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 measures 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 1) diagnosis and 2) ECT on global and local variations of hippocampal and amygdalar structure in major depression and predictors of ECT-related clinical response Methods Longitudinal changes in hippocampal and amygdala structure were examined in patients with major depression (N= 43, scanned thrice; prior to ECT, after the 2nd ECT session, and within one 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 compared to controls at baseline (p<.04). Both hippocampal and amygdalar 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 measures 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.

Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression

“…This is in line with previous studies (Nordanskog et al, 2010;Tendolkar et al, 2013;Abbott et al, 2014;Dukart et al, 2014;Nordanskog et al, 2014;Bouckaert et al, 2015;Jorgensen et al, 2015;Ota et al, 2015;Sartorius et al, 2016). Only two studies found an association between hippocampal volume increase and therapeutic efficacy (Dukart et al, 2014;Joshi et al, 2015). Our data suggest that the hippocampal volume increase after ECT is transient and reverts to baseline within 6 months, even though the antidepressant effect is sustained.…”

“…Several recent magnetic resonance imaging (MRI) studies have described hippocampal volume changes following ECT (Nordanskog et al, 2010;Tendolkar et al, 2013;Abbott et al, 2014;Dukart et al, 2014;Nordanskog et al, 2014;Joshi et al, 2015;Jorgensen et al, 2015;Ota et al, 2015;Bouckaert et al, 2015;Sartorius et al, 2016). Some of these studies have also addressed structural changes in other brain areas relevant to depressive disorders, such as dorsolateral prefrontal cortex, orbitofrontal cortex (Jorgensen et al, 2015), lateral temporal cortex (Bouckaert et al, 2015), caudate nucleus (Bouckaert et al, 2015), and amygdala (Tendolkar et al, 2013;Jorgensen et al, 2015;Joshi et al, 2015;Ota et al, 2015;Sartorius et al, 2016). Only one study did not detect gray matter volume changes (Nickl-Jockschat et al, 2016).…”

Effect of Electroconvulsive Therapy on Striatal Morphometry in Major Depressive Disorder

“…Others (Liu et al, 2009) have also reported increased subventricular zone neuroblast cell proliferation to striatal areas following seizures. Further, ECT-related structural neuroplasticity is shown in the amygdala (Tendolkar et al, 2013;Joshi et al, 2015). These subcortical limbic structures are intricately connected to the striatum, and via the cortico-striatal-pallido-thalamo-cortical loop and projections to the hypothalamus and brainstem, act together to influence emotional expression and motivation (Cardinal et al, 2002).…”

“…We and other groups have shown that ECT elicits increases in hippocampal (Nordanskog et al, 2010;Tendolkar et al, 2013;Abbott et al, 2014;Joshi et al, 2015) and amygdala volume (Tendolkar et al, 2013;Joshi et al, 2015). However, whether structural plasticity occurs in the dorsal or ventral striatum/pallidum in association with treatment and illness recovery remains unknown.…”

Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the hippocampus

“…With regard to the effects of interventions, it was elucidated earlier that conventional antidepressant drugs produce a normalization of the structural plasticity of the hippocampus, by altering the volume of the area, the number of cells (for example through decreasing apoptosis or inducing cellular genesis), the volume of the cells and inducing morphological changes of the dendrites and axons (Boldrini et al, 2012;Joshi et al, 2015). In the present work, we found evidence for the hypothesis that ketamine rapidly alters the volume of the CA1.SR and GCL areas (within 24 h) in the depressed animals.…”