Vascular endothelial growth factor and pigment epithelial-derived factor in the peripheral response to ketamine

Abstract Background Ketamine is a rapid-acting antidepressant but its mechanism remains unclear. Vascular endothelial growth factor growth factor (VEGF) has been reported in the antidepressant action of ketamine in rodents. VEGF and pigment epithelial-derived factor (PEDF) signalling are closely linked and both are dysregulated in depression. We explored the effect of a single infusion of ketamine, with midazolam as comparison, on peripheral whole blood mRNA levels of vascular endothelial growth factor A (VEGFA) and PEDF, and the VEGFA/PEDF ratio, in patients with depression. Methods Twenty-five patients with depression were randomised to either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) infusions over 40 min. Blood plasma samples were taken 1 h before the first infusion and 4 h after the infusion start. mRNA was extracted and qRT-PCR performed to analyse gene expression. Results Single infusions of ketamine and midazolam both decreased depression scores (F(1,21) = 102.40, p  Limitations Patients were on psychotropic medication and continued treatment as usual throughout the study. Conclusions These preliminary results support a role for VEGF in the action of ketamine and suggest a novel role for VEGF/PEDF in the molecular response to ketamine.