Structural abnormality of the corticospinal tract in major depressive disorder.

Background: Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ.

Results: FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p's < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule.

Conclusions: This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs.