Cannabis and Psychosis: A Systematic Review of Genetic Studies (original) (raw)
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Gene-Environment Interactions Underlying the Effect of Cannabis in First Episode Psychosis
Current Pharmaceutical Design, 2012
Cannabis use may be considered as an additional risk factor in a diathesis-stress model of schizophrenia where the risk of developing the illness would be higher in genetic vulnerable people. In this regard, much of the research on cannabis and psychosis is currently focusing on gene-environment interactions. The present review will focus on the interaction between genes and cannabis exposure in the development of psychotic symptoms and schizophrenia and the biological mechanisms of cannabis. Cannabis use has been shown to act together with other environmental factors such as childhood trauma or urbanicity producing synergistic dopamine sensitization effects. Studies on gene-environment interaction have mainly included genetic variants involved in the regulation of the dopaminergic system. The most promising genetic variants in this field are COMT, CNR1, BDNF, AKT1 and NRG1. Additionally, the interaction with other environmental factors and possible gene-gene interactions are considered in the etiological model.
International Journal of Molecular Sciences
The role of both cannabis use and genetic background has been shown in the risk for psychosis. However, the effect of the interplay between cannabis and variability at the endocannabinoid receptor genes on the neurobiological underpinnings of psychosis remains inconclusive. Through a case-only design, including patients with a first-episode of psychosis (n = 40) classified as cannabis users (50%) and non-users (50%), we aimed to evaluate the interaction between cannabis use and common genetic variants at the endocannabinoid receptor genes on brain activity. Genetic variability was assessed by genotyping two Single Nucleotide Polymorphisms (SNP) at the cannabinoid receptor type 1 gene (CNR1; rs1049353) and cannabinoid receptor type 2 gene (CNR2; rs2501431). Functional Magnetic Resonance Imaging (fMRI) data were obtained while performing the n-back task. Gene × cannabis interaction models evidenced a combined effect of CNR1 and CNR2 genotypes and cannabis use on brain activity in diff...
Psychosis-inducing effects of cannabis are related to both childhood abuse and COMT genotypes
Acta Psychiatrica Scandinavica, 2014
Evidence suggests that childhood trauma and cannabis use sinergistically impact on psychosis risk, although a non-replication of this environment-environment interaction was recently published. Gene-environment interaction mechanisms may partially account for this discrepancy. The aim of the current study was to test whether the association between childhood abuse, cannabis use and psychotic experiences (PEs) was moderated by the COMT gene. PEs, childhood abuse, cannabis use and COMT Val158Met genotypes were assessed in 533 individuals from the general population. Childhood abuse was shown to have a significant main effect on PEs (B=.08; SE=.04; p=.047). Furthermore, a significant three-way interaction among childhood abuse, cannabis use and the COMT gene was found (B=-.23; SE=.11; p=.006). This indicates that COMT genotypes and cannabis use only influenced PE scores among individuals exposed to childhood abuse. Exposure to childhood abuse and cannabis use increased PE scores in Val carriers. However, in individuals exposed to childhood abuse but who do not use cannabis, PEs increased as a function of the Met allele copies of the COMT gene. Our findings suggest that the psychosis-inducing effects of childhood abuse and cannabis use are moderated by the Val158Met polymorphism of the COMT gene, which supports a gene-environmentenvironment interaction. Cannabis use after exposure to childhood abuse may have opposite effects on the risk of PEs, depending on the COMT genotypes. Val carriers are vulnerable to the psychosis-inducing effects of cannabis.
Cannabis use and genetic predisposition for schizophrenia: a case-control study
Psychological Medicine, 2008
BackgroundCannabis use may be a risk factor for schizophrenia. Part of this association may be explained by genotype–environment interaction, and part of it by genotype–environment correlation. The latter issue has not been explored. We investigated whether cannabis use is associated with schizophrenia, and whether gene–environment correlation contributes to this association, by examining the prevalence of cannabis use in groups with different levels of genetic predisposition for schizophrenia.MethodCase-control study of first-episode schizophrenia. Cases included all non-Western immigrants who made first contact with a physician for schizophrenia in The Hague, The Netherlands, between October 2000 and July 2005 (n=100; highest genetic predisposition). Two matched control groups were recruited, one among siblings of the cases (n=63; intermediate genetic predisposition) and one among immigrants who made contact with non-psychiatric secondary health-care services (n=100; lowest geneti...
PloS one, 2018
Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). PubMed, Embase, PsychInfo. All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included...
Acta Psychiatrica Scandinavica, 2011
Navarro ME, Fan˜ana´s L. Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Objective: To examine, in a sample of young psychiatric patients, (n = 157, mean age 17.01 years (SD = 3.6)) whether i) age at first cannabis use and age at emergence of psychiatric disorders are related and ii) such a relationship is modulated by the Val158Met polymorphism in the COMT gene. Method: Cannabis use profiles and COMT Val158Met genotypes were obtained from 80 inpatients with schizophrenia-spectrum disorders and 77 inpatients with other non-psychotic disorders. Results: First, age at first cannabis use correlates with age at onset in both schizophrenia-spectrum and other psychiatric disorder groups: those who started using cannabis earlier had an earlier age at onset of psychiatric disorders. Second, the distribution of the Val158Met genotypes was not different either between diagnosis groups or between cannabis users and non-users. Third, an interaction between Val158Met genotypes and cannabis use was observed specifically on age at emergence of psychotic disorders, with Val ⁄ Val genotype carriers showing an earlier age at onset than Met carriers. Conclusion: Our results suggest the importance of brain maturation timing in which exposure to cannabis occurs. The COMT Val158Met genotype seems to modulate the association between cannabis and age at onset of psychotic disorders. These results are consistent with previous studies.