The Neurobiological Basis of Cognitive Side Effects of Electroconvulsive Therapy: A Systematic Review

Abstract

Decades of research have consistently demonstrated the efficacy of electroconvulsive therapy (ECT) for the treatment of major depressive disorder (MDD), but its clinical use remains somewhat restricted because of its cognitive side effects. The aim of this systematic review is to comprehensively summarize current evidence assessing potential biomarkers of ECT-related cognitive side effects. Based on our systematic search of human studies indexed in PubMed, Scopus, and Web of Knowledge, a total of 29 studies evaluating patients with MDD undergoing ECT were reviewed. Molecular biomarkers studies did not consistently identify concentration changes in plasma S-100 protein, neuron-specific enolase (NSE), or Aβ peptides significantly associated with cognitive performance after ECT. Importantly, these findings suggest that ECT-related cognitive side effects cannot be explained by mechanisms of neural cell damage. Notwithstanding, S-100b protein and Aβ40 peptide concentrations, as well as brain-derived neurotrophic factor (BDNF) polymorphisms, have been suggested as potential predictive biomarkers of cognitive dysfunction after ECT. In addition, recent advances in brain imaging have allowed us to identify ECT-induced volumetric and functional changes in several brain structures closely related to memory performance such as the hippocampus. We provide a preliminary framework to further evaluate neurobiological cognitive vulnerability profiles of patients with MDD treated with ECT.

Pharmacological interventions to diminish cognitive side effects of electroconvulsive therapy: A systematic review and meta‐analysis

“…Recent studies have found potential roles of oxidative stress, inflammation, neurotrophic factors, immunological factors, hormones, alterations in electrical brain activity, permeability of the blood brain barrier, brain perfusion, changes in functional networks with a lag of integration of new neurons and volume changes of the hippocampus. 9 , 84 , 85 Further study of the worthwhile pharmacological interventions in this review may help elucidate the mechanisms of cognitive side effects in ECT. In addition, the study of novel candidates may contribute to further understanding of these mechanisms.…”

Treatment-resistant depression – is magnetic seizure therapy the novel treatment?

“…It has been reported that industry-funded sponsorship might discourage the publication of unfavourable results. Furthermore, evidence has shown that papers funded by independent organisations have generated fewer positive findings than those conducted by industry-funded sponsors (Bekelman 2003).…”

“…ECT is shown to increase the volume and enhance connectivity of the temporal lobe cortices, anterior cingulate cortex and hippocampus, resulting in favourable clinical outcomes which are believed to be due to neuroplastic changes (Ota 2015;Joshi 2016;Cano 2017). However, the increase in hippocampal volume is associated with cognitive adverse effects, which evidence suggests improve as hippocampal volume decreases in the 6-12 months following completion of ECT (Bassa 2021). MST, in contrast, induces only superficial stimulation and passes through the skull unimpeded, resulting in a more targeted stimulation of focal structures (Weissman 2020).…”

Medication preventing postictal hypoperfusion and cognitive side-effects in electroconvulsive therapy: A retrospective cohort study

“…However, a recent systematic review and meta-analysis only identified a younger age as factor related to cognitive deterioration after the ECT-course ( 5 ). The literature reports several pathophysiological theories regarding negative cognitive ECT-outcome, including changes in neuroinflammation, neurotrophic factors, and hormones ( 9 ). Magnetic resonance imaging (MRI) studies have shown an increase in hippocampal volume associated with increased cognitive disturbances ( 5 ).…”