title: White matter correlates of adolescent depression: structural evidence for frontolimbic disconnectivity.
abstract: OBJECTIVE
  Despite the significant prevalence of adolescent depression, little is known about the neuroanatomical basis of this disorder. Functional dysregulation in frontolimbic circuitry has been suggested as a key neural correlate of adult and adolescent depression impeding emotional regulation. However, less is known about whether this dysregulation is overlaid on impaired white matter microstructure. Guided by neuroimaging findings, we test the a priori hypotheses that adolescent depression is associated with alterations in white matter microstructure in the uncinate fasciculus (UF) and cingulum bundles.
  
  
  METHODS
  Diffusion tensor magnetic resonance imaging (DTI) data were obtained on 52 unmedicated adolescents with major depressive disorder (MDD) and 42 matched controls. We calculated fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) for bilateral UF and cingulum. We also completed a voxelwise comparison of participants with depression and control participants using tract-based spatial statistics (TBSS).
  
  
  RESULTS
  Adolescents with depression had significantly lower FA and higher RD in bilateral UF; no significant differences were observed in cingulum. TBSS results additionally revealed lower FA values in the white matter associated with the limbic-cortical-striatal-thalamic circuit, corpus callosum, and anterior and superior corona radiata.
  
  
  CONCLUSIONS
  Unmedicated adolescent depression is associated with reduced fractional anisotropy in emotion regulatory networks, which may underlie the functional differences in frontolimbic circuitry characterizing depressive disorder. Given the relatively recent onset of depression in our sample, our findings in the context of the current literature provide preliminary evidence that reduced fractional anisotropy in the UF could be a predisposing risk factor for depression.
authors: University of California, San Francisco (UCSF). Electronic address: kaja.lewinn@ucsf.edu.
authors: Kaja Z
authors: KZ
authors: LeWinn
authors: University of California, San Francisco (UCSF).
authors: Colm G
authors: CG
authors: Connolly
authors: University of California, San Francisco (UCSF).
authors: Jing
authors: J
authors: Wu
authors: University of California, San Francisco (UCSF).
authors: Miroslav
authors: M
authors: Drahos
authors: University of California, San Francisco (UCSF).
authors: Fumiko
authors: F
authors: Hoeft
authors: University of California, San Francisco (UCSF).
authors: Tiffany C
authors: TC
authors: Ho
authors: University of California, San Diego (UCSD).
authors: Alan N
authors: AN
authors: Simmons
authors: University of California, San Francisco (UCSF).
authors: Tony T
authors: TT
authors: Yang
mesh_terms: D000293:Adolescent; D016880:Anisotropy; D003865:Major Depressive Disorder / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000473:pathology*; D009483:Neuropsychological Tests; D013223:Statistics as Topic; D066127:White Matter / Q000473:pathology*
keywords: Adolescent major depression; diffusion tensor imaging; emotion regulation; uncinate fasciculus; white matter