Background: Electroconvulsive therapy (ECT) is a well-established and effective treatment for severe depression and other conditions. Though ECT induces a generalized seizure, it is unclear why seizures are therapeutic. This study analyzed relationships between pre-treatment brain morphology, stimulation dose, and seizure duration to better understand ECT-induced seizures. Methods: Pre-existing MRI data were analyzed from four cohorts with treatment refractory depression undergoing right unilateral (RUL) ECT (n=166). Regional brain morphometry and magnitude of electrical current (|E|) were analyzed, along with seizure duration and stimulation charge at seizure threshold (ECT1) and 6x seizure threshold (ECT2&3). Linear models controlled for age, sex, and cohort, corrected using false discovery rate q<0.05. Results: Lower ECT1 stimulation charge correlated with less cortical surface area perpendicular to current flow, and greater |E| in nearby white matter. Lower ECT2&3 stimulation charge correlated with less cortical surface area and curvature near the temporal electrode, higher |E| in right amygdala and anterior hippocampus, and lower right thalamic and mid-hippocampal volume. Cortical surface area extending between electrodes (e.g., postcentral gyrus) positively correlated with ECT2&3 seizure duration. Successful antidepressant response associated with less cortical surface area near the temporal electrode and more |E| in anteromedial temporal lobe regions, the latter of which mediated the effects of the former on antidepressant response. Conclusions: Pre-treatment brain morphology influences ECT-induced seizure, particularly in regions near ECT electrodes and those relevant to seizure initiation and modulation. Personalized dosing based on head morphology and other factors may improve antidepressant outcomes and reduce side effects.

The authors have declared no competing interest.

This work was supported by the NIH, including R03 MH121769 to Dr. Leaver, R01 MH092301 and U01 MH110008 to Drs. Narr and Espinoza, P20 GM103472 and U01 MH111826 to Dr. Abbott. This content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health. This work was also supported in part through the computational resources and staff contributions provided for the Quest high performance computing facility at Northwestern University which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology. This work was also supported in part by the Muriel Harris Chair of Geriatric Psychiatry at UCLA to Dr. Espinoza.

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