BDNF is crucial for brain function and implicated in MDD development.

This study investigated whether baseline plasma BDNF levels predict future onset of MDD in middle-aged women.

Higher plasma BDNF levels predicted increased risk of developing MDD in middle-aged women.

Brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal development and neural connectivity, and has been implicated in the pathophysiology of Major Depressive Disorder (MDD). However, its predictive value for MDD onset remains unclear. This study examined whether baseline BDNF levels are associated with incident MDD in middle-aged women.

In this nested case-control study, 104 individuals (mean age = 56.0) without MDD at baseline were selected from a population-based follow-up cohort. Over five years, 52 developed MDD (cases) and 52 remained MDD-free (controls). Baseline plasma BDNF levels were measured using a Luminex assay. Associations between BDNF levels and MDD risk were assessed using multivariable logistic regression adjusted for age and BMI.

MDD cases exhibited significantly higher baseline plasma BDNF levels compared to controls (median: 2683 vs 1844 pg/ml, p = 0.01). Elevated BDNF was associated with increased MDD risk in the univariate analysis (OR = 1.78, 95 % CI = 1.20–2.78, p = 0.006) and remained significant after adjusting for age, BMI, lifestyle, and socioeconomic factors (fully adjusted OR = 1.84, 95 % CI = 1.20–3.02, p = 0.009). BDNF elevation was most pronounced in MDD cases diagnosed 2–5 years after baseline.

Our findings challenge the view that BDNF is solely protective against MDD, as our study links higher plasma BDNF levels to increased MDD risk. These results suggest that higher BDNF levels may reflect underlying mechanisms contributing to MDD onset, highlighting the need to further investigate BDNF's role as a potential risk biomarker.

Brain-derived neurotrophic factor

Major depressive disorder

risk prediction

Biomarker

© 2025 The Authors. Published by Elsevier B.V.