VEGF and depression: a comprehensive assessment of clinical data

Vascular Endothelial Growth Factor (VEGF), initially identified as an angiogenic mitogen, is believed to play a role in hippocampal neurogenesis and response to stress. It exerts neuroprotective effects and influences synaptic transmission. The possible role of VEGF in depression has been hypothesized in the context of the neurotrophic model of depression, which postulates that stress can lead to decreased level of neurotrophins. Since VEGF has emerged as a potential component in the pathophysiology of stress and stress-related disorders, animal and clinical studies have attempted to delineate its precise role. In this review article we provide a synopsis of basic studies that are of direct relevance to the clinical findings in depression and antidepressant drug action. We have classified the studies on the basis of higher, lower or no different levels of VEGF as compared to control subjects. It became evident that there is conflicting data regarding VEGF levels in depressed patients. The fact that no definitive trend is apparent in the published data is likely attributable to differences in study designs. However, promising leads have emerged in our effort to understand and clarify this wide variation in results. Further study could establish the potential use of VEGF as a biomarker to aid in making a correct diagnosis and a successful treatment plan. Delineating the relationship of VEGF and depression ultimately has the potential to shed light on the still elusive neural mechanisms underlying the pathophysiology of depression and the mechanisms by which antidepressants exert their effects.