Molecular Psychiatry (2011) 16, 960–972; published online 24 August 2010
Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis
M J Green1,2,3, S L Matheson1,2, A Shepherd1,2, C S Weickert1,2,4 and V J Carr1,2,3
1School of Psychiatry, University of New South Wales, Randwick, NSW, Australia
2Schizophrenia Research Institute, Darlinghurst, NSW, Australia
3UNSW Research Unit for Schizophrenia Epidemiology, O'Brien Centre at St Vincent's
Hospital, Darlinghurst, NSW, Australia
4Neuroscience Research Australia, Randwick, NSW, Australia
Correspondence: Dr MJ Green, c/- UNSW Research Unit for Schizophrenia Epidemiology, O'Brien Centre at St Vincent's Hospital, Level 4, Cnr Victoria St and Burton St, Darlinghurst, NSW 2010, Australia. E-mail: firstname.lastname@example.org
Received 6 May 2010; Revised 6 July 2010; Accepted 1 August 2010; Published online 24 August 2010.
Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Several studies report reduced peripheral (blood) levels of BDNF in schizophrenia, but findings are inconsistent. We undertook the first systematic review with meta-analysis of studies examining blood BDNF levels in schizophrenia compared with healthy controls, and examined potential effects of age, gender and medication. Included are individual studies of BDNF blood (serum or plasma) levels in schizophrenia (including schizoaffective disorder, or first episode psychosis), compared with age-matched healthy controls, obtained by electronic Medline and Embase searches, and hand searching. The decision to include or exclude studies, data extraction and quality assessment were completed by two independent reviewers. The initial search revealed 378 records, of which 342 were excluded on reading the Abstract, because they did not examine BDNF blood levels in schizophrenia compared with healthy controls. Of 36 papers screened in full, 17 were eligible for inclusion, but one was subsequently removed as an outlier. The remaining 16 studies provided moderate quality evidence of reduced blood BDNF levels in schizophrenia (Hedges g==−0.458, 95% confidence interval==−0.770 to −0.146, P<0.004, random effects model). Subgroup analyses reveal reduced BDNF in both drug-naïve and medicated patients, and in males and females with schizophrenia. Meta-regressions showed an association between reduced BDNF in schizophrenia and increasing age, but no effects of medication dosage. Overall, blood levels of BDNF are reduced in medicated and drug-naïve patients with schizophrenia; this evidence is of moderate quality, that is, precise but with considerable, unexplained heterogeneity across study results.
Keywords: BDNF; blood serum; plasma; schizophrenia; meta-analysis
Molecular Psychiatry ISSN 1359-4184 EISSN 1476-5578