Xenia Gonda

ABSTRACT Many common psychiatric disorders such as depression and anxiety disorders are associated with dysfunction in the monoamine neurotransmission in the central nervous system. However, the investigation of these pathophysiological processes in the human living brain is difficult. In case of functional magnetic resonance imaging (fMRI), a non-invasive method for the examination of brain activity, the activity-inducing stimulus is generally a cognitive psychological test, while during pharmacological magnetic resonance imaging (phMRI) the activation is triggered by a specific pharmacon. In the present work we review the available scientific literature related to this method using literature search in PubMed. Through application of a selective pharmacon like the selective serotonine reuptake inhibitors (SSRIs) citalopram or escitalopram in a challenge phMRI study, the serotonergic neurotransmitter system can be examined specifically, the functioning brain areas involved in its effect become observable.. With modulation phMRI we can monitor the long-term effect of an antidepressant or we can examine the immediate effect of a single dose of the medication on congitive psychological functions like emotional processing. Thus, the application of phMRI methods may help deepen our understanding of serotonergic function in the living human brain as well as of diseases related to serotonergic neurotransmitter system dysfunction.

Related to emotion regulation and mental health, adult attachment and affective temperaments are relevant research topics of contemporary psychiatry and clinical psychology. However, to date, only one study investigated the relationship between these two constructs. Thus, we aimed to further reveal adult attachment's association with affective temperaments. Affective temperament and adult attachment dimensions of 1469 Hungarian university students were assessed with self-report measures (Temperament Evaluation of Memphis, Pisa and San Diego autoquestionnaire and Experiences in Close Relationships Scale, respectively). Age and measured variables were compared between genders with ANOVAs. Associations between attachment dimensions and affective temperaments were examined with Pearson's correlations and partial correlations; the moderation effect of age and gender on these relationships was tested with PROCESS macro. Using Fisher r-to-z transformation, we also compared our resu...

Temperaments in completed suicides have never been assessed whereas there is substantial research on temperaments in attempted suicides and psychiatric patients. The significant others of 18 completed suicides participated in this study in order to provide an assessment of temperaments, hopelessness, depression and the suicide risk of their loved ones. The data were compared with data from 244 psychiatric patients of whom 83 had attempted suicide in the previous month. The following instruments were used: the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire (TEMPS-A), the Beck Hopelessness Scale (BHS), the Gotland Scale for Male Depression (GSMD), and the Mini International Neuropsychiatric Interview (MINI) module for assessing suicide risk. Individuals who died by suicide more frequently had scores of 9 or higher on the BHS and higher MINI suicide risk scores compared with patients with mood disorders who had not attempted suicide in the previous month. Completed suicides also had lower scores on the TEMPS-A Cyclothymia and Anxiety scales and on the MINI suicide risk scale than mood disorder patients with a recent suicide attempt. Proxy assessment of variables through survivors can result in underestimation of psychiatric morbidity and other parameters investigated, and limits the generalization of our results Our study adds information about temperamental subtypes and other variables in completed suicides and points to their difference from attempted suicides and non-suicidal psychiatric patients.

Alterations in the serotonin transporter (5-HTT) have been implicated in a variety of psychiatric disorders including cocaine dependence. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) appears to influence the expression of 5-HTT in human cell lines. We investigated whether 5-HTTLPR variants were related to differences in measures of platelet 5-HTT sites in cocaine-dependent patients and healthy volunteers (controls). Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism in 5-HTTLPR was performed in 138 cocaine-dependent African-American subjects and 60 African-American controls. This yielded a short (S) and a long (L) allele. Platelet 5-HTT sites were measured using the tritiated paroxetine binding assay. Relationships of 5-HTTLPR genotypes with Bmax (density of serotonin transporter) and Kd (affinity constant) were examined. Bmax values were significantly lower in cocaine-dependent patients (640 +/- 233) than controls (906 +/- 225) (P < 0.001); however, 5-HTTLPR genotype distributions or allele frequencies did not differ between the two groups. There were no significant differences in Bmax between the three genotypes among cocaine-dependent patients (LL = 690 +/- 246, LS = 620 +/- 235, SS = 587 +/- 183; P = 0.14) or controls (LL = 909 +/- 233, LS = 938 +/- 279, SS = 866 +/- 143; P = 0.65). All three genotypes in cocaine-dependent patients showed comparable reductions in Bmax from the corresponding genotypes in controls. Demographic variables, severity of substance use or depression were unrelated to Bmax or 5-HTTLPR genotypes. Although platelet 5-HTT densities are reduced in patients with cocaine dependence compared with healthy volunteers, these genotypic variations in the serotonin transporter do not seem to influence levels of platelet 5-HTT in cocaine-dependent patients or healthy volunteers.

