Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis
Abstract
Background: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT
Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine
concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic
response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response.
Methods: Searches using PubMed, Web of Science, and PsycInfo databases (03/01/2015) yielded 23 studies investigating COMT
Val158Met variation and antipsychotic response in schizophrenia and schizo-affective disorder. Responders/nonresponders
were defined using each study’s original criteria. If no binary response definition was used, authors were asked to define
response according to at least 30% Positive and Negative Syndrome Scale score reduction (or equivalent in other scales).
Analysis was conducted under a fixed-effects model.
Results: Ten studies met inclusion criteria for the meta-analysis. Five additional antipsychotic-treated samples were analyzed for
Val158Met and response and included in the meta-analysis (ntotal = 1416). Met/Met individuals were significantly more likely to respond
than Val-carriers (P = .039, ORMet/Met = 1.37, 95% CI: 1.02–1.85). Met/Met patients also experienced significantly greater improvement in
positive symptoms relative to Val-carriers (P = .030, SMD = 0.24, 95% CI: 0.024–0.46). Posthoc analyses on patients treated with atypical
antipsychotics (n = 1207) showed that Met/Met patients were significantly more likely to respond relative to Val-carriers (P = .0098,
ORMet/Met = 1.54, 95% CI: 1.11–2.14), while no difference was observed for typical-antipsychotic-treated patients (n = 155) (P = .65).
Conclusions: Our findings suggest that the COMT Val158Met polymorphism is associated with response to antipsychotics in
schizophrenia and schizo-affective disorder patients. This effect may be more pronounced for atypical antipsychotics