and G1 ACh are not decreased significantly with AD or
aging. Rivastigmine and to some extent galantamine are highly selective for the postsynaptic G1
monomer while donepezil is not selective.

© SPMM Course 14
 Miscellaneous drugs
DRUG MECHANISM
Amantadine Used in Parkinsonism. It augments dopaminergic neurotransmission through an
unknown mechanism.
Dextroamphetamine Methylphenidate, dextroamphetamine, and amphetamine are indirectly acting
Methylphenidate sympathomimetics – induce the release of dopamine and Noradrenaline from
presynaptic neurons. Dextroamphetamine and methylphenidate are also weak
inhibitors of catecholamine reuptake and inhibitors of monoamine oxidase.
Atomoxetine Tricyclic like structure – phenylpropanolamine derivative. Selective inhibitor of
the presynaptic noradrenaline reuptake (NARI) similar to the antidepressant
reboxetine.
Benztropine, Anticholinergic drugs. Used in the treatment of EPSEs induced by antipsychotics.
Biperiden,
Orphenadrine,
Procyclidine
Carbidopa Carbidopa inhibits aromatic-L-amino-acid decarboxylase (DOPA Decarboxylase).
Administered together with l-dopa as Sinemet to reduce the peripheral conversion
of dopa to dopamine. Carbidopa cannot cross the blood-brain barrier.
Dantrolene Directly affects the formation of actin-myosin complexes in skeletal muscle
through ryanodine calcium channel inhibition.
Diphenhydramine, Antihistaminic drugs against central histamine H1 receptor. Cyproheptadine has
Hydroxyzine, both a potent antihistamine and serotonin 5-HT2 receptor antagonist properties.
Promethazine, All of these agents have some antimuscarinic properties too. Cyproheptadine was
Cyproheptadine. used as anti-anorexic agent, and also to treat delayed ejaculation associated with
SSRI use.
Levodopa Dopamine precursor used in parkinsonism; is combined with carbidopa to reduce
peripheral conversion to dopamine.
Modafinil Activates hypocretin-producing neurons possibly through alpha 2 and/or alpha-1
adrenergic agonist properties (alerting effects) or some noradrenaline reuptake
blocking effects; the stimulating effect of modafinil can be attenuated by prazosin.
Pemoline Indirectly stimulates dopaminergic activity - but it has little actual
sympathomimetic activity. A stimulant. Withdrawn due to hepatotoxicity.
Reserpine Depletes the stored dopamine and other monoamines from vesicles. Can lead to
depression and suicide.
Sildenafil Phosphodiesterase-5 Inhibitor.
Propranolol Beta-adrenergic antagonist. Lipophilic and so can pass blood brain barrier and can
. have central actions. Reduces akathisia and peripheral signs of sympathetic
overdrive seen in anxiety
Pramipexole, Apomorphine, pramipexole, and ropinirole are dopamine agonists - bind about 20
ropinirole, times more selectively to dopamine D3 than D2 receptors. Bromocriptine is less
apomorphine selective 2:1. Pergolide is most selective 5:1. Bromocriptine and pergolide are
ergotamine derivatives. Pramipexole is a nonergot dopamine agonist.
Apomorphine is structurally related to morphine and other opioids.
Sumatriptan 5HT1D and 1F agonist
Yohimbine It is an alpha 2 antagonist sometimes used in treating erectile dysfunction.
© SPMM Course 15
Lorcaserin, phentermine-topiramate combination, and naltrexone-bupropion combination are
novel FDA approved treatment approaches to tackle obesity. These drugs are promoted as
anorectic agents, similar to fenfluramine-phentermine combination ('fen-phen'), rimonabant, and
sibutramine (all of the latter 3 which fell out of favour due to various adverse effects). Lorcaserin
is a serotonin 2C receptor agonist; it is prescribed twice daily with an instruction to discontinue if
5% weight loss is not achieved by 12 weeks. The commonest side effect is a headache. In diabetic
patients, this drug can induce hypoglycaemia.

Phentermine is a sympathomimetic amine while topiramate is an antiepileptic drug. This

combination is used in an extended-release preparation. Side effects include paraesthesia,
dysgeusia and dizziness. Naltrexone is an opioid antagonist while bupropion is an aminoketone
antidepressant that promotes weight loss in subjects even as a standalone drug (so a prescription
of bupropion is not advised in those with a history of eating disorders).

© SPMM Course 16
4. Neurochemical effects of ECT
 Repeated subconvulsive electrical stimulation in animals reduces the seizure threshold –
this process is called kindling. ECT does NOT produce a kindling effect; in fact it protects
against kindling in animal studies. Thus, it can be termed an anti-kindling agent. As a
result, dosing may need to be increased over the course of treatment to achieve the same
seizure-inducing effect.
 Hippocampal neuronal loss occurs in kindling. But ECT results in neurogenesis in the rat.
This could be mediated by an increased expression of brain-derived neurotrophic factor
and its receptor,
 Blood–brain barrier permeability acutely increases following ECT but returns to baseline
within 24 hours
 Imaging studies show that ECT is not associated with markers of cell loss or damage e.g.
there is no change in myelin basic protein immunoreactivity or neuron-specific enolase in
serum. Tau protein, neurofilament and S-100 beta protein, markers of neuronal and glial
damage, are also unchanged after ECT.
 EEG shows delta and theta activity after applying ECT. This pattern returns to normal
after 3 months of the end of treatment.

Variables affected by ECT Changes

Neurotrophic factors Increase in NGF,BDNF, NF3.
Cell growth and synaptic Increased esp. In hippocampus
connectivity
Hormones Increased cortisol, prolactin, TSH coincides with good response.
TRH gene expression increased in animals. Vasopressin, ACTH,
oxytocin and opioid endorphins also increase consistently.
Neurotransmitters and 5-HT-, NA-, cholinergic-, glutaminergic- and GABAergic systems,
their receptors adenosine A1-receptor & 5-HT2A – all decrease in sensitivity.
Activation of DA transmission and stimulation of 5-HT in
hippocampus and amygdala.
 An increase in 5HT2 receptors are noted in rodents after applying electrical stimulation;
this change is opposite to the changes noted after administering antidepressant drugs. But
note that using a [18F] setoperone PET scan Yatham et al. (2010) have now demonstrated
that unlike in rodents, and similar to antidepressants, ECT reduces brain 5-HT2 receptors
in individuals with depression.
 ECT also reduces β noradrenergic receptors and increases noradrenaline turnover. Further
alpha 2 receptors are reduced after ECT, similar to antidepressants.

© SPMM Course 17
5. Psychopharmacogenetics
Psychopharmacogenetics focuses on how polymorphisms in genes affecting the mechanism of action of a
drug’s effect and/or metabolism (both peripheral and central) can influence an individual’s clinical
response to the drug, in terms of both therapeutic efficacy and adverse effects.

Drug Effect Biological substrate

Nicotine replacement Response to nicotine Dopamine receptor DRD2 variant

replacement (esp. in
women)

Clozapine Drug response No association with DRD2 variants

DRD3 Ser9Gly polymorphism – controversial
DRD4 polymorphisms– no correlation
5HT2A receptor polymorphism – associated
5HT2C receptor polymorphism – associated
5HT transporter linked polymorphic region
(5HTTLPR) – associated
CYP2D6 variations – overall efficacy not affected
Methylphenidate Poor response of Homozygosity for the 10-repeat allele at DAT1
ADHD symptoms.

Clozapine Agranulocytosis HLA loci variants

Typical antipsychotics No association with DRD2 variants

DRD3 Ser9Gly polymorphism – associated
DRD4 polymorphisms– no correlation
5HT2A receptor polymorphism - associated

Typical antipsychotics Extrapyramidal Poor metabolizers of CYP2D6

symptoms, postural
hypotension &
excess sedation

Typical antipsychotics Acute akathisia Polymorphisms in DRD3 and DRD2

Typical antipsychotics Tardive dyskinesia DAT polymorphism, 5-HTTLPR and the tryptophan
hydroxylase (TPH) polymorphism and to some extent
CYP1A2 polymorphisms

Typical antipsychotics Hyperprolactinaemia DRD2 polymorphism

& NMS

© SPMM Course 18
The serotonin transporter (5-HTT) protein acts as the primary mechanism for removing 5-HT
from the synaptic cleft. Two polymorphisms have been identified within the human 5-HTT, an
insertion/deletion polymorphism in the promoter region (5-HTTLPR) results in a short (s) and a
long (l) variant, and a VNTR polymorphism in intron.

© SPMM Course 19
6. Ethnopharmacology
Ethnicity is defined as a self-ascribed belongingness to a group with common geographical
origins, race, language, religion, etc., which transcends kinship and neighbourhood. Ethnic
categories retain a strong racial component. Race on the other hand is largely perceived by
appearance and attributed to biological and genetic traits. Culture is a shared system of concepts
or mental representations established by convention and reproduced by traditional transmission.

Differences exist in the placebo response, compliance, doctor-patient relationship, social stress
and health beliefs. The following are differences in the pharmacology of drugs administered.

Absorption and availability

 Caucasians appear to have lower plasma levels of tricyclic antidepressants and attain plasma
peaks later when compared with Asians (of Far Eastern ancestry as well as those from the
Indian subcontinent). These differences have been attributed to a greater incidence of slow
hydroxylation among Asians when compared with Caucasians
 Maximal haloperidol concentration in plasma after rapid tranquillisation is significantly high
for Asians than Caucasians (Lin & Finder, Am J Psychiatry 140:490-491, 1983).

Metabolism

 In the CYP system, variations in CYP2D6 are largely determined by genetic factors. (CYP2D6
metabolizes a number of antidepressants, antipsychotics, beta-adrenoceptor blockers, and
antiarrhythmic drugs). The CYP2D6 variation is called debrisoquine/sparteine polymorphism:
4 groups exist –
1. Poor metabolizers: develop side effects quickly. Caucasians - the highest rate of poor
metabolizers (nearly 7%). East Asians - lowest – 1%. These 7% Caucasians and 1% East
Asians lack this enzyme, and so are poor metabolizers of risperidone and tricyclics
2. Intermediate metabolizers: higher in Asians (most Asians fall into this group – hence
have more side effects though good drug efficacy)
3. Extensive metabolizers
4. Ultrarapid metabolizers: need high doses. 33% North Africans have multiple copies of
CYP2D6, and so are ultra-rapid metabolizers. They require higher doses of risperidone.
Only 5% Caucasians and 1% East Asians are ultra-rapid. 25% Indians may have this
variant.
 CYP2C19 enzyme participates in the metabolism of omeprazole, propranolol and
psychotropic drugs such as hexobarbital, diazepam, citalopram, imipramine, clomipramine,
sertraline and amitriptyline. The incidence of poor metabolizers of CYP2C19 substrates is

© SPMM Course 20
 much higher in Asians (15–30%) than in Caucasians (3–6%). CYP2C19 polymorphism is
mephenytoin related.
 Unlike CYP2D6, the variations in CYP3A4 often influenced by environmental (e.g. diet)
factors.
 Nearly 40% Asians and around 60% South American Native Indians lack Aldehyde
dehydrogenase enzyme in sufficient amounts to metabolise alcohol – this serves as a natural
deterrent in these communities.

Pharmacodynamics

The long form serotonin transporter polymorphism in Caucasians is associated with better SSRI
response and tolerance while the opposite is true in South East Asians. Low COMT variant is
seen in less than 20% of Asians and Africans, but nearly 50% of Caucasians show low variant.

Adverse effects

 A well-known example from general medicine is that of Isoniazid – East Asians are most
likely to be rapid acetylators and suffer from hepatotoxicity. But they have lesser peripheral
neuropathy seen in slow acetylators.
 Chinese people had higher levels of extrapyramidal side-effects with haloperidol, and their
blood levels were comparably high on equivalent dosages.
 On the administration of antipsychotics, Asian subjects were reported to produce greater
serum prolactin levels than Caucasian subjects. This remains statistically significant after
controlling for the difference in haloperidol concentrations, suggesting that the two groups
differ in their dopamine receptor-mediated response.
 A summary of some relevant ethnic effects is given below.

African Americans Asians

 Increased diagnosis of schizophrenia  It is best to start at half of the standard
but decreased diagnosis of depression dosage of all psychiatric medications
 Have more side effects with lithium,  Clozapine better effect in lower serum
tricyclics range, but higher incidence of
 Higher tardive dyskinesia with agranulocytosis
antipsychotics.  Taiwanese have lower required
 Better, rapid response to tricyclics and therapeutic level of lithium.
lorazepam, but poor response to  Metabolise TCA slowly.
fluoxetine.  Asians use herbal remedies more often
 More depot medications received by than others.
African Americans.

© SPMM Course 21
 Gender differences in psychopharmacology
 Antipsychotic response is shown to be superior in women
 In chronically ill population, men are found to require twice as high a dose as women for
effective maintenance.
 Women have higher antipsychotic plasma levels than men after receiving the same dose
of the drug.
 The enzyme CYP1A2 appears to be less active in women than in men, leading to relatively
higher blood concentrations of olanzapine and clozapine in women.
 The volume of distribution of lipophilic drugs, such as antipsychotics, is greater in
women than in men
 In women, the blood volume is smaller, but lipid compartments are larger. This prolongs
the half-life of antipsychotics in the body, leading to accumulation over time, a
phenomenon that becomes important when administering depot injections. After a
steady state is achieved, dosing intervals for women should be longer than for men.
 Acute dystonia, long thought to be more prevalent among men, has been shown now to
be more frequent in females at equivalent doses. Earlier clinical studies had not taken into
account the fact that young male patients were commonly given higher doses than
women.
 Pulmonary embolism (a rare problem seen with drugs that have an affinity for the
serotonin 5-HT2A receptor) and tardive dyskinesia appear to be more common in women.

