Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression: a longitudinal neuroimaging study

Abstract

Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement. We assessed 12 patients with treatment-resistant depression (TRD) at four time points (pre-treatment, after the first ECT session, after the ninth ECT session and 15 days after ECT course completion) and 10 healthy participants at two time points, 5 weeks apart. Patients with TRD showed bilateral medial temporal lobe (MTL) and perigenual anterior cingulate cortex volume increases. Left MTL volume increase was associated with (i) a hippocampal N-acetylaspartate concentration decrease, (ii) a hippocampal Glutamate+Glutamine concentration increase and (iii) significant clinical improvement. The observed findings are, in part, compatible with both neuroplastic and neuroinflammatory changes induced by ECT. We postulate that such phenomena may be interrelated, therefore reconciling the neuroplasticity and neuroinflammatory hypotheses of ECT action.

Association between hippocampal volume change and change in memory following electroconvulsive therapy in late‐life depression

“…In general, an overall increase in HV was seen in our sample following ECT, which was over an average period of 54 days. This is in line with other studies reporting an ECT‐induced increase in HV in depressed patients compared to depressed patients without ECT and healthy controls , during the same time window. The increase must be interpreted with caution since random variation and measurement errors could be a cause of the change in HV over time.…”

“…Electroconvulsive seizures (ECS), the animal model of ECT, indicates that increased neuroplasticity in the dentate gyrus , might be responsible for the observed changes in HV. Also, several preclinical studies suggest that increased neuroplasticity in the hippocampus causes memory impairments , , .…”

“…The increase of HV following ECT, which is linked to altered neuroplasticity, is proven to be a robust phenomenon , and could be a potential source of cognitive dysfunction in ECT. Two recent meta‐analyses concluded that ECT induces a volume increase in fronto‐limbic areas, mostly the hippocampus , .…”

Brain structure alterations in depression: Psychoradiological evidence

“…The anterior cingulate cortex (ACC) has an anatomical connection with dorsal neocortical and ventral paralimbic regions and plays a role in cognitive processes and mood regulation . The right anterior cingulate cortex was reported to have a decreased magnetization transfer ratio in patients with treatment‐refractory MDD relative to healthy controls, which increased after electroconvulsive therapy . Previous studies have also found that prefrontal areas undergo a significant reduction in thickness, and these changes are thought to be associated with poor clinical outcomes .…”

“…27 The right anterior cingulate cortex was reported to have a decreased magnetization transfer ratio in patients with treatment-refractory MDD relative to healthy controls, 28 which increased after electroconvulsive therapy. 29 Previous studies have also found that prefrontal areas undergo a significant reduction in thickness, 4,[30][31][32] and these changes are thought to be associated with poor clinical outcomes. 33 A negative correlation was observed between the Montgomery-Asberg Depression Rating Scale score and cortical thickness in the ACC.…”