Significant Decrease in Hippocampus and Amygdala Mean Diffusivity in Treatment-Resistant Depression Patients Who Respond to Electroconvulsive Therapy

Abstract

Introduction: The hippocampus plays a key role in depressive disorder, and the amygdala is involved in depressive disorder through the key role that it plays in emotional regulation. Electroconvulsive therapy (ECT) may alter the microstructure of these two regions. Since mean diffusivity (MD), is known to be an indirect marker of microstructural integrity and can be derived from diffusion tensor imaging (DTI) scans, we aim to test the hypothesis that treatment-resistant depression (TRD) patients undergoing bilateral (BL) ECT exhibit a decrease of MD in their hippocampus and amygdala. Methods: Patients, between 50 and 70 years of age, diagnosed with TRD were recruited from the University Hospital of Toulouse and assessed clinically (Hamilton Depression Rating Scale, HAM-D) and by DTI scans at three time points: baseline, V2 (during treatment), and V3 within 1 week of completing ECT. Results: We included 15 patients, who were all responders. The left and right hippocampi and the left amygdala showed a significant decrease in MD at V3, compared to baseline [respectively: β = −2.78, t = −1.97, p = 0.04; β = −2.56, t = −2, p = 0.04; β = −2.5, t = −2.3, p = 0.04, false discovery rate (FDR) corrected]. MD did not decrease in the right amygdala. Only the left amygdala was significantly associated with a reduction in HAM-D (ρ = 0.55, p = 0.049, FDR corrected). Conclusion: MD is an indirect microstructural integrity marker, which decreases in the hippocampus and the left amygdala, during BL ECT in TRD populations. This could be interpreted as a normalization of microstructural integrity in these structures.

Vasogenic edema versus neuroplasticity as neural correlates of hippocampal volume increase following electroconvulsive therapy

“…The decrease in MD, which is in line with recent studies looking into the effects of ECT on DTI measurements [46,47], indicates that the formation of edema is a very unlikely explanation for the volumetric increase in the hippocampus. As vasogenic edema would increase the water content in the extracellular space, this could be reflected in an increase in MD or at least a no detectable change in MD (depending on the sensitivity of the IVIM framework and IVIM scan), as opposed to a decrease in MD.…”

Meta-analysis of brain structural changes after electroconvulsive therapy in depression

“…Similarly, mean diffusivity, a measure of the diffusion of water molecules in the brain, is assessed in diffusion tensor imaging to make statements about the microstructural integrity where increased values are hypothesized to reflect a low restriction of water molecules (e.g. due to cells) and thereby a degeneration of microstructural integrity; several investigations showed a decrease in mean diffusivity after a course of ECT favoring neuroplasticity as underlying mechanism over vasogenic edema that would be accompanied by an increased mean diffusivity due to accumulating extracellular fluids [18,50,74]. Still, an intracellular fluid/ion shift (cell swelling) induced by the seizure cannot be ruled out and would explain the reversibility of the volumetric effects [75].…”

Hippocampal volume and memory impairment after electroconvulsive therapy in patients with depression

“…DTI studies of the hippocampus after ECT found an MD decrease, which does not support the vasogenic edema. 54,55 Further, a recent ultra-high field (7 Tesla) MRI study, which was designed to test the presence of hippocampal edema after ECT, did not find any indication of it. 56 Cytotoxic edema is also a possibility.…”