Only a minor part of headaches are associated with an organic abnormality in the nervous system. In case of migraine and tension headache, the main provoking factor is psychological stress. Furthermore, these syndromes often occur together with depression and anxiety disorders, and when these comorbid conditions are present headache attacks tend to be more frequent, longer and stronger, causing an increase in the consumption of antimigraine agents, and at the same time increase the consumption of antidepressant and anxiolytic agents. Further to drugs, modified versions of Schultz-type autogenic training is also frequently used for anxiolysis. The aim of our research was to study the effect of the cognitive and symbol therapy enhanced autogenic training on headache and related drug consumption in three different types of primary headaches. Twenty five female patients with migraine, tension-type headache or mixed headache participated in an eight-month follow-up study. Headache frequency, analgesic, antimigraine and anxiolytic consumption were measured by means of a headache diary. During the first four months (observation phase) patients became familiar with using the diary, and in the second four months they participated in autogenic training. The data of the second, third and fourth months were considered as baseline data. Our method decreased headache frequency and drug consumption in all three headache groups. This means that the cognitive and symbol therapy enhanced autogenic training is an effective alternative for medications in the treatment of primary headaches.

Depression is frequent in primary care, but correct diagnosis of these disorders is a challenge for general practitioners. Our current study describes the point prevalence of affective syndromes meeting DSM-IV criteria for depression in 984 adult patients visiting primary care practices. General practitioners applied the Beck Depression Inventory and the PRIME-MD screening tool. In case of all depressive disorders according to DSM-IV criteria (major depression, major depression in partial remission, dysthymia, minor depression) current prevalence rate was 18.5%, while point prevalence of only major depressive episode was 7.3%. Using the Beck Depression Inventory, general practitioners could diagnose current depression with a sensitivity of 95% and a specificity of 56%, while in case of major depressive episode sensitivity was 83% and specificity was 23%. These results parallel earlier data from Hungary as well as from other countries and they also support that the PRIME-MD and the Beck Depression Inventory may be a useful screening tool for depressive disorders in general practice.

We would like to draw attention to the fact that the recently published DSM-5 (and also its predecessor, DSM-IV) contains annoying errors that are mainly logical in nature. These mistakes are undoubtedly a result of inadvertence, rather than either conceptual (professional) disagreements between authors/editors or shortage of scientific data for appropriate circumscription of diagnostic categories. The good news is that since these errors are mainly logical ones, they can be recognised and repaired.

Anxiety disorders are highly prevalent psychiatric diseases. In this short review we provide an overview of concepts of fear, anxiety and anxiety disorders. In addition, based on the recent literature, neuroanatomical structures involved in anxiety and functional/structural changes of these structures in anxiety disorders are also discussed. Furthemore, the pitfalls of anxiolytic drug discovery is also concerned in the paper.

After the original proposals of staging for psychotic disorders developed by McGorry and colleagues, a few systems have been put forward specifically for people with bipolar disorder. There is now consistent evidence that, at least for a significant portion of people with this disease, clinical course and outcome are not as benign as initially described. The evidence thus far points to relevant differences between early and late stages of bipolar disorders in the clinical course of illness, neurobiology and systemic pathology. These differences all suggest that staging is a viable addition to clinical care in bipolar disorder. Neuroprogression and Staging in Bipolar Disorder provides a comprehensive summary of the current state of the evidence regarding the use of staging systems in bipolar disorder. Edited by the leading researchers in the field, the book systematically covers the theoretical basis for staging, comparisons between different proposals, neurobiological underpinnings,...

Research studies suggest that glutamate dysfunction, in particular N-methyl-D-aspartate receptors (NMDARs) abnormalities, may be involved in the pathophysiology of major neuropsychiatric conditions. Increased glutamatergic excitotoxic activity may be found in some brain circuits of patients with major depression. According to several published reports, NMDAR antagonists may exert antidepressant activity, but the molecular changes associated with abnormal glutamatergic neurotransmission remain unclear. We have critically reviewed the current literature in order to investigate the role of NMDAR antagonists in major depression. NMDAR antagonists, such as ketamine, may be considered novel and promising pharmacological options for the rapid treatment of treatment-resistant depression patients. This is in contrast to the delayed action of the currently available antidepressant medications. Studies suggest that glutamatergic receptor modulation may enhance neuroplasticity mechanisms and ne...

