Developing Clinical Translational Tools to Communicate Genetic Risk Among Individuals Who Are at Clinical High Risk for Psychosis
Phase: PHASE1
Conditions: Psychosis
Sponsor: New York University

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Title: Developing Clinical Translational Tools to Communicate Genetic Risk among 
Individuals who are at Clinical High Risk for Psychosis 
 
NCT Number: Not applicable 
 
Date of Document: 12/19/2023 
 
 

 
2. OBJECTIVES 
 
Overview and Purpose:  
This project seeks to understand how someone already in a high-risk state will interpret genetic 
information informing risk of ‘conversion’ to a full disorder. How people interpret this possibility 
carries important consequences for how they choose to respond, which may range from 
fatalistic acceptance of the disorder to proactive preventative behavior. With the aim to 
encourage an active pro-health response, we propose developing two tools for communicating 
genetic risk and evaluate them regarding their effectiveness in inducing a positive response to 
the risk of illness. The two tools will consist of: 1) a clinician manual, designed to be used by a 
PhD level clinician with some genetic counseling training to communicate risk to CHR youth; 2) 
a high-impact, computerized tutorial (‘AutoTutor’) that has been used to convey genetic risk for 
breast cancer (i.e. BRCA gene). To create these 2 tools, experts in psychiatric genetics and 
stigma will work to develop the 2 tools to convey genetic risk information to youth and young 
adults identified as in a ‘clinical high-risk state’ (CHR) for psychosis. We assess primary 
outcomes of increased intent to engage in treatment and healthy behaviors, and a secondary 
outcome of reduction in stigma. While specific genes for risk of psychosis are not yet used in 
diagnosis or treatment, a genetic malleability (GM) framing conforms to the known genetic risk 
for psychosis, and has a strong likelihood of being used in the not too distant future. Because of 
the relatively large innovation involved, we seek to establish initial acceptability, safety, and 
efficacy of each tool. We then use a nonrandomized, within-subject, pre- vs. post design to 
examine whether providing the genetic malleability framing via each tool (n=27 CHR youth per 
tool, N=54 total) leads to improved outcomes. For each tool, participants will be conveyed 
hypothetical information proposing being identified as having a substantially elevated, 
genetically-malleable risk for developing psychosis. 
 
Specific Aims and Hypotheses: 
Aim 1: To develop 2 translational tools to convey a genetic malleability framing for psychosis-
risk, we develop a clinician manual and a computerized AutoTutor to undergo acceptability, 
safety, and initial efficacy testing.   
Rationale: We evaluate tools that provide a genetic malleable (GM)framing, which has 
been linked with: a) greater agency, hope and optimism about recovery (Dar-Nimrod et 
al., 2014; Farrell, Lee, & Deacon, 2015); b) greater perceived odds of recovery, mood 
regulation(Lebowitz & Ahn, 2018) and less hopelessness (Lebowitz, Ahn, & Nolen-
Hoeksema, 2013) in 3 experimental studies for depression, which persisted at 6 month 
follow-up (Lebowitz & Ahn, 2015). While people with psychosis show benefit from 
psychiatric genetic counseling (Inglis et al., 2015), access to such counselors is rare. 
Creating tools to beneficially convey GM framing for CHR adds greatly to public health. 
 
Aim 2: To test whether CHR youth, after being exposed to the genetic malleability framing via 
each tool, will show greater endorsement of increased intent to engage in treatment and healthy 
behaviors and less stigma when compared with pre-exposure to the tool.   
We predict that CHR youth, after receiving the GM framing via each tool, will show 
greater intent to engage in treatment and healthy behaviors and less stigma vs. pre-
exposure. 
 
-- As an exploratory analysis, we hypothesize that improvements in these outcomes will be 
associated with reductions in the mechanism of ‘genetic essentialism’.    
Re: the exploratory analysis, GM may benefit outcomes by reducing the mechanism of 
genetic essentialism (Farrell, Lee, & Deacon, 2015; Lebowitz, Ahn, & Nolen-Hoeksema, 

2013).  Studies have not tested mediating mechanisms when examining effects of 
genetic framings (Anido, Carlson, & Sherman, 2007; Dunn et al., 2008; Heshka et al., 
2008). We will use identified mechanisms to convey beneficial results (i.e. that genes do 
not imply a fixed future) via the tools. 
 
3. BACKGROUND, SIGNIFICANCE, AND RATIONALE: 
 
Great strides are being made in identifying new ‘high-risk states’ or early signs of elevated risk, 
for illnesses such as Alzheimer’s disease, diabetes, and psychosis (Tabák et al., 2012; Wang et 
al., 2013). Those in a high-risk state are distinct from asymptomatic individuals and those with 
the disorder in that signs are present but the full disorder has not yet developed (Fusar-Poli et 
al., 2014; Miller et al., 2003). Early interventions for high-risk states show promise in averting 
the full disorder or reducing its impact (Bateman et al., 2012; Boraxbekk et al., 2015; 
Buysschaert et al., 2015; Dubois et al., 2007; Fonseca, 2007; Grant et al., 2013; Lin et al., 2017; 
McGorry et al., 2012; Sadeghi et al., 2015; Schellenberg et al., 2013). Best outcomes are more 
likely with increased intent to engage in treatment/healthy behaviors, which may be shaped by 
genetic information (van Rijn et al., 2011).  
 
