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

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.