5-HT1A receptor is a receptor of surprises. Buspirone, an anxiolytic drug with a then yet unidentified mechanism of action had been marketed for years when it was discovered that it is a 5-HT1A partial agonist. Several more years had to pass before it was accepted that this receptor plays the key role in the action mechanism of buspirone. This was followed by further surprises. It was discovered that in spite of its anxiolytic effect buspirone activates the hypothalamic-pituitary-adrenal (HPA) stress axis, furthermore, it increases peripheral noradrenaline and adrenaline concentration via a central mechanism. Thus activation of this receptor leads to ACTH/corticosterone and catecholamine release and also increases beta-endorphine, oxytocin and prolactin secretion while decreasing body temperature, increasing food uptake, eliciting characteristic behavioural responses in rodents and also playing a role in the development of certain types of epilepsy. Human genetic studies revealed th...

Many common psychiatric disorders such as depression and anxiety disorders are associated with dysfunction in the monoamine neurotransmission in the central nervous system. However, the investigation of these pathophysiological processes in the human living brain is difficult. In case of functional magnetic resonance imaging (fMRI), a non-invasive method for the examination of brain activity, the activity-inducing stimulus is generally a cognitive psychological test, while during pharmacological magnetic resonance imaging (phMRI) the activation is triggered by a specific pharmacon. In the present work we review the available scientific literature related to this method using literature search in PubMed. Through application of a selective pharmacon like the selective serotonine reuptake inhibitors (SSRIs) citalopram or escitalopram in a challenge phMRI study, the serotonergic neurotransmitter system can be examined specifically, the functioning brain areas involved in its effect beco...

Arsenic-contaminated drinking water (ACDW) represents a major global public health problem. A few previous studies suggested that consuming ACDW may be associated with elevated risk for depression. Since depression is the most relevant risk factor for suicide, we hypothesized that consumption of ACDW may be also associated with suicide. To investigate this, we compared the age-standardized suicide rates (SSR) of 1639 Hungarian settlements with low (≤10μg/l), intermediate (11-30μg/l), high (31-50μg/l) and very high (≥51μg/l) levels of arsenic in drinking water. We found a positive association between SSR and consumption of ACDW. (1) we used aggregated (i.e., non-individual) data; (2) we have not adjusted our model for important medical and socio-demographic determinants of suicidal behavior; (3) we had no data on differences in bottled water consumption between settlements. Our results indicate that in addition to its well-known adverse health effects, consumption of ACDW may also be associated with suicidal behavior.

Major Depressive Disorder (MDD) is one of the most common psychiatric diagnoses, accompanied by several psychological, behavioural and emotional symptoms, and in addition to the symptoms affecting the quality of life, it can lead to severe consequences, including suicide. Sequence learning plays a key role in adapting to the environment, neural plasticity, first language acquisition, social learning and skills, at the same time it defines the behaviour of the patient and also therapeutic possibilities. The aim of this paper is to review sequence learning and its consolidation in MDD. We know little about the effects of mood disorders on sequence learning; the results are contradictory, therefore, further studies are needed to test the effects of MDD on sequence learning and on the consolidation of implicitly acquired sequence knowledge.

Current research focusing on the biological background of premenstrual syndrome suggests that both psychological and physiological factors exert their effect by means of the dysregulation of the serotonergic function. The results of several studies point to a variation in the function of the serotonergic system throughout the cycle, which is related to the plasma concentration of the gonadal steroid hormones. Certain parameters of serotonergic function show different values in the different phases of the cycle. The rise in oestrogen concentration is followed by an increase in the 5HT2A receptor expression in brain areas responsible for mood, emotion, cognition and neuroendocrine regulation. The role of serotonin is further supported by its role in depression, anxiety, aggression as well as the efficiency of serotonergic agents in the treatment of premenstrual syndrome. In our article we review the main theories concerning the biological background of the premenstrual syndrome, and w...

The most frequent serious psychological side effect of immune therapies is depression. In the present study, we tested whether social support, as a positive environmental effect, is able to moderate depression or anxiety symptoms in melanoma patients during adjuvant low-dose interferon treatment. Hundred and twenty-seven melanoma patients with negative psychiatric history were included in our longitudinal study and followed up for one year. Depression and anxiety symptoms were measured six times during treatment: at baseline, at 1st, 3rd, 6th, 9th and 12th month of the therapy. In addition, social support was investigated with the Social Dimension Scale. Depressive symptoms significantly increased during the 12-month follow-up period (p<0.001). However, social support significantly moderated the depressogenic effect of low-dose interferon treatment (p<0.001). Patients with better social support showed attenuated increase of depression. Anxiety showed no significant changes during the low-dose interferon treatment (p=0.230). Social support had no moderating effect on anxiety symptoms (p=0.745) during the follow up. Our data provide evidence that social support and interferon alpha treatment significantly interact in the development of depression. In addition, our study emphasises that enhancement of social support can reduce depressogenic side effects and increase compliance during adjuvant interferon treatment, and thus, psychological screening and psychooncological counselling should be incorporated in the treatment protocol.

