Understanding the shared genetic risk for psychosis and substance use disorders : a study of genetic markers of endogenous and exogenous cannabinoid-related Risk
Cannabis consumption during adolescence, increases the likelihood of adverse mental health outcomes, including substance abuse and psychosis. Considering that part of the etiology of these disorders are heritable, we aimed to elucidate the genetic risk for psychosis and substance use disorders and their relationships to cannabis and the endocannabinoid system. In our first work, we investigated the relationship between endocannabinoid genetic markers and alcohol use disorder in two adolescent cohorts. Through candidate gene approaches we demonstrated a significant relationship between these endocannabinoid genes and AUD, but the results were not replicated in the second cohort. In a second work, we examined if the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic like experiences (PLE) is mediated and/or moderated by cannabis use, in two cohorts. Mediation and moderation regression models were used to examine the extent to which the prospective relationship between PRS-Sz and PLE is accounted for by cannabis use. The results of both the mediation and moderation analyses were not significant, although PRS-Sz and cannabis use both independently predicted PLE. These results suggest that cannabis use remains a risk factor for psychotic-like experiences, over and above known genetic vulnerability for schizophrenia and there was no evidence that genetically vulnerable individuals were more susceptible to the psychosis-related outcomes of adolescent onset cannabis use. The work described demonstrates that the risks posed by adolescent cannabis consumption may be unrelated to one’s genetic predisposition to psychiatric disease, notwithstanding the involvement of the endocannabinoid system in the pathogenesis of these same diseases.
Endocannabinoid Cannabis Alcohol Use Disorder Psychosis candidate gene polygenic risk score