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...

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Autores: Huang, E. (Eric)|||/items/8929d023-3691-4674-9061-8a4fe5f7dc36, Zai, C.C. (Clement C.)|||/items/0786ee92-2b10-4073-9feb-df2ffeb18034, Lisoway, A. (Amanda)|||/items/697987c4-5856-462b-a4f1-a05ec91e6164, Maciukiewicz, M. (Malgorzata)|||/items/2d9a3b74-4c08-4a28-9130-cab7a8c8d88d, Felsky, D. (Daniel)|||/items/cbbe586a-43f0-4c6a-8ef7-a17323b5a09b, Tiwari, A.K. (Arun K.)|||/items/e3e3cba8-a78a-44c8-9819-ea18764765eb, Bishop, J.R. (Jeffrey R.)|||/items/6cf365f1-08e2-402d-8275-69129756c7ca, Ikeda, M. (Masashi)|||/items/23b33489-c76a-43a7-a558-a2ff0c23fb0e, Molero, P. (Patricio)|||/items/741e3eb0-ce54-4791-a178-c126bf0d4469, Ortuño-Sanchez-Pedreño, F. (Felipe)|||/items/1bd89e85-a5b7-4f2f-8935-a61c34581779, Porcelli, S. (Stefano)|||/items/a2a9d7b1-aee5-47f9-8049-9f17d37fa787, Samochowiec, J. (Jerzy)|||/items/89961d5b-53e1-4606-be89-ba01be713462, Mierzejewski, P. (Pawel)|||/items/aefa2f40-dc5e-4cee-b718-c779da10c253, Gao, S. (Shugui)|||/items/dca6ce7c-b2a5-44dd-8812-02b0daa93676, Crespo-Facorro, B. (Benedicto)|||/items/c41d1f21-25c9-4067-a29c-277786505667, Pelayo-Teran, J.M. (Jose Maria)|||/items/557b0391-7ca0-46a2-96cb-17dd2e9a1b6f, Kaur, H. (Harpreet)|||/items/e83ce93a-06d7-41bf-ad53-7c33467441bc, Kukreti, R. (Ritushree)|||/items/e3f6c9e1-c05d-4eb6-90a0-0cef4771b2c5, Meltzer, H.Y. (Herbert Y.)|||/items/4d769a35-fd0d-47e4-a1b3-65ae24eee313, Lieberman, J.A. (Jeffrey A.)|||/items/307048f0-fbc6-4352-8da1-dad3d360b480, Potkin, S.G. (Steven G.)|||/items/ad139cf5-ab1d-4259-ab52-81457d7a8ed4, Müller, D.J. (Daniel J.)|||/items/7315cbe8-088f-46b5-9355-cb65861936c2, Kennedy, J.L. (James L.)|||/items/94fc8458-2073-41e3-b8a6-2b365e1582c5
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/41857
Acceso en línea:https://hdl.handle.net/10171/41857
Access Level:acceso abierto
Palabra clave:COMT
Val158Met
Antipsychotics
Schizophrenia
Clinical response
Materias Investigacion::Ciencias de la Salud::Psiquiatría y psicología
Descripción
Sumario: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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