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

LOUREIRO, Camila Marcelino, CORSI-ZUELLI, Fabiana, FACHIM, Helene Aparecida, SHUHAMA, Rosana, DE OLIVEIRA, Adrielle Martins, MENEZES, Paulo Rossi, DALTON, Caroline F., LOUZADA-JUNIOR, Paulo, BELANGERO, Sintia Iole, COELI-LACCHINI, Fernanda, REYNOLDS, Gavin P., LACCHINI, Riccardo and DEL-BEN, Cristina Marta (2023). Lifetime cannabis use and childhood trauma associated with CNR1 genetic variants increase the risk of psychosis: findings from the STREAM study. Brazilian Journal of Psychiatry, 45 (3), 226-235.

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Abstract

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 communitybased 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 4 0.05 for all comparisons); however, both environmental risk factors showed an association with psychosis (p o 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 o 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.

Item Type:	Article
Uncontrolled Keywords:	Cannabis use; childhood trauma; first-episode psychosis; single nucleotide variants; 1103 Clinical Sciences; Psychiatry; 3202 Clinical sciences; 5203 Clinical and health psychology
Identification Number:	https://doi.org/10.47626/1516-4446-2022-2882
Page Range:	226-235
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	24 Jul 2023 14:39
Last Modified:	11 Oct 2023 13:02
URI:	https://shura.shu.ac.uk/id/eprint/32187

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