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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.
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.
Afiliação
  • Huang E; 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
  • Zai CC; 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
  • Lisoway A; 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
  • Maciukiewicz M; 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
  • Felsky D; 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
  • Tiwari AK; 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
  • Bishop JR; 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
  • Ikeda M; 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
  • Molero P; 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
  • Ortuno F; 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
  • Porcelli S; 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
  • Samochowiec J; 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
  • Mierzejewski P; 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
  • Gao S; 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
  • Crespo-Facorro B; 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
  • Pelayo-Terán JM; 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
  • Kaur H; 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
  • Kukreti R; 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
  • Meltzer HY; 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
  • Lieberman JA; 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
  • Potkin SG; 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
  • Müller DJ; 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
  • Kennedy JL; 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
Int J Neuropsychopharmacol ; 19(5)2016 05.
Article em En | MEDLINE | ID: mdl-26745992
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Transtornos Psicóticos / Esquizofrenia / Antipsicóticos / Catecol O-Metiltransferase / Variantes Farmacogenômicos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Transtornos Psicóticos / Esquizofrenia / Antipsicóticos / Catecol O-Metiltransferase / Variantes Farmacogenômicos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article