Rapid advances are being made in identifying genes associated with high-risk states. How 
those already in a high-risk state respond to genetic information regarding the risk of developing 
the full disorder may range from fatalistic acceptance to proactive preventative behavior. One 
specific genetic framing, hereafter called ‘genetic malleability’ (GM), has in itself been shown to 
promote engagement in pro-health behaviors across mental illness (Lebowitz, & Ahn, 2015; 
2018; Lebowitz, Ahn, & Nolen-Hoeksema, 2013), Alzheimer's (Chao et al., 2008), and chronic 
diseases (Aspinwall et al., 2015; Jenkins et al., 2013; Kullo et al., 2016; Meisel & Wardle, 2014), 
including the uptake of treatment and positive health behaviors (improved diet, exercise, or use 
of medication. The GM framing involves a modifiable genetic risk that can be turned on or off 
based on environmental/behavioral factors (Hakak et al., 2001; Lebowitz, 2014; Van Os, Rutten, 
& Poulton, 2008). This framing applies to high-risk states because both genetic and 
environmental/behavioral factors influence illness trajectory (Bird et al., 2010; Stevens et al., 
2015),  and risk for developing the full disorder(Benros, Eaton, & Mortensen, 2014; Gebicke-
Haerter, 2012; Oh & Petronis, 2008). Conveying genetic risk to those in high-risk states 
(Christensen et al., 2007; DiMillo et al., 2015; Lawrence et al., 2016; Meiser et al., 2005; 
Vähäsarja et al., 2015), has also been linked with higher stigma due to greater self-perceptions 
of differentness. The GM framing may help address this as it has been found to reduce stigma 
for heart disease (Robinson et al., 2016), obesity (Hilbert,2016), and Alzheimer’s (Christensen 
et al., 2007 ), thus showing promise for high-risk states. Responding to this, we seek to develop 
tools to promote potential beneficial impacts of GM beliefs, which have been shown to exert 
change on the main psychosocial outcome of intent to engage in treatment and healthy 
behaviors (Aspinwall et al., 2015; Chao et al., 2008; Jenkins et al., 2013; Kullo et al., 2016; 
Meisel & Wardle, 2014), and the secondary outcome of stigma (Corrigan & Watson, 2002). 
Because tools that convey genetic framing for high-risk states do not exist and would comprise 
a sizeable advance by enabling dissemination of a potentially beneficial genetic framing, this 
proposal focuses on these tools’ development and initial testing for safety, acceptability and 
efficacy. Confirming the tools’ utility offers a strong basis to conduct future testing via a RCT. 
 
Based on emerging studies (Beauchamp et al., 2011; Conrad, 2001; Dar-Nimrod et al., 2010; 
Einsiedel & Geransar, 2009; Schnittker, 2008; Wilde et al., 2010), we propose GM may impact 
outcomes by reducing the mechanism of genetic essentialism. The genetic essentialism 
mechanism consists of beliefs of permanence and inevitable development of the genetic 
condition (Beauchamp et al., 2011; Conrad, 2001; Dar-Nimrod et al., 2010; Einsiedel & 

Geransar, 2009; Schnittker, 2008; Wilde et al., 2010). Those holding genetic essentialist views 
were less likely to adopt preventative behaviors across conditions (e.g. heart disease 
(Hardcastle et al., 2015; Hunt et al., 2000; Senior, Marteau, & Peters, 1999), obesity (Rodriguez 
& George, 2014). Our pilot work with CHR youth shows providing the GM framing is linked with 
lower genetic essentialism. Building on this work, we propose to develop 2 new tools to facilitate 
positive intent towards treatment by reducing genetic essentialist beliefs.  
 
We assess our tools among CHR youth (16-30 yrs). Treatment of CHR, before 1st episode of 
psychosis shows promise in averting disorder onset (McGlashan et al., 2004; Morrison et al., 
2006; Nordentoft  et al., 2006; Phillips et al., 2007).  The CHR shares features with high-risk 
states such as pre-type 2 Diabetes where both: a) may begin in adolescence; b) have 
identifiable genetic and behavioral risk factors; c) are in ~1/3 of cases likely to develop the full 
disorder without intervention (American Diabetes Association, 2010; Fonseca, 2009). While 
specific risk genes for psychosis are not yet used in diagnosis, genetic heritability is viewed as a 
key contributor for psychosis (i.e., schizophrenia [SCZ], the most studied psychotic disorder 
(Doherty, O’Donovan,  & Owen, 2012; International SNP Map Working Group, 2001; Purcell et 
al., 2009; Santoro et al., 2015; Swami, 2011), with genetic risk ascribed to common and rare 
variants. For regular use of genetic testing in practice, more research confirming the predictive 
power of genetics for an individual’s development of psychosis is required (DiMillo et al., 2015; 
Hakak et al., 2001), as there is no known single-gene form of SCZ. Notably, research has linked 
lifestyle/behavioral factors (stress, cannabis use) to developing SCZ (Caspi et al., 2005; 
Gallagher III & Jones, 2016; Miller et al., 2001; Smit,  Bolier, & Cuijpers, 2004; Volkow et al., 
2016), suggesting a gene-by-environment interaction (Furrow, Christiansen, & Feldman, 2011; 
Moffitt, Caspi, & Rutter, 2006). This is supported by findings of differentially methylated regions, 
a gene X environment mechanism, at the BDNF, serotonin transporter, and FKBP5 loci (Kular & 
Kular, 2018). A GM framing fits the known genetic risk for psychosis and is very likely to be 
used in the future.  
 
