Related Experiment Video
Updated: Dec 17, 2025
Evaluating Vascular Hyperpermeability-inducing Agents in the Skin with the Miles Assay
Published on: June 19, 2018
Vascular endothelial growth factor and pigment epithelial-derived factor in the peripheral response to ketamine
Claire L McGrory1, Karen M Ryan1, Bronagh Gallagher2
1Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland; Department of Psychiatry, Trinity College Dublin, St Patrick's University Hospital, Dublin 8, Ireland.
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 < 0.000). There was a significant group × time interaction for VEGFA mRNA levels (F(1, 21) = 5.207, p = 0.029), with ketamine increasing VEGFA levels. There was no significant effect of either ketamine or midazolam on PEDF levels. There was a significant group × time interaction for VEGFA/PEDF mRNA ratio, with ketamine alone increasing this ratio (F(1, 11) = 12.085, p = 0.005).
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.
