Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: testing gene × environment moderation and mediation.
Laurent Elkrief, Bochao Lin, Mattia Marchi, Mohammad H Afzali, Tobias Banaschewski, Arun L.w. Bokde, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Hugh P Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sarah Hohmann, Juliane H Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Günter Schumann, Jurjen Luykx, Marco P Boks, Patricia Conrod
Psychological Medicine April 1, 2023 DOI: 10.1017/s0033291721003378 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 1,740 |
| Population | European adolescents from the IMAGEN cohort |
| Topics | Cannabis |
| Keywords | Polygenic risk score Psychosis risk Psychotic-like experience |
| Key findings | Cannabis use at age 16 is associated with psychotic-like experiences over and above genetic risk for schizophrenia, with no evidence of mediation or moderation by polygenic risk score. |
Abstract
It has not yet been determined if the commonly reported cannabis-psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders. We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort. PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects. These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis-psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cited by 5
- Sustratos genéticos de la psicosis asociada al cannabis Revista Española de Drogodependencias December 30, 2022
- Genetic substrates of cannabis-associated psychosis Revista Española de Drogodependencias December 30, 2022
- Cannabis Use Interacts With Psychosis Vulnerability in Borderline Personality Disorder: La consommation de cannabis interagit avec la vulnérabilité à la psychose dans le trouble de la personnalité limite The Canadian Journal of Psychiatry September 11, 2026
- Cannabis use and psychotic-like experiences: A systematic review of biological vulnerability, potency effects, and clinical trajectories. Psychiatry Research April 1, 2025
- Consensus paper of the WFSBP task force on cannabis, cannabinoids and psychosis The World Journal of Biological Psychiatry March 22, 2022
Cites 4
- Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case–control study Psychological Medicine March 18, 2020
- The association between cannabis abuse and subsequent schizophrenia: a Swedish national co-relative control study. Psychological Medicine January 2015
- Cannabis as a risk factor for psychosis: systematic review Journal of Psychopharmacology March 1, 2005
- The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology August 2004