Abstract
BackgroundNeither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive.ObjectiveA meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met).Data sourcesPubMed, Embase, PsychInfo.Study eligibility criteriaAll observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome.Study appraisal and synthesis methodsA 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 studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions".ResultsFor case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05–2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16–0.08).LimitationA substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects.ConclusionThe interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.
Highlights
Interaction between genes and environment may increase the risk to develop outcomes in the psychosis spectrum [1, 2]
For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an odds ratio (OR) of 1.45 (95% Confidence Interval = 1.05–2.00; Met/Met as the risk genotype)
Given the fact that the same environmental and genetic effects appear to impact psychosis across different clinical and non-clinical levels of the psychosis spectrum [4, 21] we studied GxE in models of transdiagnostic expression of psychosis
Summary
Interaction between genes and environment may increase the risk to develop outcomes in the psychosis spectrum [1, 2]. The transdiagnostic expression of psychosis, defined, clusters in families [4, 5]. Environmental factors such as cannabis consumption increase the risk of developing psychotic disorder or symptoms [6,7,8]. One example of gene-cannabis interaction is the hypothesized moderating effect of the catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met) in the association between cannabis use and the emergence of the psychosis phenotype [10, 11].
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