TYPE
Study Protocol
12 December 2022
10.3389/fpsyg.2022.1012776
PUBLISHED
DOI
OPEN ACCESS
EDITED BY
Edo S. Jaya,
Indonesian Psychological Healthcare
Center, Indonesia
REVIEWED BY
Brandy F. Henry,
The Pennsylvania State University,
United States
Nimaz Dewantary,
Indonesian Psychological Healthcare
Center, Indonesia
Luciana Diaz Cutraro,
Parc Sanitari Sant Joan de Déu, Spain
A multiple baseline trial of
adapted prolonged exposure
psychotherapy for individuals
with early phase psychosis,
comorbid substance misuse, and
a history of adversity: A study
protocol
*CORRESPONDENCE
Alissa Pencer
alissa.pencer@dal.ca
SPECIALTY SECTION
This article was submitted to
Psychopathology,
a section of the journal
Frontiers in Psychology
RECEIVED 05
August 2022
November 2022
PUBLISHED 12 December 2022
ACCEPTED 08
CITATION
Patterson VC, Tibbo PG, Stewart SH,
Town J, Crocker CE, Ursuliak Z, Lee S,
Morrison J, Abidi S, Dempster K,
Alexiadis M, Henderson N and
Pencer A (2022) A multiple baseline trial of
adapted prolonged exposure
psychotherapy for individuals with early
phase psychosis, comorbid substance
misuse, and a history of adversity: A study
protocol.
Front. Psychol. 13:1012776.
doi: 10.3389/fpsyg.2022.1012776
COPYRIGHT
© 2022 Patterson, Tibbo, Stewart, Town,
Crocker, Ursuliak, Lee, Morrison, Abidi,
Dempster, Alexiadis, Henderson and
Pencer. This is an open-access article
distributed under the terms of the Creative
Commons Attribution License (CC BY). The
use, distribution or reproduction in other
forums is permitted, provided the original
author(s) and the copyright owner(s) are
credited and that the original publication in
this journal is cited, in accordance with
accepted academic practice. No use,
distribution or reproduction is permitted
which does not comply with these terms.
Frontiers in Psychology
Victoria C. Patterson 1, Philip G. Tibbo 1,2,3,4, Sherry H.
Stewart 1,2,3, Joel Town 1,2,3, Candice E. Crocker 2,3, Zenovia
Ursuliak 2,3, Siranda Lee 3, Jason Morrison 2,3, Sabina Abidi 2,4,
Kara Dempster 2,3, Maria Alexiadis 2,3, Neal Henderson 3 and
Alissa Pencer 1,2,3,4*
1
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS, Canada,
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada, 3 Mental Health and
Addictions, Nova Scotia Health, Halifax, NS, Canada, 4 Mental Health and Addictions, IWK Health,
Halifax, NS, Canada
2
Background: Adversity is prevalent among people with psychotic disorders,
especially those within the first 5years of a psychotic disorder, called early
phase psychosis. Although adversity can lead to many negative outcomes
(e.g., posttraumatic stress symptoms), very few treatments for adversityrelated sequelae have been tested with individuals with psychotic disorders,
and even fewer studies have specifically tested interventions for people in early
phase psychosis. Furthermore, people who misuse substances are commonly
excluded from adversity treatment trials, which is problematic given that
individuals with early phase psychosis have high rates of substance misuse.
For the first time, this trial will examine the outcomes of an adapted 15-session
prolonged exposure protocol (i.e., PE+) to observe whether reductions in
adversity-related psychopathology occurs among people with early phase
psychosis and comorbid substance misuse.
Methods: This study will use a multiple-baseline design with randomization
of participants to treatment start time. Participants will complete baseline
appointments prior to therapy, engage in assessments between each of the
five therapy modules, and complete a series of follow-up appointments
2months after the completion of therapy. Primary hypothesized outcomes
include clinically significant reductions in (1) negative psychotic symptoms
measured using the Positive and Negative Syndrome Scale, (2) adversityrelated sequelae measured using the Trauma Symptom Checklist-40, and (3)
substance use frequency and overall risk score measured with the Alcohol,
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10.3389/fpsyg.2022.1012776
Smoking, and Substance Involvement Screening Test. We also anticipate
that clinically significant reductions in hopelessness and experiential
avoidance, measured with the Beck Hopelessness Scale and Brief Experiential
Avoidance Questionnaire, the theorized mechanisms of change of PE+, will
also be observed. A secondary outcome is a hypothesized improvement in
functioning, measured using the Clinical Global Impression and Social and
Occupational Functioning Assessment scales.
Discussion: The results of this treatment trial will contribute to the
advancement of treatment research for individuals in early phase psychosis
who have current substance misuse and a history of adversity, and the findings
may provide evidence supporting the use of hopelessness and experiential
avoidance as mechanisms of change for this treatment.
Clinical trial registration: Clinicaltrials.gov, NCT04546178; registered August
28, 2020, https://clinicaltrials.gov/ct2/show/NCT04546178?term=NCT04546
178&draw=2&rank=1.
KEYWORDS
prolonged exposure, early phase psychosis, adversity, substance misuse, cognitivebehavioral therapy
Introduction
onset of psychosis and clinical outcomes (Janssen et al., 2004; van
Os et al., 2009; Conus et al., 2010; Varese et al., 2012). The
psychosis proneness-persistence-impairment model (van Os et al.,
2009) states that psychological mechanisms, many of which are
common outcomes of adversity exposure (e.g., dissociation,
external locus of control), can sensitize an individual at risk for
psychosis, resulting in the emergence and persistence of psychotic
symptoms. Previous studies have found rates of adversity exposure
among young adults in early phase psychosis (EPP; i.e., first 5 years
of a psychotic illness) ranging from 30 to 96% (Neria et al., 2002;
Gearon et al., 2003; Bendall et al., 2007; Üçok and Bıkmaz, 2007;
Ramsay et al., 2011; Varese et al., 2012; Trauelsen et al., 2015;
DeTore et al., 2021), with a mean of four lifetime adverse event
exposures (Gearon et al., 2003; Steel et al., 2011). Adversity
exposure is associated with delays in accessing treatment for
psychosis (Veru et al., 2022), experiencing more severe psychotic
symptoms (Bailey et al., 2018), and a slower recovery during
treatment for psychosis (Aas et al., 2016). Experiencing both
adversity and EPP is associated with the development of comorbid
psychopathology (e.g., depression, post-traumatic stress disorder;
Trauelsen et al., 2015), including the development of substance
misuse (Phillips and Johnson, 2001; Khoury et al., 2010).
