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

Author(s):Show less -

Camila Marcelino Loureiro ; Fabiana Corsi-Zuelli ^[2] ; Helene Aparecida Fachim ^[3] ; Rosana Shuhama ; Adrielle Martins de Oliveira ^[5] ; Paulo Rossi Menezes ; Caroline F. Dalton ^[7] ; Paulo Louzada-Junior ^[8] ; Sintia Iole Belangero ^[9] ; Fernanda Coeli-Lacchini ^[10] ; Gavin P. Reynolds ^[11] ; Riccardo Lacchini ^[12] ; Cristina Marta Del-Ben

• Document type: Journal article
• Source: Revista Brasileira de Psiquiatria; v. 45, n. 3, p. 226-235, 2023-07-03.

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 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. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/13229-2 - Inflammatory profile in the general population: transdiagnostic dimensions in the context of the psychosis continuum
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/15752-1 - Cannabis use, childhood trauma and endocannabinoids and glutamatergic variants: risk for psychosis
• Grantee: Camila Marcelino Loureiro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/02948-7 - Study of epigenetic alterations in GABAergic neurotransmission in schizophrenia and other psychoses and in animals undergoing social isolation from weaning
• Grantee: Helene Aparecida Fachim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/05178-0 - Schizophrenia and other psychotic disorders: social and biological determinants
• Grantee: Paulo Rossi Menezes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/11167-3 - Gene-environment interactions in Schizophrenia and other psychotic disorders
• Grantee: Rosana Shuhama
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/07448-3 - Immunophenotype of immune-active psychosis patients and the role of interleukin-6
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 17/00624-5 - DNA methylation investigation in first episode of psychosis and in rats undergoing isolation rearing from weaning in the two major excitatory and inhibitory systems
• Grantee: Helene Aparecida Fachim
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor