Abstract
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.
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Acknowledgements
This project was supported by research funding from the Australian National Health and Medical Research Council (NHMRC: Project Grant 630471), the Australian Research Council (Future Fellowship: FT0991511) and the Schizophrenia Research Institute, using an infrastructure grant from the NSW Department of Health. We acknowledge Amy Sparks for assistance with production of the paper, and the following authors for the provision of raw data for inclusion in the meta-analysis: Peter Buckley, Clarissa Gama, Alex Genevsky, Ana Maria González-Pinto, TL, Huang, Yumiko Ikeda, Flávio Kapczinski, Yong-Ku Kim, Diogo Rizzato Lara, Carlos Matute, E Rizos, Eiji Shimizu, Amaia Ugarte Ugarte, Sophia Vinogradov, Reiji Yoshimura and Xiang Yang Zhang.
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Green, M., Matheson, S., Shepherd, A. et al. Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol Psychiatry 16, 960–972 (2011). https://doi.org/10.1038/mp.2010.88
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DOI: https://doi.org/10.1038/mp.2010.88
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