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.
(2023) Psychological medicine, volume 53, issue 5, pp. 1759 - 1769
(Article)
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
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(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.
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Keywords: cannabis, Polygenic risk score, psychosis risk, psychotic-like experience, Applied Psychology, Psychiatry and Mental health
ISSN: 0033-2917
Publisher: Cambridge University Press
Note: Funding Information: Dr Conrod is supported by a Tier 1 Canada Research Chair and this research was supported by a CIHR catalyst grant FRN155406 and the Canadian Cannabis and Psychosis Research Team Grant (CIHR FRN CA7170130) and National Institute on Drug Abuse, Grant/Award Numbeer: 1R01DA047119-01. This study received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network-based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), Human Brain Project (HBP SGA 2, 785907), the FP7 project MATRICS (603016), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalising Disorders and Addictions) (MR/N000390/1), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; Forschungsnetz AERIAL 01EE1406A, 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2, SFB 940/2), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1), the National Institutes of Health (NIH) funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01). Further support was provided by grants from: ANR (project AF12-NEUR0008-01 – WM2NA and ANR-12-SAMA-0004), the Eranet Neuron (ANR-18-NEUR00002-01), the Fondation de France (00081242), the Fondation pour la Recherche Médicale (DPA20140629802), the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012, the fondation de l'Avenir (grant AP-RM-17-013); the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1) and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Funding for the Utrecht cannabis cohort was provided by NWO, the Dutch council for scientific research (ZonMW TOP grant no. 91207039). Publisher Copyright: Copyright © The Author(s), 2021. Published by Cambridge University Press.
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