Gene-environment interaction between an endocannabinoid system genetic polymorphism and cannabis use in first episode of psychosis.
M. Bioque, S. Mas, M. Costanzo, B. Cabrera, A. Lobo, A. González-Pinto, E. Rodríguez-Toscano, I. Corripio, E. Vieta, I. Baeza, Á. Ibáñez, M. Fraile, M. Cuesta, G. Mezquida, A. Lafuente, M. Bernardo
European Neuropsychopharmacology June 1, 2019 DOI: 10.1016/j.euroneuro.2019.04.005 via Semantic Scholar
Summary
AI-generated from the abstractA specific genetic variation in the endocannabinoid system interacts with cannabis use to sharply increase the risk of a first episode of psychosis. Carrying two copies of the T allele of the FAAH rs2295633 gene variant, combined with cannabis use, made the probability of a first psychotic episode ten times higher compared to cannabis users without that genotype. No such increased risk appeared in non-users. The study also found that carriers of this genotype who used cannabis were more often treated with high-potency antipsychotics. The findings are preliminary and need replication.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 562 |
| Population | 321 patients with a first episode of psychosis and 241 matched healthy controls |
| Keywords | Medicine Psychology |
| Key finding | Carriers of the T allele of the FAAH rs2295633 SNP who used cannabis had a tenfold higher odds of a first episode of psychosis compared to cannabis users without this genotype. |
Abstract
Alterations of the endocannabinoid system (ECS) may play an important role in the development of schizophrenia and other psychotic disorders. Cannabis use is one of the environmental factors more repeatedly related to an increase the risk of developing a psychotic episode, while its use modifies the ECS normal function. In the present study we purposed to examine the gene by environment (GxE) interaction between 15 selected single nucleotide polymorphisms (SNPs) related to the ECS and cannabis use in a cohort of 321 patients with a first episode of psychosis (FEP) and 241 matched healthy controls. We found the fatty-acid amide hydrolase (FAAH) rs2295633 SNP genetic polymorphism was associated with a greater risk of presenting a FEP in subjects with relevant cannabis use, but not in subjects without a history of cannabis use. The probability of presenting a FEP was tenfold higher (OR: 10.69) in cannabis users who were homozygote carriers of the T allele of the FAAH rs2295633 SNP, compared to users of cannabis without this genotype. We also found that a higher a proportion of TT carriers of the FAAH rs2295633 SNP with a positive history of cannabis use was treated with high potency antipsychotic. This study has identified a GxE-environment interaction between a genetic polymorphism from the ECS and cannabis use involved in the risk of presenting a FEP. Although this preliminary data should be replicated with independent samples, our results highlight the importance of the pro-psychotic effects of exogenous cannabis use over the ECS in certain subjects.