Table 1.

Key clinical and preclinical evidence summary regarding ECT and its molecular mechanisms.

		Human Studies *
Author	Mechanism	Methodology	Results
Berggren et al. [25]	Brain interconnectivity	A total of 49 patients underwent ECT. A total of 41 patients grading improvement after the initial ECT series were compared with 8, grading no improvement. The patients underwent neuropsychiatric ratings, the measure of clinical response (defined as ≥50% reduction of pretreatment depression score), and the measure of rCBF.	The responder group had an initial 60–82%, and the nonresponder group a 30–64% clinical response throughout the follow-up. The nonresponder group showed more reported depression (p = 0.003) and vegetative anxiety (p = 0.024), with a generally higher left temporal rCBF (p = 0.045).
Joshi et al. [28]	Neurogenesis	Longitudinal changes in hippocampal and amygdala structures were examined in 43 patients with major depression, referred for ECT as part of their standard clinical care. Cross-sectional comparisons with 32 demographically similar controls established diagnosis effects.	Patients showed smaller hippocampal volumes than controls at baseline (p < 0.04). Both the hippocampal and the amygdala volumes increased with ECT (p < 0.001) and in relation to the symptom improvement (p < 0.01). Hippocampal volume at baseline predicted subsequent clinical response (p < 0.05). All structural measurements remained stable across time in controls.
Saijo et al. [52]	Dopaminergic system	A total of 7 patients with depression underwent PET scans before and after a series of 6–7 treatments with the bilateral ECT. The [(11)C]FLB 457 binding parametric images were generated on the basis of a simplified reference tissue model. Voxel-based methods were used to assess the ECT effect on D(2) receptor binding.	There were no significant differences in D(2) receptor binding between patients with depression and controls. Significant changes in D(2) receptor binding, a mean of 25.2% reduction, were found in the right rostral anterior cingulate following ECT (p < 0.001).
Burgese et al. [84]	Endocrine effects	Blood cortisol levels were measured before the beginning of treatment with ECT, at the seventh session, at the last session, and at treatment completion. Depression symptoms were assessed using the BDI.	Cortisol levels remained stable between the seventh and the last sessions of ECT; values ranged at 0.686 ± 9.6330 g/dL for women, and there was a mean decrease of 5.825 ± 6.0780 g/dL (p = 0.024). After the seventh and the last ECT sessions, patients with depression and individuals in the control group had similar cortisol levels, whereas the BDI scores remained different.
		Animal Studies *
Author	Mechanism	Methodology	Results
Roman et al. [107]	Immunological effects	Wistar rats received single or chronic treatment with ECS, once a day for 10 consecutive days, or sham ECS was administered likewise. The rats were killed 24 h after the last treatment, and peritoneal macrophages were cultured in vitro for a subsequent metabolic activity determination.	We found statistically significant changes in the biological properties of macrophages. Rats receiving chronic 10-fold ECS showed an increase in the macrophages’ metabolic activity, increased arginase activity, and a marked but statistically insignificant decrease in nitric oxide synthesis compared with the respective controls.

* Search strategy: An exhaustive bibliographical search was performed using the terms “electroconvulsive therapy”, “neurobiological effects of electroconvulsive therapy”, “electroconvulsive therapy and immune system”, “electroconvulsive therapy and the endocrine system”, “molecular mechanisms in electroconvulsive therapy”, and “electroconvulsive therapy and psychiatric disorders”. The search was later filtered using the terms “humans” and “animals” as well as “clinical” and “preclinical”. For the selection of the studies, those that were published within the past 35 years were included. Abbreviations: ECT: electroconvulsive therapy; rCBF: regional cerebral blood flow; BDI: Beck Depression Inventory; ECS: electroconvulsive shock.