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Pediatric PTSD is characterized by age- and sex-related abnormalities in structural connectivity

Abstract

Pediatric post-traumatic stress disorder (pPTSD) is a prevalent and pervasive form of mental illness comprising a disparate constellation of psychiatric symptoms. Emerging evidence suggests that pPTSD may be characterized by alterations in functional networks traversing the brain. Yet, little is known about pathological changes in the structural tracts underlying functional connectivity. In adults, PTSD is linked to widespread change in white matter integrity throughout the brain, yet similar studies with youth populations have yet to be conducted. Current understanding of the nature and treatment of pPTSD may be enhanced by examining alterations in white matter, while further untangling effects of age and sex. Here, we assess the microstructure of 12 major white matter tracts in a sample of well-phenotyped youth with PTSD. Measures of fractional anisotropy were derived from diffusion tensor images acquired from 82 unmediated youth (ages 8–18), of whom 39 met criteria for pPTSD. Diagnosis of pPTSD was linked to remarkable age- and sex-linked differences in the microstructure of major white matter tracts including the uncinate fasciculus, cingulum bundle, and inferior longitudinal fasciculus. In each case, youth with PTSD show an absence of increased white matter integrity with age, suggesting an altered pattern of neurodevelopment that may contribute to persistence or worsening of illness. Broadly, our results suggest abnormal white matter development in pediatric PTSD, a finding which may contribute to illness persistence, comorbidity with other disorders, and poorer prognosis across time. Critically, these findings further speak to the nature of pPTSD as a ‘whole-brain’ disorder.

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Fig. 1: Effect of pPTSD diagnosis on fractional anisotropy across age and sex.
Fig. 2: Johnson-Neyman Plots of Developmental Periods of Significance.

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JDR conceptualized the work, conducted the primary analyses, drafted and critically revised the paper. SAH acquired the data and provided critical revisions. DCD provided analytical tools, assisted in processing the data, and reviewed an initial draft of this work. RJH led the design of the original study, guided data acquisition, and interpretation, aided in analysis, and provided critical revisions to the paper. All authors provided final approval of the version published.

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Correspondence to Ryan J. Herringa.

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Russell, J.D., Heyn, S.A., Dean, D.C. et al. Pediatric PTSD is characterized by age- and sex-related abnormalities in structural connectivity. Neuropsychopharmacol. (2021). https://doi.org/10.1038/s41386-021-01083-6

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