Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: testing gene × environment moderation and mediation

Elkrief, Laurent; Lin, Bochao; Marchi, Mattia; Afzali, Mohammad H; Banaschewski, Tobias; Bokde, Arun L. W.; Quinlan, Erin Burke; Desrivières, Sylvane; Flor, Herta; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean-Luc; Martinot, Marie-Laure Paillère; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomáš; Poustka, Luise; Hohmann, Sarah; Fröhner, Juliane H.; Smolka, Michael N.; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Luykx, Jurjen; Boks, Marco P.; Conrod, Patricia J.; Consortium, IMAGEN

Abstract

Background
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.

Methods
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.

Results
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.

Conclusions
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.

Citation

Elkrief, L., Lin, B., Marchi, M., Afzali, M. H., Banaschewski, T., Bokde, A. L. W., …Consortium, I. (2023). Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: testing gene × environment moderation and mediation. Psychological Medicine, 53(5), 1759-1769. https://doi.org/10.1017/s0033291721003378

• Journal Article Type: Article
• Acceptance Date: Jul 26, 2021
• Online Publication Date: Sep 23, 2021
• Publication Date: 2023-04
• Deposit Date: Sep 30, 2021
• Publicly Available Date: Sep 30, 2021
• Journal: Psychological Medicine
• Print ISSN: 0033-2917
• Electronic ISSN: 1469-8978
• Publisher: Cambridge University Press
• Peer Reviewed: Peer Reviewed
• Volume: 53
• Issue: 5
• Pages: 1759-1769
• DOI: https://doi.org/10.1017/s0033291721003378
• Keywords: Psychiatry and Mental health; Applied Psychology
• Public URL: https://nottingham-repository.worktribe.com/output/6347718
• Publisher URL: https://www.cambridge.org/core/journals/psychological-medicine/article/independent-contribution-of-polygenic-risk-for-schizophrenia-and-cannabis-use-in-predicting-psychoticlike-experiences-in-young-adulthood-testing-gene-environment-moderation-and-mediati