title: Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia: A systematic review.
abstract: 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.
  
  
  OBJECTIVE
  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, p<0.001). Sensitivity analysis found that the result was stable and there was no evidence of publication bias.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huiru
authors.initials: H
authors.lastname: Cui
authors.affiliation: Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, Zhejiang Province, China.
authors.forename: Jijun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Psychology, Chinese Academy of Sciences, Beijing, China ; Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, Zhejiang Province, China.
authors.forename: Xuchu
authors.initials: X
authors.lastname: Weng
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Li