Acute and long-term effects of electroconvulsive therapy on human dentate gyrus

Abstract

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, although the underlying mechanisms remain unclear. Animal studies have consistently shown that electroconvulsive stimulation induces neuroplastic changes in the dentate gyrus. To date, few studies have investigated the effect of ECT on human hippocampal subfields. In the current study, structural magnetic resonance imaging (MRI) was conducted in 25 patients with major depressive episodes at 3 time points: before ECT (TP1), after 1 week of the last ECT (TP2) and after 3 months of the last ECT (TP3). Twenty healthy controls were scanned twice with an interval similar to patients between TP1 and TP2. Volumetric analyses of the cornu ammonis (CA)4/dentate gyrus (DG) were performed using the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm. Clinically remitted patients after ECT showed larger volume increases in the right CA4/DG than non-remitted patients. Volume increases in the right CA4/DG were negatively associated with age. Increased CA4/DG volumes after ECT returned to baseline levels after 3 months irrespective of clinical state. ECT-induced volume increase in the CA4/DG was associated with age and clinical remission. These findings are consistent with the neurotrophic processes seen in preclinical studies. Neuroplastic change in the CA4/DG might mediate some of the short-term antidepressant effects of ECT.

The dentate gyrus in depression: directions for future research

“…To answer this first question, we collaborated with a group from Tokyo University. Together with Takamiya et al we reanalyzed their previously published data [5], now reporting a significant correlation between changes in DG volume and clinical response after bilateral ECT in an independent sample using 3 tesla MRI [6]. In the aforementioned previously published study [5], Takamiya et al reported volume changes in DG volumes but did not find a simple linear correlation between difference scores in DG volume and HAM-D.…”

“…Together with Takamiya et al we reanalyzed their previously published data [5], now reporting a significant correlation between changes in DG volume and clinical response after bilateral ECT in an independent sample using 3 tesla MRI [6]. In the aforementioned previously published study [5], Takamiya et al reported volume changes in DG volumes but did not find a simple linear correlation between difference scores in DG volume and HAM-D. However, when they implemented the same repeated measures correlation [7] we used in our study [2], a significant correlation was found between a decrease in HAM-D score and an increase in right DG volume (yet not significant in left DG [6]).…”

Electroconvulsive therapy treatment responsive multimodal brain networks

“…However, a recent mega‐analysis did not find relationships between hippocampal volume enlargements observed post ECT and clinical response, suggesting enlargement is masked or at least in part driven by processes related to seizure therapy itself (Oltedal et al, ). At the same time, smaller sample size studies have found ECT‐induced volume increases in the hippocampal dentate gyrus to associate with treatment outcome specifically (Nuninga et al, ; Takamiya et al, ), and ECT response is shown to positively relate to greater structural connectivity between hippocampus and fronto‐limbic regions (Kubicki et al, ). Notably, though seemingly disparate, the above findings are in line with our results indicating that a more complex multimodal brain network, including the hippocampus and connected regions, underlies depressive symptom improvement at the brain systems level.…”

Die Bedeutung der Elektrokonvulsionstherapie (EKT) in der multimodalen Behandlung depressiver Störungen

“…Das Risiko für Schlaganfälle ist durch eine EKT-Behandlung nicht erhöht, auch nicht nach vorangegangenem Schlaganfall (Rozing et al, 2019). EKT ruft keine nachweisbaren Hirnschädigungen hervor; bisherige Studien zeigen im Gegenteil sogar Hirnvolumenzunahmen in bestimmten Regionen (Nuninga et al, 2019;Sartorius et al, 2019;Takamiya et al, 2019;zwei Metaanalysen: Gbyl & Videbech, 2018;Takamiya et al, 2018). Es gibt keinen klaren Hinweis auf ein erhöhtes Risiko nach einer EKT an einer Epilepsie zu erkranken (Bøg et al, 2018).…”