Citation

Wong SA, Lebois LAM, Ely TD, van Rooij SJH, Bruce SE, Murty VP, Jovanovic T, House SL, Beaudoin FL, An X, Zeng D, Neylan TC, Clifford GD, Linnstaedt SD, Germine LT, Bollen KA, Rauch SL, Haran JP, Storrow AB, Lewandowski C, Musey PIJ, Hendry PL, Sheikh S, Jones CW, Punches BE, Kurz MC, Swor RA, Hudak LA, Pascual JL, Seamon MJ, Pearson C, Peak DA, Merchant RC, Domeier RM, Rathlev NK, O'Neil BJ, Sergot P, Sanchez LD, Miller MW, Pietrzak RH, Joormann J, Barch DM, Pizzagalli DA, Harte SE, Elliott JM, Kessler RC, Koenen KC, McLean SA, Ressler KJ, Stevens JS, Harnett NG. Mol. Psychiatry 2023; ePub(ePub): ePub.

Copyright

(Copyright © 2023, Nature Publishing Group)

DOI

10.1038/s41380-023-02012-3

PMID

36932158

Abstract

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.

Language: en