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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Laurent Elkrief - , University of Montreal (Autor:in)
  • Bochao Lin - , Utrecht University (Autor:in)
  • Mattia Marchi - , Brain Center, University of Modena and Reggio Emilia (Autor:in)
  • Mohammad H. Afzali - , University of Montreal (Autor:in)
  • Tobias Banaschewski - , Universität Heidelberg (Autor:in)
  • Arun L.W. Bokde - , Trinity College Dublin (Autor:in)
  • Erin Burke Quinlan - , King's College London (KCL) (Autor:in)
  • Sylvane Desrivières - , King's College London (KCL) (Autor:in)
  • Herta Flor - , Universität Heidelberg, Universität Mannheim (Autor:in)
  • Hugh Garavan - , University of Vermont (Autor:in)
  • Penny Gowland - , University of Nottingham (Autor:in)
  • Andreas Heinz - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Bernd Ittermann - , Physikalisch-Technische Bundesanstalt (Autor:in)
  • Jean Luc Martinot - , Université Paris-Saclay (Autor:in)
  • Marie Laure Paillère Martinot - , INSERM - Institut national de la santé et de la recherche médicale (Autor:in)
  • Frauke Nees - , Universität Heidelberg (Autor:in)
  • Dimitri Papadopoulos Orfanos - , Commissariat à l’énergie atomique et aux énergies alternatives (CEA) (Autor:in)
  • Tomáš Paus - , University of Toronto (Autor:in)
  • Luise Poustka - , Georg-August-Universität Göttingen (Autor:in)
  • Sarah Hohmann - , Universität Heidelberg (Autor:in)
  • Juliane H. Fröhner - , Klinik und Poliklinik für Psychiatrie und Psychotherapie (Autor:in)
  • Michael N. Smolka - , Klinik und Poliklinik für Psychiatrie und Psychotherapie (Autor:in)
  • Henrik Walter - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Robert Whelan - , Trinity College Dublin (Autor:in)
  • Gunter Schumann - , King's College London (KCL), Trinity College Dublin, Humboldt-Universität zu Berlin, Leibniz Institute for Neurobiology, Fudan University (Autor:in)
  • Jurjen Luykx - , Brain Center (Autor:in)
  • Marco P. Boks - , Brain Center (Autor:in)
  • Patricia J. Conrod - , University of Montreal (Autor:in)


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.


Seiten (von - bis)1759-1769
FachzeitschriftPsychological medicine
PublikationsstatusVeröffentlicht - 23 Apr. 2023

Externe IDs

PubMed 37310336
ORCID /0000-0001-5398-5569/work/150329519
ORCID /0000-0002-8493-6396/work/150330245


Ziele für nachhaltige Entwicklung


  • Polygenic risk score, cannabis, psychosis risk, psychotic-like experience, Young Adult, Cannabinoid Receptor Agonists, Humans, Adult, Cannabis/adverse effects, Psychotic Disorders/epidemiology, Schizophrenia/epidemiology, Hallucinogens