Stress is considered as a major contributor to the development and exacerbation of psoriasis by a significant proportion of patients and dermatologists. As both stressor and its effects are subject-dependent, thus extremely difficult to measure, our understanding of the exact role of stress in disease development was limited for a long time. In the past decade several new studies were carried out which expanded our knowledge on the pathophysiologic processes linking stress to psoriasis via with their objective measurements and the applied new techniques. The authors review the current literature of both psychological (alexithymia, personality, affect) and biological (cortisol, epinephrine, neurogenic inflammation) factors influencing stress perception and response in psoriasis. Results of recent investigations support previous reports about the interaction between stress and psoriasis with objective evidence. Knowing how effective stress-reducing psychopharmacologic and psychotherapeutic interventions are in the treatment of psoriasis the authors hope that this review contributes to a wider acceptance of the psychosomatic attitude in everyday dermatologic practice.

Alterations in the serotonin transporter (5-HTT) have been implicated in a variety of psychiatric disorders including cocaine dependence. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) appears to influence the expression of 5-HTT in human cell lines. We investigated whether 5-HTTLPR variants were related to differences in measures of platelet 5-HTT sites in cocaine-dependent patients and healthy volunteers (controls). Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism in 5-HTTLPR was performed in 138 cocaine-dependent African-American subjects and 60 African-American controls. This yielded a short (S) and a long (L) allele. Platelet 5-HTT sites were measured using the tritiated paroxetine binding assay. Relationships of 5-HTTLPR genotypes with Bmax (density of serotonin transporter) and Kd (affinity constant) were examined. Bmax values were significantly lower in cocaine-dependent patients (640 +/- 233) than controls (906 +/- 225) (P < 0.001); however, 5-HTTLPR genotype distributions or allele frequencies did not differ between the two groups. There were no significant differences in Bmax between the three genotypes among cocaine-dependent patients (LL = 690 +/- 246, LS = 620 +/- 235, SS = 587 +/- 183; P = 0.14) or controls (LL = 909 +/- 233, LS = 938 +/- 279, SS = 866 +/- 143; P = 0.65). All three genotypes in cocaine-dependent patients showed comparable reductions in Bmax from the corresponding genotypes in controls. Demographic variables, severity of substance use or depression were unrelated to Bmax or 5-HTTLPR genotypes. Although platelet 5-HTT densities are reduced in patients with cocaine dependence compared with healthy volunteers, these genotypic variations in the serotonin transporter do not seem to influence levels of platelet 5-HTT in cocaine-dependent patients or healthy volunteers.

Smoking behaviour and its course is influenced by personality factors. Affective temperaments could allow a more specific framework of the role trait affectivity plays in this seriously harmful health-behaviour. The aim of our study was to investigate if such an association exists in an ageing population with a special emphasis on gender differences. 459 primary care patients completed the TEMPS-A, Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HAM-A). Subjects were characterized according to their smoking behaviour as current, former or never smokers. Univariate analysis ANOVA and logistic regression were performed to analyse differences in the three smoking subgroups to predict smoking initiation and maintenance. Current smokers were younger and less educated than former or never smokers. Males were more likely to try tobacco during their lifetime and were more successful in cessation. Depressive, cyclothymic and irritable temperament scores showed significant differences between the three smoking subgroups. Irritable temperament was a predictor of smoking initiation in females whereas depressive temperament predicted smoking maintenance in males with a small, opposite effect of HAM-A scores independent of age, education, lifetime depression and BDI scores. Whereas smoking initiation was exclusively predicted by a higher BDI score in males, smoking maintenance was predicted by younger age and lower education in females. The cross-sectional nature of the study design may lead to selective survival bias and hinder drawing causal relationships. Affective temperaments contribute to smoking initiation and maintenance independently of age, education, and depression. The significant contribution of depressive temperament in males and irritable temperament in females may highlight the role of gender-discordant temperaments in vulnerable subgroups.

Introduction This Report from the WPA Section on Pharmacopsychiatry examines the possible relationship of antiepileptic drugs with suicide-related clinical features and behaviours in patients with epilepsy. Material and methods A systematic review of the MEDLINE search returned 1039 papers, of which only 8 were considered relevant. A critical analysis of the FDA report on the increase risk for patients under antiepileptics to manifest suicidality is also included in this report. Results The analysis of these studies revealed that the data are not supportive of the presence of a 'class effect' on suicide related behaviour; on the contrary there are some data suggesting such an effect concerning treatment with topiramate, lamotrigine and levetiracetam for which further research is needed. Discussion For the majority of people with epilepsy, anticonvulsant treatment is necessary and its failure for any reason is expected to have deleterious consequences. Therefore, clinicians s...

