Acute White Matter Integrity Post-trauma and Prospective Posttraumatic Stress Disorder Symptoms

Weis, Carissa; Huggins, Ashley A.; Miskovich, Tara A.; Fitzgerald, Jacklynn M.; Bennett, Kenneth P.; Krukowski, Jessica; Webb, E. Kate; deRoon‐Cassini, Terri; Larson, Christine L.

doi:10.3389/fnhum.2021.742198

Cited by 8 publications

(8 citation statements)

References 72 publications

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“…Of note, we did not observe effects in canonical threat circuitry often associated with PTSD. Past studies have not typically considered childhood maltreatment when evaluating white matter markers of PTSD susceptibility [15][16][17][18], and it is possible that reduced IC FA may be a sequela of childhood maltreatment exposure. Moreover, although we analyzed imaging data from over 200 participants, we could have been underpowered to detect all effects with our unbiased whole-brain analytic approach.…”

Section: Discussionmentioning

confidence: 99%

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure

et al. 2023

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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.

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Section: Discussionmentioning

confidence: 99%

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure

et al. 2023

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“…However, PTSD was associated with reductions in CGC integrity, whereas neighborhood disadvantage was not. Prior work has suggested that lesser integrity of the CGC was associated with greater psychophysiological responses to threatening cues and lesser integrity is prospectively associated with future PTSD symptoms . Future directions may include evaluating the association between structure and function in populations with chronic PTSD symptoms to investigate whether this outcome is timing specific.…”

Section: Discussionmentioning

confidence: 99%

Neighborhood Disadvantage and Neural Correlates of Threat and Reward Processing in Survivors of Recent Trauma

Webb,

Ely,

Rowland

et al. 2023

JAMA Netw Open

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ImportanceDifferences in neighborhood socioeconomic characteristics are important considerations in understanding differences in risk vs resilience in mental health. Neighborhood disadvantage is associated with alterations in the function and structure of threat neurocircuitry.ObjectiveTo investigate associations of neighborhood disadvantage with white and gray matter and neural reactivity to positive and negative stimuli in the context of trauma exposure.Design, Setting, and ParticipantsIn this cross-sectional study, survivors of trauma who completed sociodemographic and posttraumatic symptom assessments and neuroimaging were recruited as part of the Advancing Understanding of Recovery After Trauma (AURORA) study between September 2017 and June 2021. Data analysis was performed from October 25, 2022, to February 15, 2023.ExposureNeighborhood disadvantage was measured with the Area Deprivation Index (ADI) for each participant home address.Main Outcomes and MeasuresParticipants completed separate threat and reward tasks during functional magnetic resonance imaging. Diffusion-weighted and high-resolution structural images were also collected. Linear models assessed the association of ADI with reactivity, microstructure, and macrostructure of a priori regions of interest after adjusting for income, lifetime trauma, sex at birth, and age. A moderated-mediation model tested whether ADI was associated with neural activity via microstructural changes and if this was modulated by PTSD symptoms.ResultsA total of 280 participants (183 females [65.4%]; mean [SD] age, 35.39 [13.29] years) completed the threat task and 244 participants (156 females [63.9%]; mean [SD] age, 35.10 [13.26] years) completed the reward task. Higher ADI (per 1-unit increase) was associated with greater insula (t274 = 3.20; β = 0.20; corrected P = .008) and anterior cingulate cortex (ACC; t274 = 2.56; β = 0.16; corrected P = .04) threat-related activity after considering covariates, but ADI was not associated with reward reactivity. Greater disadvantage was also associated with altered microstructure of the cingulum bundle (t274 = 3.48; β = 0.21; corrected P = .001) and gray matter morphology of the ACC (cortical thickness: t273 = −2.29; β = −0.13; corrected P = .02; surface area: t273 = 2.53; β = 0.13; corrected P = .02). The moderated-mediation model revealed that ADI was associated with ACC threat reactivity via cingulum microstructural changes (index of moderated mediation = −0.02). However, this mediation was only present in individuals with greater PTSD symptom severity (at the mean: β = −0.17; standard error = 0.06, t= −2.28; P = .007; at 1 SD above the mean: β = −0.28; standard error = 0.08; t = −3.35; P &lt; .001).Conclusions and RelevanceIn this study, neighborhood disadvantage was associated with neurobiology that supports threat processing, revealing associations of neighborhood disadvantage with neural susceptibility for PTSD and suggesting how altered structure-function associations may complicate symptoms. Future work should investigate specific components of neighborhood disadvantage that may be associated with these outcomes.

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“…The second sample was derived from another large longitudinal study, independent from Sample A, that was designed to identify acute posttrauma risk factors for PTSD development in adults using biospecimen, self‐report measures, cognitive and behavioral assessments, and neuroimaging (i.e., Bird et al., 2021; Webb, Weis, Huggins, Fitzgerald, et al., 2021; Webb, Weis, Huggins, Parisi, et al., 2021; Weis et al., 2021, 2022). Enrolled participants were recruited after being discharged from the ED after a single‐incident traumatic injury (86.0% nonassaultive, 14.0% assaultive trauma) and completed seven study visits.…”

Section: Methodsmentioning

confidence: 99%

Machine learning prediction of posttraumatic stress disorder trajectories following traumatic injury: Identification and validation in two independent samples

Tomas

Fitzgerald

Bergner

et al. 2022

Journal of Traumatic Stress

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Due to its heterogeneity, the prediction of posttraumatic stress disorder (PTSD) development after traumtic injury is difficult. Recent machine learning approaches have yielded insight into predicting PTSD symptom trajectories. Using data collected within 1 month of traumatic injury, we applied eXtreme Gradient Boosting (XGB) to classify admitted and discharged patients (hospitalized, n = 192; nonhospitalized, n = 214), recruited from a Level 1 trauma center, according to PTSD symptom trajectories. Trajectories were identified using latent class mixed models on PCL-5 scores collected at baseline, 1-3 months posttrauma, and 6 months posttrauma. In both samples, nonremitting, remitting, and resilient PTSD symptom trajectories were identified. In the admitted patient sample, a unique delayed trajectory emerged. Machine learning classifiers (i.e., XGB)were developed and tested on the admitted patient sample and externally validated on the discharged sample with biological and clinical self-report baseline variables as predictors. For external validation sets, prediction was fair for nonremitting versus other trajectories, areas under the curve (AUC = .70); good for nonremitting versus resilient trajectories, AUCs = .73-.76; and prediction failed for nonremitting versus remitting trajectories, AUCs = .46-.48. However, poor precision (< .57) across all models suggests limited generalizability of nonremitting symptom trajectory prediction from admitted to discharged patient samples. Consistency in symptom trajectory identification across samples supports prior studies on the stability of PTSD symptom trajectories following trauma exposure; however, continued work and replication with larger samples are warranted to understand overlapping and unique predictive features of PTSD in different traumatic injury populations.

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Acute White Matter Integrity Post-trauma and Prospective Posttraumatic Stress Disorder Symptoms

Cited by 8 publications

References 72 publications

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure

Neighborhood Disadvantage and Neural Correlates of Threat and Reward Processing in Survivors of Recent Trauma

Machine learning prediction of posttraumatic stress disorder trajectories following traumatic injury: Identification and validation in two independent samples

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