This study presents meta-analyses showing that serum brain-derived neurotrophic factor (BDNF) levels are significantly lower in individuals with major depressive disorder compared to healthy controls, and that these levels increase following antidepressant treatment. The findings suggest that BDNF may serve as a biomarker for depression and as a predictor of antidepressant response. However, the exact mechanism of BDNF's role in depression and the source of peripheral BDNF remain unclear. While BDNF levels are reduced in various psychiatric and neurological disorders, the lack of diagnostic specificity limits its clinical utility. Additionally, BDNF levels are influenced by factors such as stress, exercise, and diet, which may complicate its use as a biomarker. The study also highlights the potential of BDNF as a surrogate marker for antidepressant efficacy, as increased BDNF levels are associated with improved clinical outcomes. Despite these findings, further research is needed to determine the extent to which peripheral BDNF reflects central BDNF levels and to explore its potential in guiding clinical decision-making and drug development.This study presents meta-analyses showing that serum brain-derived neurotrophic factor (BDNF) levels are significantly lower in individuals with major depressive disorder compared to healthy controls, and that these levels increase following antidepressant treatment. The findings suggest that BDNF may serve as a biomarker for depression and as a predictor of antidepressant response. However, the exact mechanism of BDNF's role in depression and the source of peripheral BDNF remain unclear. While BDNF levels are reduced in various psychiatric and neurological disorders, the lack of diagnostic specificity limits its clinical utility. Additionally, BDNF levels are influenced by factors such as stress, exercise, and diet, which may complicate its use as a biomarker. The study also highlights the potential of BDNF as a surrogate marker for antidepressant efficacy, as increased BDNF levels are associated with improved clinical outcomes. Despite these findings, further research is needed to determine the extent to which peripheral BDNF reflects central BDNF levels and to explore its potential in guiding clinical decision-making and drug development.