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Cereb Cortex. 2017 Sep 1;27(9):4478-4491. doi: 10.1093/cercor/bhw250.

Impaired Frontal-Limbic White Matter Maturation in Children at Risk for Major Depression.

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McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, MA 02114, USA.
Psychology and Neuroscience, University of Toronto, Toronto, Canada, ON M5S 1A1.
Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
Institute for Medical Engineering and Science, MIT, Cambridge, MA 02139, USA.


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-limbic WM 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 maturational WM 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.


anterior cingulate; diffusion tensor imaging; frontal–limbic connectivity; major depression

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