Psychiatric genetic counseling to aid people adapt to the implications of genetic risk (Friesen et 
al., 2016; Resta et al., 2006), which occurs in 1 session and shows benefit even without genetic 
testing (Inglis et al., 2015), has led to more treatment engagement for people with psychosis 
(Costain et al., 2012 a, b,; Hippman et al., 2016).  An individualized, interactive dialogue with an 
expert is key to address core misconceptions (Austin & Honer, 2007; ), such as misinterpreting 
genetic risk probabilities (e.g. perceiving 1%-5% risk as ‘high’) (Austin, 2010). Yet because only 
1% of 4,000 genetic counselors in North America work in psychiatry (Fusar-Poli et al., 2014) (a 
figure that will rise when specific psychosis risk genes are identified), tools providing genetic 
knowledge for CHR via an interactive exchange could greatly expand access to the benefits of 
psychiatric genetic counseling. 
 
Tool #1-AutoTutor An interactive, automated tool that could convey genetic risk and increase 
intent to engage in treatment for CHR youth would be a major advance. Many CHR youth prefer 
technology (Alvarez-Jimenez et al., 2014; Lal et al., 2015), due to problems relating with others 
(Carrión et al., 2011; Liddle, 2000; van Rijn et al., 2011). AutoTutor, an intelligent system that 
simulates talking with a human tutor (Wolfe et al., 2015), has been effective in conveying 
genetic concepts and improving medical decision-making about genetic risk for breast cancer 
(Widmer et al., 2015; Wolfe et al., 2016). AutoTutor’s efficacy as a communication tool is why 
we will use it to educate CHR youth about GM; we reason that changing beliefs about GM will 
initiate behavior change because beliefs about GM have shown to affect changes in pro-health 
behaviors (Aspinwall et al., 2015; Chao et al., 2008; Jenkins et al., 2013; Kullo et al., 2016; 
Meisel & Wardle, 2014). Using pre-existing software developed by co-I Dr. Hu, our AutoTutor, 

PsyGist (Psychosis Genetic-risk Intelligent Semantic Tutor) will convey genetic risk to CHR 
youth. 
 
Tool #2-Clinician Manual A 2nd advance is to develop a manual for clinicians, to convey 
genetic risk to CHR youth. A standardized manual enables an interactive discussion of genetic 
risk, has been tested in people with SCZ (Costain et al., 2012a; Hippman et al., 2016) and 
suggests efficacy for high-risk states. Our expert co-I, Dr. Austin, has tested a protocol that 
provides a template for our work.   
 
A distinct strength is that a GM framing has led to more pro-health behaviors across conditions 
(Aspinwall et al., 2015; Chao et al., 2008; Jenkins et al., 2013; Kullo et al., 2016; Meisel & 
Wardle, 2014). Weaknesses in the evidence base include this framing not being used with high-
risk states and lack of tools to ease access, which are both addressed by our plan. Impacts: 
Future genetic risks for psychosis are likely to fit GM. We develop 2 tools to deliver this framing 
to increase pro-health behaviors in a high-risk state, expand access to genetic information, and 
to increase intent to use treatment and reduce stigma for CHR youth. PsyGist is one of the 1st 
intelligent systems to run from any computer with internet capabilities and promises to be 
scalable, cost-effective and high impact. The Manual offers a protocol for trained clinicians to 
convey genetic risk to CHR. Our study is among the few to attempt to modify genetic 
essentialism. Lastly, our study adds to the sparse data regarding genetic framings on youth. 
 
4. METHODS 
 
Study Design 
The study will be rolled out in two phases:  
(1) development of the translational tools; and  
(2) assessment and evaluation of the safety, acceptability and effectiveness of tools using pre-
post comparisons.  
 
A sequential assignment procedure will be used to assign participants to first the Clinician 
Manual educational session and then the PsyGist educational session. Thus, the first 27 
individuals enrolled in the study will be assigned to the Clinician Manual educational session, 
while the next 27 individuals will be assigned to the PsyGist educational session (Clinician 
Manual n=27; PsyGist n=27; Total N=54). Sequential assignment is being utilized in this 
protocol to ensure that the probability of contamination, resulting from participants sharing study 
information between educational session groups, is minimized.   
All Assessments will be presented in two 2.5-hour visits, 1 week prior and immediately after 
exposure to each Tool (Clinician Manual or PsyGist) because it would be unethical not to 
debrief youth about the hypothetical framing immediately following the session. However, we 
will take as many brief breaks throughout the sessions as necessary to accommodate the 
participant. ‘Acceptability’ measures will be administered only once after post-test measures. 
 
Inclusion and Exclusion Criteria 
All subjects will be drawn from the Center for Prevention and Evaluation Criteria (COPE’s) 
Clinical High Risk for Psychosis (CHR) participants at the New York State Psychiatric Hospital 
(see protocol information below).  
 
