Lifetime cannabis use and childhood trauma associated with CNR1 genetic variants increase the risk of psychosis: findings from the STREAM study.

Autor: Loureiro CM; Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil. Centro de Pesquisas em Saúde Mental da População, São Paulo, SP, Brazil., Corsi-Zuelli F; Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil., Fachim HA; University of Manchester, Manchester, United Kingdom., Shuhama R; Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil. Centro de Pesquisas em Saúde Mental da População, São Paulo, SP, Brazil., de Oliveira AM; Universidade Federal São Paulo, São Paulo, SP, Brazil., Menezes PR; Centro de Pesquisas em Saúde Mental da População, São Paulo, SP, Brazil. Faculdade de Medicina, USP, São Paulo, SP, Brazil., Dalton CF; Sheffield Hallam University, South Yorkshire, United Kingdom., Louzada-Junior P; Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil., Belangero SI; Universidade Federal São Paulo, São Paulo, SP, Brazil., Coeli-Lacchini F; Faculdade de Ciências Farmacêuticas, USP, São Paulo, SP, Brazil., Reynolds GP; Sheffield Hallam University, South Yorkshire, United Kingdom., Lacchini R; Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil., Del-Ben CM; Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil. Centro de Pesquisas em Saúde Mental da População, São Paulo, SP, Brazil.
Jazyk: angličtina
Zdroj: Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999) [Braz J Psychiatry] 2023 May-Jun; Vol. 45 (3), pp. 226-235. Date of Electronic Publication: 2023 Mar 14.
DOI: 10.47626/1516-4446-2022-2882
Abstrakt: Objectives: Gene-environment interactions increase the risk of psychosis. The objective of this study was to investigate gene-gene and gene-environment interactions in psychosis, including single nucleotide variants (SNVs) of dopamine-2 receptor (D2R), N-methyl-d-aspartate receptor (NMDAR), and cannabinoid receptor type 1 (CB1R), lifetime cannabis use, and childhood trauma.
Methods: Twenty-three SNVs of genes encoding D2R (DRD2: rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898) were genotyped in 143 first-episode psychosis patients (FEPp) and 286 community-based controls by Illumina HumanCoreExome-24 BeadChip. Gene-gene and gene-environment associations were assessed using nonparametric Multifactor Dimensionality Reduction software.
Results: Single-locus analyses among the 23 SNVs for psychosis and gene-gene interactions were not significant (p > 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p < 0.001). Moreover, gene-environment interactions were significant for an SNV in CNR1 and cannabis use. The best-performing model was the combination of CNR1 rs12720071 and lifetime cannabis use (p < 0.001), suggesting an increased risk of psychosis.
Conclusion: Our study supports the hypothesis of gene-environment interactions for psychosis involving T-allele carriers of CNR1 SNVs, childhood trauma, and cannabis use.
Competing Interests: GPR has received honoraria for lectures and/or advisory panel membership from Janssen, Lundbeck, Otsuka, and Sunovion, and a research grant from Sunovion. The other authors report no conflicts of interest..
Databáze: MEDLINE
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