Vascular endothelial growth factor: Potential predictor of treatment response in major depression.

OBJECTIVES: The aim of the study was to evaluate baseline plasma VEGF levels as a potential predictor of response to antidepressant pharmacotherapy. The study also sought to determine whether baseline plasma VEGF would be useful in predicting treatment outcome when two pharmacodynamically diverse agents with established antidepressant efficacy, escitalopram and quetiapine, were administered monotherapeutically to MDD patients. METHODS: Two groups of qualifying MDD subjects were enrolled. One group was treated with escitalopram and the other with quetiapine. Plasma concentrations of VEGF were measured using Randox Technologies at baseline, and at weeks 8 and 12 of treatment. RESULTS: We stratified the MDD patients into those who remitted and those who failed to respond. Mean baseline VEGF for the remitters and non-responders was 9.61 and 5.40 pg/ml, respectively (P < 0.0005). Using optimal data analysis a cut score of 7.49 pg/ml for baseline plasma VEGF distinguished remitters from non-responders with a 63% overall accuracy. The remission rate was comparable for both drugs (73 and 81% for quetiapine and escitalopram, respectively). VEGF levels did not significantly change following antidepressant treatment with either escitalopram or quetiapine when measured at 8 and 12 weeks; this result held true for both remitters and non-responders. CONCLUSIONS: Our results suggest that VEGF may predict response to antidepressant treatment and may ultimately prove to be a potential biomarker that can be measured with a routine blood draw at the point of service.

Vascular Endothelial Growth Factor: a potential diagnostic biomarker for major depression.

Despite intense research efforts undertaken by investigators throughout the world over the past half century to identify a specific biomarker for major depressive disorder (MDD), none have so far met the rigorous test of specificity, reliability and reproducibility. Vascular Endothelial Growth Factor (VEGF) has been implicated in the neurotrophic model of depression and several studies have assessed VEGF levels in depressed patients. The results have been discrepant largely due to design and assay differences among studies. The aim of this study was to assess plasma VEGF levels in a cohort of MDD subjects prior to treatment with psychotropic medication and compare them to those of healthy control (HC) subjects. Prospective study participants underwent extensive medical and psychiatric assessments before they were enrolled. Plasma concentrations of VEGF were measured by the technique marketed by Randox Technologies. The mean baseline VEGF for the healthy and depressed groups was 5.91 pg/ml (SD: 3.04) and 10.51 pg/ml (SD: 9.04), respectively, and this difference was statistically significant (p = 0.001). We detected a very low univariate relationship between VEGF and demographic and clinical variables. Using the Optimal Data Analysis a cut score of 6.64 pg/ml for baseline plasma VEGF distinguished depressed from healthy subjects with a 63% overall accuracy. We conclude these results support a role of plasma VEGF as a useful biomarker of depression that can be measured with a routine blood draw at the point of service. The specificity of this potential biomarker must be confirmed in studies that include other psychiatric disease entities.

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.