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

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.

MRI-based cortical gray/white matter contrast in young adults who endorse psychotic experiences or are at genetic risk for psychosis

“…PRS performs worse when the sample consists of individuals from different ancestries (Andreassen et al 2023), however our sample consisted mainly of white European individuals. A previous ALSPAC study did not find any association between schizophrenia PRS and psychotic experiences (Jones et al 2016), while other studies with larger samples have found associations between schizophrenia PRS and psychotic-like experiences (Barbu et al 2023;Elkrief et al 2023).…”

Post-traumatic stress disorder among LGBTQ people: a systematic review and meta-analysis

“…Interestingly, research evidence on the psychological consequences of the exposure to trauma, including adverse childhood experience, are not limited to PTSD (Elkrief et al. , 2021 ; Marchi et al. , 2022b , 2020 ).…”

Genetic substrates of cannabis-associated psychosis

“…(2021) reported in the European IMAGEN cohort that cannabis use and genetic liability for schizophrenia were associated with more frequent psychotic experiences, and there was no evidence of mediation or moderation between these two predictors (Elkrief et al, 2021). Similarly, Wainberg et al (2021) examined a large sample from the UK Biobank and found that cannabis users with high schizophrenia genetic liability were more likely to report psychotic experiences, as well as hallucinations, and delusions of reference (Wainberg et al, 2021).…”