Substance misuse (SM), defined as the problematic use of
drugs and alcohol that interferes with functioning, represents
another major individual influence on psychosis onset and clinical
outcomes (National Collaborating Centre for Mental Health (UK),
2008; Nathan and Lewis, 2021). SM is another broad term that
encompasses but is not limited to substance use disorders (SUDs),
as well as including substance use that is harmful (e.g., binge
drinking) but does not meet criteria for an SUD (Mclellan, 2017).
Similar to the proneness-persistence-impairment model above,
Adversity and substance misuse among
people with psychotic disorders
Adversity, which can be defined as the experience of a negative
life event that was stressful, uncontrollable, and either was or
could have been harmful (Burgermeister, 2007), encompasses
both traumatic events (e.g., child abuse) and non-life-threatening
events with a similarly negative impact (e.g., discrimination).
Adversity exposure is a significant individual influence on the
Abbreviations: 2SLGBTQ+: two-spirit, lesbian, gay, bisexual, transgender,
queer+individuals; APA: American Psychological Association; BEAQ: brief
experiential avoidance questionnaire; BHS: Beck hopelessness scale; CBT:
cognitive-behavioral therapy; CGI-I: clinical global impression-improvement
of illness; CGI-S: clinical global impression-severity of illness; DBT: dialectical
behavior therapy; EMDR: eye movement desensitization and reprocessing
therapy; EPP: early phase psychosis; ISTDP: intensive short-term dynamic
psychotherapy; MBD: multiple baseline design; NIH: National Institutes of
Health; NSEPP: Nova Scotia Early Psychosis Program; PCL-5: posttraumatic
stress disorder checklist-5; PE: prolonged exposure therapy; PE+: adapted
prolonged exposure therapy; PTSD: posttraumatic stress disorder; RCI: reliable
change index; RCT: randomized control trial; SM: substance misuse;
SCI-PANSS: structured clinical interview-positive and negative syndrome
scale; SOFAS: social and occupational functioning assessment scale; SRS-3:
session rating scale-3; TALE: trauma and life events checklist; TF-CBT: traumafocused cognitive-behavioral therapy; TSC-40: trauma symptom checklist-40;
WHO ASSIST: World Health Organization’s Alcohol, Smoking, and Substance
Involvement Screening Test.
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the stress and coping theory of SM (Wills and Hirky, 1996) posits
that psychological mechanisms (e.g., self-efficacy) may play a role
in the development and maintenance of SM. Estimates of SM
prevalence among individuals with EPP exceed 80% (OuelletPlamondon et al., 2017; Cookey et al., 2020), which is remarkably
elevated when compared to the 50% prevalence rate among people
who have been living with psychosis for over 10 years [i.e., chronic
psychosis (Rosenberg et al., 2007)]. Cannabis and alcohol are the
most commonly misused substances among people with EPP, with
estimated prevalence rates of 70 and 62% (Cookey et al., 2020),
and nearly 25% of those in EPP engage in polysubstance misuse
(i.e., misuse of 2 or more substances; Ouellet-Plamondon
et al., 2017).
SM is associated with more negative outcomes related to the
psychotic disorder (Lambert et al., 2005), including increased
hallucinations and delusions, lower recovery rates, and lower
functioning (González-Pinto et al., 2011; Abdel-Baki et al., 2017).
Individuals with SM, psychosis, and a history of adversity also
report more distressing hallucinations (Steel et al., 2011), a higher
likelihood of developing PTSD (Gearon et al., 2003), and an
increased risk of victimization in adulthood (Walsh et al., 2003;
Seid et al., 2021). In summary, adversity and SM are highly
prevalent among individuals with EPP, they may play a role in
psychosis onset, and they are associated with negative outcomes
that have a significant impact on the individual level.
was a major motivating factor for participants to initiate and
continue to participate in the intervention. Although the
participants reported that the intervention was distressing, they
also experienced relief and found it beneficial overall (Tong et al.,
2017). Participating in an adversity-focused intervention can also
help to foster insight into factors leading to the development and
maintenance of psychosis (e.g., avoidance), which can aid in
recovery (Halpin et al., 2016).
Despite the perceived benefits of participating in an adversityfocused intervention, people with psychosis are routinely
excluded; psychosis is the most common exclusion criteria for
adversity-specific treatment trials, used in over 90% of trials
(Ronconi et al., 2014). Additionally, the few studies that have
examined the effects of adversity-focused treatment among people
with psychosis primarily focused on individuals with chronic
psychosis or included individuals in different phases of a psychotic
disorder. Consequently, little is known about treatment effects
specifically among people with EPP.
Adversity-specific treatments for people
with psychotic disorders
Steel et al. (2017) conducted a randomized controlled trial
(RCT) of cognitive restructuring for posttraumatic stress disorder
(PTSD) in individuals with schizophrenia. This treatment did not
significantly improve either PTSD or psychotic symptoms—the
authors suggested that cognitive restructuring on its own was
insufficient and that exposure, an efficacious therapeutic
component (see Foa and McLean, 2016, for a review), may
be needed to effect clinically significant change. More recently, a
trauma-focused CBT for psychosis trial with an exposure
component (TF-CBTp; Keen et al., 2017) found that individuals
with a psychotic disorder and a complex trauma history
experienced improvements in depressive symptoms, anxiety,
delusions, PTSD symptoms, and well-being following therapy,
although hallucination frequency did not change. Qualitative
results highlighted the utility of an integrated approach to treating
psychotic symptoms and adversity sequelae. Taken together, these
findings suggest that exposure may be needed to effect clinically
significant symptom change.
