精神分裂症与外周血清BDNF水平关系的系统综述(英文)

背景 脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)在精神分裂症的发生和病程演变过程中所起的作用受到了越来越广泛的关注,但有关精神分裂症与外周血清 BDNF 水平关系的研究结果不尽一致。目的 综合国内外研究,系统评价精神分裂症患者外周血清BDNF水平的特点。方法 我们采用 Cochrane 系统综述方法和 RevMan 5.1 软件筛选研究并提取数据。通过国内外电子检索系统的检索并对获得文献的参考文献进行追溯评估,共检出268篇相关文献。其中25篇(20篇英文,5篇中文)被纳入分析,它们为 2011 年 12 月底以前公开发表的病例对照研究,研究对象为不伴有其他疾病的精神分裂症患者,采用酶联免疫吸附法检测BDNF的血清水平。系统综述的主要结局指标是病例组与对照组间合并的标准化均数差值(standardized mean difference, SMD)。由两位评价者根据 GRADE 系统的方法独立评估纳入研究的质量。采用RevMan 5.1 软件对研究的异质性、敏感性和可能的发表性偏倚进行检验。结果 累计 1663 例精神分裂症患者,1355 名对照纳入 Meta 分析。15 项被评估为低质量研究,10 项为极低质量研究。研究结果存在高度的异质性(I2=89%),但亚组分析结果表明,异质性与人种、样本量、年龄、性别、入组前是否服用抗精神病药物以及研究质量等因素不存在相关性。由于研究间异质性,采用随机效应模型计算合并SMD,结果为-0.74(95% CI, -0.99～-0.50; Z=5.99,p<0.001)。敏感性分析表明结果稳定性较好。无发表偏倚的证据。结论 尽管统计结果强有力地表明精神分裂症患者外周血 BDNF 水平低于对照人群,但由于现有研究的质量较低以及各研究之间的结果存在明显的异质性,精神分裂症患者外周血 BDNF 浓度低的证据应属较"弱"。今后需要开展高质量的前瞻性研究,对患者进行长期随访,并使用统一的入组标准和监测程序,如最终能证实这些初步结果,血清 BDNF 才有可能用作精神分裂症的生物学指标。

Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia : A systematic review

Background：There is increasing interest in the role of brain-derived neurotrophic factor（BDNF） in the onset and course of schizophrenia,but there are conflicting reports about serum levels of BDNF in patients with schizophrenia.Aim：Conduct a meta-analysis combining studies from China and other countries that have evaluated the relationship of serum BDNF levels to schizophrenia.Methods：We used Cochrane methodology and RevMan 5.1 software to identify and pool the results of studies.Electronic searches of western and Chinese registries and follow-up assessment of references located 268 potential articles.Twenty-five articles（20 in English and 5 in Chinese） published before December 2011 that used case-control methods,included patients with schizophrenia who had no concurrent disorders,and used ELISA technology to assess serum BDNF were included in the analysis.The main outcome was the pooled standardized mean difference（SMD） between cases and controls.The quality of the studies was independently assessed by two raters using the GRADE system.The heterogeneity,sensitivity and potential publication bias of the studies was evaluated using RevMan.Results：The pooled sample included 1663 patients with schizophrenia and 1355 controls.Fifteen of the included studies were rated as ‘poor quality’ and 10 were rated as‘very poor quality’.The results of the studies were quite heterogenous（I 2 =95%） but subgroup analyses found that the heterogeneity was not related to country of origin,sample size,age,gender,prior use of antipsychotic medication,or study quality.The pooled SMD（computed using a random-effect model because of study heterogeneity） was-0.74（95% CI,-0.99～-0.50;Z=5.99,p0.001）.Sensitivity analysis found that the result was stable and there was no evidence of publication bias.Conclusion：Despite the robust statistical findings of lower serum BDNF in patients with schizophrenia than in controls,given the low quality of the available studies and the substantial heterogeneity between studies,the evidence of lower serum BDNF in patients with schizophrenia must be considered‘weak’.The potential use of serum BDNF as a biomarker for schizophrenia must wait until higher-quality prospective studies that follow patients over time and that use uniform selection and monitoring procedures confirm these preliminary results.