Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis
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 h...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2016 |
| Country: | España |
| Institution: | Universidad de Cantabria (UC) |
| Repository: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Language: | English |
| OAI Identifier: | oai:repositorio.unican.es:10902/16314 |
| Online Access: | http://hdl.handle.net/10902/16314 |
| Access Level: | Open access |
| Keyword: | COMT Val158Met Antipsychotics Clinical Response Schizophrenia |
| _version_ | 1878738012129460224 |
|---|---|
| author | Huang, Eric |
| author2 | Zai, Clement C. Lisoway, Amanda Maciukiewicz, Malgorzata Felsky, Daniel Tiwari, Arun K. Bishop, Jeffrey R. PharmD Ikeda, Masashi Molero, Patricio Ortuno, Felipe Porcelli, Stefano Samochowiec, Jerzy Mierzejewski, Pawel Gao, Shugui Crespo Facorro, Benedicto|||0000-0001-9709-1276 Pelayo Terán, José María Kaur, Harpreet Kukreti, Ritushree Meltzer, Herbert Y. |
| author2_role | author author author author author author author author author author author author author author author author author author author |
| author_browse | Bishop, Jeffrey R. Crespo Facorro, Benedicto|||0000-0001-9709-1276 Felsky, Daniel Gao, Shugui Huang, Eric Ikeda, Masashi Kaur, Harpreet Kukreti, Ritushree Lisoway, Amanda Maciukiewicz, Malgorzata Meltzer, Herbert Y. Mierzejewski, Pawel Molero, Patricio Ortuno, Felipe Pelayo Terán, José María PharmD Porcelli, Stefano Samochowiec, Jerzy Tiwari, Arun K. Zai, Clement C. |
| author_facet | Huang, Eric Zai, Clement C. Lisoway, Amanda Maciukiewicz, Malgorzata Felsky, Daniel Tiwari, Arun K. Bishop, Jeffrey R. PharmD Ikeda, Masashi Molero, Patricio Ortuno, Felipe Porcelli, Stefano Samochowiec, Jerzy Mierzejewski, Pawel Gao, Shugui Crespo Facorro, Benedicto|||0000-0001-9709-1276 Pelayo Terán, José María Kaur, Harpreet Kukreti, Ritushree Meltzer, Herbert Y. |
| author_role | author |
| collection | UCrea Repositorio Abierto de la Universidad de Cantabria |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_a853a8f65ea490aa4a9499cda9bcdbfa |
| institution | Universidad de Cantabria (UC) |
| instname_str | Universidad de Cantabria (UC) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repositorio.unican.es:10902/16314 |
| publishDate | 2016 |
| publishDateSort | 2016 |
| publisher | Oxford University Press |
| publisherStr | Oxford University Press |
| reponame_str | UCrea Repositorio Abierto de la Universidad de Cantabria |
| spelling | 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. PharmD Ikeda, Masashi Molero, Patricio Ortuno, Felipe Porcelli, Stefano Samochowiec, Jerzy Mierzejewski, Pawel Gao, Shugui Crespo Facorro, Benedicto|||0000-0001-9709-1276 Pelayo Terán, José María Kaur, Harpreet Kukreti, Ritushree Meltzer, Herbert Y. COMT Val158Met Antipsychotics Clinical Response Schizophrenia 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. C.C.Z. is supported by the Brain and Behavior Research Foundation, American Foundation for Suicide Prevention and Eli Lilly. D.F. is supported by the Vanier Canada Graduate Scholarship. D.J.M. has been or is supported by the Canadian Institute of Health Research (CIHR) Operating Grant: “Genetics of antipsychotic-induced metabolic syndrome,” Michael Smith New Investigator Salary Prize for Research in Schizophrenia, NARSAD Independent Investigator Award by the Brain & Behavior Research Foundation, and Early Researcher Award from Ministry of Research and Innovation of Ontario. E.H. is supported by the Canada Graduate Scholarship. H.Y.M. has grant support from Sumitomo Dainippon, Sunovion, Boehringer Ingelheim, Eli Lilly, Janssen, Reviva, Alkermes, Auspex, and FORUM. J.A.L. has received research funding from Alkermes, Biomarin, EnVivo/Forum, Genentech, and Novartis. J.L.K. is supported the CIHR grant “Strategies for gene discovery in schizophrenia: subphenotypes, deep sequencing and interaction.” J.R.B. is supported by NIH grant MH083888. A.K.T. is supported by a NARSAD Young Investigator Award. J.S. is supported by a Pfizer independent grant. P.M. receives salary from Clinica Universidad de Navarra and has received research grants from the Ministry of Education (Spain), the Government of Navarra (Spain), the Spanish Foundation of Psychiatry and Mental Health, and Astrazeneca. S.G. is supported by the Ningbo Medical Technology Project Fund (No. 2004050), the Natural Science Foundation of Ningbo (No. 2009A610186, No. 2013A610249), and the Zhejiang Provincial Medical and Health Project Fund (No. 2015127713). S.G.P. has received research support from Otsuka, Lundbeck, FORUM, and Alkermes. Oxford University Press http://hdl.handle.net/10902/16314 |
| spellingShingle | Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis Huang, Eric COMT Val158Met Antipsychotics Clinical Response Schizophrenia |
| title | Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis |
| title_full | Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis |
| title_fullStr | Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis |
| title_full_unstemmed | Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis |
| title_short | Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis |
| title_sort | Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis |
| topic | COMT Val158Met Antipsychotics Clinical Response Schizophrenia |
| topic_facet | COMT Val158Met Antipsychotics Clinical Response Schizophrenia |
| url | http://hdl.handle.net/10902/16314 |