Journal
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
Volume 19, Issue 5, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ijnp/pyv132
Keywords
COMT; Va1158Met; antipsychotics; schizophrenia; clinical response
Funding
- Brain and Behavior Research Foundation
- American Foundation for Suicide Prevention
- Eli Lilly
- Vanier Canada Graduate Scholarship
- Canadian Institute of Health Research (CIHR)
- NARSAD - Brain & Behavior Research Foundation
- Ministry of Research and Innovation of Ontario
- Canada Graduate Scholarship
- Sumitomo Dainippon
- Sunovion
- Boehringer Ingelheim
- Janssen
- Reviva
- Alkermes
- Auspex
- FORUM
- Biomarin
- EnVivo/Forum
- Genentech
- Novartis
- CIHR
- NIH [MH083888]
- NARSAD
- Pfizer
- Clinica Universidad de Navarra
- Ministry of Education (Spain)
- Government of Navarra (Spain)
- Spanish Foundation of Psychiatry and Mental Health
- Astrazeneca
- Ningbo Medical Technology Project Fund [2004050]
- Natural Science Foundation of Ningbo [2009A610186, 2013A610249]
- Zhejiang Provincial Medical and Health Project Fund [2015127713]
- Otsuka
- Lundbeck
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Background: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Va1158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMTVa1158Met variant in relation to antipsychotic response. Here, we conducted a meta -analysis examining the relationship between COMTVa1158Met and antipsychotic response. Methods: Searches using PubMed, Web of Science, and Psyclnfo databases (03/01/2015) yielded 23 studies investigating COMT Va1158Met 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 Va1158Met and response and included in the meta -analysis (ntom, = 1416). Met/Me t individuals were significantly more likely to respond than Val-carriers (P=.039, ORmetimet = 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,t t = 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 COMTVa1158Met 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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