© SPMM Course 22
 DISCLAIMER: This material is developed from various revision notes assembled while preparing
for MRCPsych exams. The content is periodically updated with excerpts from various
published sources including peer-reviewed journals, websites, patient information leaflets and
books. These sources are cited and acknowledged wherever possible; due to the structure of
this material, acknowledgements have not been possible for every passage/fact that is
common knowledge in psychiatry. We do not check the accuracy of drug related
information using external sources; no part of these notes should be used as prescribing
information.

Notes prepared using excerpts from:

 Appleby, L. et al (Ed) Postgraduate psychiatry: Clinical and scientific foundations. 2nd ed. Page 65
 Bhugra, D & Bhui, K. Ethnic and cultural factors in psychopharmacology. Advances in Psychiatric
Treatment (1999), vol. 5, pp. 89-95
 http://www.dlc-ma.org/Resources/Health/Ethnic%20Psychopharmacology.html
 Kaplan & Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th Edition.
Lippincott Williams & Wilkins 2007
 Poolsup et al. Pharmacogenetics and psychopharmacology. Journal of Clinical Pharmacy and
Therapeutics (2000) 25, 197-220
 Seeman, M. (2004) Gender differences in the prescribing of antipsychotic drugs. Am J Psychiatry
161:1324-1333.
 Shiloh, R., Nutt, D. & Weizman, A. (2000). Atlas of psychiatric pharmacotherapy. Martin Dunitz,
London.
 Stahl, S. M. Essential psychopharmacology : neuroscientific basis and practical application 2nd ed
Cambridge University Press 2000
 Tsapakis, E. M., Basu, A. & Aitchison, K. J. (2004) Clinical relevance of discoveries in
psychopharmacogenetics. Adv Psychiatr Treat, 10, 455-465.
 Yudkin, P. (2004) Effectiveness of nicotine patches in relation to genotype in women versus men:
randomised controlled trial. BMJ, 328, 989 -990.
 Maixner D& Taylor MA. The efficacy and safety of electroconvulsive therapy. In Effective
Treatments in Psychiatry. ed. Tyrer P. Cambridge University Press, 2008.
 Wahlund, B., & von Rosen, D. (2003). ECT of major depressed patients in relation to biological and
clinical variables: a brief overview. Neuropsychopharmacology: official publication of the American
College of Neuropsychopharmacology, 28, S21-6.
 Yatham, L. N., Liddle, P. F., Lam, R. W., Zis, A. P., Stoessl, A. J., Sossi, V., ... & Ruth, T. J. (2010).
Effect of electroconvulsive therapy on brain 5-HT2 receptors in major depression. The British
Journal of Psychiatry, 196(6), 474-479.

© SPMM Course 23
  

   

Adverse  Drug  Effects  

Paper  A   Syllabic  content  4.4  
 
© SPMM Course

We claim copyright for our own text material, productions and adaptations. We claim no
rights to Images/Figures with CC-BY-SA license if they are used in this material.
©  SPMM  Course   1  
1. Types of adverse reactions
 

Type  of  reaction   Mnemonics   Features  

A:      dose-­‐‑related   Augmented   e.g.,  Lithium  toxicity  –  ataxia,  coarse  tremors,  vomiting.  
B:    non-­‐‑dose   Bizarre   Idiosyncratic  e.g.  malignant  hyperthermia,  or  lamotrigine  
related   induced  Steven  Johnson  syndrome  
C:      dose  and  time  
Continuous   Related  to  cumulative  drug  use—e.g.  long  term  lithium  use  
related   use   and  renal  damage  
D:    delayed  effect  
Delayed   Not  due  to  dose  per  se  but  due  to  the  length  of  use  of  a  
medication  e.g.  tardive  dyskinesia  in  some  cases.  
E:      Withdrawal   End  of  use   Related  to  abrupt  discontinuation  e.g.  SSRI  discontinuation  
reaction,  opioid  withdrawal  effects,  etc.  
¬ Tolerance  is  defined  as  the  need  to  use  increased  doses  of  a  drug  to  maintain  a  clinical  effect.  
Tolerance  is  seen  for  both  therapeutic  effects  and  side  effect.  This  may  be  due  to  decreased  
sensitivity  of  the  target  receptors  due  to  down-­‐‑regulation  (decrease  in  numbers  in  case  of  
agonists),  up-­‐‑regulation  (increase  in  number  of  receptors  in  case  of  antagonists),  or  reduced  
responsivity  without  alterations  in  receptor  numbers.    
¬ Drugs  with  similar  pharmacological  actions  can  exhibit  cross-­‐‑tolerance  e.g.  benzodiazepines  
and  barbiturates.  
¬ Sensitization  (aka  reverse  tolerance)  manifests  when  sensitivity  to  a  drug  effect  increases  
over  time  i.e.  the  same  dose  typically  produces  more  pronounced  effects  as  treatment  
progresses.  This  is  reported  with  the  street  use  of  cocaine.  

Note  that  up  or  down-­‐‑regulation  can  be  a  mechanism  of  therapeutic  effect  e.g.  in  case  of  SSRIs,  the  5HT1A  
autoreceptors  in  somatodendritic  zones  undergo  downregulation  secondary  to  increased  serotonin  
availability  in  the  vicinity  when  reuptake  is  blocked;  this  in  turn  leads  to  an  increase  in  serotonergic  tone  
of  the  neurons.  

¬ Withdrawal:  When  drugs  are  administered  for  a  reasonable  period  of  time,  a  physiological  
adaptation  develops  which  on  withdrawal  of  the  drug  can  get  disturbed  and  leads  to  
withdrawal  symptoms.  Abrupt  withdrawal  of  treatment  especially  for  an  agent  with  shorter  
elimination  half-­‐‑life  leads  to  clinically  significant  withdrawal  symptoms.  Hypnotics,  opiates,  
barbiturates,  SSRIs,  Venlafaxine  are  some  of  the  drugs  associated  with  discontinuation  
reaction  or  withdrawal  symptoms.  The  variables  influencing  withdrawal  symptoms  are  listed  
below:  

©  SPMM  Course   2  
 1. Half  life   Methadone  has  less  withdrawal  than  heroin  as  methadone  has  longer  
t1/2  
2. Range  of  action   Paroxetine  has  anticholinergic  properties;  withdrawal  causes  cholinergic  
rebound=d  symptoms  
3. Enzyme   Paroxetine  inhibits  its  own  metabolism  via  CYP2D6.  So  withdrawal  
interference   leads  to  loss  of  inhibition  à  excessive  paroxetine  breakdown  à  sudden  
steep  drop  in  levels  à  withdrawal  symptoms  
4. Active  metabolites   Fluoxetine  has  active  metabolite  norfluoxetine  with  long  half-­‐‑life  –  
hence  it  produces  fewer  withdrawal  symptoms  
5. Rate  of  withdrawal   Slow,  gradual  tapering  is  the  best.  10%  dose  reduction  every  2  weeks  is  
advocated  for  benzodiazepines.  
6. Co-­‐‑prescribed  drug   Prescribing  an  enzyme  inducer  can  reduce  the  effects  of  a  drug  acutely  if  
effects   its  metabolism  depends  on  the  induced  enzyme;  Similarly  prescribing  
an  antagonist  can  precipitate  withdrawal  symptoms.  This  is  the  
rationale  for  leaving  at  least  72  hours  before  prescribing  naltrexone  for  
an  opioid  detoxified  patient.  
7. Receptor  profile   Full  agonists  on  withdrawal  produce  more  discontinuation  reactions  
than  partial  agonists  e.g.  clonazepam  produces  lesser  benzodiazepine  
withdrawal  symptoms.  
 

Sustained-­‐‑release  preparations  influence  the  absorption  kinetics–  not  elimination  kinetics,  hence  
upon  withdrawal,  the  drop  in  plasma  levels  occur  at  same  rate  in  both  XL  and  plain  preparations;  
e.g.  venlafaxine  XL  has  similar  discontinuation  reaction  as  venlafaxine  normal  release.  But  depot  
preparations  have  less  withdrawal  propensity  that  corresponding  oral  drugs.  

©  SPMM  Course   3  
2. Mechanism of adverse effects
Side  effect   Receptor  
Agitation   α  2  blockade,  5HT2A/2C  stimulation,  DRI  
Akathisia   D2  blockade,  5HT2A  stimulation  (hence  some  data  on  
mirtazapine,  5HT2A  antagonist,  reducing  akathisia)  
Delirium   Anticholinergic  effect  (antimuscarinic)  
EPSE   D2  blockade  reduces  with  5HT2A  antagonism  
Hyperthermia   Antimuscarinic  action,  in  serotonin  syndrome,  may  be  mediated  
via  5HT2A/2C  
Insomnia   α  1  stimulation,  5HT2Astimulation  (hence  SSRIs  cause  insomnia)  
Amnesia  (memory  defects)   Anticholinergic  effects,  GABAA  stimulation  
Hyperprolactinaemia   D2  blockade,  5HT1A  stimulation  
Disrupted  slow  wave  sleep     SWS  is  maintained  by  5HT2A  inhibition;  5HT2A  stimulation  
disrupts  sleep  architecture  
Sweating   Cholinergic  effect  and  increases  with  noradrenaline  reuptake  
inhibition  
Postural  hypotension   α  1  antagonism  
Appetite  loss   5HT2A  stimulation  (antihistaminics  can  increase  appetite)  
GI  discomfort,  nausea,   5HT3  stimulation  
vomiting  
Weight  gain   5HT2C  antagonism  and  antihistaminic  effects  
Anticholinergic  effects   Blurred  vision,  exacerbation  of  narrow-­‐‑angle  glaucoma,  
delirium,  and  photophobia  due  to  mydriasis,  dry  secretions,  
constipation,  tachycardia,  decreased  sweating,  urinary  retention  
and  hyperthermia.  
Anorgasmia   α  1  antagonism,  5HT2A/2C  stimulation  (delayed  ejaculation  in  
SSRIs).  Retrograde  ejaculation  due  to  α  1  block,  anticholinergic  
and  antihistaminic  effects.  
Tardive  dyskinesia   Supersensitivity  of  dopamine  receptors,  which  develops  
because  of  prolonged  therapy  with  dopamine-­‐‑blocking  drugs  
Impotence   α  2  blockade,  5HT2A/2C  stimulation.  5HT2A/2c  stimulation  can  
also  reduce  libido.  
Priapism   α  1  blockade  
Obsessions   5HT1D  stimulation  can  induce  obsessions.  5HT1A  and  2A  
stimulation  reduce  OCD.  
Pathological  gambling   Habituation  of  dopamine  receptors  on  repeated  use  of  
dopamine  agonists  (e.g.  levodopa)  leading  to  dopamine  
dysregulation  syndrome  (DDS)  
 

©  SPMM  Course   4  
Weight  gain:  No  single  mechanism  can  explain  the  complex  metabolic  phenomenon  of  weight  
gain.  Antihistaminic  effects,  5HT2A/2C  antagonism,  insulin  resistance  (valproate  and  olanzapine)  
are  noted.  Genetic  factors  seem  to  involve  5-­‐‑HT2C  receptor.  Drugs  with  a  strong  5-­‐‑HT2C  affinity  
will  have  a  greater  impact  on  body  weight  of  patients  with  a  specific  variant  of  polymorphism  of  
the  5-­‐‑HT2C  receptor  promoter  regions.  Low-­‐‑potency  antipsychotics  (chlorpromazine  and  
thioridazine)  produce  more  weight  gain  and  sedation  than  high-­‐‑potency  agents  (haloperidol  and  
fluphenazine).    

©  SPMM  Course   5  
3. Antipsychotics - adverse effects
Extrapyramidal effects
Acute  extrapyramidal  syndromes  such  as  acute  dystonia,  akathisia  and  parkinsonism  are  noted  
with  high  potency  drugs  more  than  low-­‐‑potency  drugs.  Tardive  dyskinesia  and  dystonia,  
perioral  tremor  (rabbit  syndrome)  are  chronic  late  side  effects.    

PET  studies  have  indicated  that  60%–80%  occupation  of  D2  receptors  is  associated  with  
antipsychotic  efficacy.  Higher  occupancy  levels  are  associated  with  an  increased  risk  of  acute  
extrapyramidal  symptoms  as  well  as  hyperprolactinemia  from  the  blocking  of  D2  receptors  on  
anterior  pituitary  mammotrophic  cells  that  normally  are  tonically  inhibited  by  dopamine  
produced  in  the  hypothalamic  arcuate  nucleus.  

Antipsychotic  drugs  which  have  the  propensity  to  induce  Parkinsonism  (trifluoperazine,  
chlorpromazine,  raclopride,  haloperidol,  fluphenazine,  risperidone)  bind  more  tightly  than  the  
endogenous  ligand  dopamine  to  D2,  while  the  drugs  with  low  Parkinsonism-­‐‑inducing  
propensity  (quetiapine,    clozapine  etc)  bind  more  loosely  than  dopamine  to  D2  receptors.  
Compared  to  the  tightly  bound  antipsychotic  drugs,  the  loosely  bound  ones  are  weaker  in  
potency  and  thus  require  higher  doses  to  be  clinically  effective,  but  can  be  titrated  faster.  These  
loosely-­‐‑bound  drugs  may  also  dissociate  from  the  D2  receptor  more  rapidly  and  could  lead  to  
clinical  relapse  somewhat  earlier  than  the  traditional  tightly  bound  antipsychotic  drugs  (though  
ths  does  not  seem  to  be  the  case  for  clozapine).  

