Review

. 2016 Apr 29;19(5):pyv132.

doi: 10.1093/ijnp/pyv132. Print 2016 May.

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

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.

PMID: 26745992
PMCID: PMC4886669
DOI: 10.1093/ijnp/pyv132

Review

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

Eric Huang et al. Int J Neuropsychopharmacol. 2016.

. 2016 Apr 29;19(5):pyv132.

doi: 10.1093/ijnp/pyv132. Print 2016 May.

Authors

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.

PMID: 26745992
PMCID: PMC4886669
DOI: 10.1093/ijnp/pyv132

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.

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Figures

**Figure 1.**
Literature search process results.

**Figure 2.**
All studies. Meta-analysis of the association between the Val158Met polymorphism (Met/Met vs Val carrier) and antipsychotic drug response: forest plot.

**Figure 3.**
All studies. Meta-analysis of the association between the Val158Met polymorphism (Met/Met vs Val carrier) and antipsychotic drug response: funnel plot and regression plot.

**Figure 4.**
Atypical antipsychotic-treated samples. Meta-analysis of the association between the Val158Met polymorphism (Met/Met vs Val carrier) and antipsychotic drug response: forest plot.

**Figure 5.**
Atypical antipsychotic-treated samples. Meta-analysis of the association between the Val158Met polymorphism (Met/Met vs Val carrier) and antipsychotic drug response: funnel plot and regression plot.

See this image and copyright information in PMC

References

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1. Badner J, Gershon E. (2002) Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 7:405–411. - PubMed
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1. Bertolino A, Caforio G, Blasi G, De Candia M, Latorre V, Petruzzella V, Altamura M, Nappi G, Papa S, Callicott JH. (2004) Interaction of COMT Val108/158 Met genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry 161:1798–1805. - PubMed

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

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

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