Altered white-matter architecture in treatment-naive adolescents with clinical depression

• Published in: Psychological medicine 2014-08, Vol.44 (11), p.2287-2298
• Main Authors: Aghajani, M., Veer, I. M., van Lang, N. D. J., Meens, P. H. F., van den Bulk, B. G., Rombouts, S. A. R. B., Vermeiren, R. R. J. M., van der Wee, N. J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Adult and adolescent clinical studies; Architecture; Biological and medical sciences; Brain; Child & adolescent psychiatry; Depression; Depressive Disorder - pathology; Diffusion Tensor Imaging; Emotional wellbeing; Female; Humans; Male; Medical sciences; Mental depression; Miscellaneous; Mood disorders; Neural Pathways - pathology; Neuropsychology; Original Articles; Pathophysiological aspects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; White Matter - pathology
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291713003000

Depressive disorders are highly prevalent in adolescence and confer a heightened risk of recurrence in adulthood. Insight into the developmental neurocircuitry of depression could advance our understanding of depression and aid the development of effective treatment strategies. Whereas white-matter (WM) abnormalities are strongly implicated in adult depression, we still lack a firm understanding of WM architecture in adolescent depression. Using diffusion tensor imaging (DTI), we set out to investigate WM microstructure in a sample of clinically depressed adolescents relative to matched controls. We employed tract-based spatial statistics (TBSS) to examine WM microstructure in 25 treatment-naive adolescents with clinical depression relative to 21 matched controls. Using TBSS, we examined fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD). Threshold-free cluster enhancement (TFCE) with family-wise error (FWE) correction was used to control for multiple comparisons. Our analysis revealed abnormal WM microstructure in clinically depressed adolescents. More specifically, whole-brain analysis revealed that patients had lower FA values in the body of the corpus callosum (CC), coupled with elevated RD and MD, and preserved AD. Conversely, region-of-interest analysis revealed that patients had higher FA values in the uncinate fasciculus (UF), coupled with elevated AD, reduced RD and preserved MD. In line with neurocircuitry models of depression, our findings suggest that WM abnormalities within pathways facilitating cognitive and emotional functioning are involved in the pathophysiology of depression. Importantly, our findings show that these WM abnormalities are already present early in the course of the disorder.