双相障碍氢质子磁共振波谱研究谷氨酸代谢水平的Meta分析

摘要

目的 通过Meta分析综合评价双相障碍患者氢质子磁共振波谱(1H-magneticresonance spectroscopy,1H-MRS)研究中相对定量指标谷氨酸的代谢水平.方法 检索Pubmed、Medline、Web of science、荷兰医学文摘数据库(excerpta medica database,EMBASE)、Cochrane图书馆、中国生物医学文献服务系统(China biomedical literature service system,SinoMed)、中国期刊全文数据库(China national knowledge infrastructure,CNKI)、万方数据1990年1月至2016年6月公开发表的有关双相障碍1H-MRS研究的中英文文献,提取文献中双相障碍患者组和健康对照组谷氨酸(glutamate)、谷氨酸/肌酸(creatine)、谷氨酸复合物(glutamate/glutamine,Glx)及Glx/肌酸指标的测量数据,以Newcastle-Ottawa Scale (NOS)评价工具进行文献质量方法学评估.采用Review Manager 5.3及STATA12.0统计学软件对纳入文献的数据进行汇总分析.结果 共纳入27篇文献,均为英文文献.Meta分析结果显示,双相障碍组Glx (SMD:0.45,Z=2.39,P＜0.05)及Glx/肌酸(SMD:0.50,Z=2.14,P＜0.05)的标准均数差与健康对照组相比差异有统计学意义;而谷氨酸(SMD:0.14,Z=0.67,P＞0.05)及谷氨酸/肌酸(SMD:0.06,Z=0.28,P＞0.05)的标准均数差与健康对照组相比差异无统计学意义.亚组分析显示,与健康对照组相比,Glx在双相障碍未用药组、成人组及非缓解期组明显升高.亚组各综合效应值之间比较,除Glx/肌酸指标在缓解期组高于非缓解期组外,其他谷氨酸代谢指标综合效应值在用药组低于未用药组、儿童青少年组低于成人组,缓解期组低于非缓解期组.结论 双相障碍患者Glx及Glx/肌酸水平较健康对照者明显升高,药物治疗后及缓解期谷氨酸代谢指标有降低趋势.%Objective The objective of this study was to conduct a meta-analysis from the literature on brain glutamate in bipolar disorder (BD) as measured by 1H-magnetic resonance spectroscopy (1H-MRS).Methods A search was conducted of Pubmed,Medline,Web of science,excerpta medica database (EMBASE),Cochrane library,China biomedical literature service system (SinoMed),China National Knowledge Infrastructure (CNKI),Wan Fang data from January 1990 to June 2016 for those studies that used 1H-MRS to measure glutamate (Glu),or the Glu/creatine (Cr) ratio,Glu + glutamine or Glu/glutamine (Glx) and the Glx/Cr ratio in any brain region in adult or child/adolescent patients with BD and healthy controls.Study quality was assessed using the Newcastle-ottawa quality assessment scale (NOS).A meta-analysis of the pooled data was conducted by using Review Manager 5.3 and STATA 12.0 software.Results A total of 27 English articles fulfilled the inclusion and exclusion criteria.Meta-analysis showed that Glx (SMD:0.45,Z=2.39,P＜0.05) and Glx/Cr (SMD:0.50,Z=2.14,P＜0.05) were significantly increased in BD cornpared to healthy controls while there were no significant difference in Glu (SMD:0.14,Z=0.67,P＞ 0.05) and Glu/Cr (SMD:0.06,Z=0.28,P＞0.05).Subgroup analyses showed Glx was significantly increased in non-medicated,adults and non-euthymic group when compared to healty controls.The effect size of the brain glutamate metabolic indexes were decreased in medicated,child/adolescent and euthymic group when compared to non-medicated,adults and non-euthymic group except Glx/Cr index of the mood state subgroup when compared between subgroups.Conclusion The results of this meta-analysis suggest that brain Glx and Glx/Cr levels are increased in BD patients and there is a decreased trend of brain glutamate metabolic indexes levels after medication and in euthymic episodes,which support the idea that glutamate might play an important role in the pathophysiology of BD.