Prolonged Exposure (PE) therapy is an evidence-based form
of cognitive behavioral therapy that includes a significant exposure
component. PE is one of the most rigorously studied treatment
options for people with a psychotic disorder and a history of
adversity. An RCT of adults with chronic psychosis and PTSD
(mean age = 41) compared PE and EMDR to a waitlist control
group (van den Berg et al., 2015). This study found that, compared
to the waitlist control group, the PE group experienced a
significant reduction in PTSD symptoms and greater rates of
PTSD diagnosis remission, even when participants had a
dissociative subtype of PTSD (van Minnen et al., 2016). PE
therapy also appeared to significantly reduce paranoia and
depressive symptoms and improve functioning (de Bont et al.,
Benefits of adversity-specific treatment
in EPP
Psychological treatments may be especially effective for people
with EPP, a history of adversity, and SM. This type of treatment
can target adversity-related sequelae that trigger and maintain
psychosis and SM (e.g., avoidance and dissociation). In addition,
treatment can target common comorbid psychopathology (e.g.,
depression and anxiety) that may be lowering functioning
(Scheller-Gilkey et al., 2004), causing distress, and lowering the
quality of life.
There is some evidence that psychological interventions
targeting adversity-related sequelae delivered to individuals with
psychotic disorders may improve long-term outcomes for both
psychosis and adversity-related psychopathology (e.g., improved
quality of life and increased remission rates; Crumlish et al., 2009;
van den Berg et al., 2016), especially for those with a substantial
history of adversity (Kilian et al., 2020). Furthermore, compared
to individuals with chronic psychosis, young adults in EPP may
be able to better engage in and benefit from an adversity-focused
psychological intervention because they have not yet sustained the
same degree of biological and psychological burden of a long-term
psychotic illness (Lieberman et al., 2001).
Importantly, young adults with EPP want treatment for
difficulties related to adversity. Australian individuals in EPP
discussed their experiences receiving an adversity-focused
intervention (Tong et al., 2017), noting that a desire for change
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2016). Grubaugh et al. (2017) replicated these results among
veterans with a psychotic disorder and PTSD (Mage = 46.8). Most
participants who completed at least eight PE treatment sessions
experienced PTSD symptom remission by the end of treatment.
In short, PE therapy appears to effectively reduce psychopathology
in individuals with chronic psychosis.
Although some work examines PE treatment among people
with psychosis and a history of adversity, there are no PE treatment
trials that have included individuals with a psychotic disorder,
history of adversity, and SM. In fact, SUDs (previously specified
as ‘substance dependence’) are the second most common exclusion
criteria for adversity-focused treatment trials, after psychosis,
meaning that many individuals with EPP have likely been
excluded from previous PE treatment research due to the high
rates of substance misuse (a term inclusive of SUDs) among those
with EPP. A better understanding of the impact of SM on adversity
treatment effects and the effects of adversity-focused treatment on
SM may help optimize adversity-focused treatment for individuals
with psychotic disorders.
amongst clinicians of exacerbating psychotic symptoms through
exposure (Cragin et al., 2017). More recently, a systematic
review of intervention studies for psychotic disorders and
trauma (Bloomfield et al., 2020) suggested that future treatments
should include many third-wave elements or strategies, such as
emotion regulation, psychological acceptance, interpersonal
skills, attachment work, strategies to manage dissociation, and
trauma memory reprocessing. The review findings indicated
that although several studies used an 8-session protocol, future
trials should include more sessions to potentially increase the
magnitude of treatment effects (van den Berg et al., 2015; Spidel
et al., 2019). Overall, the literature supports the use of an
integrated treatment approach that uses most core elements of
a standard PE protocol with the addition of third-wave
strategies and an increased treatment length.
Aims and hypotheses
The specific aim of this project will be to address the
identified treatment gap in early intervention care by applying
an adapted PE therapy protocol, called PE+, to a younger EPP
population with a history of adversity and current substance
misuse. We plan to (1) establish the impact of PE+ on the
severity of psychotic symptoms, substance misuse, adversityrelated symptoms (e.g., anxiety) and (2) discern whether
clinically significant change occurs between sessions 8 and 15,
which if true would provide support for the argument that
longer treatment duration results in significant symptom change
in this cohort. We hypothesize that PE+ treatment will result in
clinically significant reductions in (1) negative psychotic
symptoms (e.g., anhedonia), (2) adversity-related sequelae (e.g.,
anxiety and insomnia), and (3) the frequency and quantity of
SM, and (4) that all reductions will be maintained by 2-months
post-treatment. We also anticipate clinically significant
reductions in hopelessness and experiential avoidance, the
theorized mechanisms of change of PE+. In terms of secondary
outcomes, we hypothesize that participants will experience a
global improvement in social and occupational functioning
from pre-post PE+ therapy that will be maintained 2 months
post-treatment.
Treatments for adversity-related sequelae in
people with EPP with SM
Given the existing evidence supporting the efficacy of PE
among people with chronic psychosis, adapting a PE protocol
for people in EPP with SM may be the optimal path forward.
People with EPP are often younger (Mage = 22.83; Cookey et al.,
2020) than those with chronic psychosis (Mage = 41.2; van den
Berg et al., 2015), and people with EPP may be in a better
position to benefit from treatment compared to those with
chronic psychosis because they have not yet sustained the same
degree of biological and psychological burden of substance
misuse or a long-term psychotic illness (Lieberman et al., 2001).
