Cannabis and childhood trauma interacted to lower the age when psychosis first appeared

Among 1,185 participants (397 controls, 209 bipolar-I, 279 schizoaffective, 300 schizophrenia), cannabis use and childhood trauma interacted in survival analysis to predict earlier psychosis onset. At high levels, either factor alone was sufficient to affect onset age (ceiling effect). Hippocampal volume partially mediated the trauma-onset relationship specifically in cannabis users before psychosis onset. Cannabis use before onset was associated with higher schizophrenia polygenic risk scores and younger age at first cannabis use.

Cross-sectional case-control study across 5 US metropolitan sites. Included neuroimaging, Childhood Trauma Questionnaire, self-reported cannabis use, clinical interviews, cognition testing, and schizophrenia polygenic risk score calculation. Survival analysis, mediation analysis, and polygenic score analyses conducted.

This study suggests cannabis and childhood trauma may represent different but converging pathways to psychosis, with the hippocampus as a shared biological mechanism. This has implications for early intervention targeting both risk factors.

If cannabis and childhood trauma converge on the hippocampus to accelerate psychosis onset, screening for both risk factors together could identify individuals at highest risk for early intervention.

Cross-sectional design limits causal conclusions. Retrospective self-reported cannabis use and trauma. Cannot fully separate effects of cannabis from confounding factors. Polygenic scores explain only a fraction of genetic risk.