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Anxious/depressed symptoms are related to microstructural maturation of white matter in typically developing youths

  • Matthew D. Albaugh (a1), Simon Ducharme (a2), Sherif Karama (a2), Richard Watts (a1), John D. Lewis (a2), Catherine Orr (a1), Tuong-Vi Nguyen (a2), Robert C. Mckinstry (a3), Kelly N. Botteron (a3), Alan C. Evans (a2), James J. Hudziak (a1) and The Brain Development Cooperative Group...


There are multiple recent reports of an association between anxious/depressed (A/D) symptomatology and the rate of cerebral cortical thickness maturation in typically developing youths. We investigated the degree to which anxious/depressed symptoms are tied to age-related microstructural changes in cerebral fiber pathways. The participants were part of the NIH MRI Study of Normal Brain Development. Child Behavior Checklist A/D scores and diffusion imaging were available for 175 youths (84 males, 91 females; 241 magnetic resonance imagings) at up to three visits. The participants ranged from 5.7 to 18.4 years of age at the time of the scan. Alignment of fractional anisotropy data was implemented using FSL/Tract-Based Spatial Statistics, and linear mixed model regression was carried out using SPSS. Child Behavior Checklist A/D was associated with the rate of microstructural development in several white matter pathways, including the bilateral anterior thalamic radiation, bilateral inferior longitudinal fasciculus, left superior longitudinal fasciculus, and right cingulum. Across these pathways, greater age-related fractional anisotropy increases were observed at lower levels of A/D. The results suggest that subclinical A/D symptoms are associated with the rate of microstructural development within several white matter pathways that have been implicated in affect regulation, as well as mood and anxiety psychopathology.


Corresponding author

Address correspondence and reprint requests to: Matthew D. Albaugh, Vermont Center for Children, Youth and Families, University of Vermont College of Medicine, University Health Center Campus, 1 South Prospect Street, Burlington, VT 05401; E-mail:


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This project was funded in whole or in part with federal funds from the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Neurological Disorders and Stroke (Contract Numbers N01-HD02-3343, N01-MH9-0002, N01-NS-9-2314, N01-NS-9-2315, N01-NS-9-2316, N01-NS-9-2317, N01-NS-9-2319, and N01-NS-9-2320). Key personnel from the six pediatric study centers may be found online at Dr. Albaugh is funded by a grant from the Child and Adolescent Psychology Training and Research Foundation, Dr. Ducharme has received funding from the Fonds de Recherche du Québec-Santé and the Montreal General Hospital Foundation, and Dr. Karama is supported by the Fonds de Recherche en Santé du Québec. The authors report no biomedical financial interests or potential conflicts of interest related to this article. The views herein do not necessarily represent the official views of the National Institute of Child Health and Human Development, the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institutes of Health, the US Department of Health and Human Services, or any other agency of the United States government.



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