An adapted PE protocol must be capable of addressing common
adverse events experienced by people with EPP (e.g., restraint
during hospitalization for psychosis; Carr et al., 2018),
accounting for the links between adversity sequelae and both
psychosis and SM, and adhering to treatment recommendations
for adversity sequelae in EPP. Cragin et al. (2017) interviewed
49 early psychosis treatment experts about suggested clinical
treatment guidelines for people with psychotic disorders and
comorbid adversity-related sequelae. An integrated treatment
approach (i.e., one clinician treating both types of disorders at
the same time) was endorsed by experts more often than other
possible approaches (e.g., sequenced and parallel). Experts
also recommended the following treatment elements: anxiety
or stress management, psychoeducation, meditation or
mindfulness,
cognitive
restructuring,
interpersonal
effectiveness, emotion-focused interventions, and case
management. Exposure was rated as a second-line intervention,
despite prior evidence that exposure seems necessary for
clinically significant symptom change (Taylor et al., 2003; Foa
and McLean, 2016). This finding likely speaks to clinicians’
hesitancy to recommend adversity-specific exposure treatments
for people with psychotic disorders, given a common fear
Frontiers in Psychology
Materials and methods
Design, randomization, and blinding
This study will use a multiple-baseline design (MBD;
Kratochwill et al., 2010), a type of single-case experimental
design ideal for stringently examining intervention effects.
MBDs are AB designs, meaning they have a baseline (‘A’ phase)
and intervention (‘B’ phase), and they do not repeat phases,
given that behavioral interventions cannot be rescinded after
application. Notably, MBDs temporally stagger intervention
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Exclusion criteria
start time across participants, thereby creating a control group
composed of each participant’s pre-intervention scores.
Participants will be randomized to a 2-, 3-, or 4-week baseline
condition, thereby staggering the intervention start times;
participants will be randomized to a treatment start time using
a random sampling/assignment generator.1 Randomization is
used to increase internal validity and minimize bias by
preventing participants from being assigned to a treatment
start time based on need or symptom severity, especially given
that participants are recruited from an outpatient clinic
(Kratochwill, 2010). Randomization order will be delivered
using sequentially ordered sealed envelopes that will
be opened at the time of randomization. Randomization
breakdown is as follows: 2-week delay (40%), 3-week delay
(25%), 4-week delay (35%).
1. Aged 36 and older;
2. Aged 18 and younger;
3. Scoring in the ‘high risk’ range for cocaine use on the
WHO ASSIST2, suggesting significant misuse;
4. Participant does not speak or understand English;
5. Current involuntary inpatient admission in a hospital or
under a Community Treatment Order;
6. Documented, diagnosed intellectual disability; and/or
7. Currently participating in any intervention designed to
change substance use or treat adversity-related sequelae
(e.g., other clinical trials, psychological therapy).
Measures
Participants and setting
Eligibility
The study will take place at the Nova Scotia Early Psychosis
Program (NSEPP), an early psychosis clinic with approximately
250 active patients that is located within a Canadian academic
psychiatric hospital in Halifax, Nova Scotia. Most patients are
young adults; the mean age of individuals entering the program is
23 years. Individuals must meet the following criteria to participate
in the study:
The TALE checklist (Carr et al., 2018) is a yes/no scale that
asks participants which of the listed events they have experienced
in their lifetime (e.g., traumatic entry into care), whether these
events occurred more than once, and at what age(s) the event(s)
occurred. Additionally, participants will be asked whether any
adverse events experienced are currently affecting them in any
way and to what degree (0, “Not at all” to 10, “Extremely”). The
TALE was created as a measure of adverse events specifically for
individuals with psychosis, and psychometrics suggest good test–
retest reliability ( r = 0.90, p < 0.001), adequate convergent validity
with the Trauma History Questionnaire ( r = 0.69, p < 0.001), and
moderate construct validity in terms of correlations with Trauma
Symptom Questionnaire outcomes ( r = 0.37, p = 0.02). The WHO
ASSIST (WHO ASSIST Working Group, 2002), an 8-item
interview, will be used to measure substance use frequency, urge
to use, substance-related difficulties in functioning, and challenges
with substance use reduction. Responses are made on a 5-point
scale (“Never” to “Daily or almost daily”) and scores can range
from 0 to 39 for each substance-specific subscale, with higher
scores indicating greater substance misuse. The total score for each
substance will be used as an indicator of substance misuse. When
used with individuals with first-episode psychosis, the WHO
ASSIST was significantly correlated with a measure of alcohol use
( r = 0.53, p < 0.001) and substance dependence ( r = 0.44,
p < 0.001), and it had appropriate internal consistency ratings for
the total score (MCronbach alpha = 0.90) and substance-specific
subscales (MCronbach alpha = 0.79, SD = 0.08; Humeniuk et al., 2008;
Hides et al., 2009).
Inclusion criteria
1. Current patient at the NSEPP for the duration of the study;
2. Aged 19–35 years;
3. Diagnosis of a primary psychotic disorder (i.e., schizotypal
disorder, delusional disorder, brief psychotic disorder,
schizophreniform disorder, schizophrenia, schizoaffective
disorder,
substance/medication-induced
psychotic
disorder, other specified schizophrenia spectrum or other
psychotic disorder, or unspecified schizophrenia spectrum
or other psychotic disorder);
4. Diagnosis of a primary psychotic disorder within the past
5 years; participants must not surpass this 5-year diagnostic
window while enrolled in the study;
5. Have experienced 1 or more negative, distressing lifetime
adverse events (e.g., child abuse, discrimination) listed on
the Trauma and Life Events (TALE) checklist that are
currently affecting the participant;
6. At least one score within the “moderate” or “high” risk
range for any substance (excluding tobacco products)
on the World Health Organization’s Alcohol, Smoking
and Substance Involvement Screening Test (WHO
ASSIST); and
7. Speaks and understands English.
2
High cocaine use may be too treatment-interfering and prevent
meaningful treatment gains given its significant impact on executive
functions (Fernández-Serrano et al., 2010), therefore individuals with high
1
www.randomizer.org
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levels of cocaine use are excluded.
