Background: The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus’ functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0 . Methods: Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability. Results: After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl – T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure. Conclusion: Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).

Objective: Prior trauma history is a reliable and robust risk predictor for PTSD development. Obtaining an accurate measurement of prior trauma history is critical in research of trauma-related outcomes. The Life Events Checklist (LEC) is a widely used self-report measure of trauma history that categorizes events by the proximity to trauma exposure; however, the field has published multiple scoring methods when assessing the LEC. Herein, we propose a novel scoring procedure in which total scores from the LEC are weighted according to the proximity of trauma exposure with "experienced" events weighted most and "learned about" events weighted least. Method: The utility of this weighted score was assessed in two traumatically-injured civilian samples and compared against previously published scoring methods, including a nonweighted score including all events experienced, witnessed, and learned about, as well as a score consisting of only experienced events. Results: Results indicated the standard total score was most reliable, followed by the weighted score. The experienced events score was least reliable, but the best predictor of future PTSD symptoms. Conclusions: One method to balance the predictive strength of experienced events and the excellent reliability of a total LEC score, is to adopt the newly proposed weighted score. Future use of this weighted scoring method can provide a comprehensive estimate of lifetime trauma exposure while still emphasizing the direct proximity of experienced events compared with other degrees of exposure. Clinical Impact StatementThe Life Events Checklist (LEC) is a widely used self-report measure of trauma history that categorizes events by the proximity of trauma exposure; however, the field has published multiple scoring methods for the LEC. We proposed a novel scoring procedure in which total scores are weighted according to the proximity of trauma exposure with "experienced" events weighted most and "learned about" events weighted least. Results assessed in two traumatically injured civilian samples indicated the weighted score is reliable and valid. Future utilization of this scoring method will provide a comprehensive estimate of lifetime trauma while emphasizing proximity of trauma exposure.

Nearly 14 percent of Americans live in a socioeconomically disadvantaged neighborhood. Lower individual socioeconomic position (iSEP) has been linked to increased exposure to trauma and stress, as well as to alterations in brain structure and function; however, the neural effects of neighborhood SEP (nSEP) factors, such as neighborhood disadvantage, are unclear. Using a multi-modal approach with participants who recently experienced a traumatic injury ( N = 185), we investigated the impact of neighborhood disadvantage, acute post-traumatic stress symptoms, and iSEP on brain structure and functional connectivity at rest. After controlling for iSEP, demographic variables, and acute PTSD symptoms, nSEP was associated with decreased volume and alterations of resting-state functional connectivity in structures implicated in affective processing, including the insula, ventromedial prefrontal cortex, amygdala, and hippocampus. Even in individuals who have recently experienced a traumatic injury, and after accounting for iSEP, the impact of living in a disadvantaged neighborhood is apparent, particularly in brain regions critical for experiencing and regulating emotion. These results should inform future research investigating how various levels of socioeconomic circumstances may impact recovery after a traumatic injury as well as policies and community-developed interventions aimed at reducing the impact of socioeconomic stressors.

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Posttraumatic stress disorder is a heterogeneous disorder with disturbances in hyperarousal or avoidance behaviors and intrusive or reexperiencing thoughts. The uncinate fasciculus and cingulum bundle are white matter pathways implicated in stress and trauma pathophysiology, yet their structural integrity related to posttraumatic stress disorder symptom domains is yet to be understood. Forty-four trauma-exposed young adults underwent structural and diffusion-weighted magnetic resonance imaging. Stress and trauma exposure indices and severity of posttraumatic stress disorder symptoms were collected and used to predict current integrity of the uncinate fasciculus and cingulum bundle. Severity of reexperiencing posttraumatic stress disorder symptoms was significantly related to increased fractional anisotropy (r ¼.469 p < .001) and decreased mean diffusivity (r ¼ À.373, p ¼ .013) of the right posterior cingulum bundle. No other findings emerged with respect to stress exposure or of hyperarousal (p's > 0.05) or avoidance (p's > 0.2) posttraumatic stress disorder symptoms. The posterior cingulum connects medial temporal lobe structures with visual areas in the occipital lobe and has been implicated in visual memory and self-referential thought. Increased structural connectivity along this pathway may therefore explain the emergence of reexperiencing posttraumatic stress disorder symptoms. This along with the lack of results with respect to stress exposure suggests that structural aberrations in white matter pathways are more strongly linked with the actual experience of stress-related psychological symptoms than just exposure to stress.