Brain-derived neurotrophic factor as a predictor of post-stroke depression: An updated systemic review and meta-analysis

The aim of this review was to examine if Brain-Derived Neurotrophic Factor (BDNF) could be a predictor for post-stroke depression (PSD). We searched Web of Science, Embase, PubMed, and Scopus databases for all relevant studies, with no language restrictions from inception of databases to 1st September 2025. We analyzed average BDNF levels in PSD versus non-PSD groups to estimate the Mean Difference (MD) with 95% confidence intervals (CI). Additionally, pooled odds ratios (OR) with 95% CI were determined to assess the link between reduced BDNF levels and PSD risk. Ten studies were included. In the meta-analysis of nine studies, patients with PSD had significantly lower circulating BDNF levels compared with non-PSD patients (MD: −4.21, 95% CI −6.65 to −1.77; I2 = 97%). Six studies reporting OR showed that low BDNF was associated with an increased risk of PSD (OR 0.84: 95% CI 0.76–0.92; I2 = 77%). Publication bias was noted in the later analysis. Sensitivity analyses confirmed the stability of results, and subgroup analyses demonstrated consistent associations across study location, stroke type, follow-up duration, and diagnostic method. BDNF may be a potential biomarker for PSD. Lower levels of BDNF are noted in PSD as compared to non-PSD patients. Lower levels of BDNF seem to be significantly associated with higher risk of PSD. Evidence must be interpreted with caution given the presence of publication bias. Further studies are needed to increase the validity of these conclusions.