Several studies have shown that electroconvulsive therapy (ECT) results in increased hippocampal volume. It is likely that a multitude of mechanisms including neurogenesis, gliogenesis, synaptogenesis, angiogenesis, and vasculogenesis contribute to this volume increase. Neurotrophins, like vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) seem to play a crucial mediating role in several of these mechanisms. We hypothesized that two regulatory SNPs in the VEGF and BDNF gene influence the changes in hippocampal volume following ECT. We combined genotyping and brain MRI assessment in a sample of older adults suffering from major depressive disorder to test this hypothesis. Our results show an effect of rs699947 (in the promotor region of VEGF) on hippocampal volume changes following ECT. However, we did not find a clear effect of rs6265 (in BDNF). To the best of our knowledge, this is the first study investigating possible genetic mechanisms involved in hippocampal volume change during ECT treatment.