Impaired frontal-limbic white matter maturation in children at risk for major depression

Yuwen Hung, Zeynep M. Saygin, Joseph Biederman, Dina Hirshfeld-Becker, Mai Uchida, Oliver Doehrmann, Michelle Han, Xiaoqian J. Chai, Tara Kenworthy, Pavel Yarmak, Schuyler L. Gaillard, Susan Whitfield-Gabrieli, John D.E. Gabrieli

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Depression is among the most common neuropsychiatric disorders. It remains unclear whether brain abnormalities associated with depression reflect the pathological state of the disease or neurobiological traits predisposing individuals to depression. Parental history of depression is a risk factor that more than triples the risk of depression. We compared white matter (WM) microstructure cross-sectionally in 40 children ages 8-14 with versus without parental history of depression (At-Risk vs. Control). There were significant differences in age-related changes of fractional anisotropy (FA) between the groups, localized in the anterior fronto-limbicWM pathways, including the anterior cingulum and the genu of the corpus callosum. Control children exhibited typical increasing FA with age, whereas At-Risk children exhibited atypical decreasing FA with age in these fronto-limbic regions. Furthermore, dorsal cingulate FA significantly correlated with depressive symptoms for At-Risk children. The results suggest maturationalWM microstructure differences in mood-regulatory neurocircuitry that may contribute to neurodevelopmental risk for depression. The study provides new insights into neurodevelopmental susceptibility to depression and related disabilities that may promote early preventive intervention approaches.

Original languageEnglish (US)
Pages (from-to)4478-4491
Number of pages14
JournalCerebral Cortex
Issue number9
StatePublished - 2017
Externally publishedYes


  • Anterior cingulate
  • Diffusion tensor imaging
  • Frontal-limbic connectivity
  • Major depression

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Impaired frontal-limbic white matter maturation in children at risk for major depression'. Together they form a unique fingerprint.

Cite this