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

ABSTRACT: 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.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.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.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.

SUBMITTER: Joshi SH

PROVIDER: S-EPMC4561035 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Project description:BackgroundElectroconvulsive therapy (ECT) is the treatment of choice for severe mental illness including treatment-resistant depression (TRD). Increases in volume of the hippocampus and amygdala following ECT have consistently been reported.AimsTo investigate neuroplastic changes after ECT in specific hippocampal subfields and amygdala nuclei using high-resolution structural magnetic resonance imaging (MRI) (trial registration: clinicaltrials.gov - NCT02379767).MethodMRI scans were carried out in 14 patients (11 women, 46.9 years (s.d. = 8.1)) with unipolar TRD twice before and once after a series of right unilateral ECT in a pre-post study design. Volumes of subcortical structures, including subfields of the hippocampus and amygdala, and cortical thickness were extracted using FreeSurfer. The effect of ECT was tested using repeated-measures ANOVA. Correlations of imaging and clinical parameters were explored.ResultsIncreases in volume of the right hippocampus by 139.4 mm3 (s.d. = 34.9), right amygdala by 82.3 mm3 (s.d. = 43.9) and right putamen by 73.9 mm3 (s.d. = 77.0) were observed. These changes were localised in the basal and lateral nuclei, and the corticoamygdaloid transition area of the amygdala, the hippocampal-amygdaloid transition area and the granule cell and molecular layer of the dentate gyrus. Cortical thickness increased in the temporal, parietal and insular cortices of the right hemisphere.ConclusionsFollowing ECT structural changes were observed in hippocampal subfields and amygdala nuclei that are specifically implicated in the pathophysiology of depression and stress-related disorders and retain a high potential for neuroplasticity in adulthood.Declaration of interestS.K. has received grants/research support, consulting fees and/or honoraria within the past 3 years from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Celegne GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH, KRKA-Pharma, Lundbeck A/S, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe and Servier. R.L. received travel grants and/or conference speaker honoraria from Shire, AstraZeneca, Lundbeck A/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, and Roche Austria GmbH.

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

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