THE CENTER OF PREVENTION AND EVALUATION (COPE): A PROSPECTIVE STUDY OF 
SYMPTOMS AND COGNITION (FORMERLY 5567R) PI: Ragy Girgis (Protocol Number: 
6654R) 
 

Below are the overall inclusion criteria for the Center for Prevention and Evaluation Criteria 
(COPE), which is the recruitment site.  Note that below we have specific recruitment criteria that 
identify a subset of the COPE respondents. 
 
INCLUSION CRITERIA  
METHOD OF ASCERTAINMENT  
1. Male or females between the ages of 14-
30      
Phone screen and interview 
2. Capacity to give informed consent for 
participants 18 and over OR participant’s 
assent plus informed consent from parent for 
participants under the age of 18 
Interview; assessment by clinician not 
involved in the study 
3. English-speaking (for participants) 
Phone screen and interview 
 
4. Identified as at clinical high risk for 
psychosis as defined as  
a)attenuated positive symptoms 
b)brief intermittent positive symptoms 
c) schizotypal disorder or family history of 
psychotic 
disorder with recent decline in functioning (30 
GAF points) 
Structured Interview for Psychosis-Risk 
Syndromes (SIPS)/Scale of Psychosis-Risk 
Symptoms (SOPS) 
 
The exclusion criteria for COPE below are as follows: 
EXCLUSION CRITERIA  
METHOD OF ASCERTAINMENT  
1. Psychosis diagnosis                  
Clinical interview and Structured Interview for 
Psychosis-Risk Syndromes (SIPS)/Scale of 
Psychosis-Risk Symptoms (SOPS) 
 
2. History of neurological, 
neuroendocrine or other medical 
conditions known to affect the 
brain 
 
Clinical interview and collateral 
information from patient's treaters 
(with their authorization for release) 
3. IQ < 70 
 
WTAR < 6 
4. Moderate or severe risk of harm 
to self or others 
Clinical interview, and Columbia 
Suicide Severity Rating Scale 
Below are the Specific Inclusion Criteria for this protocol: 
INCLUSION CRITERIA  
METHOD OF ASCERTAINMENT  
1. Male or females between the ages of 16-
30     
 
Phone screen and interview 
2. Enrolled in COPE  
Enrollment record 
 

3. Identified as at clinical high risk for 
psychosis as defined as having at least one 
of the following:  
a)attenuated positive symptoms 
b)brief intermittent positive symptoms 
 
Structured Interview for Psychosis-Risk 
Syndromes (SIPS)/Scale of Psychosis-Risk 
Symptoms (SOPS) 
 
Below are the Exclusion criteria for this protocol: 
EXCLUSION CRITERIA  
METHOD OF ASCERTAINMENT  
1.Meeting CHR via only the Genetic risk and 
deterioration (GRD) syndrome. If the 
participant meets the GRD syndrome only, 
we exclude the rare Genetic risk + 
deterioration (GRD) syndrome (comprising 
<1% of CHR cases) because GRD requires 
having a 1st degree relative with any 
psychotic disorder, which may be linked with 
stronger reactions to genetic framings. 
 
Clinical interview and Structured Interview for 
Psychosis-Risk Syndromes (SIPS)/Scale of 
Psychosis-Risk Symptoms (SOPS) 
2. IQ < 80 
 
The Test of Premorbid Functioning (TOPF)  
3. Inability to adopt hypothetical situation  
Hypothetical situation screener (see 
procedures section for description) 
 
 
• 
Adults unable to consent (individuals with impaired decision making capacity) 
• 
Will not be included in this study 
• 
Individuals who are not yet adults (infants, children, teenagers) 
• 
Will be included in this study (16-30 years old) (see inclusion/exclusion 
criteria) 
• 
Pregnant women 
• 
Will not be included in this study 
• 
Prisoners 
• 
Will not be included in this study 
 
Description of Subject Population: 
All subjects will be recruited from The Center for Prevention and Evaluation’s (COPE) prodromal 
population at The New York State Psychiatric Institute (NYSPI).  
 
Population to be Recruited: Individuals at Risk for Psychosis (CHR)  
 
Number of completers required to accomplish study aims: n=27/tool (PsyGist & Clinician 
Manual); N=54 total participants between both groups (PsyGist & Clinician Manual) 
Projected number of subjects who will be enrolled to obtain required number of completers: 
N=100 
 
Age range of subject population: 16-30 years old  
 
5. PROCEDURES 
 

Study Timeline  
Timeline 
Month 0-2 
Months 3-5 
Months 6-22 
Months 23-34 
Task 
Obtain IRB 
Approval 
Develop 2 
Tools 
Test Tools (n=27 
CHR youth/tool) 
Refine Tools, Data 
Analysis + Manuscripts 
 
Pre-Educational Session Protocol (Pre-Assessment):  
Following successful enrollment into the study, and one-week prior to exposure to the 
educational session (either PsyGist or Clinician Manual), a trained research assistant will 
conduct pre- assessments. Participants will be assessed on: (1) covariates including socio-
demographic variables, personality traits, exposure to genetic framing, barriers to mental health 
care, symptoms, cognition, quantification of perception of ‘substantial psychosis risk’ (0-100%) 
(2) ‘genetic essentialism’ (mechanism); (3) intent to engage in treatment and healthy behaviors 
(primary outcome); (4) stigma (secondary outcome). Data will be collected using REDCap with 
the exception of the following which may use an external site to collect data: (1) the Implicit 
Association Test for assessing stigma, and (2) the computerized behavioral task for assessing 
intent to engage in healthy behaviors. REDCap is a secure data collection tool that meets 
HIPAA compliance standards. REDCap will allow either the participant or the research assistant 
to fill out the measures being collected using this online tool.  
 
