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 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 J Conrod
Psychological medicine April 1, 2023 DOI: 10.1017/s0033291721003378 via PubMed
Summary
AI-generated from the abstractCannabis use at age 16 is associated with psychotic-like experiences (PLEs) even after accounting for genetic risk for schizophrenia, according to an analysis of 1740 European adolescents from the IMAGEN cohort and replicated in 1223 individuals from a Dutch cohort. Polygenic risk scores for schizophrenia predicted both cannabis use and PLEs, and cannabis use remained a significant predictor of PLEs in models including genetic risk. However, no evidence was found that genetic risk mediates or moderates the cannabis–psychosis link. The findings suggest cannabis use is a risk factor for PLEs independent of genetic vulnerability to schizophrenia.
Study at a glance
| 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 finding | 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.