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Primary and secondary outcome measures
Secondary
Functioning will be measured using the Social and
Occupational Functioning Assessment Scale (SOFAS; Morosini
et al., 2000), a single-item clinician-reported instrument. Ratings
range from ‘Persistent inability to maintain minimal personal
hygiene/unable to function without harming self or others or
without considerable external support’ (1-10) to ‘Superior
functioning in a wide range of activities’ (91-100); lower scores
indicate greater impairment in functioning. The Clinical Global
Impression—Severity of Illness (CGI-S; Guy, 1976) measures the
clinician’s judgement of the severity of the participant’s symptoms
of mental illness at this time and the Clinical Global Impression
–Improvement of Illness (CGI-I; Elliott and Briere, 1992)
measures the clinician’s judgement of the degree of improvement
from baseline. The CGI-I and-S will serve as additional measures
of functioning that differ from the SOFAS in that they provide
global estimates of illness severity and improvement, respectively.
We will use the total severity score of the CGI-S, which ranges
from ‘Normal, not ill at all’ (1) to ‘Among the most extremely ill’
(7), and the total improvement score of the CGI-I, which ranges
from ‘Very much improved’ (1) to ‘Very much worse’ (7). Higher
scores indicate more severe symptoms on the CGI-S and symptom
worsening on the CGI-I. Symptom measures do not necessarily
provide information about impairment, therefore the SOFAS will
be used to estimate symptom impairment, and the CGI-S will
be used as a global rating of severity, given its holistic view of
participant symptoms (i.e., accounts for all symptoms, rather than
specific symptom domains).
The PTSD Checklist-5 (PCL-5; Weathers et al., 1993; Price
et al., 2016) is a shortened 8-item version of the PCL that will
screen for PTSD symptomatology (e.g., intrusive thoughts,
negative beliefs) and function as a treatment progress monitoring
tool. All items are rated on a 5-point scale ranging from ‘Not at all’
(0) to ‘Extremely” (4), and the total score can range from 0 to 32
with higher scores indicating greater PTSD symptomatology. In a
community sample, the total score internal consistency for the
8-item PCL-5 measure was high ( α = 0.90; Price et al., 2016). A
recent study of the 20-item version of the PCL-5 (Penney et al.,
2021) found that this measure had appropriate psychometrics
amongst people with psychosis, although the factor structure did
differ amongst this group; no analyses of the psychometrics of the
abbreviated 8-item PCL-5 measure have been completed to date
with people with psychotic disorders.
A measure of therapeutic alliance, the Session Rating-3
(SRS-3; Duncan et al., 2003), will be administered following each
therapy session to account for fluctuations in the therapistparticipant relationship on assessment scores. This 4-item
assessment tool measures the patient’s perception of the
therapeutic relationship, goals and topics covered in session,
therapist approach/method, and the therapy session overall for
each session. Participants will place the SRS-3 directly in a sealed
envelope; therapists will not have access to this information during
therapy. Total scores can range from 0 to 40 with higher scores
indicating greater therapeutic alliance.
Primary
The primary outcome measures are psychotic symptoms,
adversity-related sequelae, and substance misuse. Adversityrelated sequelae is the core outcome we are targeting; however,
we are also interested in whether it possible to use an integrated
treatment approach that also effects change on both psychotic
symptoms and substance misuse. Psychotic symptoms will
be measured with the use of the Structured Clinical InterviewPositive and Negative Syndrome Scale (SCI-PANSS; Kay et al.,
1987), a semi-structured clinical interview measuring both
positive and negative symptoms of psychosis. We will use the
total score for each of the positive and negative scales; each
total score can range from 7 to 49 with higher scores indicating
greater positive or negative symptoms. In an early psychosis
sample, the SCI-PANSS positive and negative scales had
appropriate internal consistency ( α Positive scale = 0.89; α Negative
scale = 0.90). The Trauma Symptom Checklist-40 (TSC-40; Elliott
and Briere, 1992) will measure adversity-related sequelae (e.g.,
depression, insomnia). Response options range from ‘Never’
(0) to ‘Often’ (3). We will use the total score and the subscale
scores (i.e., dissociation, anxiety, depression, sleep disturbance,
sexual problems, and sexual abuse trauma index). Total scores
can range from 0 to 120, with higher scores indicating the
presence of greater psychopathology, while subscale score
ranges vary by concept. Several studies have used the TSC-40
with people with psychotic disorders (Pec et al., 2014; Spidel
et al., 2019) although psychometrics have not been computed
with this population. Studies with non-psychosis populations
have estimated strong reliability for the TSC-40 total score
( Ω = 0.93; Rizeq et al., 2020). Substance misuse will
be measured using the WHO ASSIST, described within the
‘Eligibility measures’ section above.
In addition to the above outcomes, we will also measure
changes to hypothesized treatment targets that may function as
mechanisms of symptom maintenance: (1) experiential avoidance,
and (2) hopelessness. The Brief Experiential Avoidance
Questionnaire (BEAQ; Gámez et al., 2014) is a 15-item measure
of experiential avoidance; we will use the overall score on this
measure as an indicator of avoidance. Response options are on a
6-point scale ranging from ‘Strongly disagree’ (1) to ‘Strongly
agree’ (6). Total scores can range from 15 to 90 with higher scores
indicating higher experiential avoidance. Across three groups (i.e.,
students, patients, community), internal consistency was
estimated to be good (Mean α = 0.84). Hopelessness will
be measured with the 20-item Beck Hopelessness Scale (BHS;
Beck et al., 1974). Response options are true/false, and we will use
the total score on this measure as an indicator of hopelessness.
Scores can range from 0 to 20, with higher scores indicating
greater hopelessness. In a chronic psychosis population, BHS total
score internal consistency (α = 0.85) and subscale internal
consistency ( α Negative expectations = 0.84; ± Loss of motivation = 0.81) were
considered good (Kao et al., 2012).
