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

Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPLOUREIRO, Camila MarcelinoCORSI-ZUELLI, FabianaFACHIM, Helene AparecidaSHUHAMA, RosanaOLIVEIRA, Adrielle Martins deMENEZES, Paulo RossiDALTON, Caroline F.LOUZADA-JUNIOR, PauloBELANGERO, Sintia IoleCOELI-LACCHINI, FernandaREYNOLDS, Gavin P.LACCHINI, RiccardoDEL-BEN, Cristina Marta2023-10-302023-10-302023BRAZILIAN JOURNAL OF PSYCHIATRY, v.45, n.3, p.226-235, 20231516-4446https://observatorio.fm.usp.br/handle/OPI/56156Objectives: 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 < 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.engopenAccessCannabis usechildhood traumafirst-episode psychosissingle nucleotide variantsmultifactor dimensionality reductionmajor depressive disorderschizophreniaassociationpharmacogeneticspolymorphismsvalidationreceptorsbiologyLifetime cannabis use and childhood trauma increase risk of psychosis in carriers of CNR1 genetic variants: findings from the STREAM studyarticleCopyright ASSOC BRASILEIRA PSIQUIATRIA10.47626/1516-4446-2022-2882Psychiatry1809-452X