In vivo evidence of increased vascular endothelial growth factor in patients with major depressive disorder

Background: Vascular endothelial growth factor (VEGF) is a candidate mediator of blood-brain barrier (BBB) disruption in depression. However, previous studies have mainly focused on peripheral blood VEGF levels, and the results are heterogeneous. Here we use astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma to explore the in vivo changes of VEGF levels in patients with major depressive disorder (MDD).

Methods: Thirty-five unmedicated patients with MDD and 35 healthy controls (HCs) were enrolled, and plasma ADEVs were isolated from each participant. VEGF levels in ADEVs and glial fibrillary acidic protein (GFAP) in plasma were measured. Additionally, Alix and CD81, two established extracellular vesicle markers, were quantified in ADEVs.

Results: At baseline, MDD patients exhibited significantly increased levels of VEGF in ADEVs and GFAP in plasma. Following four weeks of selective serotonin reuptake inhibitor treatment, these target protein levels did not significantly change. ROC curve analysis revealed an AUC of 0.711 for VEGF in ADEVs. In exploratory analysis, VEGF levels in ADEVs were positively correlated with Alix and CD81.

Limitations: Multiple factors regulate BBB permeability. This study focused solely on VEGF and the sample size for longitudinal analysis was relatively small.

Conclusion: Our study is the first to confirm increased ADEV-derived VEGF levels in patients with MDD, thereby providing preliminary evidence supporting the hypothesis that the BBB is disrupted in depression.

Astrocyte; Astrocyte-derived extracellular vesicle; Blood-brain barrier; Major depressive disorder; Vascular endothelial growth factor.