Major depressive disorder (MDD) is a complex psychiatric condition associated with alterations in brain neuroplasticity. Brain-derived neurotrophic factor (BDNF), a key regulator of neuronal survival, synaptic plasticity, and neurogenesis, has been widely studied as a biological marker of neuroplasticity in depression. This review and meta-analysis evaluated the relationship between BDNF levels and clinical improvement in depression. A systematic search of Medline, Cochrane Central, SciELO, and reference lists identified clinical studies comparing blood BDNF levels in depressed patients before and after antidepressant treatment or with healthy controls. Twenty studies involving 1504 participants met the inclusion criteria. The analysis demonstrated that BDNF levels significantly increased following antidepressant treatment (effect size 0.62, 95% CI 0.36–0.88). Furthermore, a significant correlation was observed between changes in BDNF concentrations and improvements in depression scores (p=0.02). Depressed patients showed markedly lower BDNF levels compared with healthy individuals prior to treatment (effect size 0.91), while treated patients still exhibited slightly lower but improved levels (effect size 0.34). Evidence from experimental and clinical studies indicates that chronic stress and depression are associated with impaired neuroplasticity, including neuronal atrophy and synaptic loss in brain regions such as the hippocampus and medial prefrontal cortex. Traditional monoamine-based antidepressants often require several weeks to produce clinical effects, highlighting the need for faster and more effective therapeutic strategies. Emerging treatments targeting neuroplasticity include modulation of the glutamatergic system and non-invasive brain stimulation techniques. In particular, NMDA receptor antagonists such as ketamine demonstrate rapid antidepressant effects by enhancing synaptic plasticity. Additionally, non-invasive brain stimulation methods such as transcranial magnetic stimulation and transcranial direct current stimulation have shown potential in improving depressive symptoms through neuroplastic mechanisms. Overall, these findings support the concept that improvement in depression is closely associated with restoration of neuroplasticity and increased BDNF activity.
Yadav et al. (Wed,) studied this question.