Serum VEGF levels in major depression and the effect of antidepressant treatment

Identifying reliable biomarkers for depression remains a major research focus. Vascular endothelial growth factor (VEGF) has been proposed as a candidate due to its involvement in neurovascular processes. This study evaluated the diagnostic and therapeutic significance of VEGF in major depressive disorder (MDD). This prospective, observational case–control study was conducted at a single academic center between July 2022 and June 2023. The sample comprised 17 patients with MDD and 30 healthy controls. Depression severity was assessed using the Hamilton Depression Rating Scale. Serum VEGF levels were measured with enzyme-linked immunosorbent assay (ELISA) at two time points in patients (during a depressive episode and after treatment response), while controls underwent a single measurement. Analyses were adjusted for potential confounders, including age, body mass index, smoking, and prior antidepressant use. VEGF levels did not significantly differ between patients and controls. However, post-treatment VEGF levels in patients were significantly lower than those of controls. No significant within-group change was observed between pre- and post-treatment measurements in patients. These findings provide limited support for the neurotrophic hypothesis of depression. The observed post-treatment decline in VEGF suggests a complex regulatory mechanism rather than a simple neuroprotective effect. Given the small sample size and reliance on peripheral VEGF measurements, larger studies incorporating central VEGF assessments are needed to clarify its role in depression.