Genetic and Clinical Psychosis Risk Groups Had Opposite Patterns of Substance Use

CHR-P youth had significantly higher substance use across tobacco, alcohol, and cannabis compared to controls, while 22qDel carriers had significantly lower use. In CHR-P youth, substance use was associated with higher psychosis symptoms, dysphoric mood, social functioning, and IQ. Higher social anhedonia was associated with lower substance use in both groups. These patterns persisted at one-year follow-up.

Prospective longitudinal study comparing two cohorts: 89 carriers of 22q11.2 deletion syndrome with 65 matched controls, and 1,288 clinical high-risk for psychosis (CHR-P) youth with 371 matched controls from NAPLS-2 and NAPLS-3. Substance use, clinical symptoms, and neurobehavioral measures assessed at baseline and 12-month follow-up.

The opposite substance use patterns in genetic versus clinical psychosis risk suggest that the link between cannabis and psychosis is not simply about vulnerability. Social and cognitive factors may determine whether at-risk individuals are exposed to substances at all.

This study reframes the cannabis-psychosis debate. If genetic psychosis risk does not lead to cannabis use (and may even protect against it through neurodevelopmental factors), then the cannabis-psychosis association in clinical populations may be driven by social and environmental factors rather than shared biology.

Two different cohorts with different recruitment strategies and demographics. 22qDel is a specific and rare genetic condition that may not generalize to other genetic risk factors for psychosis. Self-reported substance use may underestimate use in both groups.