Catechol-O-methyltransferase Val158Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizo-affective disorder patients: a meta-analysis
Huang E (1), Zai CC (1), Lisoway A (1), Maciukiewicz M (1), Felsky D (1), Tiwari AK (1), Bishop JR (2), Ikeda M (3), Molero P (4), Ortuno F (4), Porcelli S (5), Samochowiec J (6), Mierzejewski P (7), Gao S (8), Crespo-Facorro B (9), Pelayo-Terán JM (9), Kaur H (10), Kukreti R (10), Meltzer HY (11), Lieberman JA (12), Potkin SG (13), Müller DJ (1), Kennedy JL (14).
(1) Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
(2) Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN.
(3) Department of Psychiatry, Fujita Health University, Toyoake, Aichi, Japan.
(4) Departamento de Psiquiatria, Clinica Universidad de Navarra, Pamplona, Spain.
(5) Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
(6) Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland.
(7) Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland.
(8) Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, China.
(9) Department of Psychiatry, CIBERSAM, University Hospital Marqués de Valdecilla-IDIVAL, School of Medicine, University of Cantabria, Santander, Spain.
(10) Institute of Genomics and Integrative Biology, Delhi, India.
(11) Feinberg School of Medicine, Northwestern University, Chicago, IL.
(12) Department of Psychiatry, Columbia University Medical Center, New York, NY.
(13) Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA.
(14) Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
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.
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/non-responders 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% PANSS score reduction (or equivalent in other scales). Analysis was conducted under a fixed-effects model.
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=0.039, 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=0.030, SMD=0.24, 95% CI: 0.024-0.46). Post hoc 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=0.0098, ORMet/Met=1.54, 95% CI: 1.11-2.14), while no difference was observed for typical-antipsychotic-treated patients (n=155)(p=0.65).
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.
CITA DEL ARTÍCULO Int J Neuropsychopharmacol. 2016 Jan 8. pii: pyv132. doi: 10.1093/ijnp/pyv132.