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FIGURE 1
PE+ treatment components, target mechanisms, and clinical outcomes.
psychoeducation about adversity, SM, and the interplay of both
with psychosis; (2) emotion identification and regulation; (3)
imaginal exposure and identifying thoughts and beliefs, (4) in vivo
exposures, and (5) planning for termination and maintenance.
Module 1 involves an intake interview that includes a suicide risk
assessment, followed by psychoeducation about the short and
long-term effects of adversity, and the relationship of adversity
with psychosis and SM. Psychoeducation will form the foundation
upon which the participant can then start to build connections
between these experiences within their own life, culminating in a
joint case conceptualization at the end of this module. Participants
begin discussing their adverse experiences at the end of this first
module. Module 2 is focused on aiding participants to develop or
enhance their emotional identification and regulation skills, which
may help participants effectively process their past experiences.
Skills include mindfulness (e.g., nonjudgmental observation),
cognitive restructuring (e.g., check the facts), and distress
tolerance (i.e., Temperature, Intense exercise, Paced breathing,
Paired muscle relaxation) adopted from Dialectical Behavior
Therapy (DBT; Linehan, 2014). Modules 3 and 4 are the imaginal
and in vivo exposure modules. Participants will begin imaginal
exposure in the first session of module 3 and in vivo exposures will
begin the first session of module 4; both types of exposures will
continue until the end of treatment (i.e., imaginal exposure across
9 sessions, in vivo exposure across 6 sessions). Exposure (i.e.,
imaginal, in vivo) is the core therapeutic ingredient of PE+
treatment, resulting in its greater use across sessions. Imaginal
exposures will become more targeted over time to focus on the
most difficult moments of past adverse experiences. Module 5
Intervention
This study’s psychotherapeutic intervention, PE+, will consist
of a 15-session course of weekly 90-min sessions of adapted PE
therapy. The primary theoretical ‘active ingredient’ of PE+ is
exposure (i.e., imaginal, in vivo; see Figure 1), an effective
therapeutic component with substantial evidence supporting its
efficacy in treating a variety of mental health challenges, including
PTSD and anxiety disorders (see Foa and McLean, 2016, for a
review). PE+ uses PE’s theoretical framework, emotional
processing theory, which posits that by repeatedly exposing an
individual to feared stimuli (e.g., thoughts, feelings, and objects)
related to their adverse experience(s), they may generate alternate
beliefs and associations with that experience and associated
stimuli that may result in a less threatening perspective on the
initially feared situation. The American Psychological Association’s
(APA) treatment guidelines for CBT therapies for PTSD
recommend 4 to 16 sessions of treatment (American Psychological
Association, 2017); while fewer sessions might be viewed as more
efficient and less costly, several studies testing psychological
interventions for adversity-related psychopathology among people
with psychosis found that both researchers and participants
believed eight sessions was too few (de Bont et al., 2016; Spidel
et al., 2019). Therefore, a treatment duration on the longer end of
the APA treatment guidelines (i.e., 15 sessions) was selected for
the current study.
Treatment will be divided into five modules; each module
consists of three sessions. The modules are as follows: (1)
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consists of relapse prevention strategies, including identifying
helpful aspects of treatment, a final joint case conceptualization,
and discussions of preventing symptom relapse. Throughout
therapy, participants will be encouraged to practice and further
develop the emotional regulation and distress tolerance skills
learned in the second module, and participants are asked to listen
to recordings of in-session imaginal exposure throughout modules
three–five. Homework adherence will be rated at the beginning of
every session by participants’ therapist. All session protocols and
materials were reviewed and discussed during the design phase of
the study with the research team’s patient partner (SL); her
expertise was used to modify clinical procedures to improve
feasibility for potential participants (e.g., reduction of betweensession imaginal exposures).
The study therapists will be three senior PhD students in
Clinical Psychology with 3–5 years of clinical experience who have
completed training in PE therapy. Training will involve the
completion of an online PE certification through PEWeb3 and
completing and reviewing roleplays of PE treatment elements
(e.g., imaginal exposure) as a group over the course of 4 months.
Study therapists will be working under the supervision of a clinical
psychologist, AP, who has over 20 years of experience providing
evidence-based treatment, including CBT for psychosis and
substance misuse, and PE for PTSD. Therapists will participate in
weekly supervision with AP to discuss session challenges, ethical
issues, and treatment fidelity. In addition, study therapists will
receive monthly group-based psychodynamic supervision, using
video-review of treatment tapes, to identify and formulate
participant dissociative processes from an integrative perspective.
Prior to delivering treatment, all therapists will complete a
two-hour video-based training to supplement supervision. This
will be provided by JT, a clinical psychologist with over 15 years of
experience and expertise in intensive short-term dynamic
psychotherapy (ISTDP) and psychotherapy research. The rationale
for the inclusion of this additional training and supervision is the
necessity to identify and address dissociative processes as they are
occurring as dissociation may interfere with treatment effects.
Study therapists will also conduct study assessments, although no
therapist will also act as an assessor for the same participant;
therapists will be blinded to assessment results during treatment.
Any instances of unblinding will be reported in the publication of
trial results.
treatment fidelity to assess treatment fidelity within this trial using
both direct (e.g., review of videotaped therapy sessions) and
indirect (e.g., questionnaires, adherence checklists) assessment
strategies (see Supplementary material for a full description of
study treatment fidelity strategies).
We will use a study manual with manualized treatment
sessions to ensure equivalent delivery across participants, and
therapists will be trained in all treatment and assessment
components together to ensure standardized training across
clinicians. Therapists will participate in training that includes a
significant role-playing and videotape review component to
ensure therapist competence is achieved before beginning
treatment delivery. Following the completion of all therapy
sessions, 10% of therapy session videos will be randomly selected
for adherence review by two independent raters experienced in
psychotherapy delivery. Video reviewers will use a predetermined
checklist of session components to rate videos with each item
score ranging from ‘0’ (did not include) to ‘2’ (complete inclusion);
session scores must total at least 80% of the total possible score
based on the predetermined elements for that session to
be considered adherent. There is little agreement in the field about
what constitutes an appropriate benchmark for within-session
treatment adherence. However, a previous study found that the
mean session adherence rate for therapists was approximately
80%, which was considered highly adherent (Huppert et al., 2001).
