Brain volumetric correlates of electroconvulsive therapy versus transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are effective neuromodulation therapies for treatment-resistant depression (TRD). While ECT is generally considered the most effective antidepressant, rTMS is less invasive, better tolerated and leads to more durable therapeutic benefits. Both interventions are established device antidepressants, but it remains unknown if they share a common mechanism of action. Here we aimed to compare the brain volumetric changes in patients with TRD after right unilateral (RUL) ECT versus left dorsolateral prefrontal cortex (lDLPFC) rTMS. METHODS: We assessed 32 patients with TRD before the first treatment session and after treatment completion using structural magnetic resonance imaging. Fifteen patients were treated with RUL ECT and seventeen patients received lDLPFC rTMS. RESULTS: Patients receiving RUL ECT, in comparison with patients treated with lDLPFC rTMS, showed a greater volumetric increase in the right striatum, pallidum, medial temporal lobe, anterior insular cortex, anterior midbrain, and subgenual anterior cingulate cortex. However, ECT- or rTMS-induced brain volumetric changes were not associated with the clinical improvement. LIMITATIONS: We evaluated a modest sample size with concurrent pharmacological treatment and without neuromodulation therapies randomization. CONCLUSIONS: Our findings suggest that despite comparable clinical outcomes, only RUL ECT is associated with structural change, while rTMS is not. We hypothesize that structural neuroplasticity and/or neuroinflammation may explain the larger structural changes observed after ECT, whereas neurophysiological plasticity may underlie the rTMS effects. More broadly, our results support the notion that there are multiple therapeutic strategies to move patients from depression to euthymia.

Longitudinal trajectory of response to electroconvulsive therapy associated with transient immune response & white matter alteration post-stimulation.

Research suggests electroconvulsive therapy (ECT) induces an acute neuroinflammatory response and changes in white matter (WM) structural connectivity. However, whether these processes are related, either to each other or to eventual treatment outcomes, has yet to be determined. We examined the relationship between levels of peripheral pro-inflammatory cytokines and diffusion imaging-indexed changes in WM microstructure in individuals with treatment-resistant depression (TRD) who underwent ECT. Forty-two patients were assessed at baseline, after their second ECT (T2), and after completion of ECT (T3). A Montgomery Åsberg Depression Rating Scale improvement of >50% post-ECT defined ECT-responders (n = 19) from non-responders (n = 23). Thirty-four controls were also examined. Tissue-specific fractional anisotropy (FAt) was estimated using diffusion imaging data and the Free-Water method in 17 WM tracts. Inflammatory panels were evaluated from peripheral blood. Cytokines were examined to characterize the association between potential ECT-induced changes in an inflammatory state and WM microstructure. Longitudinal trajectories of both measures were also examined separately for ECT-responders and non-responders. Patients exhibited elevated Interleukin-8 (IL-8) levels at baseline compared to controls. In patients, correlations between IL-8 and FAt changes from baseline to T2 were significant in the positive direction in the right superior longitudinal fasciculus (R-SLF) and right cingulum (R-CB) (psig = 0.003). In these tracts, linear mixed-effects models revealed that trajectories of IL-8 and FAt were significantly positively correlated across all time points in responders, but not non-responders (R-CB-p = .001; R-SLF-p = 0.008). Our results suggest that response to ECT in TRD may be mediated by IL-8 and WM microstructure.