Volume of the human hippocampus and clinical response following electroconvulsive therapy

Background: Hippocampal enlargements are commonly reported following electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome. Methods: Longitudinal neuroimaging and clinical data from ten independent sites participating in the Global ECT-MRI Research Collaboration were obtained for mega analysis.

Hippocampal volumes were extracted from structural MR images, acquired before and after patients (n=281) experiencing a major depressive episode completed an ECT treatment series using right unilateral (RUL) and bilateral (BL) stimulation. Untreated non-depressed controls (n=95) were scanned twice. Results: The linear component of hippocampal volume change was 0.28%, 0.08 SE, per ECT session, p<0.001.

Volume change varied by electrode placement in the left (BL: 3.3 ± 2.2%, d=1.5; RUL: 1.6 ± 2.1%, d=0.8; p<0.0001), but not the right hippocampus (BL: 3.0 ± 1.7%, d=1.8; RUL: 2.7 ± 2.0%, d=1.4; p=0.36,). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (MADRS change -1.0, 0.35 SE, per 1% volume increase, p=0.005), although effects were not significant after controlling for ECT number (slope: -0.69, 0.38 SE, p=0.069).

Conclusions: The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. Results suggest the high efficacy of ECT is not explained by hippocampal enlargement, which alone, might not serve as a viable biomarker for treatment outcome.