The International Journal of Neuropsychopharmacology


A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression

André Russowsky Brunonia1a2, Mariana Lopesa1 and Felipe Fregnia1 c1

a1 Berenson–Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

a2 Department and Institute of Psychiatry, University of Sao Paulo, Brazil


Several clinical studies on major depressive disorder (MDD) have shown that blood brain-derived neurotrophic factor (BDNF) – a factor used to index neuroplasticity – is associated with depression response; however, the results are mixed. The purpose of our study was to evaluate whether BDNF levels are correlated with improvement of depression. We performed a systematic review and meta-analysis of the literature, searching Medline, Cochrane Central, SciELO databases and reference lists from retrieved articles for clinical studies comparing mean BDNF blood levels in depressed patients pre- and post-antidepressant treatments or comparing depressed patients with healthy controls. Two reviewers independently searched for eligible studies and extracted outcome data using a structured form previously elaborated. Twenty articles, including 1504 subjects, met our inclusion criteria. The results showed that BDNF levels increased significantly after antidepressant treatment (effect size 0.62, 95% CI 0.36–0.88, random effects model). In addition, there was a significant correlation between changes in BDNF level and depression scores changes (p=0.02). Moreover, the results were robust according to the sensitivity analysis and Begg's funnel plot results did not suggest publication bias. Finally, there was a difference between pre-treatment patients and healthy controls (effect size 0.91, 95% CI 0.70–1.11) and a small but significant difference between treated patients and healthy controls (effect size 0.34, 95% CI 0.02–0.66). Our results show that BDNF levels are associated with clinical changes in depression; supporting the notion that depression improvement is associated with neuroplastic changes.

(Received March 18 2008)

(Reviewed May 28 2008)

(Revised July 15 2008)

(Accepted July 22 2008)

(Online publication August 28 2008)


c1 Address for correspondence: F. Fregni, M.D., Ph.D., 330 Brookline Ave – KS 452, Boston, MA 02215, USA. Tel.: (617) 667-5272 Fax: (617) 975-5322 E-mail: