The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis.

BACKGROUND: Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. OBJECTIVE: A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). DATA SOURCES: PubMed, Embase, PsychInfo. STUDY ELIGIBILITY CRITERIA: All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. STUDY APPRAISAL AND SYNTHESIS METHODS: 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 studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". RESULTS: For 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). LIMITATION: A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. CONCLUSION: The 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.

The relationship between catechol-O-methyltransferase gene Val158Met (COMT) polymorphism and premorbid cannabis use in Turkish male patients with schizophrenia.

BACKGROUND/AIM: One of the risk factors for increasing psychotic disorders is the use of cannabis. It has been shown that the inactivation of dopamine and other catecholamines causes a common polymorphism generating substantial variations in COMT enzyme activity. We aimed to understand the role of cannabis in the etiology of schizophrenia with and without pre-morbid usage. PATIENTS AND METHODS: The study group consisted of 80 male patients and genotyping of COMT enzyme Val158Met gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: It was found that the Val/Val genotype is significantly higher in patients with premorbid cannabis use (88.9%) compared to patients without pre-morbid cannabis use (68.4%). Also, the mean total positive and negative syndrome scale (PANSS) score seen in the Val/Val genotype group is significantly higher than the scores of the patients with the Met allele. CONCLUSION: The findings from this study confirm the association between COMT Val158 Met polymorphism and pre-morbid cannabis use in causing schizophrenia.