Drug-­‐‑induced  parkinsonism  is  seen  in  15-­‐‑20%  of  patients  treated  with  antipsychotics,  seen  
within  90  days  of  treatment  (5  to  90)  and  is  characterized  by  muscle  stiffness,  cogwheel  rigidity,  
shuffling  gait,  stooped  posture,  and  drooling.  The  pill-­‐‑rolling  tremor  of  idiopathic  Parkinsonism  
is  not  seen  in  drug-­‐‑induced  EPSEs  -­‐‑  but  a  regular  coarse  tremor  is  seen.    Elderly  and  female  are  
under  higher  risk.  Low  potency  drugs  and  those  with  higher  anticholinergic  effects  cause  less  
EPSEs.  It  is  thought  that  higher  than  80%  receptor  occupancy  of  brain  D2  by  antipsychotics  can  
cause  EPSEs.  Atypical  drugs  cause  low  EPSEs  probably  due  to  anticholinergic  effects,  HT2A  
antagonism  or  less  avidity  of  binding  i.e.  hit  and  run  profile  especially  for  clozapine  and  
quetiapine.  Anticholinergics  can  be  used  for  short  period  of  up  to  6  weeks  to  treat  the  
parkinsonian  symptoms.  As  tolerance  can  develop  for  EPSE,  the  anticholinergics  should  be  
withdrawn  after  4  to  6  weeks;  also,  longer  chronic  anticholinergic  prescription  increases  the  risk  
of  TD.    

The  rabbit  syndrome  is  a  tremor  affecting  the  lips  and  perioral  muscles  and  occurs  late  in  the  
course  of  treatment.  

©  SPMM  Course   6  
Dystonias  are  brief  or  prolonged  contractions  of  specific  groups  of  muscles  resulting  in  
symptoms  such  as  oculogyric  crises,  tongue  protrusion,  trismus,  torticollis,  blepharospasm.  
Rarely  pharyngeal  dystonia  can  occur  resulting  in  dysarthria,  dysphagia,  and  even  respiratory  
choking.  Dystonias  occur  early  in  treatment  course  and  can  reduce  compliance.  It  is  often  seen  in  
younger  men  receiving  a  high  dose  of  high-­‐‑potency  medications.  It  is  more  common  with  IM  
administration.  Dopaminergic  hyperactivity  in  the  basal  ganglia  occurring  when  plasma  levels  
fluctuate  may  be  the  mechanism  behind  dystonias.  Dystonias  show  spontaneous  fluctuations,  
response  to  reassurance  and  to  anticholinergic  drugs.    

Akathisia  includes  both  subjective  and  objective  -­‐‑  feelings  and  signs  of  restlessness.  (Possibly  due  
to  higher  D2  occupancy  in  striatum).  Patients  may  exhibit  inability  to  relax,  jitteriness,  pacing,  
rocking  with  alternation  of  sitting  and  standing.  Akathisia  
can  be  caused  by  not  only  neuroleptics  but  also   RISK  FACTORS  FOR  TARDIVE  
antidepressants  and  sympathomimetics.  Dose  reduction,   DYSKINESIA  
changing  the  drug  or  adding  beta  blocker/anticholinergic  
! Female  gender  
drugs  or  benzodiazepines  or  cyproheptadine  are   ! Elderly  
recommended.  Akathisia  may  be  associated  with  an  increase   ! Diabetics  
! Previous  brain  damage  
in  absconsion,  suicides  and  violence  if  left  undiagnosed  and  
! Affective  illness  rather  than  pure  
untreated  in  some  cases.     psychotic  disorder  
! Children  
Tardive  dyskinesia  is  a  late  side  effect  occurring  in  nearly  25%  
! Learning  disabled  
patients  usually  only  after  (at  least  6  months)  1  –  2  years  of   ! Afro-­‐‑Caribbean  race  
treatment.  It  presents  as  abnormal,  involuntary,  irregular   ! Long  term  co-­‐‑prescription  of  
choreoathetotic  movements  of  the  muscles  of  the  head,  limbs,   anticholinergics  
! Frequent  drug  holidays  –  will  lead  
and  trunk.  Perioral  movements  are  the  most  common.  In  
to  high  dose  prescription  with  each  
some  serious  cases,  patients  may  have  breathing  and   relapse  
swallowing  muscles  involved  leading  to  aerophagia  and  
 
grunting.  TD  is  exacerbated  by  stress  but  is  absent  during  sleep.  The  absence  of  insight  about  the  
movement  disorder  is  striking  in  patients.  

Most  cases  remit  spontaneously.  Elderly  have  a  poor  spontaneous  resolution.  Tardive  dyskinesia  
is  less  likely  to  remit  in  elderly  patients  than  in  young  patients,  however.  Clozapine  can  reduce  
the  risk  and  also  treat  TD.  Dose  reduction,  withdrawal  of  the  drug,  switch  to  newer  atypicals  or  
adding  clonazepam  can  be  considered.    

Neuroleptic  Malignant  Syndrome  

¬ Can  occur  at  any  time  during  treatment  with  neuroleptics  

©  SPMM  Course   7  
¬ Consists  of  the  tetrad  of  extreme  hyperthermia,  severe  muscular  rigidity  and  confusion,  and  
autonomic  fluctuations  (BP  and  pulse  rate).  Patients  may  be  akinetic  and  mute.  
¬ Increased  WBC  count,  creatinine  phosphokinase,  liver  enzymes,  plasma  myoglobin,  and  
myoglobinuria  are  noted.  
¬ Subacute  onset  in  24  to  72  hours,  and  if  untreated  lasts  10  to  14  days.    
¬ More  common  in  young  men,  after  agitation  and  when  using  high  potency  drugs  especially  in  
rapid  tranquillisation  situations.  Dopaminergic  drugs  on  withdrawal  can  produce  NMS.  
¬ The  mechanism  may  be  related  to  dopamine  blockade  or  hypothalamic  sympathetic  
dysregulation.  
¬ The  mortality  rate  is  around  20-­‐‑30%  if  untreated  and  higher  if  depot  is  used.  
¬ Symptomatic  management  of  vital  signs  instability,  fluid  replacement  and  prevention  of  renal  
failure  secondary  to  myoglobinuria  and  prevention  of  aspiration  pneumonia  are  main  
treatment  methods  after  immediate  stopping  of  offending  psychotropic.  Dantrolene,  
Bromocriptine  or  amantadine  can  be  used.  Low  potency  or  atypical  must  be  used  following  
recovery  for  an  antipsychotic  prescription.    

Agranulocytosis
Occurs  in  around  1  per  100  patients  on  clozapine.  This  is  15  to  30  times  higher  than  the  risk  
associated  with  phenothiazines  and  olanzapine.  The  maximum  risk  is  between  4  and  18  weeks,  
and  after  a  year  the  risk  is  same  as  with  phenothiazines.  

Weekly  monitoring  of  the  white  cell  count  is  required  for  26  weeks  in  most  countries,  with  the  
frequency  decreasing  to  biweekly  or  monthly  thereafter.  
Many  side  effects  of  clozapine  such  as  
In  the  UK,  yellow,  green  and  red  signals  are  used  in  WBC  
salivation,  sedation,  and  weight  gain,  
monitoring.  When  a  result  is  red,  clozapine  must  be  
fatigue  and  lowering  of  seizure  threshold  
stopped  and  never  tried  again.  If  yellow,  then  monitoring   are  dose  related.  But  agranulocytosis  
frequency  must  be  increased  until  a  green  signal  is   and  myocarditis  can  occur  at  any  dose.  
obtained  again.    

Benign  neutropenia  is  common  especially  in  south  Asian  and  Afro-­‐‑Caribbean  race.  Lithium  can  
increase  WBC  count  albeit  transiently.  Some  anecdotal  evidence  supports  using  lithium  in  
patients  with  benign  ethnic  neutropenia  in  preparation  for  clozapine  use.  But  lithium  and  
clozapine  together  can  increase  the  risk  of  seizures  and  confusion.  

Clozapine,  when  combined  with  carbamazepine,  phenytoin,  propylthiouracil,  sulfonamides,  and  

captopril,  can  increase  the  risk  of  agranulocytosis  further.    

Paroxetine  may  precipitate  clozapine-­‐‑associated  neutropenia.    

©  SPMM  Course   8  
Transient  leucopenia  can  occur  with  typical  neuroleptics.  But  agranulocytosis  is  the  rare  effect.  

Sexual dysfunction:
Increased  dopaminergic  transmission  can  enhance  sexual  arousal  and  penile  erection.  
Hyperprolactinaemia  can  result  in  loss  of  sexual  arousal  and  erectile  dysfunction  in  men;  
amenorrhoea,  reduced  sexual  desire  and  hirsutism  in  women.  Antipsychotics  reduce  sexual  
performance  both  directly  by  reducing  dopaminergic  transmission  and  indirectly  through  
inducing  hyperprolactinaemia.  43%  of  those  taking  antipsychotics  report  sexual  dysfunction  at  
some  point,  not  all  of  this  attributable  to  the  drug.    

Neuroleptic  agents  commonly  cause  ejaculatory  problems.  Total  inhibition  of  ejaculation  (dry-­‐‑
ejaculation),  reduced  ejaculatory  volume  and  ‘retrograde’  ejaculation  are  the  various  effects  
associated  with  conventional  neuroleptics  and  also  clozapine,  risperidone  and  olanzapine.  

Drug-­‐‑induced  priapism  is  related  to  simultaneous  α1-­‐‑adrenergic  blockade  and  anticholinergic  
activity.  The  most  commonly  reported  associations  are  with  antipsychotic  drugs  (20%  of  all  
reported  priapisms)  followed  by  trazodone.  Antipsychotics  implicated  in  this  problem  include  
risperidone,  chlorpromazine  clozapine,  olanzapine  and  thioridazine.  The  risk  is  dose-­‐‑
independent  and  can  occur  at  any  time  during  the  course  of  treatment  (duration-­‐‑independent).  
Priapism  is  a  urological  emergency  and  can  lead  to  permanent  impotence  if  untreated.    

Dopaminergic  agonist  bromocriptine  is  used  to  treat  sexual  dysfunction  in  men  that  is  associated  
with  hyperprolactinaemia.    

Other side effects

¬ Seizure  threshold  is  lowered  especially  by  low  potency  antipsychotics.  Molindone  may  be  
the  least  epileptogenic.  This  is  a  dose-­‐‑dependent  effect.  
¬ Chlorpromazine  is  the  most  sedating  typical  antipsychotic  –  mediated  by  H1  
antihistaminic  action  –  tolerance  usually  develops  for  this  effect.    
¬ Low  potency  agents  can  also  cause  anticholinergic  syndrome  (see  TCAs).  
¬ Neuroleptics  can  decrease  cardiac  contractility,  increase  circulating  levels  of  
catecholamines,  and  prolong  atrial  and  ventricular  conduction  time.  Low-­‐‑potency  drugs  
are  more  cardiotoxic  than  high-­‐‑potency  drugs.  ECG  shows  QT  and  PR  prolongation,  
blunting  of  the  T  waves,  and  ST  depression.  Thioridazine  and  droperidol,  in  particular,  
can  cause  torsade  de  pointes.    
¬ Antipsychotic  related  sudden  death  may  be  due  to  cardiac  arrhythmias  or  even  seizures  
asphyxiation  or  malignant  hyperthermia.  Drugs  causing  QT  prolongation  are  associated  
with  more  sudden  deaths  (e.g.  thioridazine).  Postural  hypotension  is  most  common  with  

