Association of plasma VEGF levels and the antidepressant effects of ketamine in patients with depression

Abstract

Aims: Growing evidence suggests that vascular endothelial growth factor (VEGF) may be involved in the neuronal mechanisms underlying both depression aetiology and the response to ketamine treatments. The aim of this study was to examine whether changes in plasma VEGF levels are associated with the antidepressant effects of repeated ketamine infusions in patients with depression. Methods: Ninety-six patients with depression were enrolled and received six ketamine infusions during a 12-day period. Depressive symptom severity and plasma VEGF levels were measured by the Montgomery–Åsberg Depression Rating Scale (MADRS) and an enzyme-linked immunosorbent assay (ELISA) respectively, at baseline, 13 days and 26 days. Results: Despite a significant improvement in MADRS scores after patients received six ketamine infusions ( p < 0.001), no changes in plasma VEGF levels were observed at 13 days when compared with baseline. Moreover, no significant difference in plasma VEGF levels at baseline and 13 days was found between ketamine responders and nonresponders. No association was found between the antidepressant effects of repeated ketamine treatments and plasma VEGF levels. Conclusion: This study indicated that VEGF may not be a potential predictor of antidepressant response to repeated intravenous administration of ketamine in patients with depression.

Association of VEGF With Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Treatment-Refractory Depression

“…However, our data failed to demonstrate that plasma VEGF concentrations were significantly associated with ketamine's rapid antianhedonic effects in subjects with TRD. Similarly, a recent study also found that VEGF does not play a critical role in the observed antidepressant response to ketamine in depressed patients (24). However, the association of VEGF and ketamine's antisuicidal effects is unclear.…”

“…All blood samples of seventy-eight subjects with treatment-refractory MDD or BD were collected preinfusion and again at days 13 and 26. Consistent with a recent study ( 24 ), a Human VEGF Immunoassay enzyme-linked immunosorbent assay (ELISA) kit (R&D Systems, Minneapolis, USA) was used to measure the plasma concentrations of VEGF.…”

“…Similarly, serum BDNF levels were increased in chronic ketamine users (21) and change in plasma BDNF levels following subanesthetic ketamine infusion are associated with acute and 24 h resting-state functional connectivity (RSFC) changes (22). Findings on the association of VEGF and ketamine's antidepressant effects have been inconsistent (18,(23)(24)(25). For example, the expression of VEGF is necessary for the antidepressant-like behaviors of ketamine (18,19).…”

“…For example, the expression of VEGF is necessary for the antidepressant-like behaviors of ketamine ( 18 , 19 ). A recent study supported a role for VEGF in the antidepressant action of ketamine ( 25 ), but two recent studies found that ketamine does not change the plasma concentrations of VEGF ( 23 , 24 ). However, evidence on the role of plasma VEGF concentrations in ketamine's antianhedonic effects is still lacking.…”

Plasma VEGF Concentrations and Ketamine's Effects on Suicidal Ideation in Depression With Suicidal Ideation

“…Recently, Deyama et al found that the rapid antidepressant response to ketamine was associated with neuronal VEGF-Flk-1 signaling in the medial prefrontal cortex (mPFC) ( 28 ). Finding on the relationship between VEGF and ketamine's antidepressant effect in depressed patients were inconsistent ( 29 , 30 ). For instance, McGrory et al found that VEGF plays an essential role in the antidepressant action of ketamine ( 30 ).…”