儿茶酚-O-甲基转移酶Val158Met多态性与精神分裂症和分裂情感性障碍患者抗精神病治疗的临床反应：一项荟萃分析。
Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis.
作者信息
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
机构信息
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 of Psychiatry, Fujita Health University, Toyoake, Aichi, Japan (Dr Ikeda); Departamento de Psiquiatria, Clinica Universidad de Navarra, Pamplona, Spain (Drs Molero and Ortuno); Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy (Dr Porcelli); Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland (Dr Samochowiec); Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland (Dr Mierzejewski); Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, China (Dr Gao); Department of Psychiatry, CIBERSAM, University Hospital Marqués de Valdecilla- IDIVAL, School of Medicine, University of Cantabria, Santander, Spain (Dr Pelayo-Terán); Institute of Genomics and Integrative Biology, Delhi, India (Drs Kaur and Kukreti); Feinberg School of Medicine, Northwestern University, Chicago, IL (Dr Meltzer); Department of Psychiatry, Columbia University Medical Center, New York, NY (Dr Lieberman); Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA (Dr Potkin).
出版信息
Int J Neuropsychopharmacol. 2016 Apr 29;19(5). doi: 10.1093/ijnp/pyv132. Print 2016 May.
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.
背景
儿茶酚-O-甲基转移酶（COMT）在多巴胺降解过程中起关键作用，COMT Val158Met多态性（rs4680）与酶活性的显著差异相关，进而与前额叶皮质中的多巴胺浓度相关。多项研究分析了COMT Val158Met变体与抗精神病药物反应之间的关系。在此，我们进行了一项荟萃分析，以研究COMT Val158Met与抗精神病药物反应之间的关系。
方法
通过搜索PubMed、科学网和PsycInfo数据库（2015年1月3日），获得了23项研究，这些研究调查了精神分裂症和分裂情感性障碍中COMT Val158Met变异与抗精神病药物反应的关系。根据每项研究的原始标准定义反应者/无反应者。如果未使用二元反应定义，则要求作者根据阳性和阴性症状量表评分至少降低30%（或其他量表中的等效值）来定义反应。在固定效应模型下进行分析。
结果
10项研究符合荟萃分析的纳入标准。另外对5个接受抗精神病药物治疗的样本进行了Val158Met与反应的分析，并纳入荟萃分析（n总计=1416）。与携带Val的个体相比，Met/Met个体有显著更高的反应可能性（P = 0.039，ORMet/Met = 1.37，95% CI：1.02 - 1.85）。相对于携带Val的个体，Met/Met患者的阳性症状改善也显著更大（P = 0.030，SMD = 0.24，95% CI：0.024 - 0.46）。对接受非典型抗精神病药物治疗的患者（n = 1207）进行的事后分析表明，相对于携带Val的个体，Met/Met患者有显著更高的反应可能性（P = 0.0098，ORMet/Met = 1.54，95% CI：1.11 - 2.14），而在接受典型抗精神病药物治疗的患者（n = 155）中未观察到差异（P = 0.65）。
结论
我们的研究结果表明，COMT Val158Met多态性与精神分裂症和分裂情感性障碍患者对抗精神病药物的反应相关。这种效应可能在非典型抗精神病药物中更为明显。
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