©  SPMM  Course   9  
 low-­‐‑potency  drugs,  and  tolerance  develops  soon.  Patients  should  avoid  all  caffeine  and  
alcohol,  drink  plenty  of  fluid  and  liberal  salt  in  food.    
¬ Low-­‐‑potency  drugs  can  cause  weight  gain  but  not  as  much  as  is  atypical  drugs.    
¬ Nearly  50%  of  men  taking  antipsychotics  report  ejaculatory  and  erectile  disturbances.  
Thioridazine  is  particularly  associated  with  decreased  libido  and  retrograde  ejaculation  in  
men.    
¬ Allergic  dermatitis  and  photosensitivity  can  occur  with  low-­‐‑potency  agents.  Long-­‐‑term  
chlorpromazine  use  can  cause  blue-­‐‑gray  discoloration  of  skin  areas  exposed  to  sunlight.  
This  is  reversible.  Irreversible  retinal  pigmentation  is  associated  with  the  use  of  high  dose  
thioridazine  (above  1000  mg  a  day).  An  early  symptom  of  the  side  effect  can  sometimes  be  
nocturnal  confusion  associatd  to  difficulty  with  night  vision.  This  pigmentation  is  
irreversible  and  can  progress  even  after  stopping  thioridazine.  Chlorpromazine  related  
pigmentation  of  the  anterior  lens  and  the  posterior  cornea  is  seen  as  whitish  brown  stellate  
granular  deposits  noted  in  slit  lamp  –  this  is  benign  and  not  vision  impairing.  This  can  
resolve  gradually  unlike  thioridazine  related  retinal  damage.    
¬ Chlorpromazine  is  associated  with  cases  of  obstructive  or  cholestatic  jaundice  especially  
in  the  first  month  of  treatment  associated  with  rash  and  eosinophilia.  Immediate  
discontinuation  and  avoidance  of  rechallenge  are  advised.  
¬ Haloperidol  isone  of  the  safest  typical  antipsychotics  in  overdose.  After  an  overdose,  the  
electroencephalogram  (EEG)  shows  diffuse  slowing  and  low  voltage.    
¬ QT  prolongation:  Prolongation  of  the  QT  interval  is  mediated  by  blockade  of  the  rapid  
component  of  the  delayed  rectifier  potassium  current  (IKr)  responsible  for  repolarisation  
of  cardiac  Purkinje  cells  and  myocardial  cells.  Many  drugs,  including  certain  
antipsychotics  and  antidepressants,  bind  to  this  potassium  channel  and  thereby  decrease  
the  outward  movement  of  potassium.  Some  antipsychotics  –  especially  droperidol,  
pimozide,  sertindole  and  thioridazine  –  have  a  greater  capacity  than  others  to  cause  IKr  
blockade.  
¬ InAdvertent  IntraVascular  injection  event  (IAIV)  or  postinjection  delirium  sedation  
syndrome  (PDSS)  has  been  described  after  olanzapine  pamoate  (long-­‐‑acting  depot)  
injections.    Within  20  min  to  3  hours  of  injection,  patients  present  with  sedation,  confusion,  
dizziness,  altered  speech/dysarthria,  and  somnolence,  symptoms  that  are  consistent  with  
those  reported  in  the  case  of  oral  olanzapine  overdose.  Rarely  deep  coma  may  ensue.    
Medical  hospitalization  and  supportive  medical  care  are  usually  sufficient    to  ensure  full  
recovery  (usually  within  3–72  hours).  This  effect  is  linked  to  accidental  punctures  of  a  
vessel  or  injections  into  a  rich  capillary  bed  during  administration,  leading  to  quick  
dissolution  and  release  of  free  olanzapine.  Eli  Lilly  has  recommended  a  postinjection  

©  SPMM  Course   10  
 observation  period  of  at  least  1  -­‐‑  3  hours  in  a  healthcare  facility  and  to  avoid  driving  or  
operating  heavy  machinery  in  the  24  hours  after  injection.  

Metabolic syndrome
Metabolic  syndrome  is  a  cluster  of  disorders  comprising  obesity  (central  and  abdominal),  
dyslipidaemias,  glucose  intolerance,  insulin  resistance  (or  hyperinsulinaemia)  and  hypertension.  
It  is  highly  predictive  of  type  2  diabetes  mellitus  and  cardiovascular  disease.  

World  Health  Organization  criteria  for  metabolic  syndrome

• Insulin  resistance  and/or  impaired  fasting  glucose  and/or  impaired  glucose  tolerance  
AND  two  or  more  of  the  following:  
• Waist  -­‐‑  hip  ratio  >0.90  (men),  >0.85  (women)  OR  body  mass  index  30  kg/m2;  
• Triglyceride  level  1.7  mmol/l  OR  high-­‐‑density  lipoprotein  <0.9  mml/l  (men),  <1.0  mmol/l  
(women);  
• Blood  pressure  140/90  mmHg  (or  treated  hypertension);  
• Microalbuminuria.  (This  is  not  presented  in  some  revised  criteria  for  metabolic  
syndrome)

¬ Diabetes  Mellitus  is  twice  as  prevalent  among  schizophrenia  cohorts  than  in  the  general  
population  
¬ Unaffected  first-­‐‑degree  relatives  of  patients  with  schizophrenia  share  a  propensity  for  type  
2  diabetes  mellitus  (19-­‐‑30%);  this  suggests  a  genetic  association  between  these  two  
disorders    

Olanzapine  /   aripiprazole/  
MOST clozapine quetiapine risperidone ziprasidone lurasidone LEAST

¬ Schizophrenia  patients  have  3  times  greater  intra-­‐‑abdominal  fat  (IAF)  than  the  control  
group,  increasing  the  risk  for  metabolic  syndrome.  
¬ In  the  pre-­‐‑antipsychotic  era  over  15%  of  drug-­‐‑naïve  individuals  with  first-­‐‑episode  
schizophrenia  had  impaired  fasting  glucose  levels,  hyperinsulinaemia  and  high  levels  of  
cortisol.    
¬ Both  typicals  and  atypicals  increase  the  risk  of  metabolic  syndrome  in  schizophrenia  
manifold.  But  antipsychotics  cannot  explain  all  the  metabolic  dysfunctions  noted  in  
schizophrenia.  
¬ The  frequency  of  metabolic  syndrome  was  2-­‐‑4  times  higher  in  a  group  of  people  with  
schizophrenia  treated  with  either  typical  or  atypical  antipsychotics.  

©  SPMM  Course   11  
 ¬ In  Clinical  Antipsychotic  Trials  of  Intervention  Effectiveness  (CATIE)  Schizophrenia  Trial  
baseline  data  (n  =  689),  the  metabolic  syndrome  was  prevalent  in    51.6%  of  female  patients  
and  36.0%  of  male  patients.    
¬ Females  with  schizophrenia  have  a  higher  risk  than  males  with  schizophrenia  when  
compared  with  a  reference  population.  
¬ Mean  weight  increases  during  the  first  year  of  therapy    
o 12  to  14lb  for  clozapine  (5  to  6  kg)    
o 15  to  26lb  for  olanzapine  (7  to  12kg)  
o 6  to  12lb  for  quetiapine  (2.5  to  5kg)  
o Up  to  5lb  for  risperidone  (2  to  2.5kg)  
o Less  than  2lb  for  Ziprasidone  and  aripiprazole    

For  patients  with  schizophrenia,  the  best-­‐‑studied  options  for  weight  control  include  diet  and  
exercise.  But  controlled  behavioral  programs  for  weight  reduction  in  schizophrenia  have  high  
dropout  rates  and  are  not  always  accessible.  Switch  to  relatively  weight  neutral  drugs  can  be  
considered  in  resistant  cases.  

CATIE  summary  

¬ CATIE  stands  for  Clinical  Antipsychotic  Trials  of  Intervention  Effectiveness.  

¬ The  study  design  was  double-­‐‑blind  pragmatic  RCT.  
¬ 1493  patients  with  chronic  schizophrenia  (mean  duration  of  illness  =  14  years),  57  sites,  2001  to  2004  
¬ Olanzapine,  quetiapine,  Risperidone,  ziprasidone  (added  later  in  the  trial),  perphenazine  
¬ Primary  outcome  is  a  ‘real-­‐‑world’  measure  –  discontinuation  for  any  reason,  either  patient-­‐‑initiated  or  
physician  initiated  
¬ 76%  power  to  detect  12%  difference  in  primary  outcome  
¬ Irrespective  of  the  prescribed  drug  –  74%  discontinued  treatment  in  18  months  (surprisingly  high  despite  
naturalistic  design).  The  median  time  to  stop  was  4.6  months.    
¬ Olanzapine  had  lowest  discontinuation  rate  (still  64%)  –  but  highest  side  effect  burden.  64%  discontinued  
olanzapine;  75%,  perphenazine;  82%,  quetiapine;  74%,  risperidone;  and  79%,  ziprasidone.  
¬ Olanzapine  caused  most  weight  gain  while  quetiapine  caused  most  anticholinergic  symptoms;  perphenazine  
had  highest  EPSE  related  discontinuation.  
¬ Those  who  did  not  respond  after  18  months  (those  who  discontinued  for  the  ineffectiveness  of  therapy)  were  
re-­‐‑randomised  in  phase  2  trial  (n=99),  and  Clozapine  was  compared  to  other  atypical  agents  (efficacy  
pathway).  Clozapine  had  lowest  discontinuation  rate  –  median  at  10  months.  This  time-­‐‑to-­‐‑discontinuation  
was  nearly  3  times  longer  than  time-­‐‑to-­‐‑discontinuation  with  the  other  SGAs.  Quetiapine  had  comparatively  
less  EPSEs.  
¬ As  a  part  of  the  phase  2  CATIE  study  (tolerance  pathway)  those  who  terminated  phase  1  for  ‘‘intolerable  side  
effects’’  (444  volunteers)  were  tested  with  olanzapine,  risperidone,  quetiapine,  or  ziprasidone.  Of  these  
treatments,  olanzapine  and  risperidone  had  equivalent  effectiveness,  and  both  were  better  than  quetiapine  or  
ziprasidone  by  significant  but  modest  margins.    
¬ CATIE  Controversies    
o Quite  complicated  study  design  and  many  outcomes  were  analysed  from  the  dataset.  
o Decisions  to  add  ziprasidone  to  the  protocol  was  made  after  recruitment  began    
o Perphenazine  was  used  only  in  one  randomized  phase  (phase  1)  of  the  study  generating  controversy.    

©  SPMM  Course   12  
 o The  decision  to  use  double-­‐‑blinded  treatments  decreased  the  resemblance  of  the  study  procedures  to  
those  of  routine  clinical  care  
§ The  mean  doses  used  remain  controversial  though  it  is  claimed  that  the  study  was  designed  
to  be  pragmatic  and  not  purely  experimental.    

CUtLASS  summary:  

¬ CUtLASS  stands  for  Cost  Utility  of  the  Latest  Antipsychotic  Drugs  in  Schizophrenia  Study    
¬ It  is  an  unblinded  randomised  controlled  trial  comparing  first-­‐‑generation  v.  second-­‐‑generation  antipsychotics    
¬ The  primary  outcome  was  the  quality  of  life  at  1  year  and  symptom  measures  were  the  main  secondary  
outcome.    
¬ 1,  227  people  with  schizophrenia  who  were  being  assessed  by  their  clinical  team  for  medication  review  
because  of  poor  response  or  adverse  effects  were  randomised.  
¬ The  second-­‐‑generation  drugs  were  amisulpride,  olanzapine,  quetiapine  or  risperidone.  
¬ The  rate  of  follow-­‐‑up  interview  was  81%  at  1  year.    
¬ The  results  showed  no  advantage  of  second-­‐‑generation  drugs  in  terms  of  quality  of  life  or  symptom  burden  
over  1  year  with  those  on  first-­‐‑generation  antipsychotic  doing  relatively  better.    
¬ Participants  reported  no  clear  preference  for  either  class  of  drug.    
¬ The  second  phase  -­‐‑  CUtLASS  2  trial  was  of  similar  design  and  compared  clozapine  with  other  second-­‐‑
generation  drugs  in  136  patients  who  had  not  responded  well  to  two  or  more  previous  drugs.  Results  
showed  that  there  was  a  significant  advantage  for  clozapine  in  symptom  improvements  over  1  year;  
moreover,  patients  significantly  preferred  it.  

©  SPMM  Course   13  
4. Antidepressants - adverse effects
Tricyclic agents
¬ Side  effects  of  TCAs  are  related  to  anticholinergic,  antihistaminic  and  antiadrenergic  
properties.  Clomipramine  is  a  more  selective  inhibitor  of  serotonergic  reuptake  selective;  
desipramine  is  the  most  noradrenergic  selective  of  TCAs.  Amoxapine,  nortriptyline,  
desipramine,  and  maprotiline  have  the  least  anticholinergic  activity;  doxepin  has  the  most  
antihistaminic  activity.    
¬ The  TCAs  are  less  likely  to  cause  sexual  dysfunction  and  insomnia  than  the  SSRIs.  
¬ Amitriptyline  is  associated  with  weight  gain  (antihistaminic  effect  –  weight  gain  can  also  
occur  secondary  to  5HTc  antagonism  in  other  antidepressants).    
¬ TCAs  may  cause  QT  prolongation.  Even  at  therapeutic  doses,  the  TCAs  cause  tachycardia,  
flattened  T  waves,  prolonged  QT  intervals,  and  depressed  ST  segment.  
¬ TCAs  are  lethal  in  overdose,  causing  cardiac  arrhythmias  and  anticholinergic  delirium.  
This  may  occur  3-­‐‑4  days  after  overdose  due  to  the  long  half-­‐‑life.  No  specific  antidote  
available;  needs  lavage  and  QRS  monitoring.    
¬ Anticholinergic  delirium  is  characterized  by  symptoms  often  described  as    ‘Mad  as  a  hatter,  
(confusion,  disorientation,  visual  hallucinations),  Hot  as  a  hare  (hyperpyrexia),  Blind  as  a  bat  (loss  
of  visual  accommodation),  Red  as  a  beet  (peripheral  vasodilatation)  and  Dry  as  a  bone  (drying  of  
mucous  membranes)’.    
¬ Amoxapine  can  cause  hyperprolactinemia  as  it  has  dopamine  antagonistic  effects.    
¬ SIADH  and  hyponatremia  can  occur  with  TCAs.    
¬ Fine  rapid  tremor  and  dysarthria  are  sometimes  reported  with  TCAs.  
¬ Tricyclic  agents  such  as  amitriptyline  and  imipramine  and  the  nontricyclic  agents  such  as  
mianserin  hydrochloride  have  been  documented  to  precipitate  an  attack  of  angle  closure  
glaucoma.  
¬ TCA  discontinuation:  Can  cause  cholinergic  rebound  –  best  to  reduce  25  to  50mg  per  2-­‐‑3  
days.  Discontinuation  reaction  may  occur  as  early  as  48  hours  or  as  late  as  2  weeks  after  
discontinuation.  Propantheline  or  reinstitution  of  withdrawn  TCA  can  reduce  cholinergic  
rebound  symptoms.  

