Abstract
Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm3 voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation.
Highlights
Despite the availability of effective treatments for major depressive disorder (MDD), only half to two-thirds of patients can expect to achieve remission.[1,2,3,4] Understanding the mechanisms of treatment response is a priority for improving health outcomes
We examined diffusion tensor imaging (DTI) correlates of white matter (WM) structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD
As white matter (WM) architecture accounts for structural connectivity, and the strength and persistence of functional connectivity is shown to reflect and be constrained by structural connectivity,[10,11] microstructural properties of WM may have an important role in the pathophysiology of MDD and in treatment response
Summary
Despite the availability of effective treatments for major depressive disorder (MDD), only half to two-thirds of patients can expect to achieve remission.[1,2,3,4] Understanding the mechanisms of treatment response is a priority for improving health outcomes. Targeting changes in WM microstructure in association with treatment may help determine which WM pathways are most relevant to disease processes as well as indicate how neuroplasticity in structural networks relates to therapeutic response. One. To better determine the neurobiological effects of rapid treatment response, we used DTI to assess changes in WM microstructure in 20 patients with MDD followed prospectively while receiving ECT. Since neural models of MDD support a dysregulation between under reactive dorsal (DLPFC and DMPFC and dorsal ACC) and over active ventral (orbitofrontal, subgenual ACC, amygdala) fronto-limbic circuitry,[36,37,38,39] we hypothesized that treatment-related changes in structural connectivity would occur in dorsal and ventral pathways involved in mood regulation and emotion
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
