Changes of white matter microstructure after successful treatment of bipolar depression

Diffusion tensor imaging (DTI) measures suggest a widespread alteration of white matter (WM) microstructure in patients with bipolar disorder (BD). The chronotherapeutic combination of repeated total sleep deprivation and morning light therapy (TSD+LT) can acutely reverse depressive symptoms in approximately 60% of patients, and it has been confirmed as a model antidepressant treatment to investigate the neurobiological correlates of rapid antidepressant response.We tested if changes in DTI measures of WM microstructure could parallel antidepressant response in a sample of 44 patients with a major depressive episode in course of BD, treated with chronoterapeutics for one week. We used both a tract-wise and a voxel-wise approach for the whole-brain extraction of DTI measures of WM microstructure: axial (AD), radial (RD), and mean diffusivity (MD), and fractional anisotropy (FA).Compared to baseline level, at one-week follow up we observed a significant increase in average FA measures paralleled by a significant decrease in MD measures of several WM tracts including cingulum, corpus callosum, corona radiata, cortico-spinal tract, internal capsule, fornix and uncinate fasciculus. The degree of change was associated to clinical response.This is the first study to show changes of individual DTI measures of WM microstructure in response to antidepressant treatment in BD. Our results add new evidence to warrant a role for chronotherapeutics as a first-line treatment for bipolar depression and contribute identifying generalizable neuroimaging-based biomarkers of antidepressant response.