Effect of D2R, NMDAR and CB1R genetic variants associated with cannabis use and childhood trauma in first-episode psychosis in a Brazilian population
C. Loureiro, F. Corsi-Zuelli, H. Fachim, R. Shuhama, P. Menezes, C. Dalton, P. Louzada-Júnior, S. Belangero, F. Coeli-Lacchini, G. P. Reynolds, R. Lacchini, C. Del-Ben
European Psychiatry March 1, 2023 DOI: 10.1192/j.eurpsy.2023.584 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Case-control study Peer reviewed |
|---|---|
| Sample size | 429 |
| Population | First-episode psychosis patients and community-based controls of both sexes aged 16 to 64 years in Brazil |
| Duration | 3-year recruitment period |
| Measures | Cannabis Experience Questionnaire, Childhood Trauma Questionnaire |
| Topics | Cannabis |
| Key findings | No single nucleotide variant among 23 tested was associated with psychosis alone, but the authors report gene-environment interactions: CNR1 rs12720071 combined with lifetime cannabis use (p<0.001) and with childhood trauma (p<0.05), and CNR1 rs7766029 when both environmental factors were modeled together (p<0.001), were associated with increased psychosis risk. The authors conclude the results support gene-environment interactions involving CNR1 variants, childhood trauma, and cannabis use in psychosis. |
Abstract
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