Electroconvulsive therapy is associated with increased immunoreactivity of neuroplasticity markers in the hippocampus of depressed patients

Electroconvulsive therapy (ECT) is an effective therapy for depression, but its cellular effects on the human brain remain elusive. In rodents, electroconvulsive shocks increase proliferation and the expression of plasticity markers in the hippocampal dentate gyrus (DG), suggesting increased neurogenesis. Furthermore, MRI studies in depressed patients have demonstrated increases in DG volume after ECT, that were notably paralleled by a decrease in depressive mood scores. Whether ECT also triggers cellular plasticity, inflammation or possibly injury in the human hippocampus, was unknown. We here performed a first explorative, anatomical study on the human post-mortem hippocampus of a unique, well-documented cohort of bipolar or unipolar depressed patients, who had received ECT in the 5 years prior to their death. They were compared to age-matched patients with a depressive disorder who had not received ECT and to matched healthy controls. Upon histopathological examination, no indications were observed for major hippocampal cell loss, overt cytoarchitectural changes or classic neuropathology in these 3 groups, nor were obvious differences present in inflammatory markers for astrocytes or microglia. Whereas the numbers of proliferating cells expressing Ki-67 was not different, we found a significantly higher percentage of cells positive for Doublecortin, a marker commonly used for young neurons and cellular plasticity, in the subgranular zone and CA4 / hilus of the hippocampus of ECT patients. Also, the percentage of positive Stathmin 1 cells was significantly higher in the subgranular zone of ECT patients, indicating neuroplasticity. These first post-mortem observations suggest that ECT has no damaging effects but may rather have induced neuroplasticity in the DG of depressed patients.

Automated summary

This anatomical study investigated the effects of electroconvulsive therapy (ECT) on the human hippocampus in depressed patients. The results indicated that ECT may induce neuroplasticity in the hippocampus, as evidenced by increased expression of markers for young neurons and cellular plasticity. There were no major cell loss or classic neuropathological changes observed.