Altered white matter integrity of forebrain in treatment-resistant depression: A diffusion tensor imaging study with tract-based spatial statistics

BackgroundThe association between alterations of the white matter (WM) integrity in brain regions and mood dysregulation has been reported in major depressive disorder (MDD). However, there has never been a neuroimaging study in patients who have treatment-resistant depression (TRD) and are in a current treatment-resistant state. In the present study, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) method to investigate the WM integrity of different brain regions in patients who had TRD and were in a current treatment-resistant state.MethodsTwenty-three patients with TRD and Hamilton Rating Scale total score of ≥ 18 and 19 healthy controls matched with age, gender, and education level to patients were scanned with DTI. Thirty 4 mm thick, no gap, contiguous axial slices were acquired and fractional anisotropy (FA) images were generated for each participant. An automated TBSS approach was used to analyze the data.ResultsVoxel-wise statistics revealed that patients with TRD had lower FA values in the right anterior limb of internal capsule, the body of corpus callosum, and bilateral external capsule compared to healthy subjects. Patients with TRD did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain region and patients' demographics and the severity of illness.ConclusionsOur findings suggest the abnormalities of the WM integrity of neuronal tracts connecting cortical and subcortical nuclei and two brain hemispheres may play a key role in the pathogenesis of TRD.

► TRD may exhibit abnormalities of WM integrity in regions associated with emotional regulation ► The MDD patients enrolled in the present study were in current treatment-resistant state ► TBSS method could detect WM tracts integrity alterations in patients and controls. ► Alterations of projection fibers and corpus callosum integrity attribute to the pathogenesis of TRD