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

• Published in: Psychological medicine Vol. 53; no. 5; pp. 1759 - 1769
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.04.2023; Cambridge University Press (CUP)
• Subjects: Adult; Cannabinoid Receptor Agonists; Cannabis; Cannabis - adverse effects; Child development; Genetic susceptibility; Hallucinogens; Health risk assessment; Humans; Hypotheses; Life Sciences; Longitudinal studies; Marijuana; Mental disorders; Moderation; Original; Original Article; Psychosis; Psychotic Disorders; Psychotic Disorders - epidemiology; Psychotic Disorders - genetics; Risk factors; Schizophrenia; Schizophrenia - epidemiology; Schizophrenia - genetics; Sensitivity analysis; Vulnerability; Young Adult; Young adults; Polygenic risk score; cannabis; psychotic-like experience; psychosis risk; Sulcal variability; Temporal lobe; Occipito-temporal sulcus; Rhinal sulcus; Collateral sulcus; Twin heritability
• ISSN: 0033-2917; 1469-8978; 1469-8978
• DOI: 10.1017/S0033291721003378

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 ( = 0.027) and PLE ( = 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 ( = 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.