Electroconvulsive therapy induces rapid microstructural and macrostructural changes, but microstructural changes are longer-lasting

Electroconvulsive therapy (ECT) is an effective treatment for major depressive episodes, though its mechanisms remain unclear. Its use is limited by stigma and potential cognitive side-effects. Repeated magnetic resonance imaging (MRI) may provide further insights into brain changes related to ECT’s efficacy and cognitive outcomes. We analyzed cognitive, efficacy, and MRI data from depressed patients undergoing ECT in two prospective longitudinal trials (NCT04028596, NL-OMON43040), using 26 matched healthy controls (2020-BC-12375) to control for test-retest effects. All participants were scanned on the same MRI system. Structural and diffusion tensor imaging (DTI) scans were acquired at baseline, after the initial ECT sessions, within two weeks post-treatment, and at three-month follow-up. Linear and nonlinear changes in grey matter (GM) volume, white matter (WM) volume, mean diffusivity (MD), and fractional anisotropy (FA) were assessed. Early brain changes were examined in relation to clinical outcomes. After the 3rd ECT session (n = 19), subcortical GM volume increased with a right-lateralized MD decrease. Two weeks post-ECT (n = 30), cortical GM volume increased, returning to baseline by three months. In WM, MD increased linearly post-ECT and remained elevated at follow-up, with no widespread FA changes (n = 30). ECT transiently impaired verbal learning (n = 23, pbonferroni = 0.04), letter fluency (n = 22, pbonferroni = 0.04), and animal fluency (n = 62, pbonferroni = 0.02). Early brain changes were not associated with cognitive or efficacy outcomes. These results suggest that ECT induces rapid changes in brain macrostructure and microstructure. While macrostructural increases are temporary, microstructural changes in brain structure are longer-lasting.