We will adopt a similar standard, especially given that treatment
fidelity checklists are detailed, thereby creating a conservative
standard for adherence. The video review process will
be supervised by a licensed clinical psychologist, AP, who will
provide training during this study. In addition, therapists will
be provided with weekly supervision, including video review, to
minimize therapist drift.
Procedure
All new NSEPP patients are routinely asked whether they
consent to being contacted for research purposes, with
approximately 80% agreeing to be contacted. Patients can selfrefer to the study or, with their consent, their NSEPP clinician can
refer them. Potential participants will be screened with the WHO
ASSIST (Hides et al., 2009; Humeniuk and World Health
Organization, 2010) and the Trauma and Life Events checklist
(TALE; Carr et al., 2018). See Table 1 for measure information, see
Figure 2 for procedure details. If the individual is eligible for the
study, they will participate in a consent appointment with study
research staff that will involve discussing the study and asking
participants to sign an informed consent form, followed by either
scheduling their baseline assessment for a future date or
completing a baseline appointment immediately following the
consent process. Baseline assessments will include four self-report
instruments, the BEAQ, BHS, PCL-5, and TSC-40, in addition to
several clinician-administered measures, such as the SCI-PANSS,
which will be used to assess psychotic symptoms, and the CGI-I
Treatment fidelity monitoring
As part of the National Institutes of Health’s (NIH) Behavior
Change Consortium, Bellg et al. (2004) outlined a series of
strategies to enhance treatment fidelity in treatment studies. These
strategies facilitate the five elements of treatment fidelity: (1)
treatment adherence, (2) therapist competence, (3) treatment
differentiation, (4) treatment receipt, and (5) treatment enactment.
We will use the NIH Behavior Change Consortium framework of
3 http://pe.musc.edu/
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TABLE 1 Measures for PE+ study.
Variable
Measure
Adversity occurrence
TALE Carr et al. (2018)
Substance misuse
WHO ASSIST WHO ASSIST
Items
Timepoints
Report type
21
Eligibility assessment, post-therapy follow-up 1
Self-report
8
Baseline assessment, Assessments 1–6, Post-
Clinician-administered
Working Group (2002)
Psychotic symptoms
SCI-PANSS Kay et al. (1987)
therapy follow-ups 1–2
109a
Baseline assessment, Assessment 1, Assessment
Clinician-administered
6, Post-therapy follow-up 1
Adversity-related symptoms
TSC-40 Elliott and Briere (1992)
40
Baseline assessment, Baseline follow-ups 1–3,
Self-report
Assessments 1–6, Post-therapy follow-ups 1–2
Experiential avoidance
BEAQ Gámez et al. (2014)
15
Baseline assessment, Baseline follow-ups 1–3,
Hopelessness
BHS Beck et al. (1974)
20
Baseline assessment, Baseline follow-ups 1–3,
Self-report
Assessments 1–6, Post-therapy follow-ups 1–2
Self-report
Assessments 1–6, Post-therapy follow-ups 1–2
Social and occupational functioning
SOFAS Morosini et al. (2000)
1
Baseline assessment, Baseline follow-ups 1–3,
Clinician report
Assessments 1–6, Post-therapy follow-ups 1–2
Illness severity
CGI-S Guy (1976)
1
Baseline assessment, Assessment 1, Assessment
Clinician report
6, Post-therapy follow-up 1
Improvement of illness
CGI-I Guy (1976)
1
Assessment 1, Assessment 6, Post-therapy
PTSD symptoms
PCL-5 American Psychological
8
Baseline assessment, Baseline follow-ups 1–3,
Clinician report
follow-up 1
Association (2017)
Therapeutic alliance
a
SRS-3 Duncan et al. (2003)
Self-report
Assessments 1–6, Post-therapy follow-ups 1–2
4
Therapy sessions 1–15
Self-report
Positive and negative SCI-PANSS items only.
and-S, along with the SOFAS, which will assess illness severity,
symptom change, and functioning. Demographic information
related to participants’ age, gender, race, ethnicity, and sexual
orientation will also be collected; these variables are critical to
collect as participants from a marginalized community (e.g.,
2SLGBTQ+) may have different experiences than those who are
not a part of marginalized groups.
This assessment will be followed by 1–3 brief follow-up
assessments, depending on the randomization to start time (i.e.,
2-, 3-, or 4-week delay between initial interview and therapy) to
establish a symptom baseline. The participant’s treatment start
time, determined by randomization, will be communicated to the
participant at the baseline interview, although the randomization
to treatment start time will be communicated to the participant as
a part of the consent process. The participant will also participate
in an assessment prior to beginning the intervention. The BHS,
BEAQ, and TSC-40 will be administered, in addition to the
completion of the SOFAS, CGI-I and-S, WHO ASSIST, and
SCI-PANSS. After each therapy session, participants will complete
the SRS-3 to account for the influence of fluctuations in the
therapist-participant relationship on assessment scores, and after
each therapy module (i.e., 3 sessions each), current symptoms and
SM will be assessed using the instruments above (i.e., BEAQ, BHS,
TSC-40, PCL-5, and WHO ASSIST). Psychotic symptoms will
be reassessed using the SCI-PANSS after the final session of
treatment has been completed. There will also be two follow-up
sessions 2-months post-intervention to assess maintenance of
therapeutic gains using all the same instruments as at the baseline
assessment; each session will take approximately 75 min.
Frontiers in Psychology
Participants will also be asked for their feedback on how to further
optimize PE+ therapy for use with patients with EPP in the future
and this feedback will be reported and used to optimize this
treatment in the future. All participants will be informed that they
may discontinue their study participation at any time, and that if
psychotic symptoms worsen significantly, they will be referred to
their clinician in the early psychosis program for an appointment.
