White matter abnormalities in adolescents with major depressive disorder.

The purpose of this study was to identify areas of abnormal white matter microstructure in adolescents with Major Depressive Disorder (MDD) using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values representing preferential diffusivity along major tracts were examined using tract-based spatial statistics across the whole brain in adolescents ages 13-19 with MDD (n = 31) compared with demographically-matched healthy controls (n = 31). We not only examined frontal lobe tracts that have been most frequently identified as abnormal in previous DTI studies of older depressed patients, but also tested for FA group differences across the whole brain to determine if adolescent depression was related to any other regional white matter abnormality. MDD-diagnosed adolescents had significantly lower FA in many regions concentrated predominantly in the frontal lobe. There also was strong evidence for lower FA in bilateral anterior/posterior limbs of the internal capsules, as well as tracts through the midbrain, left external capsule, right thalamic radiation and left inferior longitudinal fasciculus. Consistent with previous findings in depressed young and elderly adults, the current study found evidence for abnormal microstructure in white matter connections of the frontal lobe in MDD adolescents. There also was strong evidence for FA abnormalities in corpus callosum genu, internal and external capsule tracts, thalamus and midbrain, notable for both the relative magnitude of these effects and absence from most previous white matter studies of depression. These abnormalities might represent important markers of early life-onset depression.