It is unclear whether there is a direct link between economic crises and changes in suicide rates. The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates. Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation. There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged. Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.

Predominant polarity (PP) is a proposed course specifier for bipolar disorder, which was not incorporated in the DSM-5 as a descriptor for the nosology of bipolar disorder (BD). Here we perform a systematic review of original studies about PP. A computerized search of MEDLINE/Pubmed, EMBASE and Web of Science databases from inception to October 6th, 2013 was performed with keywords, including 'bipolar disorder', 'polarity' and 'predominant polarity'. A total of 19 studies met inclusion criteria. A unifying definition and conceptualization for PP is lacking. A PP is found in approximately half of BD patients. Most studies that included type I BD patients found the manic PP to be more prevalent, while studies that included type II BD participants found a higher prevalence of depressive PP. The depressive PP has been consistently associated with a depressive onset of illness, a delayed diagnosis of BD, type II BD and higher rates of suicidal acts. The manic PP is associated with a younger onset of illness, a first episode manic/psychotic and a higher rate of substance abuse. Evidence suggests that PP may influence responses to acute treatment for bipolar depression. Furthermore, evidences indicate that PP should be considered for the selection of maintenance treatments for BD. There are few prospective studies on PP. There were disparate definitions for PP across studies. The concept of PP provides relevant information for clinicians. Future studies should investigate the genetic and biological underpinnings of PP.

ABSTRACT There is a marked overlap between the neuronal pathways involved in sleep/wake regulation and depression. Both the structure and the organization of sleep are altered in depressed patients; they enter the rapid eye movement (REM) sleep earlier, the amount of REM is increased and also the non-REM sleep is reduced in the first sleep cycle.Serotonin reuptake inhibitor antidepressants (SSRIs) exert their therapeutic effect on the serotonergic system, which has a central role in the modulation of mood and vigilance.AimsThe aim of this study was to investigate the acute and long-term effect of the SSRI escitalopram on REM sleep in rats.Methods The effect of a single (10 mg/kg i.p.) and chronically administered (10 mg/kg/day, released by an osmotic mini pump for 21-day-long) escitalopram was studied in male Wistar rats. Electroencephalogram, electromyogram and motility were recorded for three hours starting at light onset.ResultsThe acutely administered escitalopram significantly reduced the time spent in REM sleep in the first three hours, compared to control. However, this REM-reducing effect was abolished after chronic administration.Conclusion There was a clear difference in the effect of escitalopram on REM sleep following acute and chronic administration, providing evidence for the adaptive changes of serotonin receptors, which take several weeks to evolve, and considered to have a role in the development of therapeutic effect of SSRIs in the treatment of depression. This study was supported by the TAMOP-2.2.1. B-09/1/KMR-2010-0001 and by Richter Gedeon Plc.

ABSTRACT Altered serum levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNFalpha) have been implicated in therapy response of depression. We analyzed effects of 4 functional SNPs of VEGF and TNF alpha genes on MDD to test their possible role in pathomechanism of MDD.We recruited 293 inpatients diagnosed for major depressive disorder (MDD) and 443 healthy volunteers. MDD was diagnosed by DSM-IV criteria and measured by Montgomery-Asberg Depression Scale (MADRS). DNA was extracted from buccal mucosa samples given by all participants. Likelihood ratio tests for case-control and mutlivariate linear analysis for quantitative phenotype models were performed in SPSS 17.0 software. We identified a protective allele against MDD as the frequency of G allele of rs1800629 (previously associated with lower TNFa serum level) was 2.7 fold higher in the control group compared to MDD group (LRT = 4.197; p = 0.040). Higher frequency of the same allele was found among SSRI responders compared to non-responders (LRT = 6.281; p = 0.012). Significant GxG interactions were shown within MDD group: epistatic effect of allele variants and also genotypes of the four investigated SNPs were significant on MADRS score (for risk alleles: pmodell = 0.024; pinteraction = 0.005; Adj.R2 = 0.259; for genotypes: pmodell = 0.035; pinteraction = 0.007; Adj.R2 = 0.371). These findings suggest that TNFalpha and VEGF genes are associated with MDD and SSRI response. Our results support the molecular crosstalk between VEGF and TNFalpha pathway by a genetic interaction.This study was supported by the Hungarian Scientific Research Fund Grant (OTKA CK 80289/2009).