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

The takeaway

Youth at clinical high risk for psychosis had elevated rates of tobacco, alcohol, and cannabis use, while those with 22q11.2 deletion syndrome (genetic psychosis risk) had strikingly lower rates, with neurodevelopmental factors like IQ and social anhedonia helping explain the difference.

Researchers studying the cannabis-psychosis relationship and clinicians working with psychosis-risk youth

Opposite patterns by risk type

What the researchers found

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.

Why it matters

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.

The numbers in context

89 22qDel carriers + 65 controls; 1,288 CHR-P youth + 371 controls; CHR-P had elevated substance use vs controls; 22qDel had lower use; social anhedonia predicted lower use in both groups; patterns stable at 1-year follow-up

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

Large prospective cohort with both genetic and clinical risk groups, but different cohort designs limit direct comparison

When this study was published

2023 study

The bigger picture

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.

Questions still open

Does social anhedonia protect against substance use by reducing peer interaction opportunities? Would 22qDel carriers who do use substances have worse psychosis outcomes? Can the protective factors in 22qDel inform prevention strategies for CHR-P youth?

Common questions

Do people at genetic risk for psychosis use more cannabis?

Surprisingly, no. Youth with 22q11.2 deletion syndrome (a genetic psychosis risk factor) had significantly lower rates of substance use than controls, opposite to the pattern seen in clinically at-risk youth.

Why would genetic psychosis risk lead to less substance use?

The study suggests that neurodevelopmental factors associated with 22qDel (lower IQ, higher social anhedonia, more autism spectrum features) reduce exposure to social contexts where substance use occurs.

Read the original research

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

Frontiers in psychiatry, 14, 1143315

View on PubMed ↗Publisher’s paper ↗

Citation

Amir, Carolyn M; Kapler, Simon; Hoftman, Gil D; Kushan, Leila; Zinberg, Jamie; Cadenhead, Kristin S; Kennedy, Leda; Cornblatt, Barbara A; Keshavan, Matcheri; Mathalon, Daniel H; Perkins, Diana O; Stone, William; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Cannon, Tyrone D; Addington, Jean; Bearden, Carrie E. (2023). Neurobehavioral risk factors influence prevalence and severity of hazardous substance use in youth at genetic and clinical high risk for psychosis.. Frontiers in psychiatry, 14, 1143315. https://doi.org/10.3389/fpsyt.2023.1143315