Decreased Synthesis of Brain-derived Neurotrophic Factors in Vascular Endothelial Cells of Clinically Depressed Patients: Implications for Depression Pathogenesis and Treatment

Major depressive disorder (MDD), although one of the most common psychiatric illnesses, has an unknown etiology. Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of MDD. However, post-mortem studies have not always shown decreased BDNF levels in MDD patients. In contrast, many clinical studies have consistently demonstrated that serum BDNF levels were decreased in MDD patients, and that antidepressant treatment reversed this deficit. Serum BDNF is synthesized primarily in vascular endothelial cells and stored in platelets. Antidepressant treatments and exercise, which have been shown to protect vascular endothelium and increase blood BDNF levels, can alleviate depression. I hypothesize that low serum BDNF is a cause of low brain BDNF, and not a consequence of it, and thus that low serum BDNF is a cause of major depression. Low serum BDNF levels in depressed patients may be the result of decreased BDNF synthesis in vascular endothelial cells in response to stress. Attempts to confirm the association between decreased BDNF synthesis in vascular endothelium and MDD pathogenesis may lead to the development of novel approaches for the prevention and treatment of this common disorder.