Abnormal Prefrontal Development in Pediatric Posttraumatic Stress Disorder: A Longitudinal Structural and Functional
Sara A Heyn1, Taylor J Keding2, Marisa C Ross2
1Neuroscience and Public Policy Program, University of Wisconsin-Madison, Madison, Wisconsin; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin.
Background:
Prior studies of pediatric posttraumatic stress disorder (PTSD) have reported cross-sectional and age-related structural and functional brain abnormalities in networks associated with cognitive, affective, and self-referential processing. However, no reported studies have comprehensively examined longitudinal gray matter development and its intrinsic functional correlates in pediatric PTSD.
Methods:
Twenty-seven youths with PTSD and 21 nontraumatized typically developing (TD) youths were assessed at baseline and 1-year follow-up. At each visit, youths underwent structural magnetic resonance imaging and resting-state functional magnetic resonance imaging. Regions with volumetric abnormalities in whole-brain structural analyses were identified and used as seeds in exploratory intrinsic connectivity analyses.
Results:
Youths with PTSD exhibited sustained reductions in gray matter volume (GMV) in right ventromedial prefrontal cortex (PFC) and bilateral ventrolateral PFC. Group-by-time analyses revealed aberrant longitudinal development in dorsolateral PFC, where typically developing youths exhibited normative decreases in GMV between baseline and follow-up, and youths with PTSD showed increases in GMV. Using these regions as seeds, patients with PTSD exhibited atypical longitudinal decreases in intrinsic PFC-amygdala and PFC-hippocampus connectivity, in contrast to increases in typically developing youths. Specifically, youths with PTSD showed decreasing ventromedial PFC-amygdala connectivity as well as decreasing ventrolateral PFC-hippocampus connectivity over time. Notably, volumetric abnormalities in ventromedial PFC and ventrolateral PFC were predictive of symptom severity.
Conclusions:
These findings represent novel longitudinal volumetric and connectivity changes in pediatric PTSD. Atypical prefrontal GMV and prefrontal-amygdala/hippocampus development may underlie persistence of PTSD in youths and could serve as future therapeutic targets.
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