Below is the information regarding the IAT and the new computerized behavioral tasks. We 
have updated the information concerning the administration of the website. While we don’t plan 
to administer the IAT right now due to the study moving online, we may decide to administer this 
in the near future once we can better accommodate technical aspects of administration in an 
online format, while maintaining ethical standards.  
 
Implicit Association Test (IAT): After completion of the pencil-and-paper stigma scale, 
participants will complete the IAT. The IAT will be administered on a secured and encrypted 
laptop. Research assistants will first review the instructions for the IAT, making certain that 
participants understand the process by which they must compete the task. Before starting the 
IAT, participants will be able to practice through the IAT’s practice module.  
 
Distress Protocol: Study staff will also be trained to administer a distress protocol (See 
description in “Post-Educational Session Protocol”) throughout all phases of the study to monitor 
if participants exhibit signs of agitation, shaking or crying during or after exposure to the tool/ 
interview. The distress protocol will identify signs of distress, and prompt referral to the a 
clinician. A clinician, either Dr. Girgis (the director of COPE), Dr. Brucato (chief psychologist at 
COPE), or our clinician who is administering our clinician manual (Dr. Carol Cohen-Romano), 
will be available for participants who require referral to a clinician based on the distress protocol.  
 
Educational Session-specific Protocol:  
PsyGist procedures. During online administration, PsyGist, will be accessed by participants via 
logging into a platform. Research assistants will provide detailed information to participants 
regarding basic use and guidelines for this program. PsyGist has 3 parts: (1) assessment of the 
youth’s causal model for their high-risk state; (2) an individualized ‘pre-tutorial’ vignette matched 
to their causal model; (3) a ‘tutorial’ presenting the ‘genetic malleability’ framing. PsyGist will 
guide participants through its three components. First, PsyGist will assess the participant’s 
causal model for their high-risk state by presenting a 1-item visual analog scale asking, ‘Is your 
high-risk state caused by environmental factors, genetic factors, or both?’ Then a slider on the 
scale will be used to assign youth to 1 of 3 individualized pre-tutorial vignettes developed from 
prior genetic counseling materials ‘primarily genetic’, ‘primarily environmental’ or ‘combined’. 

Identifying a user’s causal model enables the Genetic Malleability framing conveyed via the 
interactive Tutorial to better fit pre-existing beliefs. Participants will interact with a PsyGist 
Genetic Malleability Tutorial, taking an anticipated 12 to 13 turns. PsyGist will propose a prompt 
(e.g. ‘How do genes affect psychosis risk?’) which youth will answer. The tutorial will impart key 
Genetic Malleability concepts, such as ‘risk genes may be turned on or off by lifestyle factors. 
While CHR samples show some cognitive impairment, AutoTutor has been used in cognitively-
impaired individuals and BRCA Gist has effectively increased genetic knowledge in lower-
educated groups. Furthermore, PsyGist text is tailored to users’ literacy as it uses variations of 
users own words. The Health Literacy Adviser software will also be used to rephrase PsyGist’s 
text at an 8th grade level.  
 
The research assistant will be present (online) throughout the presentation of PsyGist to answer 
any questions.  
 
Clinician Manual Procedures. Participants in the Clinician Manual arm will be introduced to a 
trained Ph-D level clinician with some genetic counseling training and will complete one 60-
minute session covering equivalent topics addressed in the PsyGist program. The manual will 
consist of: (1) a section exploring the youth’s causal model for their high-risk state; (2) 
individualization per their causal model; and (3) tutorials that convey the main concepts of 
genetic malleability. Clinicians will assess individual causal models via discussion with CHR 
youth about their at-risk state. Individualization of genetic framing will occur using youths’ causal 
models and will fall into 1 of 3 categories (per PsyGist): ‘primarily genetic’, ‘primarily 
environmental’ or ‘combined’. Visual aids will be used to elicit discussion. The session between 
the clinician and the participant will be audio recorded with the participant’s permission. 
Participants will be able to initial whether they agree to or do not agree to be audio recorded 
during their meeting with the clinician. This will allow respondents to consent to the study and 
decide whether or not they would like to be audio recorded. A participant deciding not to be 
audio recorded will not exclude them from participating.  
 
To accommodate recording during our virtual session and ensure participant confidentiality, we 
will ensure that the video part of the meeting is not recorded (i.e. the recording will be audio 
only; this feature is available via HIPAA-compliant video teleconferencing ) and the audio 
recording will be saved to a secured laptop.  
 
The research assistant will not be present for the 60-minute session but will reconvene with the 
participant for post-educational session assessments.  
 