©  SPMM  Course   14  
 Mechanism  of  Serotonin  Syndrome

•Serotonin  syndrome  is  a  result  of  excessive  serotonergic  transmission  in  brain.  Although  no  
single  mechanism  appears  to  be  responsible  for  all  of  the  noted  effects,  most  CNS  symptoms  are  
possibly  mediated  via  5HT  2A  receptor  stimulation.

Features  of  serotonin  syndrome

•It  is  characterized  by  diarrhea,  myoclonus,  diaphoresis,  hyperactive  reflexes,  ataxia,  hypomanic  
or  labile  mood,  tremors  and  disorientation.
•  It  may  mimic  NMS  or  anticholinergic  syndrome  in  those  receiving  psychotropics.

Drugs  with  high  risk  of  serotonin  syndrome:

•Any  serotonergic  agent  on  overdose  –  including  SSRI  and  TCA  antidepressants,  fenfluramine,  
LSD,  ecstasy,  anti-­‐‑migraine  (e.g.  sumatriptan)  drugs.  
•High  risk  with  combinations  of  SSRI  and  MAOI  or  RIMA  or  SSRI  themselves,  or  TCAs  especially  
serotonergic,  or  SNRI,  lithium  or  l-­‐‑tryptophan.  TCA  and  MAOI  combinations.  Tramadol,  
pethidine,  meperidine  can  also  cause  serotonin  syndrome  on  combination  with  the  above  agents.  
•Oxazolidinone  antibacterial  linezolid  (which  is  a  reversible  non-­‐‑selective  MAOI),    tetrabenazine  
(acts  via  dopamine  and  serotonin  depletion  at  nerve  endings),  entacapone  (COMT  inhibitor)  and  
selegiline  are  also  implicated.

Treatment  of  Serotonin  syndrome:

•Withdraw  the  offending  agent

•Supportive  care:  correction  of  vital  signs
•Benzodiazepines
•5HT2A  antagonists:  cyproheptadine,  atypical  antipsychotics,  chlorpromazine  (?  mirtazapine  –  
controversial  reports)
•In  severe  cases  neuromuscular  paralysis  and  intubation  may  be  required
 

NMS  vs.  serotonin  syndrome  

NMS   Serotonin  syndrome  

Dopamine  antagonism  and  suspected   Excess  serotonin  availability  
hypothalamic  mediated  sympathetic  
overdrive.  
Onset  subacute  –  days  to  weeks   Sudden  minutes  to  hours  onset  

Resolves  in  2  weeks    -­‐‑  depending  on  t1/2   Resolves  as  soon  as  excess  serotonin  is  
of  offending  drug   reduced  –  in  24  hours  generally  

No  myoclonus   Myoclonus  prominent  

Hypomania,  not  a  feature   Hypomania  may  be  seen  
Reflexes  normal  or  absent   Hyperreflexia  seen  
Rhabdomyolysis,  resultant  renal  failure   Muscle  breakdown  not  common  
and  acidosis  occur  commonly  

©  SPMM  Course   15  
CPK  elevation  common;  WBC  also   These  laboratory  abnormalities  are  less  
elevated   frequent  in  serotonin  syndrome  

SSRI antidepressants
¬ Nausea,  vomiting,  anorexia,  and  diarrhea  are  common  side  effects  of  SSRIs  –  these  are  
somewhat  dose-­‐‑dependent  and  can  be  lessened  by  dose  reduction  or  a  slower  titration.  
SSRIs  (similar  to  TCAs,  but  less  frequently)  cause  weight  gain  in  up  to  30%  of  patients  
especially  in  long-­‐‑term  maintenance  phase.    
¬ During  initial  treatment  insomnia  and  anorexia  are  often  present.  Desensitization  and  
down-­‐‑regulation  of  receptors  may  explain  the  reversal  of  the  initial  SSRI  appetite-­‐‑
suppressing  effects,  which  can  ultimately  lead  to  weight  gain  late  during  therapy.  
¬ Sexual  difficulties  such  as  reduced  libido,  impotence,  ejaculatory  dysfunction,  and  
anorgasmia  are  reported  with  SSRIs.  The  incidence  of  sexual  dysfunction  is  nearly  every  1  
in  3  patients  treated.  
¬ Akathisia  like  effects,  EPSEs  and  galactorrhea  are  rarely  reported  with  SSRIs.    
¬ Also,  fluoxetine  is  associated  with  a  change  in  the  duration  of  menstrual  period  –  
significance  of  this  is  unknown.    
¬ SSRIs  can  cause  functional  impairment  of  platelet  aggregation  (thrombasthenia),  but  not  a  
reduction  in  platelet  number.  This  can  cause  easy  bruising  or  prolonged  bleeding  in  those  
with  gastric  ulcers  or  bleeding  diathesis.    
¬ SIADH  is  also  reported;  this  is  often  troublesome  in  alcoholics  and  the  elderly  causing  
hyponatremia,  hyperkalemia,  hypo-­‐‑osmolality  in  serum  and  increased  osmolality  of  urine.  
Stopping  the  offending  drug,  using  demeclocycline  and  fluid  restriction  can  help.  
¬ Severe  sweating  especially  nocturnally  is  seen  in  some  patients;  Terazosin  is  effective  in  
counteracting  sweating.  
¬ Nocturnal  myoclonus  is  reported  with  SSRIs.  The  repetitive  leg  movements  occur  every  20  
to  60  seconds,  with  extensions  of  the  large  toe  and  flexion  of  the  ankle,  the  knee,  and  the  
hips.  Benzodiazepines  and  levodopa  may  be  tried.  
¬ In  restless  leg  syndrome,  patients  complain  of  creeping  deep  sensations  that  cause  an  
irresistible  urge  to  move  the  legs  –  disturbing  sleep.    It  is  associated  with  SSRIs  and  
treatment  is  possible  using  ropinirole  or  benzodiazepines  and  levodopa.  
¬ Duloxetine,  venlafaxine,  citalopram,  fluoxetine  and  paroxetine  can  induce  acute  angle-­‐‑
closure  glaucoma.  The  pathophysiological  mechanism  of  SSRI  –precipitated  glaucoma  
remains  unclear;  anticholinergic  effects  or  increased  level  of  serotonin,  which  cause  partial  
pupillary  dilation  have  been  implicated.  
¬ SSRI  discontinuation  syndrome:  The  abrupt  withdrawal  of  SSRI  especially  paroxetine  
(additional  cholinergic  rebound)  or  fluvoxamine  (shorter  half-­‐‑life),  is  associated  with  a  
discontinuation  syndrome.  It  usually  requires  at  least  4-­‐‑6  weeks  of  treatment  before  
©  SPMM  Course   16  
 discontinuation  and  resolves  spontaneously  in  3  weeks.  Those  who  have  significant  SSRI  
intolerance  during  treatment  onset  will  have  more  discontinuation  reactions.  Fluoxetine  is  
the  SSRI  least  likely  to  cause  withdrawal  syndrome  as  its  metabolite  has  a  long  half-­‐‑life  
(more  than  1  week),  producing  a  slow  self-­‐‑tapering  effect  in  plasma.  Fluoxetine  in  some  
cases  can  be  used  to  even  treat  discontinuation  syndrome  or  to  prevent  it  when  stopping  
another  SSRI  agent.    But  a  delayed  withdrawal  syndrome  has  been  reported  with  
fluoxetine  in  some  cases.  

SSRI  discontinuation  syndrome  

Criterion  A   Discontinuation  or  reduction  of  dose  of  SSRI  after  at  least  1  month  use  

Criterion  B   2  or  more  of  the  following  seen  within  1-­‐‑7days  of  criterion  A  causing  significant  
functional  impairment  and  not  due  to  a  general  medical  condition:  
• Dizziness,  lightheadedness,  shock-­‐‑like  sensations  (paresthesias),  diarrhea,  
fatigue,  gait  instability,  headache,  insomnia,  nausea,  tremors,  visual  
disturbances  
¬ Suicide  risk  and  SSRIs:  A  link  between  antidepressant  use  and  suicidal  ideation  among  those  
up  to  age  24  in  short-­‐‑term  (4  to  16  weeks),  placebo-­‐‑controlled  trials  of  nine  antidepressant  
drugs  has  been  reported.  The  average  risk  of  suicidal  thinking  or  behavior  during  the  first  few  
months  of  treatment  in  those  receiving  antidepressants  was  4  percent  while  placebo  produces  
a  risk  of  2  percent.  Ecological  studies  indicate  that  since  the  introduction  of  large  scale  SSRI  
prescription  for  every  10%  rise  in  prescription  3%  decline  in  suicide  rates  has  happened  in  
certain  countries.  It  is  also  noted  that  patients  were  significantly  more  likely  to  
attempt/commit  suicide  in  the  month  before  they  began  drug  therapy  than  in  the  6  months  
after  starting  it.  But  the  issue  still  remains  controversial,  and  MHRA  has  advised  against  
certain  SSRI  prescriptions  in  children  and  adolescents.    
¬ SSRIs  increase  the  risk  of  upper  GI  bleeding  especially  in  the  elderly  and  in  those  using  
NSAIDs.  SSRIs  inhibit  the  uptake  of  serotonin  into  platelets;  serotonin  is  crucial  for  the  
haemostatic  response  of  promoting  platelet  aggregation.  Further,  SSRIs  also  increase  gastric  
acid  secretion  thus  elevating  the  risk  of  gastric  erosion,  ulcer  and  bleeding.  Alcohol  intake  and  
being  positive  for  H.pylori  will  also  increase  the  risk  of  GI  bleeding  when  prescribing  SSRIs.  
Antidepressants  with  low  inhibition  of  serotonin  reuptake  (e.g.  nortriptyline,  doxepin,  
trazodone)  are  safer  in  this  regard  when  compared  to  those  with  high  inhibition  of  serotonin  
reuptake  (e.g.  clomipramine,  paroxetine,  sertraline,  fluoxetine).  
¬ Increased  serotonergic  neurotransmission  can  adversely  affect  sexual  performance;  this  
explains  SSRI-­‐‑induced  sexual  dysfunction.  Some  antidepressants  (bupropion,  mirtazapine,  
moclobemide,  nefazodone  and  reboxetine)  may  be  associated  with  a  relatively  lower  
incidence  of  sexual  dysfunction.  5-­‐‑HT2  antagonists,  (e.g.  cyproheptadine,  mirtazapine),  5-­‐‑HT1a  

©  SPMM  Course   17  
 agonists,  (e.g.  buspirone)  and  bupropion  (being  a  dopamine  reuptake  inhibitor)  can  reverse  
sexual  dysfunction  related  to  SSRI  use.  
¬ A  nitric  oxide-­‐‑dependent  second  messenger  (cGMP)  mediates  penile  vasodilatation.  cGMP  is  
eventually  broken  down  by  phosphodiesterase  type  5  enzyme.    Sildenafil  is  an  inhibitor  of  
phosphodiesterase  type  5,  an  action  that  enhances  penile  erection  in  patients  with  erectile  
dysfunction.  Sildenafil  (Viagra)  has  been  tried  successfully  in  the  treatment  of  SSRI-­‐‑induced  
erectile  dysfunction.  The  side  effects  of  sildenafil  include  headaches  (most  common),  
dizziness,  blurred  vision  and  a  blue  tinge  to  vision.  Very  rarely,  persistent  painful  erection  
(priapism)  can  occur.  Sildenafil  must  be  avoided  by  patients  with  arrhythmias,  unstable  
angina  /  uncontrolled  hypertension.  
 

Other antidepressants
¬ Venlafaxine:  Sweating  is  more  common  than  in  SSRIs  and  is  treated  by  terazosin.  Significant  
numbers  of  patients  receiving  doses  above  300mg/day  experience  an  increase  in  diastolic  
blood  pressure.  This  risk  is  not  restricted  to  those  with  preexisting  hypertension.  Mydriasis  
and  exacerbation  of  angle  closure  glaucoma  are  reported  with  venlafaxine;  significant  
discontinuation  reactions  are  reported  due  to  the  shorter  half-­‐‑life  of  venlafaxine  –  tapering  
gradually  over  2-­‐‑4  weeks  is  recommended.  Duloxetine  has  side  effects  similar  to  venlafaxine,  
but  fewer  propensities  to  affect  blood  pressure.  
¬ Trazodone  is  associated  with  priapism  that  can  be  serious  if  unattended.  The  first  step  in  the  
emergency  management  of  priapism  is  the  intracavernosal  injection  of  an  alpha1  agonist  such  
as  metaraminol  or  epinephrine.  The  risk  of  priapism  is  greatest  during  the  early  phase  of  
treatment.  Nefazodone  inhibits  CYP3A4  and  can  cause  serious  hepatic  damage  and  hence  not  
used  as  often  now.  Though  anticholinergic  effects  are  predominantly  absent,  alpha1  
antiadrenergic  effects  can  produce  pseudo-­‐‑anticholinergic  symptoms.  Afterimage  formation  
similar  to  the  LSD  related  tracking  phenomenon  is  reported  in  up  to  12%  patients  on  
nefazodone.  Both  trazodone  and  nefazodone  have  a  favourable  profile  for  elderly  and  those  
with  cardiac  illness.    
¬ Bupropion  has  a  very  different  side-­‐‑effect  profile  than  the  conventional  antidepressants.  It  
has  no  anticholinergic  effects,  does  not  cause  sedation  or  weight  gain  and  cause  almost  
negligible  sexual  side  effects  compared  to  other  classes  of  antidepressants.  It  does  not  cause  
orthostatic  hypotension  or  cardiac  side  effects.  It  can  exacerbate  ADHD,  eating  disorders  and  
tics  in  those  with  ADHD.  It  can  enhance  sexual  activity  unlike  SSRIs;  it  increases  the  risk  of  
seizures  in  a  dose-­‐‑dependent  fashion.  Headache,  insomnia,  dry  mouth,  tremor,  and  nausea  
are  the  most  common  side  effects  of  bupropion.  Severe  anxiety  or  panic  can  be  exacerbated  by  
bupropion.  Due  to  its  effects  on  dopaminergic  neurotransmission  bupropion  can  cause  

