Abnormal neuritic microstructures in the anterior limb of internal capsules in treatment-resistant depression - A cross-sectional NODDI study

Background: Microstructural deficits of brain tissue are implicated in the pathophysiology of major depressive disorder (MDD). Recent studies have highlighted the neurotrophic mechanisms underlying effective treatments such as ketamine for treatment-resistant depression (TRD). However, little is known about microstructural changes in TRD. Neurite orientation dispersion and density imaging (NODDI) has enabled in vivo investigation of gray matter (GM) and white matter (WM) microstructure. This study sought to examine microstructural abnormalities in gray and white matter in patients with TRD using NODDI. Methods: This study compared the neurite density index (NDI) and orientation dispersion index (ODI) of neurites in 70 patients with TRD and 35 healthy controls. We fitted separate optimal NODDI models for gray and white matter. The locations of microstructural deficit were identified using region-based and voxel-based analysis. The affected white matter fibers were tracked with correlational tractography analysis. Results: An increase of ODI at the middle to the ventral part of the right anterior limb of the internal capsule (ALIC) was observed in patients with TRD compared with healthy controls. The quantitative anisotropy of frontothalamic fibers passing through the ALIC negatively correlated with the ODI increase in the TRD group. Conclusion: The microstructural disorganization of the frontothalamic pathway could be linked to the pathophysiology and individual heterogeneity of TRD.