Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis

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

doi:10.1093/ijnp/pyv132

Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis

Int J Neuropsychopharmacol. 2016 Apr 29;19(5):pyv132. doi: 10.1093/ijnp/pyv132. Print 2016 May.

Authors

Eric Huang¹, Clement C Zai¹, Amanda Lisoway¹, Malgorzata Maciukiewicz¹, Daniel Felsky¹, Arun K Tiwari¹, Jeffrey R Bishop¹, Masashi Ikeda¹, Patricio Molero¹, Felipe Ortuno¹, Stefano Porcelli¹, Jerzy Samochowiec¹, Pawel Mierzejewski¹, Shugui Gao¹, Benedicto Crespo-Facorro¹, José M Pelayo-Terán¹, Harpreet Kaur¹, Ritushree Kukreti¹, Herbert Y Meltzer¹, Jeffrey A Lieberman¹, Steven G Potkin¹, Daniel J Müller¹, James L Kennedy²

Affiliations

¹ Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada (Mr Huang, Dr Zai, Ms Lisoway, Dr Maciukiewicz, Mr Felsky, Dr Tiwari, Dr Müller, and Dr Kennedy); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN (Dr Bishop); Department of Psychiatry, Fujita Health University, Toyoake, Aichi, Japan (Dr Ikeda); Departamento de Psiquiatria, Clinica Universidad de Navarra, Pamplona, Spain (Drs Molero and Ortuno); Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy (Dr Porcelli); Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland (Dr Samochowiec); Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland (Dr Mierzejewski); Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, China (Dr Gao); Department of Psychiatry, CIBERSAM, University Hospital Marqués de Valdecilla- IDIVAL, School of Medicine, University of Cantabria, Santander, Spain (Dr Pelayo-Terán); Institute of Genomics and Integrative Biology, Delhi, India (Drs Kaur and Kukreti); Feinberg School of Medicine, Northwestern University, Chicago, IL (Dr Meltzer); Department of Psychiatry, Columbia University Medical Center, New York, NY (Dr Lieberman); Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA (Dr Potkin).
² Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada (Mr Huang, Dr Zai, Ms Lisoway, Dr Maciukiewicz, Mr Felsky, Dr Tiwari, Dr Müller, and Dr Kennedy); Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN (Dr Bishop); Department of Psychiatry, Fujita Health University, Toyoake, Aichi, Japan (Dr Ikeda); Departamento de Psiquiatria, Clinica Universidad de Navarra, Pamplona, Spain (Drs Molero and Ortuno); Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy (Dr Porcelli); Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland (Dr Samochowiec); Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland (Dr Mierzejewski); Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, China (Dr Gao); Department of Psychiatry, CIBERSAM, University Hospital Marqués de Valdecilla- IDIVAL, School of Medicine, University of Cantabria, Santander, Spain (Dr Pelayo-Terán); Institute of Genomics and Integrative Biology, Delhi, India (Drs Kaur and Kukreti); Feinberg School of Medicine, Northwestern University, Chicago, IL (Dr Meltzer); Department of Psychiatry, Columbia University Medical Center, New York, NY (Dr Lieberman); Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA (Dr Potkin). jim.kennedy@camh.ca.

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.

Keywords: COMT; Val158Met; antipsychotics; clinical response; schizophrenia.

Publication types

Meta-Analysis
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Antipsychotic Agents
COMT protein, human
Catechol O-Methyltransferase

Abstract

Publication types

MeSH terms

Substances

Grants and funding