©  SPMM  Course   18  
 psychotic  symptoms  as  well  as  delirium.  Bupropion  can  cause  word-­‐‑finding  difficulties  in  
some  patients.    
¬ Agranulocytosis  is  reported  with  mirtazapine  use.  Hence,  signs  of  infection  need  to  be  
promptly  followed.  
¬ Buspirone  can  increase  concentrations  of  haloperidol.  Buspirone  +  MAOI  can  cause  serotonin  
syndrome;  2-­‐‑week  washout  period  is  recommended.  CYP3A4  inhibitors  such  as  
erythromycin,  itraconazole,  nefazodone  and  grapefruit  juice,  increase  buspirone  plasma  
concentrations.  Buspirone  does  not  cause  weight  gain,  sexual  dysfunction,  discontinuation  
symptoms,  or  significant  sleep  disturbance.  It  does  not  produce  sedation.  
¬ Mianserin  and  mirtazapine  produce  drowsiness  during  the  first  weeks  of  treatment  but  has  a  
low  propensity  to  produce  orthostatic  hypotension  or  cardiac  effects.  Increased  weight  gain  
and  appetite  are  also  noted  while  sexual  side  effects  are  minimal.    5-­‐‑HT3  blockade  is  
associated  with  a  reduction  in  nausea  and  vomiting;  hence  to  treat  depression  associated  with  
cancer  chemotherapy,  mirtazapine  is  a  preferred  option.  
¬ Reboxetine  is  a  noradrenaline  reuptake  inhibitor  (NARI)  with  negligible  serotonergic  effects.  
It  has  a  safe  cardiovascular  profile  and  can  be  used  in  the  elderly.  Atomoxetine  belongs  to  the  
same  group  but  not  used  as  an  antidepressant;  it  is  used  in  ADHD.  Reboxetine  has  a  specific  
side-­‐‑effect  profile  linked  to  the  noradrenergic  system.  Urinary  hesitancy  has  been  observed  in  
around  10%  of  male  patients  taking  part  in  the  clinical  trials.  Relief  from  this  side  effect  could  
be  achieved  by  using  tamsulosin,  a  peripheral  alpha1-­‐‑receptor  blocker  or  doxazosin  with  a  
similar  mechanism  of  action  as  tamsulosin.  
¬ MAOIs  such  as  phenelzine  can  induce  orthostatic  hypotension,  pedal  edema  and  insomnia.  
Apart  from  cheese  reaction,  MAOIs  can  also  cause  serotonin  syndrome  in  combination  with  
serotonergic  agents.  Tranylcypromine,  and  phenelzine  to  some  extent  can  have  stimulating  
effects  leading  to  insomnia  –  hence  the  last  dose  is  best  given  before  6  PM.  Weight  gain  and  
sexual  dysfunction  are  also  reported.  
¬ Cheese  reaction:    
o MAOIs  and  tyramine  (and  other  monoamine)  rich  foods  interact  to  cause  cheese  reaction  
or  tyramine  reaction.    
o Tyramine  has  both  direct  and  indirect  (via  vesicular  release)  sympathomimetic  actions  
that  develop  20  min  to  1  h  following  ingestion  of  food.    
o It  is  characterized  by  nausea,  apprehension,  occasional  chills,  sweating,  restlessness  and  
hypotension  with  occipital  headache,  palpitations,  and  vomiting.    
o Sympathetic  overdrive  manifests  as  piloerection  dilated  pupils  and  fever.  If  severe  
cerebral  hemorrhage  and  death  can  occur.    

©  SPMM  Course   19  
 o In  terms  of  the  frequency  and  severity  of  the  hypertensive  crisis,  the  reversible  MAOIs  are  
safer.    
o Food  materials  to  be  avoided  include  any  mature  cheese  such  as  Stilton,  blue  cheese,  old  
cheddar  and  mozzarella.  Fish,  cured  meats,  sausage  must  be  avoided  together  with  
mature  poultry,  wild  game  etc.,  liqueurs  and  concentrated  yeast  extract.    
o An  MAOI-­‐‑induced  hypertensive  crisis  can  be  treated  with  alpha-­‐‑adrenergic  antagonists  
such  as  phentolamine  or  even  chlorpromazine,  which  is  immediately  available  in  most  
psychiatric  wards.  This  can  lower  blood  pressure  in  few  minutes.  
 

©  SPMM  Course   20  
5. Antimanic agents - adverse effects
Renal effects
Certain  side  effects  including  polyuria  seems  to  be  associated  with  peak  lithium  levels;  once  daily  
instead  of  twice  daily  dosing  can  reduce  these  problems.  Nearly  1/3rd  of  those  treated  will  have  
this  side  effect,  but  tolerance  develops  in  due  course;  functional  antagonism  of  ADH  by  lithium  
ion  is  considered  to  be  the  underlying  mechanism.  Use  of  K+  sparing  diuretics  such  as  amiloride  
or  spironolactone  can  control  polyuria.  

Renal  damage  may  occur  in  severe,  prolonged  toxicity  –  but  cumulative  lithium  use  rather  than  
toxicity  leads  more  commonly  to  renal  failure  in  lithium  users.  Chronic  exposure  longer  than  10  
years  induces  interstitial  fibrosis  resulting  in  chronic  renal  damage.    

Lithium  has  a  narrow  therapeutic  index.  Lithium  toxicity  occurs  in  conditions  of  overdose  or  
dehydration.  Non-­‐‑specific  gastrointestinal  symptoms  usually  precede  the  more  serious  
neurological  symptoms  and  renal  shutdown.  Immediate  cessation  of  lithium  followed  by  urgent  
medical  attention  is  required  as  some  patients  may  require  a  hemodialysis  if  levels  exceed  
4mEq/L.    

Topiramate  is  a  weak  inhibitor  of  carbonic  anhydrase  and  can  promote  the  development  of  renal  
stones.    

SIADH  may  be  seen  with  valproate  use  though  more  common  with  carbamazepine;  it  is  
dependent  on  the  dose  prescribed.  

Oxcarbazepine  is  a  10-­‐‑keto  derivative  of  CBZ  with  an  identical  profile  but  less  enzyme  induction  
and  fewer  drug–drug  interactions.  It  produces  less  rash  and  neurotoxicity  but  more  
hyponatremia  than  CBZ.  

Cardiac effects
ECG  effects  of  therapeutic  lithium  dose  are  similar  to  hypokalemia  –  with  flat  T  waves,  or  
inverted  T.  Lithium  can  depress  sinus  node  activity  and  so  is  contraindicated  in  sick  sinus  
syndrome.  

Endocrine effects
Lithium  can  cause  a  variety  of  thyroid  problems  –  the  most  common  being  a  benign  hypothyroid  
state.  5%  patients  may  develop  goiter,  and  overt  hyperthyroidism  is  also  reported  in  some  cases.  
Thyroid  deficiency  is  common  in  those  with  high  risk  for  preexisting  antithyroid  antibodies  
(especially  middle-­‐‑aged  women).  The  risk  is  3-­‐‑4:1  in  women  and  is  high  in  first  2  years  of  
treatment.  Rapid  cycling  patients  are  at  higher  risk.  High  TSH  is  seen  in  nearly  1/3rd  of  chronic  
lithium-­‐‑treated  patients  even  in  the  absence  of  clinical  hypothyroidism.  In  resistant  depression  
©  SPMM  Course   21  
and  in  non-­‐‑responsive  rapid  cyclers  with  bipolar  disorder,  using  thyroxine  to  treat  subclinical  
hypothyroidism  may  be  beneficial  for  the  mood  disorder.    

Polycystic  ovaries  (PCO):  25  -­‐‑  33%  UK  population  of  adult  females  have  PCO  morphology  
notable  in  ultrasound.  5-­‐‑26%  may  have  actual  PCOD,  which  is  defined  as  having  PCO  in  
ultrasound  with  hyperandrogenism  or  LH  disturbance.  10%  woman  on  valproate  have  new  onset  
PCOD.  The  relative  risk  is  7.5  for  PCOD.    On  stopping  most  people  remit  from  PCOD.    

The  exact  mechanism  by  which  valproate  might  causes  PCOD  remains  unknown,  although  
several  mechanisms  are  proposed.  For  example,  valproate  increases  ovarian  androgen  
production.  It  also  can  result  in  weight  gain  and  insulin  resistance,  both  risk  factors  for  PCOD.  In  
the  liver,  the  drug  can  increase  unbound  testosterone.  

Epilepsy,  for  which  valproate  is  widely  used,  is  tipped  to  increase  PCOD  occurrence.  Such  
association  has  not  been  established  so  far  for  bipolar  disorder.      

Almost  all  patients  who  develop  oligomenorrhea  develop  it  in  first  year  of  treatment  with  
valproate.    

Haematological effects
Lithium  can  cause  leucocytosis  that  can  be  therapeutically  utilized  in  some  cases  of  benign  
neutropenia  related  to  clozapine  use.  This  is  not  widely  practiced.  

Around  10%  of  individuals  taking  carbamazepine  will  see  gradual  onset  leucopenia  in  first  
3months  of  treatment.  This  is  reversible  on  continued  treatment  or  dose  reduction.  

Thrombocytopenia  is  a  dose-­‐‑related  effect  of  valproate  and  carbamazepine  –  a  reduction  in  dose  
is  required  if  bruising,  or  bleeding  gums  is  noted.    

Neurological effects
Fine  tremor  is  a  common  benign  side  effect  of  lithium,  and  coarse  tremor  is  a  sign  of  toxicity.  
Propranolol  can  be  used  in  treating  lithium-­‐‑induced  fine  tremor  at  therapeutic  levels.    

Lamotrigine  is  generally  well  tolerated  but  can  cause  dizziness,  ataxia,  headache,  sedation,  
tremor,  and  nausea.    

Topiramate  can  produce  word  finding  difficulties  (anomia)  and  poor  concentration  

Vigabatrin,  an  antiepileptic  with  no  significant  antimanic  efficiency,  has  been  tried  in  some  open-­‐‑
label  trials.  It  has  a  peculiar  side  effect  of  causing  visual  field  defects.    

©  SPMM  Course   22  
 Gastrointestinal effects
Valproate  inhibits  hepatic  enzymes;  in  some  cases  the  acute  liver  injury  may  occur  though  this  is  
rare  in  clinical  practice.  Of  persons  taking  valproate,  5  to  40  percent  experience  a  persistent  but  
clinically  insignificant  elevation  in  liver  transaminases  up  to  three  times  the  upper  limit  of  
normal,  which  is  usually  asymptomatic  and  resolves  after  discontinuation  of  the  drug  (termed  
‘transaminitis’).    

Liver  failure  is  reported  with  valproate,  lamotrigine,  topiramate  and  carbamazepine.  Risk  factors  
include  young  age  and  combination  therapy.  This  is  caused  by  2  mechanisms:  1.  Metabolic  
toxicity  e.g.  due  to  4-­‐‑en  valproate,  a  metabolite  of  valproate.  2.  Hypersensitivity  -­‐‑    dose-­‐‑
independent  effect  is  resulting  in  fulminant  failure.  Severe  hepatic  damage  associated  with  
valproate  is  seen  especially  in  those  with  learning  disability  when  undiagnosed  urea  cycle  
disorders  are  present  (less  than  2  years  often).    

Another  rare  side  effect  of  valproate  is  acute  pancreatitis.  This  is  a  hypersensitivity  reaction;  dose  
reduction  will  not  be  helpful.  

Hyperammonemia  can  be  associated  with  coarse  tremor  and  carbamazepine  co-­‐‑prescription;  it  
may  respond  to  L-­‐‑carnitine  administration.  Valproate  competes  with  carnitine  transport  and  can  
induce  a  state  of  carnitine  depletion  especially  in  children  and  in  epileptics.    

Teratogenic effects
The  most  common  teratogenic  effect  of  lithium  involves  cardiac  valves  especially  Ebstein'ʹs  
anomaly  of  the  tricuspid  valves.  The  risk  of  Ebstein'ʹs  malformation  in  lithium-­‐‑exposed  fetuses  is  
1  of  1,000  (20  times  the  risk  in  the  general  population).  Lithium’s  teratogenic  effects  are  somewhat  
lower  than  that  caused  by  the  use  of  valproate  or  carbamazepine.  Lithium  is  excreted  into  breast  
milk,  and  signs  of  lithium  toxicity  in  infants  include  lethargy,  cyanosis  and  sluggish  neonatal  
reflexes.  

Valproate  causes  neural  tube  defects  as  a  teratogenic  effect  in  1%  to  4%  mothers.  Folate-­‐‑vitamin  
B  complex  supplementation  for  all  young  women  of  childbearing  potential  may  reduce  risk  
though  it  is  best  to  avoid  valproate  totally.    

Learning  disability  and  low  IQ    in  children  is  the  most  common  teratogenic  effect  of  valproate.    

Skin effects
Exacerbation  of  acne  and  psoriasis  are  associated  with  lithium  therapy.  

