ECT-induced cognitive side effects are associated with hippocampal enlargement

Abstract

Electroconvulsive therapy (ECT) is of the most effective treatments available for treatment-resistant depression, yet it is underutilized in part due to its reputation of causing cognitive side effects in a significant number of patients. Despite intensive neuroimaging research on ECT in the past two decades, the underlying neurobiological correlates of cognitive side effects remain elusive. Because the primary ECT-related cognitive deficit is memory impairment, it has been suggested that the hippocampus may play a crucial role. In the current study, we investigated 29 subjects with longitudinal MRI and detailed neuropsychological testing in two independent cohorts (N = 15/14) to test if volume changes were associated with cognitive side effects. The two cohorts underwent somewhat different ECT study protocols reflected in electrode placements and the number of treatments. We used longitudinal freesurfer algorithms (6.0) to obtain a bias-free estimate of volume changes in the hippocampus and tested its relationship with neurocognitive score changes. As an exploratory analysis and to evaluate how specific the effects were to the hippocampus, we also calculated this relationship in 41 other areas. In addition, we also analyzed cognitive data from a group of healthy volunteers (N = 29) to assess practice effects. Our results supported the hypothesis that hippocampus enlargement was associated with worse cognitive outcomes, and this result was generalizable across two independent cohorts with different diagnoses, different electrode placements, and a different number of ECT sessions. We found, in both cohorts, that treatment robustly increased the volume size of the hippocampus (Cohort 1: t = 5.07, Cohort 2: t = 4.82; p < 0.001), and the volume increase correlated with the neurocognitive T-score change. (Cohort 1: r = −0.68, p = 0.005; Cohort 2: r = −0.58; p = 0.04). Overall, our research indicates that novel treatment methods serving to avoid hippocampal volume increase may result in a better side effect profile.

High-frequency repetitive transcranial magnetic stimulation alleviates the cognitive side effects of electroconvulsive therapy in major depression

“…Our data showed that ECT, not HF-rTMS, impairs cognitive function with the decline of MoCA scores ( Figures 4A,B ). The results are consistent with previous studies, which have found that ECT potentially has detrimental cognitive side effects, including amnesia and slowing of reaction times ( 48 , 49 ). Furthermore, HF-rTMS could reverse the cognitive impairment induced by ECT ( Figures 4A,B ).…”

European Psychiatric Association guidance on treatment of cognitive impairment in schizophrenia

“…ECT, however, is frequently associated with cognitive adverse effects, including transient cognitive impairment and memory deficits [149,150]. TMS is based on the electromagnetic induction principle:…”

“…ECT entails the induction of generalized cerebral seizures under general anesthesia, producing brain chemistry changes by influencing neurogenesis, neurotrophic signaling, and neuroplasticity [ 148 ]. ECT, however, is frequently associated with cognitive adverse effects, including transient cognitive impairment and memory deficits [ 149 , 150 ]. TMS is based on the electromagnetic induction principle: focal electromagnetic pulses penetrate the skull through a wire coil to focally stimulate target areas by inducing secondary electric current flows modulating neuronal firing rates [ 151 ].…”

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.…”