White matter alterations in the internal capsule and psychomotor impairment in melancholic depression.

Matthew P Hyett,Michael Breakspear,Wei Wen,Alistair Perry,Gordon B Parker,Linda Chao

doi:10.1371/journal.pone.0195672

Abstract

Emerging evidence suggests that structural brain abnormalities may play a role in the pathophysiology of melancholic depression. We set out to test whether diffusion-derived estimates of white matter structure were disrupted in melancholia in regions underpinning psychomotor function. We hypothesized that those with melancholia (and evidencing impaired psychomotor function) would show disrupted white matter organization in internal capsule subdivisions. Diffusion magnetic resonance imaging (dMRI) data were acquired from 22 melancholic depressed, 23 non-melancholic depressed, and 29 healthy control participants. Voxel-wise fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) values were derived for anterior, posterior, and retrolenticular limbs of the internal capsule and compared between groups. Neuropsychological (reaction time) and psychomotor functioning were assessed and correlated against FA. Fractional anisotropy was distinctly increased, whilst RD was decreased, in the right anterior internal capsule in those with melancholia, compared to controls. The right anterior limb of the internal capsule correlated with clinical ratings of psychomotor disturbance, and reduced psychomotor speed was associated with increased FA values in the right retrolenticular limb in those with melancholia. Our findings highlight a distinct disturbance in the local white matter arrangement in specific regions of the internal capsule in melancholia, which in turn is associated with psychomotor dysfunction. This study clarifies the contribution of structural brain integrity to the phenomenology of melancholia, and may assist future efforts seeking to integrate neurobiological markers into depression subtyping.

Highlights

Melancholic depression has been positioned as the prototypical depressive disorder [1], with a range of proposed neurobiological causes spanning brain structure and function
Clinical studies suggest that melancholia can be subtyped into “structural melancholia”–a late-onset form of the disorder arising from compromised neurovascular functioning—and “functional melancholia”, commencing in adolescence and young adulthood and believed to arise from perturbed brain function
Given the location and associational nature of the internal capsule–where the anterior limb extends from the thalamus, via the basal ganglia, to the frontal cortex—these studies [4,5] provide support for the hypothesis that at least some depressive sub-types are associated with disruptions to the integrity of cortical-subcortical circuitry, and may help explain psychomotor disturbance in those with the melancholic depressive sub-type

Summary

Introduction

Melancholic depression has been positioned as the prototypical depressive disorder [1], with a range of proposed neurobiological causes spanning brain structure and function. Diffusion magnetic resonance imaging (dMRI) data have been used to highlight white matter abnormalities in both the internal and external capsule in depressed younger and older adults with and without melancholic features [2,3,4,5] All such samples likely include a proportion of ‘true’ melancholic patients, providing support for a functional melancholia class. Reduced FA values have been reported for internal and external capsule fibers in those with melancholic major depression compared to non-depressed controls [2] Despite such evidence, previous studies [2,3,4,5] have not systematically investigated associations between white matter alterations and functional changes (e.g., neuropsychological function)

Results

Discussion

Conclusion