Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression

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.

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

“…96 This is an interesting finding given evidence that ECT may mediate the neuro plasticity of white matter microstructure in patients with major depression. 103 Furthermore, a recent review has reported that although the mechanisms of its action are still not completely understood, DBS for TRD has shown encouraging therapeutic effects, demonstrating significant and sustained improvements in depressive symptomatology, with remission in a large percentage of cases. 98 To our knowledge, only a limited number of studies of nondrug therapies involving a small patient sample size have been conducted so far.…”

Desynchronization and Plasticity of Striato-frontal Connectivity in Major Depressive Disorder

“…is less focal and yet most effective at reducing symptoms of depression, eliciting generalized seizures associated with more widespread neural changes (Perrin et al 2012;Abbott et al 2013;Tendolkar et al 2013;Zhang et al 2013;Dukart et al 2014;Lyden et al 2014;van Waarde et al 2015;Joshi et al 2015). However, the exact nature of network dysfunction responsible for depressive disorders, and how this dysfunction is best targeted by current neurostimulation therapies, remains poorly understood.…”

“…Twenty-four patients returned for the third timepoint; only these patients were used in analyses assessing treatment response, and they received either right unilateral ECT (RUL; n = 18) or a combination of right unilateral and bifrontal ECT (RUL + BF; n = 6) using standard procedures (d'Elia 1970;Zhang et al 2013;Lyden et al 2014), 3 times a week during the index series (mean/SD number of treatments = 11.79/3.34; Table 1) at UCLA Resnick Neuropsychiatric Hospital. A group of healthy never-depressed "control" volunteers were also scanned twice, at baseline and at a 2-to 4-week follow-up, to establish normative values and test-retest reliability of resting-state fMRI variables.…”

“…ECT uses specific lead placements (usually right unilateral or bifrontal for depression) to elicit generalized seizures and has been shown to associate with lasting changes throughout the brain, including the hippocampus, thalamus, PFC, dorsal ACC, and other regions (Perrin et al 2012;Abbott et al 2013;Tendolkar et al 2013;Zhang et al 2013;Dukart et al 2014;Lyden et al 2014;van Waarde et al 2014;Joshi et al 2015). In the current study, we targeted brain regions with strong differences in RSFC between patients and healthy volunteers prior to analyzing longitudinal effects to reveal novel findings that indicate restored striato-frontal connectivity with ECT.…”

Is Electroconvulsive Therapy for Depression More Effective Than Placebo? A Systematic Review of Studies Since 2009

“…Forty seven of the 89 were observational studies (Azuma et al, 2011;Bär et al, 2010;Bayless et al, 2010;Beall et al, 2012;Bersani et al, 2014;Bilgen et al, 2014;Burgese & Bassitt, 2015;Casarotto et al, 2013;Chiaie et al, 2013;Dannlowski et al, 2013;Dukart et al, 2014;Ebert et al, 2010;Galletly, Paterson, & Burton, 2012;Goto et al, 2012;Guloksuz et al, 2015;Hu et al, 2010;Johansson, Ehnvall, Friberg, & Myredal, 2010;Joshi et al, 2015;Kalogerakou et al, 2015;Kautto et al, 2015;Lin et al, 2013;Loo, Mahon, Katalinic, Lyndon, & Hadzi-Pavlovic, 2011;Lucca et al, 2010;Lyden et al, 2014;McCall et al, 2013;Medda et al, 2014;Meeter, Murre, Janssen, Birkenhager, & van den Broek, 2011;Minelli et al, 2014;Nickl-Jockschat et al, 2015;Nordanskog, Larsson, Larsson, & Johanson, 2014;Ota et al, 2015;Oudega et al, 2011;Perrin et al, 2012;Piccinni et al, 2013;Rapinesi et al, 2015;Rapinesi et al, 2013;Royster et al, 2012;Saijo et al, 2010;Samuelsson, Gerdin, Öllinger, & Vrethem, 2012;Tendolkar et al, ...…”