Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not.
Level 4 - case-series / case-control
Observational case-control and cross-sectional genetic association study assessing retrospective exposures.
PubMed 28967348 · doi:10.1017/S0033291717001209
What was done
Researchers calculated schizophrenia polygenic risk scores (SZ-PGRS) using Psychiatric Genomics Consortium data for an independent sample of 381 schizophrenia spectrum cases, 220 bipolar disorder spectrum cases, and 415 healthy controls (total N = 1,016). They compared SZ-PGRS in patients with weekly-to-daily cannabis use before their first psychotic episode against those with infrequent or no premorbid use, with follow-up analyses evaluating early frequent use before age 18.
What was found
Patients with weekly to daily cannabis use before illness onset had significantly higher SZ-PGRS than non-frequent or never users (p = 0.02, Cohen's d = 0.33). The largest difference was observed between patients with weekly to daily use before age 18 and those with infrequent or no use (p = 0.003, Cohen's d = 0.42).
Why it matters
This study suggests that genetic liability for schizophrenia is linked to premorbid frequent cannabis use, pointing to a potential gene-environment correlation rather than purely environmental causation.
Limits
Premorbid cannabis exposure was measured retrospectively, leaving room for recall bias. The abstract does not report cumulative exposure amounts, cannabis potency, or adjustments for other substance use, and the observed effect sizes were modest.