Alopecia  /  hair  loss  occurs  in  5  to  10  percent.  It  is  not  clear  if  zinc  and  selenium  supplementation  
can  reverse  or  prevent  the  latter  effect.    

©  SPMM  Course   23  
Valproate  can  cause  obesity,  hyperandrogenism  and  PCOD  associated  with  hirsutism.  

Anticonvulsant  hypersensitivity  syndrome  is  seen  in  0.1%  of  patients  taking  anticonvulsants.  
Aromatic  compounds  (lamotrigine,  carbamazepine,  phenytoin  and  phenobarbitone)  are  
especially  risky.    
5  to  20%  of  those  taking  aromatic  anticonvulsants  will  experience  a  rash.  Lamotrigine  can  cause  a  
rash  in  10%  of  patients.  Risk  factors  for  rash  include  rapid  initial  dose  escalation,  concurrent  VPA,  
and  age  less  than  16  years.  As  benign  rashes  cannot  be  distinguished  from  potentially  serious  
ones,  any  rash  requires  discontinuation  of  the  drug.  
Lamotrigine  carries  a  significant  risk  of  Steven  Johnson  Syndrome  (SJS  –  risk  of  1  in  3000)  
especially  if  administered  together  with  Valproate  as  the  enzyme  inhibiting  effects  of  Valproate  
may  increase  lamotrigine  levels.  SJS  starts  with  a  rash,  pharyngitis  and  fever.    Systemic  
involvement  follows  quickly  if  the  drug  is  not  stopped.    

Drug   Dose-­‐‑related  effects   Idiosyncratic  reactions  

Carbamazepine    Visual  disturbances,  GI   Hematological  reactions  including  
disturbances,  cognitive   agranulocytosis  or  aplastic  anemia,  idiosyncratic  
impairment,  vertigo  and,  dizziness.    
Stevens-­‐‑Johnson  syndrome,  fulminant  hepatic  
damage,  and  pancreatitis.  SIADH  is  more  
common  in  the  elderly  
Valproate   Hyperammonemia,  Teratogenicity,   Hepatotoxicity,  pancreatitis,  rash  and  rarely  acute  
Sedation,  Thrombocytopenia   dermatitis.  
 

Weight related effects

Weight  gain  is  common  (70%  of  those  taking  valproate  and  40%  of  those  taking  carbamazepine  over  12  
months  will  experience  weight  gain);  valproate  induced  weight  gain  is  considered  to  be  due  to  impaired  
beta-­‐‑oxidation  of  fatty  acids,  and  thus  independent  of  calorie  intake.  Lamotrigine  is  often  weight  neutral  

Topiramate  is  weight  neutral  and  can  even  cause  weight  loss.  Topiramate  can  be  potentially  used  to  
counteract  the  weight  gain  caused  by  many  psychotropic  drugs.    

©  SPMM  Course   24  
6. Other agents - adverse effects
Cholinesterase  inhibitors:  Donepezil  causes  nausea,  diarrhea,  insomnia,  vomiting,  muscle  
cramps  commonly.  Rivastigmine  causes  similar  symptoms  albeit  at  a  higher  frequency  of  some.    
Galantamine  too  has  a  similar  profile.  Tacrine  is  not  used  anymore  in  UK  due  to  reports  of  fatal  
hepatotoxicity.    

By  increasing  central  and  peripheral  cholinergic  stimulation  cholinesterase  inhibitors,  can  

1.  Increase  the  risk  for  GI  bleeding  especially  in  NSAID  users  or  patients  with  
peptic  ulcer.  
2.  Produce  bradycardia,  especially  in  those  with  supraventricular  conduction  
delay,    
3.  Exacerbate  COPD  
4.  Cause  urinary  retention  
5.  Increase  seizure  risk  
6.  Prolong  the  effects  of  succinylcholine-­‐‑type  muscle  relaxants  
Rivastigmine’s  metabolism  does  not  depend  on  liver  P450  enzymes,  and,  therefore,  no  drug  
interactions  related  to  the  P450  system  have  been  observed. Memantine  does  not  inhibit  or  
induce  hepatic  microsomal  enzymes;  because  it  is  excreted  in  the  urine  predominantly  as  
unchanged  drug,  it  is  unlikely  to  be  affected  by  drugs  that  affect  hepatic  enzyme  function.    

Stimulants  and  other  drugs  used  for  ADHD:  The  most  common  adverse  effects  are  anxiety,  
irritability,  insomnia,  tachycardia,  cardiac  arrhythmias,  and  dysphoria  with  decreased  appetite.  
Tolerance  usually  develops  for  appetite  loss.  Less  commonly  self-­‐‑limited  exacerbation  of  
movement  disorders,  such  as  tics  and  dyskinesias,  may  occur.  

Stimulants  are  linked  to  growth  suppression.  Bruxism  and  restlessness  are  also  reported.  
Pemoline  is  associated  with  fulminant  hepatic  failure  and  is  no  longer  used  widely.  Dependence  
can  occur  with  methylphenidate  though  this  is  rare  at  doses  used  for  ADHD.    

Side  effects  of  atomoxetine  are  appetite  loss,  sexual  dysfunction  and  dizziness;  severe  liver  injury  
in  has  also  been  reported.    

Clonidine  is  not  a  popular  option  for  treating  tics/ADHD  due  to  high  rates  of  hypotension  
associated  with  it.  
 
Hypnotics:  Overdose  of  benzodiazepines  can  produce  slurred  speech,  incoordination,  unsteady  
gait,  nystagmus,  impairment  in  attention  or  memory,  stupor  or  coma  and  behavioural  changes  
(inappropriate  sexual  or  aggressive  behaviour,  mood  lability,  impaired  judgment  etc.).    

©  SPMM  Course   25  
High-­‐‑potency  benzodiazepines  such  as  triazolam  can  cause  anterograde  amnesia.    

Paradoxical  disinhibition  is  seen  in  a  few  patients  especially  when  preexisting  brain  damage  is  
present.  Triazolam  is  banned  in  UK  since  1991  following  reports  of  disinhibition  and  aggression.  

Benzodiazepines  can  produce  respiratory  impairment  especially  in  those  with  COPD  or  sleep  
apnea.  Benzodiazepines  are  better  avoided  in  those  with  myasthenia  gravis,  head  injury  or  
porphyria  due  to  this  risk.  

Alprazolam  can  cause  weight  gain  via  appetite  stimulation.    

Cleft  palate  and  lips  are  teratogenic  effects  associated  with  benzodiazepines;  withdrawal  
syndrome  is  seen  in  a  neonate  with  third  trimester  use.    

Z-­‐‑hypnotics  have  more  potential  to  cause  upset  stomach  and  diarrhea  compared  with  
benzodiazepines.    

Eszopiclone’s  unique  temporary  side  effect  is  an  unpleasant  taste.  It  can  also  cause  dry  mouth  
especially  in  the  elderly  in  a  dose-­‐‑dependent  fashion.    
The  occurrence  of  benzodiazepine  withdrawal  syndrome  depends  on    
¬ The  duration  of  treatment,  
¬ The  dosage  prescribed,    
¬ The  rate  of  tapering  and  
¬ The  half-­‐‑life  of  the  compound.    

Benzodiazepine  withdrawal  is  characterized  by  anxiety,  diaphoresis,  kinaesthetic  hallucinations,  

restlessness,  irritability,  light-­‐‑headedness,  tremor,  insomnia,  autonomic  hyperactivity,  and  
weakness.  In  severe  cases,  depression,  paranoia,  delirium,  and  grand  mal  seizures  are  seen.  The  
syndrome  can  occur  after  1  or  2  weeks  in  long-­‐‑acting  benzodiazepines.  Alprazolam  and  
lorazepam  are  associated  with  immediate  and  severe  withdrawal  syndrome  and  should  be  
tapered  gradually.  

Using  prescribed  benzodiazepines  for  4  weeks  or  less  rarely  results  in  significant  withdrawal  
symptoms.  But  if  used  for  4  months  –  5-­‐‑10%  have  withdrawals;  in  2  years  –  25-­‐‑45%  and  in  6-­‐‑
8years  –  75%  develop  withdrawal  syndrome  and  dependence  pattern  (Law  et  al.  2004).  

Slow  taper  at  a  rate  of  25%  per  week,  use  of  longer  acting  agents  when  tapering,  avoiding  long-­‐‑
term  use  of  short-­‐‑acting  benzodiazepines,  use  of  carbamazepine  to  assist  discontinuation  are  the  
various  strategies  employed  to  manage  withdrawal  symptoms.    

7. Psychiatric effects of non-psychiatric drugs

 
©  SPMM  Course   26  
Non-­‐‑psychiatric  drugs   Psychiatric  side  effects  
Beta-­‐‑blockers   Sedation,  nightmares,  dysphoria  (nearly  50%  in  some  samples)  and  depression.  
Psychiatric  effects  are  seen  only  with  lipophilic  compounds  e.g.  metoprolol  and  
propranolol.  

Angiotensin-­‐‑ Increased  arousal,  anxiety,  fatigue,  insomnia  and  increased  psychomotor  

converting  enzyme   activity  (4-­‐‑8%)  
(ACE)  inhibitors  
Clonidine   Sedation  or  lethargy  (35%);  anxiety  (3%),  agitation  (3%),  depression  (1%),  and  
insomnia  (1%).  

Nitrates/nitrites   Delirium,  psychosis  (including  delusions),  anxiety,  restlessness,  agitation,  and  

hypomania.  

Digoxin   Depression  and  delirium  (even  in  therapeutic  levels)  

Statins   Uncertain  association  with  depression  (evidence  inconclusive)  
Corticosteroids   Mood  changes  (mania  more  than  depression),  anxiety,  agitation,  lethargy.  
Dose-­‐‑dependent.  1  in  6  patients  has  psychiatric  side  effects  if  prednisolone  is  
prescribed  in  doses  above  80mg/day.  Symptoms  start  within  2  weeks.  More  
common  in  females  and  those  with  past  psychiatric  history.    

Anabolic  androgenic   Acute  paranoia,  delirium,  mania  or  hypomania,  homicidal  rage,  aggression,  
steroids   and  extreme  mood  swings,  as  well  as  a  marked  increase  in  libido,  irritability,  
agitation,  and  anger.  Usually  dose-­‐‑dependent  and  resolve  in  1-­‐‑4  weeks  after  
  stopping  the  steroids.    

Gonadotropin-­‐‑ Depressive  symptoms  

releasing  hormone  
(GnRH)  agonists  (e.g.  
leuprolide)    

Interferon-­‐‑alpha   Nearly  40%  develop  psychiatric  side  effects;  ~20%  experience  depression.  Seen  
in  first  12  weeks  of  treatment.    

Penicillin   Sedation,  anxiety  and  hallucinations  

Cephalosporins   Delirium  

Ciprofloxacin  and   Restlessness,  irritability,  lethargy,  tremors,  insomnia,  mania,  depression,  

ofloxacin   psychosis,  delirium,  seizures,  or  catatonia  (incidence  ≤1%)  

Isoniazid   Delirium,  mania,  depression,  and  psychosis.  

Tetracyclines   Depression,  insomnia,  and  irritability  at  high  dosages.  

Antihistamines  and   Atropine-­‐‑like  psychosis  

©  SPMM  Course   27  
decongestants  

Proton  pump   Confusion,  agitation,  depression,  and  hallucinations—  mainly  in  geriatric  
inhibitors  &  H2-­‐‑ patients  with  impaired  hepatic-­‐‑renal  function.  
antagonists  used  for  
peptic  ulcer  disease    

Ondansetron   Anxiety  

Isotretinoin   Severe  depression  and  suicidal  behavior.  

Aminophylline  and   Agitation,  insomnia,  euphoria,  and  delirium  

salbutamol  

Depressogenic  drugs  

• Beta  blockers  
• Calcium  channel  blockers  
•  Interferons  (alpha  >  beta)  
•  Steroids  
•  Cyproterone,  progesterone  
•  Varenicline  
•  Isotretinoin  
•  Ezetimibe  

 Rimonabant:  Two  endocannabinoid  receptors  CB1  and  CB2  are  identified;  based  on  the  clinical  
observations  of  cannabis  related  increase  in  appetite  (the  “munchies”),  researchers  have  studied  
the  involvement  of  endocannabinoid  system  in  the  control  of  energy  balance.  Rimonabant,  the  
first  of  the  CB1-­‐‑receptor  antagonists,  was  developed  as  an  anti-­‐‑obesity  agent  on  the  premise  that  
blocking  central  cannabinoid  activity  might  reduce  food  intake.  But  there  is  compelling  evidence  
that  rimonabant  is  associated  with  the  development  of  severe  adverse  psychiatric  events  (2.5  
times  more  depression;  suicidal  ideas  and  3  times  more  anxiety).    

Animal  studies  have  consistently  shown  that  pharmacological  blockade  of  the  CB1  receptor  
impaired  the  anti  depressant-­‐‑reducing  or  anxiety-­‐‑reducing  actions  of  endocannabinoids.  FDA  
has  issued  a  warning  now  on  the  use  of  this  agent.    

©  SPMM  Course   28  
8. Prescribing controlled drugs
 

1971  MISUSE  OF  DRUGS  ACT  UK  

Class  A  drugs:  Ecstasy,  LSD,  heroin,  cocaine,  crack,  magic  mushrooms  (whether  prepared  or  fresh),  
methylamphetamine  (crystal  meth),  other  amphetamines  if  prepared  for  injection  
o Penalties  for  possession:  Up  to  seven  years  in  prison  or  an  unlimited  fine.  Or  both  
o Penalties  for  dealing:  Up  to  life  in  prison  or  an  unlimited  fine.  Or  both  

Class  B  drugs:  Amphetamines,  Methylphenidate  (Ritalin),  Pholcodine  

o Penalties  for  possession:  Up  to  five  years  in  prison  or  an  unlimited  fine.  Or  both  
o Penalties  for  dealing:  Up  to  14  years  in  prison  or  an  unlimited  fine.  Or  both.  

