Acute and transient change in brain water content induced by a single electroconvulsive therapy session

BACKGROUND: While electroconvulsive therapy (ECT) is the most effective treatment for severe depression, there is a concern regarding its potential adverse effects on the brain. It is unclear whether a single ECT session (i.e., an electrically induced seizure) leads to physiological microstructural changes or causes lasting adverse biological effects. METHODS: This study examined longitudinal changes in multishell diffusion MRI-derived metrics in 25 individuals with depression, with scans acquired 2 h before and after their first ECT session. Follow-up scans were collected within 14 days and 6 months after the last ECT session. To control for potential confounding effects of anesthesia and repeated measurements, two additional groups were included: 16 individuals undergoing short-acting anesthesia and 16 healthy controls without interventions. A multicompartment model was applied to explore extracellular free water and intracellular/extracellular compartments. RESULTS: Whole-brain voxel-wise analyses identified increased extracellular free water in bilateral periventricular and subcortical regions surrounding the hippocampus, with minimal involvement of cortical regions, following a single ECT session. These changes were not observed in either control group, and were not associated with post-ictal reorientation time (r = 0.11, p = 0.92). Follow-up assessments confirmed that the alterations in tissue free water resolved within 14 days. CONCLUSIONS: A single ECT-induced seizure induces a transient increase in extracellular water content without evidence of cytotoxic edema indicative of cellular injury. Our findings suggest that ECT-related brain water shifts are reversible and unlikely to reflect permanent damage to brain tissue.