White matter changes in healthy adolescents at familial risk for unipolar depression: a diffusion tensor imaging study

Abstract

Alterations in white matter integrity of several cortical and subcortical circuits have been reported in relation to unipolar major depressive disorder. It is not clear whether these white matter changes precede the onset of illness. In all, 13 adolescent volunteers with no personal or family history of a psychiatric disorder (controls) and 18 adolescent volunteers with no personal history of a psychiatric illness including depression, but who were at high risk for developing unipolar depression by virtue of parental depression (high-risk youth), underwent diffusion tensor imaging studies. An automated tract-based spatial statistics method, a whole-brain voxel-by-voxel analysis, was used to analyze the scans. Population average diffusion parameter values were also calculated for each tract. Adolescents at high risk for unipolar depression had lower fractional anisotropy (FA) values in the left cingulum, splenium of the corpus callosum, superior longitudinal fasciculi, uncinate, and inferior fronto-occipital fasciculi than did controls. Altered white matter integrity in healthy adolescents at familial risk for unipolar depression suggests that it might serve as a vulnerability marker for the illness.

Figure 1

Illustration of tract-based quantification of fractional anisotropy of white matter tracts. Skeleton of the averaged FA, shown in green in panel (a), is overlaid on the gray-scale averaged FA map. Panel (b) shows the correspondent axial slice of JHU digital white matter atlas with left side average diffusion weighted image and right side color-encoded DTI map. As an example, by transforming the labeling of GCC from the atlas (b) to (a), the GCC voxels are in yellow (c) averaged FA value at the skeleton voxels covered by yellow in (c) is used to represent FA of this tract. GCC, genu of the corpus callosum; ACR, anterior corona radiata; EC, external capsule; PLIC, posterior limb of internal capsule; RLIC, retrolenticular limb of internal capsule; PTR, posterior thalamic radiation; SCC, splenium of the corpus callosum; CgC, cingulate cortex; SLF, superior longitudinal fasciculus; FX, fornix; ALIC, anterior limb of internal capsule.

Figure 2

The significant clusters obtained from voxel-wise comparisons between control and high-risk groups. Green color indicates white matter skeletons, and red color shows clusters with significant FA reduction in the high-risk group (p<0.001). Underlying gray scale images are the averaged FA maps, depicting different tracts. The left, middle, and right columns of each panel show the images of axial, coronal, and sagittal views, respectively. White arrows indicate clusters of the specified white matter tracts in the left cerebral hemisphere if multiple clusters are shown in the image. FA, fractional anisotropy; CG-L, left cingulate, SLF-L, left superior longitudinal fasciculus; SCC, splenium of the corpus callosum; UNC-IFO-L, left uncinate-inferior fronto-occipital fasciculus.