The role of serum BDNF levels in cognitive dysfunction among psychiatric disorders

Brain-derived neurotrophic factor (BDNF) is a key regulator of neuroplasticity, synaptic integrity and cognitive function and its dysregulation has been implicated across major psychiatric disorders. However, its transdiagnostic association with cognitive performance remains incompletely understood. In this cross-sectional study, 160 participants were examined, including individuals with schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD) and healthy controls (HC) (n = 40 per group). Serum BDNF concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA), Trail Making Tests (TMT-A/B) and Digit Span (Forward/Backward). Significant group differences were observed for both serum BDNF levels and cognitive performance. Serum BDNF concentrations were lowest in SCZ (18.2 ± 4.6 ng/mL) and MDD (19.5 ± 5.1 ng/mL), intermediate in BD (23.7 ± 5.9 ng/mL) and highest in HC (26.3 ± 6.2 ng/mL) (F(3156) = 15.47, p < 0.001). Cognitive impairment followed a parallel gradient, with SCZ exhibiting the most severe deficits (p < 0.001). Across the full cohort, serum BDNF showed moderate positive associations with global cognition (MoCA: r = 0.42, p < 0.001) and working memory (Digit Span Backward: r = 0.38, p < 0.001) and a negative association with executive dysfunction as indexed by TMT-B completion time (r = -0.46, p < 0.001). These findings indicate that serum BDNF is modestly but consistently associated with cognitive performance across major psychiatric disorders, supporting its role as a transdiagnostic neurobiological correlate of impaired neuroplasticity rather than a disorder-specific or deterministic biomarker.