3 results
Effect of D2R, NMDAR and CB1R genetic variants associated with cannabis use and childhood trauma in first-episode psychosis in a Brazilian population
- 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, G. P. Reynolds, R. Lacchini, C. M. Del-Ben
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S255
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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.
ObjectivesTo 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.
MethodsIn 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).
ResultsSingle 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).
ConclusionsOur 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 InterestNone Declared
Voxel-based morphometric imaging in first-episode psychosis: interrogating the role of familial liability
- F. C. Corsi-Zuelli, F. L. Souza Duran, C. M. Loureiro, A. C. dos Santos, G. Busatto, P. R. Menezes, C. M. Del-Ben
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S549
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Introduction
Neuroanatomical abnormalities are reported in psychotic disorders compared to healthy controls; nevertheless, less is known about the role of familial liability to psychosis in morphological brain changes.
ObjectivesUsing an exploratory voxel-based morphometry (VBM) analyses of the whole brain, we evaluated differences on GMVs across the whole brain among first-episode psychosis (FEP) patients, community-controls, and healthy siblings of patients to interrogate the role of familial liability.
MethodsData were retrieved from a study (STREAM) conducted in Ribeirão Preto/SP Brazil. We included 71 first-episode psychosis patients (67.6% males, mean age±SD: 18.7±10.8), 24 unaffected siblings of patients (37.5% males, mean age±SD 30.8±10), and 36 controls (71.9% males, mean age±SD: 10±10.5). All magnetic resonance imaging (MRI) scans were acquired on a 3T Philips scanner. VBM data were processed using Statistical Parametric Mapping (SPM) software in MATLAB the MNI coordinate system. We performed exploratory voxel-wise comparisons of GMVs among the three groups using an analysis of covariance (ANCOVA) model in SPM. Results were considered significant if they retained significance after family-wise error (FWE) correction for multiple comparisons (p<0.05). All the analyses were adjusted for age, sex, education in years, and total brain GMV.
ResultsThe whole-brain exploratory analyses revealed no significant findings at the p<0.05 level (FWE-corrected). However, pairwise comparisons revealed significant changes betweeen FEP patients and their unaffected siblings. In particular, FEP patients had decreased volumes in the right side of the following regions (FEW = 0.047): superior temporal cortex, Rolandic operculum, insula, Heschel’s gyrus, supramarginal gyrus, superior temporal pole, hippocampus, parahippocampal gyrus, fusiform gyrus, amydgala, olfactory, inferior frontal operculum, cerebellum, posterior and medial orbital frontal cortex, rectus, medial temporal, medial frontal, and putamen. FEP patients also showed decreased volumes on the left side of the following regions (FWE 0.049): frontal superior medial gyrus, superior frontal gyrus, frontal middle part, caudate, anterior cingulate cortex, thalamus, and pallidum. Patients also showed widespread reduced GMV in various GMVs regions compared to controls at FWE<0.05. However, no difference was found between siblings and controls (FWE: >0.05).
ConclusionsThe study of healthy siblings of patients with heritable illnesses could help in the understanding of the contribution of genetic background and environmental factors to illness state and predisposition. Differences between patients and their siblings could be attributed to the disease state, considering that the unaffected sibling group and unrelated healthy control group did not differ. We will next evaluate biological and environmental contributors to the reported differences.
Disclosure of InterestNone Declared
Immune regulatory gene polymorphisms, frequent cannabis use, and psychosis: implications to Treg hypofunction
- F. Corsi-Zuelli, C. Loureiro, R. Shuhama, D. Quattrone, B. Deakin, P. Menezes, R. Lacchini, F. Coeli-Lacchini, P. Louzada-Junior, C. Del-Ben
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- Journal:
- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, p. S698
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Introduction
We have previously shown that the association between frequent cannabis use and psychosis is more likely in subgroups with low-grade inflammation than subgroups without (PMID: 33736715). The role of immune-related polymorphisms remains unknown.
ObjectivesTo explore whether polymorphisms affecting the function of key immune regulatory proteins moderate the association between cannabis and psychosis, namely: ENTPD1 and NT5E, involved in the synthesis of CD39, CD73, respectively, and anti-inflammatory adenosine; CTLA4 and FOXP1, essential for Treg functional capacity.
MethodsWe genotyped blood samples from 283 community-based controls and 140 recent-onset psychosis patients in Brazil (EU-GEI consortium, Ribeirão Preto/SP) for twelve polymorphisms (ENTPD1: rs3814159, rs3176891, rs10748643; NT5E: rs9444348, rs2295890; CTLA4: rs3087243, rs231775, rs5742909, rs4553808; FOXP1: rs6803008, rs6786408, rs830599; Illumina Human Core Exome-24). Cannabis frequency (daily, less than daily, never) was assessed by self-report (Cannabis Experience Questionnaire). Binary logistic regression models (OR,95%CI) included case status as the outcome, genotype (dominant model), cannabis frequency, and an interaction term between the two as exposure, adjusting for confounders (age, sex, ethnicity, tobacco smoking).
ResultsWe found significant interactions between cannabis use and polymorphisms for ENTPD1 (rs3814159), NT5E (rs9444348), and FOXP1 (rs6786408). Less than daily or daily use were, in a dose-response fashion, only associated with psychosis in those with the variant and heterozygous genotypes; less than daily: ENTPD1 AG/GG (3.34,1.71-6.50); NT5E AG/AA (3.71,1.87-7.33); FOXP1 AC/CC (2.98,1.54-5.77); daily: ENTPD1 AG/GG (16.81;5.89-47.96); NT5E AG/AA (21.20,6.81-66.01); FOXP1 AC/CC (13.75,5.22-36.21).
ConclusionsVariation in genes that affect Treg function appears to modify the effect of cannabis consumption on psychosis in keeping with Treg hypofunction hypothesis (PMID:33713699).
DisclosureNo significant relationships.