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

The takeaway

In 1,185 participants across 5 US sites, cannabis use and childhood trauma interacted to predict earlier psychosis onset, with the hippocampus partially mediating the relationship in cannabis users.

Psychosis researchers, developmental neuroscientists, early intervention clinicians

Cannabis and trauma each sufficient to affect psychosis onset age at high levels

What the researchers found

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.

Why it matters

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.

The numbers in context

1,185 participants across 5 US sites; 397 controls; 209 bipolar-I; 279 schizoaffective; 300 schizophrenia; hippocampal mediation significant in cannabis users; higher SZ-PGRS in pre-onset cannabis users

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

Large multi-site study with neuroimaging and genetic data, though cross-sectional design and retrospective exposure assessment limit causal interpretation.

When this study was published

Published 2023

The bigger picture

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.

Questions still open

Would trauma-focused interventions in cannabis-using youth delay or prevent psychosis onset? Can hippocampal changes be detected early enough to serve as biomarkers for intervention?

Common questions

Do cannabis and childhood trauma together increase psychosis risk?

Yes. In this study of 1,185 people, cannabis use and childhood trauma interacted to predict earlier psychosis onset. At moderate levels they compounded each other, while at severe levels either factor alone was sufficient.

How might cannabis and trauma lead to psychosis biologically?

The hippocampus partially mediated the relationship between childhood trauma and psychosis onset specifically in people who used cannabis, suggesting these risk factors converge on a shared brain structure.

Read the original research

Characterization of childhood trauma, hippocampal mediation and Cannabis use in a large dataset of psychosis and non-psychosis individuals.

Schizophrenia research, 255, 102-109

View on PubMed ↗Publisher’s paper ↗

Citation

Del Re, Elisabetta C; Yassin, Walid; Zeng, Victor; Keedy, Sarah; Alliey-Rodriguez, Ney; Ivleva, Elena; Hill, Scott; Rychagov, Nicole; McDowell, Jennifer E; Bishop, Jeffrey R; Mesholam-Gately, Raquelle; Merola, Giovanni; Lizano, Paulo; Gershon, Elliot; Pearlson, Godfrey; Sweeney, John A; Clementz, Brett; Tamminga, Carol; Keshavan, Matcheri. (2023). Characterization of childhood trauma, hippocampal mediation and Cannabis use in a large dataset of psychosis and non-psychosis individuals.. Schizophrenia research, 255, 102-109. https://doi.org/10.1016/j.schres.2023.03.029