Electroconvulsive therapy (ECT) is the treatment of choice in severe geriatric depression. High remission rates may be influenced by specific brain morphology characteristic of geriatric depression. Our objective was to identify the relationship between brain structure, symptom profile, and ECT response. In a naturalistic cohort of 55 patients with a major depressive disorder, structural magnetic resonance imaging (MRI) was performed before ECT. Voxel-based morphometry was applied to determine regional differences in gray matter (GM) volume between patients and 23 matched healthy controls. Depressed patients with psychotic symptoms showed significantly higher remission rates and smaller regional GM volume of the left inferior frontal gyrus (IFG). Patients with late onset depression showed smaller regional GM volume of the bilateral lateral temporal cortex. Larger size of response in the whole patient group was related to smaller pretreatment regional GM volume of the right lateral temporal cortex, whereas faster speed of response was related to smaller pretreatment regional GM volume of the right IFG. ECT is most effective in depressed patients with psychotic symptoms. In this study the presence of psychotic symptoms was related to pretreatment smaller GM volume of the left IFG and bilateral temporal cortex. Smaller volume of the IFG pretreatment was related to faster treatment response, and smaller volume of the right lateral temporal cortex pretreatment was related to larger response to ECT. These results are possibly explained by the connectivity between these brain regions and an interconnected network that is particularly activated by the ECT-induced seizures.