Study staff will be trained to administer a distress protocol (See description in “Post-Educational 
Session Protocol”) throughout all phases of the study to monitor if participants exhibit signs of 
agitation, shaking or crying during or after exposure to the tool/ interview. The distress protocol 
will identify signs of distress, and prompt referral to a clinician. A clinician, either Dr. Girgis (the 
director of COPE), Dr. Brucato (chief psychologist at COPE), or our clinician who is 
administering our clinician manual (Dr. Carol Cohen-Romano), will be available for participants 
who require referral to a clinician based on the distress protocol. 
Post-Educational Session Protocol:  
Post-educational assessment protocol will be equivalent to pre-educational session assessment 
protocol, with the addition afterwards of the new computerized behavioral task and an 
acceptability assessment, followed by debriefing. Additionally, the following measures will be 
administered only as part of the pre-education session protocol: demographics, barriers to 
mental healthcare, exposure to genetic framing, life orientation test, tolerance for uncertainty.   

New Computerized Behavioral Task:  Research assistants will administer a new computerized 
behavioral task to assess intent to engage in healthy behaviors via measurement of time spent 
by youth (in seconds) and engagement (measured in number of clicks) with a social media 
platform. During online administration the research assistant will send the participant a link to 
the website and ask the participant to share their screen while they are viewing the website. 
Unlike other measures, this computerized measure captures the amount of engagement with a 
health-promoting social media platform as our behavioral outcome. The interviewer will show 
the participant the website, developed by our team to be educational and interactive. The 
computerized behavioral task will be presented while participants are being asked to consider 
the hypothetical genetic malleability framing. The website has these sections: i) Information on 
ways to improve mental health; ii) Ways to find help; and iii) Social support blog, which offers 
access to an online support community of other youth with psychotic symptoms. Each section 
has options for the viewer to click and read. Using Google Analytics, a website feature, we will 
capture metrics for each participant such as: 1) the time in seconds the participant spends on 
each page, and; 2) the number of interactions with the website. This computerized measure 
promises to expand measurement of behavioral intention in a novel way, thus capturing an 
important new element of health-promoting behavioral change.  
 
Acceptability assessment. Acceptability of each educational session will be assessed via 
audiotaped individual interviews wherein youth will be asked to "think aloud" about the content 
of the educational session. Youth will be queried regarding their cognitive processes about the 
educational session. Youth will be asked to report their understanding and any other cognitive 
process surrounding the overall content of the educational session. The following questions will 
be asked as part of the acceptability assessment.  
 
Can you tell me what you think the educational session is about? (open ended question) 
What did you learn? (open ended question) 
 
What did you think about the educational session? (open ended question) 
 
Follow-up question: Were you able to understand it? (open ended question) 
Follow-up question: Was there anything that was confusing to you? (open ended 
question) 
Follow-up question: Is there anything you would change? (open ended question) 
 
Did you understand that this session was about genetic malleability, or the idea that genes may 
put someone at risk to develop psychosis but there are environmental or lifestyle factors that 
can keep the gene from turning on? Answer choices: Yes/No 
 
Further, participants will be asked to complete a brief usability questionnaire. If stress is 
indicated at any point regarding interacting with the tool or clinician, participants will be carefully 
probed for the source of any stress or adverse and serious adverse events, and will be 
immediately referred to a clinician, either Dr. Girgis (the director of COPE), Dr. Brucato (chief 
psychologist at COPE), or our clinician who is administering our clinician manual (Dr. Carol 
Cohen-Romano).  
Debriefing: Immediately following completion of the post- educational session assessments, 
participants will be debriefed (1st debriefing) via: (1) discussing any concern about the genetic 
framing; (2) reinforcing that while researchers are beginning to identify genes that combine with 
each other to increase risk of development to psychosis,  the genetic framing is hypothetical 
(that no clear genetic markers or biological tests yet exist for psychosis) followed by a 
True/False quiz testing knowledge of the current state of genetics in psychosis (described 
below); and (3) identifying distress via a distress protocol (see below) and an adverse and 

serious adverse event (SAE) checklist (see below). To ensure that participants understand that 
the genetic framing is hypothetical, each participant will be asked 8 True/False questions 
following being told that the situation is hypothetical (e.g., “Currently, genes only suggest that a 
person may be at a higher risk of developing psychosis. It does not mean that he or she would 
definitely get the disorder”). Respondents will answer each question, and the interviewer will 
discuss any item that the respondent gets wrong to ensure understanding. 
 
A second debriefing will occur 2-weeks after study completion, and again at 3-months after 
study completion. If any distress or adverse reaction is found, referral to Dr. Brucato, Dr. Girgis, 
or Dr. Cohen-Romano will occur immediately.  
 
Debriefing for Behavioral, Computerized Measure of Intent to Engage in Treatment: After the 
post-assessment, participants are further debriefed about the computerized measure to assess 
intent to engage in treatment. Participants are told that this website is not a real website but that 
our study website was modeled after a real website entitled “Strong365.org”. During debriefing, 
participants are shown this real website, which offers similar up-to-date informational content 
and a blog where youth can interact and share personal stories. 
 
Distress Protocol: Notably, to address potential distress, study staff will administer a “Distress 
protocol” to identify signs of distress and will be sensitive to the potential that distress may lead 
to an adverse event or serious adverse event. This will consist of the following steps and 
structured scales listed below.  
 
