Association Between the COMT Val158Met Polymorphism and Antipsychotic Efficacy in Schizophrenia: An Updated Meta-Analysis

Background: Catechol-O-methyltransferase (COMT) contributes to the control of synaptic dopamine (DA) transmission by catalyzing DA degradation in the presynaptic space. The COMT Val158Met polymorphism (rs4680) substantially alters enzymatic activity and consequently synaptic DA concentration in the prefrontal cortex and hippocampus. The COMT genotype could, therefore, exert a major influence on antipsychotic treatment response as many of these agents also target dopaminergic transmission. Objective: The present meta-analysis aimed to test a putative relationship between the COMT Val158Met polymorphism and antipsychotic response across different populations and antipsychotic types. Methods: Searches of PubMed, Web of Science, EMBASE, OVID, Google Scholar, and Baidu Scholar databases yielded 30 peer-reviewed studies published before January 2020 with a pooled total of 6291 participants. The Lipták-Stouffer Z score method for meta-analysis was applied to combine data. The Z score was also calculated separately for Caucasian and Asian subgroups. Results: Pooled results indicated a highly significant association between COMT Val158Met and antipsychotic response (Z = 6.709, P = 9.8 × 10^-12). Further, this relationship remained significant in subgroup analyses of Caucasian patients (Z = 3.180, P = 7.4 × 10^-4) and Asian patients (Z = 4.487, P = 3.6 × 10^-6). Conclusion: Pooled evidence supports the hypothesis that the COMT Val158Met polymorphism influences the antipsychotic response in Caucasian and Asian schizophrenia patient populations. Prediction of antipsychotic response by patient genotyping may warrant closer consideration in randomized clinical trials of efficacy.