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Effect of D2R, NMDAR and CB1R genetic variants associated with cannabis use and childhood trauma in first-episode psychosis in a Brazilian population

Published online by Cambridge University Press:  19 July 2023

C. M. Loureiro ,
F. Corsi-Zuelli ,
H. A. Fachim ,
R. Shuhama ,
P. R. Menezes ,
C. F. Dalton ,
P. Louzada-Junior ,
S. I. N. Belangero ,
F. B. Coeli-Lacchini  and
G. P. Reynolds
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C. M. Loureiro*
Affiliation:
1Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 2Population Mental Health Research Centre, São Paulo, Brazil
F. Corsi-Zuelli
Affiliation:
1Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto
H. A. Fachim
Affiliation:
3University of Manchester, Manchester, United Kingdom
R. Shuhama
Affiliation:
1Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 2Population Mental Health Research Centre, São Paulo, Brazil
P. R. Menezes
Affiliation:
2Population Mental Health Research Centre, São Paulo, Brazil 4Preventive Medicine, University of São Paulo, São Paulo, Brazil
C. F. Dalton
Affiliation:
5Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, United Kingdom
P. Louzada-Junior
Affiliation:
6Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto
S. I. N. Belangero
Affiliation:
7Morphology and Genetics, Universidade Federal de São Paulo, São Paulo
F. B. Coeli-Lacchini
Affiliation:
6Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto
G. P. Reynolds
Affiliation:
5Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, United Kingdom
R. Lacchini
Affiliation:
8Ribeirao Preto College of Nursing, University of São Paulo, Ribeirão Preto, Brazil
C. M. Del-Ben
Affiliation:
1Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 2Population Mental Health Research Centre, São Paulo, Brazil
*
*Corresponding author.

Abstract

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Introduction

Gene-environment interactions increase psychosis risk (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657). However, identifying the genetic variants involved and how they interact with environmental risk factors underlying psychosis remains challenging.

Objectives

To investigate whether there are gene-environment interactions in the relationships of childhood trauma, lifetime cannabis use, and single nucleotide variants (SNVs) of dopamine D2 receptor (D2R: DRD2), N-methyl-d-aspartate receptor (NMDAR: GRIN1, GRIN2A and GRIN2B) and cannabinoid receptor type 1 (CB1R: CNR1) with psychosis.

Methods

In a population-based case-control study nested in an incident study (STREAM, Brazil) (Del-Ben et al. Br J of Psychiatry 2019; 215(6):726-729), part of the EU-GEI consortium (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657), 143 first-episode psychosis patients and 286 community-based controls of both sexes aged between 16 and 64 years were included over a period of 3 years. Twenty-three SNVs of D2R (rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R genes (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip. Environmental adversities were evaluated using the Cannabis Experience Questionnaire (Di Forti et al. The Lancet Psychiatry 2009; 6(5):427–436) and the Childhood Trauma Questionnaire (Grassi-Oliveira et al. Rev Saude Publica 2006; 40(2):249-55). Associations between SNVs and environmental risk factors were performed using the nonparametric multifactor dimensionality reduction software (version 3.0.2).

Results

Single locus analysis showed no association among the 23 SNVs with psychosis; however, gene-environment analysis was significant for the polymorphic loci rs12720071 and rs7766029 in CNR1. The best association models were the two-factor representing by the combination of CNR1 rs12720071 with lifetime cannabis use (p<0.001), and CNR1 rs12720071 with childhood trauma (p<0.05), both suggesting an increased risk of psychosis. Additionally, when considering the interaction of both environmental factors in the same model, we found CNR1 rs7766029 to be associated with psychosis (p<0.001).

Conclusions

Our study supports the hypothesis of gene-environment interactions for psychosis involving the T allele carriers of CNR1 SNVs (rs12720071 and rs7766029), childhood trauma and lifetime cannabis use in psychosis.

Disclosure of Interest

None Declared

Type
Abstract
Information
European Psychiatry , Volume 66 , Special Issue S1: Abstracts of the 31st European Congress of Psychiatry , March 2023 , pp. S255
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of the European Psychiatric Association
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