Whole blood BDNF is lower in patients with depression and unchanged by escitalopram in patients and healthy controls

Brain-derived neurotrophic factor (BDNF) plays a key role in neuroplasticity and has been implicated in both the pathophysiology of Major Depressive Disorder (MDD) and treatment effects. Unlike serum BDNF (s-BDNF), which largely reflects platelet-derived BDNF released during coagulation, whole blood BDNF (wb-BDNF) measures the total blood BDNF pool, minimizing confounds related to platelet aggregation. This study aims to assess whether wb-BDNF levels can serve as a biomarker for MDD and/or as a predictor of antidepressant treatment response. We measured wb-BDNF before and after 4–12 weeks of escitalopram intervention in two studies: a non-randomized, single-arm clinical trial of 97 unmedicated patients with MDD and a randomized, double-blind, placebo-controlled trial with 66 healthy controls (HC). The BDNF Val65Met polymorphism was also determined. Unmedicated patients with MDD had 14 % lower wb-BDNF than HC, but wb-BDNF prior to intervention was not associated with symptom severity, nor did it predict drug treatment outcome in the patients. Further, improvements in depression scores after 8 and 12 weeks of escitalopram was not associated with changes in wb-BDNF. In HC, wb-BDNF was similar in the placebo and escitalopram groups after 4 weeks of intervention. BDNF polymorphism was similar between HC and MDD, and responders and non-responders, and was not associated with wb-BDNF levels. wb-BDNF reflects the total blood BDNF pool and avoids platelet aggregation-related confounds seen in s-BDNF measures. wb-BDNF could be used as diagnosis but not as a prognosis biomarker, in MDD. Further research is needed to investigate changes in BDNF reservoirs and their implications. • Whole blood BDNF is reduced in MDD vs HC but shows no association with baseline depression severity in MDD patients. • Escitalopram intake does not change whole blood BDNF in patients with depression, nor in healthy controls. • Whole blood BDNF offers distinct insights into depression, complementing previous serum BDNF findings, by reflecting total blood BDNF independent of platelet aggregation effects.