Peripheral Brain-Derived Neurotrophic Factor and Oxytocin Dynamics During Early Antidepressant Treatment in Unipolar Major Depressive Disorder

Abstract

Background: Brain-derived neurotrophic factor (BDNF) and oxytocin (OXT) have been independently implicated in the pathophysiology of major depressive disorder (MDD), yet few longitudinal studies have examined their concurrent modulation during early antidepressant treatment. This study investigated changes in plasma BDNF and oxytocin concentrations over the first four weeks of pharmacological treatment in patients with unipolar MDD and explored their association with changes in depressive symptom severity. Methods: Twenty-six medication-free patients with unipolar major depressive disorder were assessed at baseline, before antidepressant initiation, and after four weeks of treatment. Depressive severity was measured using the 17-item Hamilton Depression Rating Scale (HAMD-17). Plasma BDNF and oxytocin concentrations were quantified using enzyme-linked immunosorbent assay kits (ELISA). Within-subject changes were analysed using the Wilcoxon signed-rank test, and associations between changes in clinical severity and biomarker levels were examined using Spearman’s rank correlation coefficients.
Results: Depressive symptom severity significantly decreased after four weeks of treatment. Plasma BDNF and oxytocin levels also demonstrated significant changes over the same period. A moderate negative correlation was observed between reductions in HAMD-17 scores and the change in BDNF concentrations (ρ = −0.554, p = 0.003), indicating that greater clinical improvement was associated with greater increases in plasma BDNF levels. A moderate positive correlation was found between changes in depressive severity and changes in oxytocin concentrations (ρ = 0.414, p = 0.035). No statistically significant differences in biomarker changes were observed across antidepressant classes; however, these subgroup analyses should be interpreted cautiously given the limited sample sizes in each treatment subgroup.
Conclusions: Early antidepressant treatment in unipolar MDD is accompanied by modulation of peripheral neurotrophic and neuropeptidergic markers. The association between symptom improvement and BDNF dynamics supports the relevance of neuroplasticity-related mechanisms during early treatment, while oxytocin alterations may reflect parallel adaptation within stress-regulatory systems. Larger longitudinal studies are required to clarify the predictive and mechanistic significance of these findings.