1) First, the distress protocol consists of an adapted quantitative measure used to assess 
distressed mood and stress following the study procedures (3 subscales assessing Depression 
[8 items], Fatigue [4 items] and Stress [4 items] stemming from the study procedures on a 5-
point scale; 0= not at all; 1=a little; 2=moderately; 3=quite a bit; 4=extremely) (see questions 
below). A positive quantitative rating of distress will be indicated by ≥2 items endorsed as 
“moderately” or more, and will trigger referral to a clinician.  
 
Quantitative Distress Protocol Measures: 
Due to your participation in this study, please answer the following questions.  
Based on your meeting with the clinician or [interaction with AutoTutor], how [blank] do you feel? 
Scale: 0= not at all; 1=a little; 2=moderately; 3=quite a bit; 4=extremely 
1. Stressed (stress sub-scale) 
2. Jittery (stress sub-scale) 
3. Tense (stress sub-scale) 
4. Overworked (stress sub-scale) 
5. Unhappy (depression sub-scale) 
6. Sad (depression sub-scale) 
7. Blue (depression sub-scale) 
8. Hopeless (depression sub-scale) 
9. Discouraged (depression sub-scale) 
10. Miserable (depression sub-scale) 
11. Helpless (depression sub-scale) 
12. Worthless (depression sub-scale) 
13. Worn-out (fatigue sub-scale) 
14. Fatigued (fatigue sub-scale) 
15. Exhausted (fatigue sub-scale) 
16. Weary (fatigue sub-scale) 
Again, a positive quantitative rating of distress will be indicated by ≥2 items endorsed as 

“moderately” or more, and will trigger referral to a clinician. 
 
2) Second, interviewers will ask semi-structured, open-ended questions at the end of the 
interview to assess distress due to the study procedures (see below).  
Due to your participation in this study, please answer “yes” or “no” the following questions.  
1. Are you experiencing a high level of stress or emotional distress? 
2. Are you currently having thoughts of harming yourself? 
3. Are you currently having thoughts of harming someone else?  
 
If participants answer “yes” to any of the above questions they will be referred to a clinician.  
3) Third, interviewers will be trained to pay attention to crying, shaking, agitation (pacing, 
breaking away from the task) during the interview. RA’s will have completed or will be actively 
completing a clinical placement at COPE. If participants exhibit distress during exposure to the 
tool/interview, interviewers will stop the study procedures and ask if participants would like to 
discontinue the study. If so, the participant will be removed from the study and immediately 
referred to a clinician.  
 
In sum, participants will indicate a “positive” distress rating on the “Distress Protocol” if they: 1) 
score “positive” on the quantitative items (see above); 2) respond affirmatively to the semi-
structured, open-ended questions following all study procedures (see above); 3) exhibit distress 
during exposure to the tool/interview. If participants rate “negative” on all three components, 
participants will still be asked if they would like to check in with a clinician. 
 
**All participants regardless of whether they demonstrate any distress during the 
protocol will also be asked the below questions after completion of all study procedures 
as part of the debriefing protocol:  
 
True/False Quiz Administered As Part of Debriefing Protocol  
1) There currently exists a blood test to identify genetic risk for psychosis (F) 
2) Scientists have identified genes that definitely cause psychosis (F) 
3) Only genes determine one's chance of developing psychosis (F) 
4) If you have a genetic risk for psychosis, this means that you will definitely develop psychosis 
(F).  
5) Currently, genes only suggest that a person may be at a higher risk of developing psychosis. 
It does not mean that he or she would definitely get the disorder. (T) 
6) The situation that we presented to you today about a blood test for psychosis was not real (T) 
7) Psychosis may be caused by many factors, and genes could be one of them. (T) 
8)  Many other factors, for example, one’s environment and/or lifestyle, could impact how genes 
function. (T) 
 
Assessment of Adverse Event. Unfavorable occurrences that may be related to participation 
in the study, including: (1) exacerbation of CHR symptoms; (2) distress or anxiety (see “Distress 
Protocol” above); and (3) suicidal ideation, will be reviewed by the PI, and scored based on: a) 
how attributable the event is to the study (from a scale of [1] “Unrelated” to [5] “Definitely 
related”) and b) the severity of the event (on a scale of [1] “No adverse event” to [5] “life-
threatening/disabling/fatal)”. Adverse Events that are at least “somewhat attributable” and 
“somewhat severe” (i.e. marked and non-transient psychological distress greater than a few 
days) [3 or more on both scales] will be submitted to the NHGRI program Officer with the annual 
progress report and will also be submitted to the DSMB and IRB. 
 

Serious Adverse Event (SAE). A Serious Adverse Event (SAE) will be one that results in death 
or the immediate risk of death, hospitalization, or persistent or significant disability/incapacity. 
These may include: (1) suicide attempt or completed suicide; (2) violent behaviors towards 
others; and (3) psychiatric hospitalization related to the study. In addition to immediately dealing 
with the event, the study PI will score adverse events based on: a) how attributable the event is 
to the study (from a scale of [1] “Unrelated” to [5] “Definitely related”) and b) the severity of the 
event (on a scale of [1] “No adverse event” to [5] “life-threatening/disabling/fatal)”. Serious 
Adverse Events that are at least “somewhat attributable” and “somewhat severe” (i.e. suicidal 
ideation) [3 or more on both scales] will be submitted to NHGRI’s Program Officer, the DSMB, 
and the IRB within 10 business days of study team becoming aware of the event. Deaths will be 
reported within 5 days of the study team becoming aware of the event.  
 
