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Multicenter Study
. 2018 Oct 15;84(8):574-581.
doi: 10.1016/j.biopsych.2018.05.017. Epub 2018 May 29.

Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy

Free PMC article
Multicenter Study

Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy

Leif Oltedal et al. Biol Psychiatry. .
Free PMC article


Background: Hippocampal enlargements are commonly reported after 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 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice.

Results: The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery-Åsberg Depression Rating Scale change -1.0 [SE 0.35], per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope -0.69 [SE 0.38], p = .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. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.

Keywords: Antidepressant response; Biomarker; Brain; Depression; ECT; Neuroimaging.

Conflict of interest statement

Financial Disclosures

Anders M. Dale is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is also a member of the Scientific Advisory Board of Human Longevity, Inc. (HLI), and receives funding through research agreements with General Electric Healthcare (GEHC). The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.

The other authors declare that they have no competing interests.


Figure 1 |
Figure 1 |. Differential effect of ECT on hippocampal volume and clinical outcome.
A, Scatter plot of volume change of the right hippocampus, computed as (posttreatment – pretreatment score)/pretreatment score × 100, versus number of ECTs; n = 241. Slope (controlling for number of ECTs squared, Age, Sex, Site, baseline depression score, and baseline hippocampal volume), 0.28 ± 0.08, (t(225) = 3.35, p < 0.001. B, Scatter plot of change in MADRS score, computed as pretreatment – posttreatment score, versus volume change of the right hippocampus; n = 248. Slope (controlling for Age, Sex, Site, baseline depression score and baseline hippocampal volume), −1.0 ± 0.35, t(233) = −2.84, p < 0.005. C, Boxplot comparing volume change of the right hippocampus in non-responders (MADRS reduction < 50%) versus responders (MADRS reduction > 50%), n = 248, t(234.13) = 2.62, p = 0.009. D, Scatter plot of change in MADRS score versus number of ECTs; n = 268. Slope (controlling for age, Sex and Site), − 0.28 ± 0.16, t(256) = −1.80, p = 0.074). Non-responders received more ECT sessions (13.2 ± 4.7 versus 11.5 ± 5.3, t(232.11) = 2.74, p = 0.007) than responders.
Figure 2 |
Figure 2 |. Effect of electrode placement on change in left and right hippocampal volume.
A. Changes in right hippocampal volume per number of ECT sessions for bilateral (BL, dashed line) and right unilateral (RUL, solid line) lead placement. Both slope and change in volume was similar for BL and RUL ECT (slope: both ~.13; BL volume increase: 3.0 ± 1.7 %, RUL volume increase: 2.7 ± 2.0 %). B. Changes in left hippocampal volume per number of ECT sessions for BL (dashed line) and RUL (solid line) lead placement. Slope was steeper and volume change was greater for BL (slope: 0.18 ± 0.03; volume increase: 3.3 ± 2.2 %) than RUL (slope: 0.06 ± 0.04; volume increase: 1.6 ± 2.1%) stimulation.

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