Developing Clinical Tools to Communicate Genetic Risk for Individuals Who Are Clinical High Risk for Psychosis

Developing Clinical Translational Tools to Communicate Genetic Risk Among Individuals Who Are at Clinical High Risk for Psychosis

While great strides are being made in identifying early signs that place people at a 'high risk state' for different illness conditions, at the same time, advances are being made in the identification of genes associated with 'high-risk states'. This study proposes to develop two innovative clinical tools that could greatly facilitate dissemination of a beneficial genetic malleability framing to high-risk youth in order to encourage increased treatment engagement and uptake of healthy behaviors. The impact of genetic information assumes special importance in the 'high-risk state' because achieving the best possible outcome is more likely if individuals actively choose to engage in beneficial treatment and health-promoting behaviors.

Study Overview

• Status: Completed
• Conditions: Psychosis
• Intervention / Treatment: Behavioral: PsyGist and Clinician Manual

Detailed Description

This project seeks to understand how individuals already in a high-risk state will interpret genetic information informing risk of 'conversion' to a full disorder. How individuals 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, the investigators 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 trained clinicians 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 two tools, experts in psychiatric genetics and stigma will work to develop the two tools to convey genetic risk information to youth and young adults identified as in a 'clinical high-risk state' (CHR) for psychosis. The investigators 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, the investigators seek to establish initial acceptability, safety, and efficacy of each tool. The investigators 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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or females between the ages of 16- 30
• Current or previous COPE participant
• 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

Exclusion Criteria:

• Meeting CHR via only the Genetic risk and deterioration (GRD) syndrome. If the participant meets the GRD syndrome only, the investigators 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.
• IQ < 80
• Inability to adopt hypothetical situation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Clinician Manual; Participants in the Clinician Manual arm will be introduced to a trained clinician 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'.	Behavioral: PsyGist and Clinician Manual; This is a pre-post test design aimed at conveying future genetic risk information to those at clinical high risk for psychosis. Participants will be assigned to either complete the Clinician Manual intervention (n= 27 participants) or PsyGist intervention (n=27 participants).
Other: AutoTutor (PsyGist); AutoTutor is an intelligent system that simulates talking with a human tutor. Our AutoTutor, called 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.	Behavioral: PsyGist and Clinician Manual; This is a pre-post test design aimed at conveying future genetic risk information to those at clinical high risk for psychosis. Participants will be assigned to either complete the Clinician Manual intervention (n= 27 participants) or PsyGist intervention (n=27 participants).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Perceived Treatment Efficacy	Asks participants to rate the likelihood that engaging in treatment and adaptive behaviors will reduce the risk for developing psychosis, if they were told they had a genetic risk for psychosis. Items are measured on a 4-point scale (1=very unlikely, 2=somewhat unlikely, 3=somewhat likely, 4=very likely), with higher scores indicating greater perceived efficacy. Measure is divided into four sub-scales: a) avoiding unhealthy behaviors (4 items range 4-16), b) engaging in healthy behaviors (5 items range 5-20), c) utilizing specialized CHR services (3 items range 3-12), and d) help-seeking behaviors (6 items range 6-24). Changes in scores from pre- to post-intervention are reported.	Baseline, immediately post-intervention, up to 30 minutes
Change From Baseline in Intention to Use Treatment	Asks participants to rate the likelihood of engaging in treatment and adaptive behaviors, if they were told they had a genetic risk for psychosis. Items are measured on a 4-point scale (1=very unlikely, 2=somewhat unlikely, 3=somewhat likely, 4=very likely), with higher scores indicating greater intention. The measure was divided into four sub-scales: a) avoiding unhealthy behaviors (4 items range 4-16), b) engaging in healthy behaviors (5 items range 5-20), c) utilizing specialized CHR services (2 items range 2-8), and d) help-seeking behaviors (6 items range 6-24). Changes were measured pre- and post-intervention.	Baseline, Immediately post-intervention, up to 30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Self-Stigma About Genetic Risk for Psychosis Development	Assess participants self-stigma if they were told they had a genetic risk for psychosis. 7 items are included: I believe I would be fundamentally different from most people (range 1-4), I would be more likely to do something violent towards other people (range 1-4), I would be more likely to do something violent towards myself (range 1-4), I would be more likely to be unpredictable (range 1-4), I would feel ashamed of myself (range 1-4), I would feel embarrassed about myself (range 1-4), I would think of myself as less competent (range 1-4). each measured on a 4-point scale (1=strongly disagree, 2=somewhat disagree, 3=somewhat agree, 4=strongly agree), with higher scores indicating greater stigma. Change in scores from pre- to post-intervention are reported.	Baseline, Immediately post-intervention, up to 30 minutes
Change in Anticipated Discrimination From Others Due to Genetic Risk for Psychosis Development	Assess participants anticipated discrimination if they were told they had a genetic risk for psychosis. 18 items (each with a range of 1-4) are measured on a 4-point scale (1=very unlikely, 2=somewhat unlikely, 3=somewhat likely, 4=very likely), with higher scores indicating greater anticipated stigma. Because this is an exploratory R21 trial, the investigators are also testing and validating new measures for this specific group and purpose however, this is based off a published discrimination scale (Wahl, 1999). Change in scores from pre- to post-intervention for each item are reported.	Baseline, Immediately post-intervention, up to 30 minutes
Anticipated Rejection From Others Due to Genetic Risk for Psychosis Development	Assess participants anticipated rejection if they were told they had a genetic risk for psychosis. 3 items (each with a range of 1-4) measured on a 4-point scale (1=very unconcerned, 2=somewhat unconcerned, 3=somewhat concerned, 4=very concerned), with higher scores indicating greater anticipated rejection. Because this is an exploratory R21 trial, the investigators are also testing and validating new measures for this specific group and purpose; however, these items are based off of a published rejection sensitivity scale (Link, Wells, Phelan, Yang, 2015). Change in scores from pre- to post- intervention for each item are reported.	Baseline, Immediately post-intervention, up to 30 minutes

Collaborators and Investigators

• Sponsor: New York University
• Collaborators: New York State Psychiatric Institute
• Investigators: Principal Investigator: Lawrence Yang, PhD, New York University

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2020
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): July 31, 2022

Study Registration Dates

• First Submitted: October 31, 2019
• First Submitted That Met QC Criteria: March 26, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: 1R21HG010420 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No