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.

• Authors: Eric Huang, Clement C Zai, Amanda Lisoway, Malgorzata Maciukiewicz, Daniel Felsky, Arun K Tiwari, Jeffrey R Bishop, Masashi Ikeda, Patricio Molero, Felipe Ortuno, Stefano Porcelli, Jerzy Samochowiec, Pawel Mierzejewski, Shugui Gao, Benedicto Crespo-Facorro, José M Pelayo-Terán, Harpreet Kaur, Ritushree Kukreti, Herbert Y Meltzer, Jeffrey A Lieberman, Steven G Potkin, Daniel J Müller, James L Kennedy
• Journal: The international journal of neuropsychopharmacology (Int J Neuropsychopharmacol) Vol. 19 Issue 5 (05 2016) ISSN: 1469-5111 [Electronic] England
• PMID: 26745992 (Publication Type: Journal Article, Meta-Analysis, Review, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of CINP.

Chemical References

• Antipsychotic Agents
• COMT protein, human
• Catechol O-Methyltransferase

Topics

• Antipsychotic Agents (adverse effects, therapeutic use)
• Catechol O-Methyltransferase (genetics)
• Humans
• Odds Ratio
• Pharmacogenetics
• Pharmacogenomic Testing
• Pharmacogenomic Variants
• Polymorphism, Genetic
• Psychotic Disorders (drug therapy, enzymology, genetics, psychology)
• Remission Induction
• Risk Factors
• Schizophrenia (drug therapy, enzymology, genetics)
• Schizophrenic Psychology
• Treatment Outcome