Class  C  drugs:  Cannabis,  tranquilisers,  some  painkillers,  GHB  (Gamma-­‐‑hydroxybutyrate),  ketamine  

o Penalties  for  possession:  Up  to  two  years  in  prison  or  an  unlimited  fine.  Or  both  
o Penalties  for  dealing:  Up  to  14  years  in  prison  or  an  unlimited  fine.  Or  both  

2001 MISUSE OF DRUGS REGULATIONS  

Schedule   Examples   Regulations  

1   Coca  leaf,  cannabis,  LSD,  mescaline   No  recognized  medicinal  use.  Supply  is  limited  to  
research  or  other  special  purposes  judged  to  be  in  the  
public  interest.    Requires  Home  Office  licence  to  
possess.  

2   Diamorphine,    dipipanone,   Subject  to  special  prescription  requirements  and  safe  

morphine,  remifentanil,  pethidine,   custody  requirements  (with  the  exception  of  
secobarbital,  glutethimide,   secobarbital).  Stock  drugs  must  be  recorded  in  a  
amphetamine  and  cocaine   register  that  meets  the  requirements  of  the  2001  
Regulations,  and  drug  stock  must  only  be  destroyed  
  in  the  presence  of  an  appropriately  authorized  person.  

3   The  barbiturates  (except   These  drugs  are  subject  to  the  special  prescription  
secobarbital),  buprenorphine,   requirements  (except  for  temazepam)  but  not  to  the  
diethylpropion,  mazindol,   safe  custody  requirements  (except  for  buprenorphine,  
meprobamate,  pentazocine,   diethylpropion,  flunitrazepam  and  temazepam)  or  to  
phentermine,  and  temazepam   the  need  to  keep  a  register,  although  there  are  
requirements  for  the  retention  of  invoices  for  2  years  

4   Part  1   Benzodiazepines  (not  temazepam)   These  drugs  are  not  subject  to  the  special  prescription  
and  zolpidem   requirements  or  to  safe  custody  requirements.  There  

©  SPMM  Course   29  
 Part  2   Androgenic  and  anabolic  steroids,   is  no  need  to  keep  a  register,  although  there  are  
clenbuterol,  chorionic   requirements  for  the  retention  of  invoices  for  2  years  
gonadotrophin  (HCG),  non-­‐‑human  
chorionic  gonadotrophin,  
somatotropin,  somatrem,  and  
somatropin  

5   Weak  preparations  of  drugs  usually   Exempt  from  all  controlled  drug  regulations  except  
in  other  schedules,  for  example,   the  need  to  keep  invoices  for  at  least  2  years  
morphine,  codeine  

All  controlled  drug  prescriptions  should  have    

¬ The  patient’s  full  name,  address  and  age  
¬ If  a  patient  is  homeless,  ‘no  fixed  abode’  is  an  acceptable  address    
¬ The  name  and  form  of  the  drug  MUST  be  written  
¬ The  strength  of  the  preparation,  where  appropriate    
¬ The  dose  to  be  taken  MUST  be  written  
¬ The  total  quantity  of  the  preparation,  or  the  number  of    dose  units,  to  be  supplied  in  both  
words  and  figures      
¬ A  patient  identifier  number  (e.g.  NHS  number)  should  be  included  on  prescriptions  for  
controlled  drugs    
¬ Prescriptions  must  be  signed  by  the  prescriber  with  their  usual  signature  (this  must  be  
handwritten)  along  with  GMC  number  as  a  good  practice  
¬ The  validity  period  of  prescriptions  for  Schedule  1,  2,  3  and  4  controlled  drugs  have  been  
restricted  to  28  days.  
¬ Schedule  2  and  3  drugs  cannot  be  prescribed  on  repeat  prescriptions  or  under  repeat  
dispensing  schemes.  
¬ Patients  ideally  should  collect  the  controlled  drug  in  person  after  showing  their  
identification  on  the  first  occasion  and  signing  the  back  of  the  prescription  form.  
¬ Substitute  opioids  should  be  prescribed  in  daily  instalments  whenever  required.  
Prescriptions  of  instalments  must  specify    
o The  number  of  instalments    
o The  interval  between  instalments,    
o Instructions  for  supplies  at  weekends  or  bank    holidays    
o The  total  quantity  to  provide    treatment  for  a  period  (this  must  not  be  exceeding  14  
days  generally)  
o The  quantity  to  be  supplied  in  each  instalment  along  with  the  duration  of  the  
instalments  to  be  set  out  on  the  prescription,  for  example  ‘dispense  daily  for  
fourteen  days  starting  on  3rd  September  2015’.    

©  SPMM  Course   30  
9. ADR Databases
It  is  vital  that  adverse  drug  reactions  (ADRs)  that  are  hitherto  unreported  are  detected  rapidly  
and  recorded  to  reduce  the  hazards  of  medical  prescribing.  Such  reports  will  also  trigger  
regulatory  action  to  ensure  further  patient  safety.  

MHRA  encourages  reporting  adverse  reaction  through  Yellow  Card  system  even  if  it  is  not  
certain  that  the  drug  has  caused  it,  or  if  the  reaction  is  well  recognised,  if  an  overdose  has  been  
taken  or  if  other  drugs  have  been  given  at  the  same  time.  Prescribers,  patients,  carers  and  
pharmacists  can  all  use  the  yellow  card  scheme.    

The  black  triangle  symbol  is  used  to  inform  that  a  preparation  is  newly  licensed  and  requires  
additional  monitoring  by  the  European  Medicines  Agency.  For  medicines  with  the  black  triangle  
symbol,  the  MHRA  requires  that  all  suspected  reactions  (including  those  that  are  not  serious)  be  
reported.  For  all  other  drugs,  the  yellow  cards  can  be  sued  to  report  side  effects  that  are  serious,  
medically  significant,  or  result  in  harm.  Adverse  drug  reactions  that  result  from  a  medication  
error  are  also  reportable  using  Yellow  cards.    

Term  used  to  describe  frequency   Rates  observed    

Very  common   Greater  than  1  in  10  

Common   1  in  100  to  1  in  10  

Uncommon  or  ‘less  commonly’  in  BNF   1  in  1000  to  1  in  100  

Rare   1  in  10  000  to  1  in  1000  

Very  rare   Less  than  1  in  10  000  

WHO  established  an  international  system  for  monitoring  adverse  reactions  to  drugs  (ADRs)  in  
1971.  This  is  located  at  WHO  Collaborating  Centre  for  International  Drug  Monitoring,  Uppsala  
Monitoring  Centre,  (UMC),  in  Sweden.  The  ADRs  database  held  by  WHO  contains  over  three  
million  reports  of  suspected  ADRs.  Similar  reporting  systems  exist  in  many  other  developed  
nations.  The  Canada  Vigilance  Adverse  Reaction  Online  Database  and  the  European  
Medicines  Agency  ADR  Reporting  systems  are  some  examples  of  other  well-­‐‑developed  
national/international  ADR  databases.    

 
©  SPMM  Course   31  
  

DISCLAIMER: This material is developed from various revision notes assembled while preparing for
MRCPsych exams. The content is periodically updated with excerpts from various published
sources including peer-reviewed journals, websites, patient information leaflets and books. These
sources are cited and acknowledged wherever possible; due to the structure of this material,
acknowledgements have not been possible for every passage/fact that is common knowledge
in psychiatry. We do not check the accuracy of drug related information using external sources;
no part of these notes should be used as prescribing information.

Notes prepared using excerpts from:

! Ashton,  H  &  Young,  A.  SSRIs,  drug  withdrawal  and  abuse:  Problem  or  treatment?  Selective  
Serotonin  Reuptake  Inhibitors  (SSRIs):  Past,  Present  and  Future,  Chapter  5,  1999.    
http://www.benzo.org.uk/ssri.htm  
! Bolland,  W.,  &  Simon,  C.  (2008).  Controlled  drugs:  regulations  and  prescribing.  InnovAiT:  The  
RCGP  Journal  for  Associates  in  Training,  1(2),  163-­‐‑171.  
! Brown  E  &  Chanlder  S.  Mood  and  Cognitive  Changes  During  Systemic  Corticosteroid  Therapy.  
Prim  Care  Companion  J  Clin  Psychiatry.  2001  Feb;  3(1):  17–21.    
! Di  Lorenzo,  R  &  Brogli,  A.  Neuropsychiatr Dis Treat. 2010; 6: 573–581.  
! Edwards  IR,  Aronson  JK.  Adverse  drug  reactions:  definitions,  diagnosis  and  management.  Lancet  
2000;  356:1255-­‐‑9.  
! http://www.evidence.nhs.uk/formulary/bnf/current/yellow-­‐‑card-­‐‑scheme  
! Jones,  O.  Managing  a  suspected  adverse  drug  reaction.  Student  BMJ  2001;  09:261-­‐‑304  
! Kaplan  &  Sadock'ʹs  Synopsis  of  Psychiatry:  Behavioral  Sciences/Clinical  Psychiatry,  10th  Edition.  
Lippincott  Williams  &  Wilkins  2007.  Pg  982.  
! Kasper,  S.  (2002)  Managing  reboxetine-­‐‑associated  urinary  hesitancy  in  a  patient  with  major  
depressive  disorder:  a  case  study.  Psychopharmacology,  159,  445-­‐‑446.  
! Lewis  S  &  Lieberman,  J.  T  he  British  Journal  of  Psychiatry  Mar  2008,  192  (3)  161-­‐‑163  
! Paton  C,  Ferrier  IN.  SSRIs  and  gastrointestinal  bleeding  BMJ  2005;  331  :529    
! Seeman  P,  Tallerico,  P.  Mol  Psychiatry.  1998  Mar;3(2):123-­‐‑34.  
! Shiloh,  R.,  Nutt,  D.  &  Weizman,  A.  (2000).  Atlas  of  psychiatric  pharmacotherapy.  Martin  Dunitz,  
London.  Page  18    
! Sidhu  KS  &  Balon  R  (2008).  Watch  for  nonpsychotropics  causing  psychiatric  side  effects.  Current  
Psychiatry;  7(4);  61  
! Swann,  A.  Major  system  toxicities  and  side  effects  of  anticonvulsants.  J  Clin  Psych  2001;  62  [16-­‐‑21]  
! Szabadi,  E.  (1998)  Doxazosin  for  reboxetine-­‐‑induced  urinary  hesitancy.  The  British  Journal  of  
Psychiatry,  173,  441b-­‐‑442.  
! Thakore,  JH.  The  British  Journal  of  Psychiatry  Jun  2005,  186  (6)  455-­‐‑456;  
! UK  Home  Office  http://drugs.homeoffice.gov.uk/drugs-­‐‑laws/misuse-­‐‑of-­‐‑drugs-­‐‑act/  
 
©  SPMM  Course   32  
 Psychotropics Adverse Effects Chart
© SPMM Course Worsening of glaucoma: paroxetine,
quetiapine, TCAs
Retinal pigmn: Thioridazine
Corneal deposits: CPZ
Visual field defects: vigabatrin
EPSEs: all neuroleptics (less for
Anticholinergic neuroleptics e.g. CPZ), higher
dose atypicals
Delirium: Anticholinergic TCAs, Anticholinergic
antipsychotics
Hypersalivation: clozapine
Seizures: bupropion, clozapine
Bruxism: stimulants
Tics: stimulants
Hypothyroidism: Li
Amnesia: BDZ

Myocarditis / Pul Embolism: clozapine

QT prolong: all antipsychotics esp
Hepatic damage: nefazodone, VPA, tacrine .Thioridazine, Pimozide, droperidol
Enz induction: CBZ, phenytoin, barbiturates Arrythmias: high dose TCAs
Ac. Pancreatitis: VPA High BP: VFX, TCAs
P.ileus: clozapine
GI bleed: SSRIs, AChEs

Fine tremors: therapeutic dose of lithium,

Wt gain: all antipsychotics (less for APZ, TCAs
ZPD), TCAs, Li, VPA, CBZ Coarse tremors: antipsychotic Parkinsonism,
Wt loss: Topiramate, Bupropion toxic lithium, valproate

Osteoporosis: hyperprolatinaemic
antipsychotics
Renal damage: Lithum WBC suppression: ^zapines(olanz, mirtaz,
Nephrolithiasis: topiramate cloz, carbama), mianserin
Haemolytic anaemia: nomifensine

Priapism: Trazodone, risperidone

PCOD: Valproate
Erectile dysfunction: all TCAs,
antipsychotics
Delayed ejacln or anorgasmia: SSRIs
U. Incontinence/hesitancy: reboxetine
Guillian Barre: Zimeldine
Pedal oedema: MAOIs
Rashes, SJS: CBZ, Lamotrigine Cramps: AchEs
Thrombocytopenia: Valproate Orthostatic hypotension: all TCAs, all
Sweating: all SSRIs, TCAs, esp. VFX antipsychotics
Acne, psoriasis: Li

AchEs: Anticholinesterases, BDZ: Benzodiazepines, CBZ: carbamazepine, CPZ: Chlorpromazine VFX: Venlafaxine VPA:
Valproate, SJS: Steven Johnson Syndrome,