Structural Plasticity of the Hippocampus and Amygdala Induced by Electroconvulsive Therapy in Major Depression

Abstract

Background: Electroconvulsive therapy (ECT) elicits a rapid and robust clinical response in patients with refractory depression. Neuroimaging measurements of structural plasticity relating to and predictive of ECT response may point to the mechanisms underlying rapid antidepressant effects and establish biomarkers to inform other treatments. Here, we determine the effects of diagnosis and of ECT on global and local variations of hippocampal and amygdala structures in major depression and predictors of ECT-related clinical response.

Methods: Longitudinal changes in hippocampal and amygdala structures were examined in patients with major depression (N = 43, scanned three times: prior to ECT, after the second ECT session, and within 1 week of completing the ECT treatment series), referred for ECT as part of their standard clinical care. Cross-sectional comparisons with demographically similar controls (N = 32, scanned twice) established effects of diagnosis.

Results: Patients showed smaller hippocampal volumes than controls at baseline (p < .04). Both the hippocampal and the amygdala volumes increased with ECT (p < .001) and in relation to symptom improvement (p < .01). Hippocampal volume at baseline predicted subsequent clinical response (p < .05). Shape analysis revealed pronounced morphometric changes in the anterior hippocampus and basolateral and centromedial amygdala. All structural measurements remained stable across time in controls.

Conclusions: ECT-induced neuroplasticity in the hippocampus and amygdala relates to improved clinical response and is pronounced in regions with prominent connections to ventromedial prefrontal cortex and other limbic structures. Smaller hippocampal volumes at baseline predict a more robust clinical response. Neurotrophic processes including neurogenesis shown in preclinical studies may underlie these structural changes.

Keywords: Antidepressant; Brain stimulation; ECT; Limbic; Neuroimaging; Neuroplasticity.

Conflict of interest statement

FINANCIAL DISCLOSURES

All authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Schematic showing the study research design and types of analyses conducted on the hippocampus and amygdala.

Figure 2

Cross-sectional effects (after controlling for age, gender and total brain volume) of diagnosis and longitudinal effects of ECT in patients and time in controls on hippocampal (top) and amygdala (bottom) volume (mm3).

Figure 3

Longitudinal effect of ECT on local hippocampal shape. Left panel shows significant local expansion in the right anterior hippocampus in patients across all time points (T1, T2, and T3). Right panel shows significant expansions in the right anterior hippocampus that extend into more posterior CA2 and C3 regions in patients at T3 compared to T1. P-values are corrected for FDR (37) (q=0.05).

Figure 4

Longitudinal effect of ECT on local amygdalar shape. Top left panel shows significant local bilateral expansion in the dorsomedial amygdala as well as the left basolateral amygdala in patients across treatment time points. Top right panel shows significant expansions in the left basolateral amygdala in patients at T3 compared to T1. P-values are corrected for FDR (37) (q=0.05). The bottom panel shows the surface anatomy of the amygdala and hippocampus along with labeled orientations.

Figure 5

A: Treatment effect of ECT on mood scores; HAM-D, F(2, 29.62) = 35.99, p < .0001, QIDS-SR scores, F(2, 29.44) = 50.03, p < .0001 and MADRS, F(2, 29.08) = 47.5, p < .0001. B: Significant associations of hippocampal (top) and amygdala (bottom) volumes with improvement in mood scores across all time points T1, T2 and T3. C: Association of baseline volumes of the hippocampus and change in clinical response over the course of ECT. The left hippocampus is significantly correlated with improvement in percentage change in HAMD between T1 and T3.