Psychosis-inducing effects of cannabis are related to both childhood abuse and COMT genotypes (original) (raw)
Related papers
Schizophrenia Research, 2013
Background: Cannabis use and childhood maltreatment are independent risk factors for the development of psychotic symptoms. These factors have been found to interact in some but not all studies. One of the reasons may be that childhood maltreatment and cannabis primarily induce psychotic symptoms in genetically susceptible individuals. In this context, an extensively studied psychosis vulnerability gene is catechol-methyl-transferase (COMT). Therefore, we aimed to examine whether the COMT Val 158 Met polymorphism (rs4680) moderates the interaction between childhood maltreatment and cannabis use on psychotic symptoms in the general population. Method: The discovery sample consisted of 918 individuals from a cross-sectional study. For replication we used an independent sample of 339 individuals from the general population. Results: A significant three-way interaction was found between childhood maltreatment, cannabis use, and the COMT genotype (rs4680) in the discovery sample (P = 0.006). Val-homozygous individuals displayed increased psychotic experiences after exposure to both cannabis use and childhood maltreatment compared to Metheterozygous and Met-homozygous individuals. Supportive evidence was found in the replication sample with similar effect and direction even though the results did not reach statistical significance (P = 0.25). Conclusions: These findings suggest that a functional polymorphism in the COMT gene may moderate the interaction between childhood maltreatment and cannabis use on psychotic experiences in the general population. In conclusion, the COMT Val 158 Met polymorphism may constitute a genetic risk factor for psychotic symptoms in the context of combined exposure to childhood maltreatment and cannabis use.
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.
Cannabis and Psychosis: A Systematic Review of Genetic Studies
Current Psychiatry Reviews, 2013
Though the basic pathophysiology of psychosis is largely unknown, there is reliable evidence that genes contribute to its aetiology. Epidemiologic studies suggested that chronic use of cannabis is a risk factor for the development of psychosis. Recent researches have focused on the identification of genetic variants that moderate the effect of cannabis on psychosis occurrence.
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.
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...
Brain and behavior, 2017
COMT rs4680 (Val158Met) genotype moderates the effect of cannabis on the age of onset of psychosis (AoP). We investigated the association between rs4680 and AoP, after adjusting for relevant covariates, in a Canadian Caucasian sample. One hundred and sixty-nine subjects with psychosis were recruited. AoP, defined as age of DSM-IV diagnosis was established using the Structured Clinical Interview for DSM-IV. Cannabis use data were collected using a self-report computerized questionnaire. DNA was extracted from saliva and genotyping of the COMT Val158Met polymorphism was done by SNaPshot and TaqMan assays. Logistic regression and Kaplan-Meier analysis results are reported. In those who had used cannabis before 20 years of age, rs4680 had a trend level effect on AoP (median AoP: Val/Val < Val/Met < Met/Met 19.37, 20.95, 21.24 years, respectively; log-rank test p = .051). Our data are indicative of the need to further investigate the association between the COMT rs4680 variant and ...
Cannabis use and psychosis: re-visiting the role of childhood trauma
Psychological Medicine, 2011
Background. Cannabis consumption continues to be identified as a causal agent in the onset and development of psychosis. However, recent findings have shown that the effect of cannabis on psychosis may be moderated by childhood traumatic experiences.