Catechol-O-methyltransferase Val158Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizo-affective disorder patients: a meta-analysis.

Huang E1, Zai CC1, Lisoway A1, Maciukiewicz M1, Felsky D1, Tiwari AK1, Bishop JR2, Ikeda M3, Molero P4, Ortuno F4, Porcelli S5, Samochowiec J6,Mierzejewski P7, Gao S8, Crespo-Facorro B9, Pelayo-Terán JM9, Kaur H10, Kukreti R10, Meltzer HY11, Lieberman JA12, Potkin SG13, Müller DJ1, Kennedy JL14.

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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/non-responders 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% PANSS 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=0.039, 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=0.030, SMD=0.24, 95% CI: 0.024-0.46). Post hoc 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=0.0098, ORMet/Met=1.54, 95% CI: 1.11-2.14), while no difference was observed for typical-antipsychotic-treated patients (n=155)(p=0.65).

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.