Publication

Neurobehavioral risk factors influence prevalence and severity of hazardous substance use in youth at genetic and clinical high risk for psychosis

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Last modified
  • 06/25/2025
Type of Material
Authors
    Carolyn M Amir, University of California, Los AngelesSimon Kapler, University of California, Los AngelesGil D Hoftman, University of California, Los AngelesLeila Kushan, University of California, Los AngelesJamie Zinberg, University of California, Los AngelesKristin S Cadenhead, University of California, San DiegoLeda Kennedy, University of California, San DiegoBarbara A Cornblatt, Zucker Hillside HospitalMatcheri Keshavan, Beth Israel Deaconess Medical CenterDaniel H Mathalon, University of California, San FranciscoDiana O Perkins, The University of North Carolina at Chapel HillWilliam Stone, Beth Israel Deaconess Medical CenterMing T Tsuang, University of California, San DiegoElaine Walker, Emory UniversityScott W Woods, Yale School of MedicineTyrone D Cannon, Yale UniversityJean Addington, Hotchkiss Brain InstituteCarrie E Bearden, University of California, Los Angeles
Language
  • English
Date
  • 2023-01-01
Publisher
  • Frontiers
Publication Version
Copyright Statement
  • © 2023 Amir, Kapler, Hoftman, Kushan, Zinberg, Cadenhead, Kennedy, Cornblatt, Keshavan, Mathalon, Perkins, Stone, Tsuang, Walker, Woods, Cannon, Addington and Bearden.
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 14
Grant/Funding Information
  • This work was supported by the National Institute of Mental Health (grants U01MH081984, U01 MH081928, P50 MH080272 to JA, grants R01 MH60720, U01 MH082022, and K24 MH76191 to TC; grant U01MH082004-01A1 to DP, grant U01MH08202 to SW, grant UO1 MH081857-05 to BC; grants R01 MH085953, U01MH101779 to CB), NIH National Center for Advancing Translational Science (grant UL1TR001881 to GH), UCLA Friends of the Semel Institute Research Scholar Award (GH), Karen Seykora NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (GH), Harvey L. and Maud C. Sorensen Foundation Fellowship (GH), Burroughs Wellcome Fund Career Award for Medical Scientists (GH), and the Commonwealth of Massachusetts (grant SCDMH82101008006 to Seidman).
Abstract
  • Background: Elevated rates of alcohol, tobacco, and cannabis use are observed in both patients with psychotic disorders and individuals at clinical high risk for psychosis (CHR-P), and strong genetic associations exist between substance use disorders and schizophrenia. While individuals with 22q11.2 deletion syndrome (22qDel) are at increased genetic risk for psychosis, initial evidence suggests that they have strikingly low rates of substance use. In the current study, we aimed to directly compare substance use patterns and their neurobehavioral correlates in genetic and clinical high-risk cohorts. Methods: Data on substance use frequency and severity, clinical symptoms, and neurobehavioral measures were collected at baseline and at 12-month follow-up visits in two prospective longitudinal cohorts: participants included 89 22qDel carriers and 65 age and sex-matched typically developing (TD) controls (40.67% male, Mage = 19.26 ± 7.84 years) and 1,288 CHR-P youth and 371 matched TD controls from the North American Prodrome Longitudinal Study-2 and 3 (55.74% male; Mage = 18.71 ± 4.27 years). Data were analyzed both cross-sectionally and longitudinally using linear mixed effects models. Results: Controlling for age, sex, and site, CHR-P individuals had significantly elevated rates of tobacco, alcohol, and cannabis use relative to TD controls, whereas 22qDel had significantly lower rates. Increased substance use in CHR-P individuals was associated with increased psychosis symptom severity, dysphoric mood, social functioning, and IQ, while higher social anhedonia was associated with lower substance use across all domains at baseline. These patterns persisted when we investigated these relationships longitudinally over one-year. CHR-P youth exhibited significantly increased positive psychosis symptoms, dysphoric mood, social functioning, social anhedonia, and IQ compared to 22qDel carriers, and lower rates of autism spectrum disorder (ASD) compared to 22qDel carriers, both at baseline and at 1 year follow-up. Conclusion: Individuals at genetic and CHR-P have strikingly different patterns of substance use. Factors such as increased neurodevelopmental symptoms (lower IQ, higher rates of ASD) and poorer social functioning in 22qDel may help explain this distinction from substance use patterns observed in CHR-P individuals.
Author Notes
Keywords
Research Categories
  • Psychology, Behavioral
  • Health Sciences, Mental Health

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