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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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
Total Authors: 13
Document type: Journal article
Source: Revista Brasileira de Psiquiatria; v. 45, n. 3, p. 226-235, 2023-07-03.

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: 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: 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: 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: 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: 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: 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
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