Adverse and Serious Adverse events will be reported according to the following NIH guidelines: 
Reportable Event 
Timeline for Reporting 
Reported by 
IRB/DSMB suspensions or 
terminations 
Within 3 business days of 
receipt (to NHGRI) 
DSMB and PI 
Protocol violations 
With the annual progress 
report (to NHGRI Program 
Officer, and DSMB) 
PI 
Unanticipated Problems, 
involving risks to subjects 
or others 
Within 10 business days of 
study team becoming 
aware of the event (to 
NHGRI Program Officer, 
DSMB, and IRB) 
PI 
Adverse Events, expected 
and/or unrelated to study 
participation 
With the annual progress 
report (to NHGRI Program 
Officer, DSMB, and IRB) 
PI 
Unexpected Serious 
Adverse Events (SAE) 
related to study 
participation 
Within 10 business days of 
study team becoming 
aware of the SAE (to 
NHGRI Program Officer, 
DSMB, and IRB) 
PI 
Deaths related to study 
participation 
Within 5 business days of 
PI first learning of event (to 
NHGRI Program Officer, 
DSMB, and IRB) 
PI 
 
 
6. STATISTICAL ANALYSIS PLAN 
 
We will assess variables’ distributions. We use bivariate tests to compare pre- vs post-
intervention outcomes via paired t-test and Mann-Whitney Signed Rank tests. Primary and 
secondary outcomes will be assessed. We will stratify the sample by key covariates (e.g., 
IQ) and test for significant pre- vs post-mean difference scores by stratification.  
7. DATA MANAGEMENT 
 
Confidentiality of all participants will be preserved by coding all datasheets and other data 
sources and maintaining them in locked files/drawers in the study clinicians office/PI’s office or 
will be kept on a secure computer by the study clinician/PI. ID numbers will be determined by 
order of participant entry into the study and will not be related in any way to participant 

identifying data (i.e., the first participant who is recruited into the study will be subject #1, etc.). 
Data will be entered into a computerized database. The database is on a computer, which 
requires a password to access the data. Public dissemination of the results of this research will 
be reported on subjects collectively and will contain no identifying information about individual 
participants. 
 
A deidentified dataset will be transmitted from Dr. Girgis to Dr. Yang (PI) at NYU only via 
encrypted, password protected files via secure email or an encrypted flashkey.  
 
To accommodate the virtual administration of this protocol and ensure confidentiality, we 
will use a telephone or HIPAA-compliant video teleconferencing. We believe this will 
ensure that the virtual meeting is secure. 
 
Protocol Violations 
Any deviations from the IRB protocol will be first reviewed by BRANY’s IRB and will 
subsequently be submitted in the annual progress report to NHGRI’s Program Officer and to the 
DSMB.  
 
Unanticipated Problems  
Unexpected incidents, experiences or outcomes that are potentially related to participation and 
suggest that the research places the participants at a greater risk of harm than was previously 
known or recognized, will be reported to the NHGRI Program Officer, the DSMB, and the IRB 
within 10 business days of the study team becoming aware of the event. 
 
Discontinuation criteria 
Regarding discontinuation criteria and who will determine if a participant is too ill to continue to 
participate, a participant will discontinue the study under the following conditions: (1) if the 
participant decides not to continue the study for personal reasons; and (2) if the patient presents 
with acute or imminent harm to themselves or others, or suffers other incapacitating conditions 
(i.e., exacerbation of prodromal psychosis symptoms to the point of requiring in patient 
hospitalization) he or she may be removed from the study; and (3) if the participant develops full 
symptoms due to psychosis. In all cases, the participant’s treating clinician will consult with the 
PI and be informed about the discontinuation of study participation. 
 
Data Safety and Monitoring Board:  
Given that the proposed study is an NIH-defined Phase I clinical trial, and that we are recruiting 
children, a Data and Safety Monitoring Board will be appointed. Members of the DSMB will 
include three established and well-recognized experts in stigma and psychosis/CHR who are 
doctoral-level clinicians and researchers who have had at least 5 years of clinical experience 
working with psychosis/CHR. The following members will comprise the DSMB, all of whom have 
no affiliation or role in the project: Phil Yanos, Kristen Woodberry, and Dan Shapiro.  The DSMB 
will convene every six months and in the event of a serious adverse event.  
Review/monitoring activities will include reviewing the protocol, risk-benefit considerations, 
informed consent documents and plans for data safety and monitoring; evaluating the progress 
of the study, including periodic assessments of data quality and timeliness, participant 
recruitment, accrual and retention; and other factors that can affect study outcomes; considering 
factors external to the study such as scientific or therapeutic developments that may have an 
impact on the safety of the participants; protecting the safety of the study participants and 
reporting on the safety and scientific progress of the trial. In addition to having the power to 
recommend to the PI that the study be stopped or modified, the DSMB can determine whether 

any adverse event or serious adverse event affects the risk-benefit ratio of the study, and 
whether modifications to the protocol or consent forms are required. 
 
 
 
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