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. LiebermanSteven G. Potkin, Daniel J. Müller, James L. Kennedy

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Article number132
JournalInternational Journal of Neuropsychopharmacology
Volume19
Issue number5
DOIs
Publication statusPublished - 01-01-2016

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Catechol O-Methyltransferase
Mood Disorders
Antipsychotic Agents
Meta-Analysis
Schizophrenia
Therapeutics
Dopamine
Prefrontal Cortex
PubMed
Databases
Enzymes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Huang, Eric ; Zai, Clement C. ; Lisoway, Amanda ; Maciukiewicz, Malgorzata ; Felsky, Daniel ; Tiwari, Arun K. ; Bishop, Jeffrey R. ; Ikeda, Masashi ; Molero, Patricio ; Ortuno, Felipe ; Porcelli, Stefano ; Samochowiec, Jerzy ; Mierzejewski, Pawel ; Gao, Shugui ; Crespo-Facorro, Benedicto ; Pelayo-Terán, José M. ; Kaur, Harpreet ; Kukreti, Ritushree ; Meltzer, Herbert Y. ; Lieberman, Jeffrey A. ; Potkin, Steven G. ; Müller, Daniel J. ; Kennedy, James L. / Catechol-O-methyltransferase Val158Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizo-affective disorder patients : A meta-analysis. In: International Journal of Neuropsychopharmacology. 2016 ; Vol. 19, No. 5.
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title = "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.",
author = "Eric Huang and Zai, {Clement C.} and Amanda Lisoway and Malgorzata Maciukiewicz and Daniel Felsky and Tiwari, {Arun K.} and Bishop, {Jeffrey R.} and Masashi Ikeda and Patricio Molero and Felipe Ortuno and Stefano Porcelli and Jerzy Samochowiec and Pawel Mierzejewski and Shugui Gao and Benedicto Crespo-Facorro and Pelayo-Ter{\'a}n, {Jos{\'e} M.} and Harpreet Kaur and Ritushree Kukreti and Meltzer, {Herbert Y.} and Lieberman, {Jeffrey A.} and Potkin, {Steven G.} and M{\"u}ller, {Daniel J.} and Kennedy, {James L.}",
year = "2016",
month = "1",
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doi = "10.1093/ijnp/pyv132",
language = "English",
volume = "19",
journal = "International Journal of Neuropsychopharmacology",
issn = "1461-1457",
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Huang, E, Zai, CC, Lisoway, A, Maciukiewicz, M, Felsky, D, Tiwari, AK, Bishop, JR, Ikeda, M, Molero, P, Ortuno, F, Porcelli, S, Samochowiec, J, Mierzejewski, P, Gao, S, Crespo-Facorro, B, Pelayo-Terán, JM, Kaur, H, Kukreti, R, Meltzer, HY, Lieberman, JA, Potkin, SG, Müller, DJ & Kennedy, JL 2016, 'Catechol-O-methyltransferase Val158Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizo-affective disorder patients: A meta-analysis', International Journal of Neuropsychopharmacology, vol. 19, no. 5, 132. https://doi.org/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. / Huang, Eric; Zai, Clement C.; Lisoway, Amanda; Maciukiewicz, Malgorzata; Felsky, Daniel; Tiwari, Arun K.; Bishop, Jeffrey R.; Ikeda, Masashi; Molero, Patricio; Ortuno, Felipe; Porcelli, Stefano; Samochowiec, Jerzy; Mierzejewski, Pawel; Gao, Shugui; Crespo-Facorro, Benedicto; Pelayo-Terán, José M.; Kaur, Harpreet; Kukreti, Ritushree; Meltzer, Herbert Y.; Lieberman, Jeffrey A.; Potkin, Steven G.; Müller, Daniel J.; Kennedy, James L.

In: International Journal of Neuropsychopharmacology, Vol. 19, No. 5, 132, 01.01.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Catechol-O-methyltransferase Val158Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizo-affective disorder patients

T2 - A meta-analysis

AU - Huang, Eric

AU - Zai, Clement C.

AU - Lisoway, Amanda

AU - Maciukiewicz, Malgorzata

AU - Felsky, Daniel

AU - Tiwari, Arun K.

AU - Bishop, Jeffrey R.

AU - Ikeda, Masashi

AU - Molero, Patricio

AU - Ortuno, Felipe

AU - Porcelli, Stefano

AU - Samochowiec, Jerzy

AU - Mierzejewski, Pawel

AU - Gao, Shugui

AU - Crespo-Facorro, Benedicto

AU - Pelayo-Terán, José M.

AU - Kaur, Harpreet

AU - Kukreti, Ritushree

AU - Meltzer, Herbert Y.

AU - Lieberman, Jeffrey A.

AU - Potkin, Steven G.

AU - Müller, Daniel J.

AU - Kennedy, James L.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

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