The VEGF protein levels, miR-101-3p, and miR-122-5p are dysregulated in plasma from adolescents with major depression

Background: Major depressive disorder (MDD) is a common and serious psychiatric disorder that affects millions of individuals worldwide. Although the underlying mechanisms are still poorly understood, mounting evidence is indicating a role of growth factors, among them the vascular endothelial growth factor (VEGF or VEGFA). Methods: To further explore the importance of VEGF, the plasma protein VEGF levels in hospitalized children and adolescents with MDD were investigated before and after antidepressant treatment (10 days on average) and compared to healthy controls. Subsequently, an expression study with 28 microRNAs (miRNAs) targeting VEGF was performed. The study included 39 hospitalized children and adolescents with MDD and 20 healthy controls. Results: VEGF protein levels were significantly increased in depressed adolescents compared to healthy controls and a short antidepressant treatment significantly decreased the levels in both adolescents and children. In continuation, we found that miR-101-3p was up- and miR-122-5p was down-regulated in depressed adolescents compared to healthy controls and that factors such as age, sex, antidepressant treatment, and haemolysis of the blood samples impact the miRNA results. Limitations: Small sample size and short treatment period with different pharmacological treatment (fluoxetine, vortioxetine, and venlafaxine). Conclusion: This study substantiates the use of peripheral VEGF as a biomarker of MDD in children and adolescents and highlights the importance of understanding the underlying regulatory mechanisms.