Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure
Authors: Wong Samantha A. , Lebois Lauren A. M. , Ely Timothy D. , van Rooij Sanne J. H. , Bruce Steven E. , Murty Vishnu P. , Jovanovic Tanja , House Stacey L. , Beaudoin Francesca L. , An Xinming , Zeng Donglin , Neylan Thomas C. , Clifford Gari D. , Linnstaedt Sarah D. , Germine Laura T. , Bollen Kenneth A. , Rauch Scott L. , Haran John P. , Storrow Alan B. , Lewandowski Christopher , Musey Paul I. , Hendry Phyllis L. , Sheikh Sophia , Jones Christopher W. , Punches Brittany E. , Kurz Michael C. , Swor Robert A. , Hudak Lauren A. , Pascual Jose L. , Seamon Mark J. , Pearson Claire , Peak David A. , Merchant Roland C. , Domeier Robert M. , Rathlev Niels K. , O’Neil Brian J. , Sergot Paulina , Sanchez Leon D. , Miller Mark W. , Pietrzak Robert H. , Joormann Jutta , Barch Deanna M. , Pizzagalli Diego A. , Harte Steven E. , Elliott James M. , Kessler Ronald C. , Koenen Karestan C. , McLean Samuel A. , Ressler Kerry J. , Stevens Jennifer S. , Harnett Nathaniel G. 
Published: March 2023

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [−0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.