Data analysis
The goal of this intervention study is to determine the effect of
PE+ therapy on psychotic symptoms, substance misuse, adversityrelated illness (e.g., PTSD), and functioning. Therefore, the desired
outcomes of the analyses will be the significance of symptom
change and its maintenance over time. Given the small projected
study sample size, inferential statistics are not appropriate. As a
result, it is not possible to compute a power analysis; however, a
sample of 20 participants is typical for studies using the MBD based
on previously published studies using this design (Frueh et al.,
2009). Instead of inferential statistics, the Reliable Change Index
(RCI; Jacobson and Truax, 1991) will be used to classify
participants’ post-intervention score category: recovered (i.e., met
criteria for clinical change), improved (i.e., have statistically
significant change but not large enough to be considered a full
recovery), unchanged (i.e., no change over time), and deteriorated
(i.e., significant worsening of symptoms over time). We have
calculated the numerical criteria needed to assess symptom change
using previously published means and standard deviations of the
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FIGURE 2
PE+ study procedures.
measures we are using (e.g., SCI-PANSS, TSC-40 scores; see clinical
trial registration statistical plan at clinicaltrials.gov). The change
criterion being used is moderate, meaning clinically significant
change is defined as participants’ post-intervention assessment
scores falling between the scores of a healthy population and a
mentally ill population. This criterion is the most realistic given
that we are aiming to treat a multitude of psychological symptoms
rather than a single symptom domain (e.g., PTSD symptoms).
We will use the RCI to assess whether clinically significant change
occurred in (1) hopelessness and avoidance scores, (2) negative
psychotic symptoms (e.g., anhedonia), (3) frequency and quantity
of substance misuse, and (4) functioning scores, with gains in all
symptom domains maintained at 2 months-post treatment.
treatment within an existing early intervention service will aid with
recruitment by using direct clinician referrals as well as providing
a built-in safeguard for participants by allowing follow-up clinical
care with clinicians for those participants who may experience
psychotic symptom deterioration or relapse. A significant strength
of this study is the inclusion of a patient partner on the research
team; their experience increased the breadth of the team’s expertise
and allowed for the patient perspective when creating the treatment
protocol and designing treatment materials. Finally, randomization
and comprehensive measures of treatment fidelity will help support
the internal validity of the empirical findings of this study.
Despite this study’s many strengths, there will be several
limitations to its future findings. There is no requirement for
participants to meet criteria for a PTSD diagnosis to receive the
PE+ intervention, which introduces variability into the results.
Participants must present with substance misuse and a history of
adversity and ongoing distress related to the event, but their
symptom presentation may vary. This approach was felt to be more
appropriate for an initial adaptation of this therapeutic approach.
In addition, recruitment processes were not standardized, meaning
there may be bias introduced via clinician referral. All efforts will
be made to approach every eligible person; however, some eligibility
criteria are not possible to determine without an interview,
therefore some potential eligible participants may be missed.
In conclusion, the results of this study may provide support
for the use of an adapted PE protocol to treat adversity-related
mental health challenges among individuals with early-phase
psychosis and current substance misuse, a common clinical
presentation, and provide a tailored treatment option for this
group of affected individuals in the future. The use of this
treatment may help improve long-term outcomes of individuals
within early intervention services, reduce the high burden of
comorbid psychopathology, and improve social and occupational
functioning within this group. Finally, this trial may provide
evidence of the promise of this intervention thereby stimulating
further research using larger samples and more rigorous designs
(e.g., RCT).
Discussion
The results of this novel adaptation study have the potential to
further treatment research by determining whether PE+
contributes to clinically meaningful symptom change for
individuals with EPP who are experiencing adversity-related
mental health challenges and substance-use related issues.
This study has several strengths. PE has been studied within
individuals with psychotic disorders; however, adaptations of
treatment for those in EPP have not yet been tested. Furthermore,
no previous treatment studies have specifically recruited individuals
with comorbid SM and directly measured the effect of PE on
SM. The inclusion of SM within this study provides a necessary and
novel contribution to the literature, whilst the focus on an EPP
population extends the existing body of knowledge of adversityfocused treatment in psychotic disorders. The study intervention
will take place within a comprehensive early intervention service
with an embedded research program; recruiting participants from
this service and delivering the PE+ intervention within an existing
clinical setting will help enhance the ‘real-world applicability’ of
this study’s results, given that this treatment is meant to be delivered
in an early intervention service. Moreover, the integration of this
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Ethics statement
Scotia programs for funding the first author, and the Canada
Research Chairs (CRC) program for funding SHS with a Tier 1
CRC in Addictions and Mental Health. PGT acknowledges the
endowed research chair position he holds, the Paul Janssen
Chair in Psychotic Disorders at Dalhousie University. Great
thanks to Sarah Bendall for sharing her experience and wisdom
with the first author during the study design phase of
this project.
The studies involving human participants were reviewed and
approved by Nova Scotia Health Research Ethics Board
(REB#1025608). The patients/participants provided their written
informed consent to participate in this study.
Author contributions
Conflict of interest
VP and AP conceptualized the study with significant input
from PT. SS and JT helped to refine the direction of the study and
contributed to planning data collection and analyses. All other
authors contributed to the refinement of the protocol and
manuscript. All authors contributed to the article and approved
the submitted version.
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Publisher’s note
Funding
All claims expressed in this article are solely those of the
authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.
The study is funded by the QEII Foundation through a
Translating Research Into Care (TRIC) Level 2 grant [#1025210,
awarded 2020] (PT, NH as co-PIs, written by VP). The funding
source was not involved in the study design and will not provide
input about the study execution, analyses, or interpretation of
the results.
Supplementary material
Acknowledgments
The Supplementary material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fpsyg.
2022.1012776/full#supplementary-material
The authors would like to thank the QEII Foundation for
funding this study, the Killam Scholar and Research Nova
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