Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.

Importance Differences 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. Objective To 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 Participants In 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. Exposure Neighborhood disadvantage was measured with the Area Deprivation Index (ADI) for each participant home address. Main Outcomes and Measures Participants 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. Results A 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 < .001). Conclusions and Relevance In 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.

Background: Higher subjective social status (SSS) or a person’s perception of their social standing is related to better health outcomes, but few studies examined SSS in relation to obesity. Emotional eating and food addiction have been linked to obesity. Some studies indicated that manipulating SSS may lead to altered food intake, but the relationship between SSS and dysregulated eating, such as emotional eating and food addiction (FA), has not been examined. The goal of this study was to examine the associations between SSS in the community and the larger society, dysregulated eating (emotional eating and FA), and body mass index (BMI) in a majority racial minority sample. Methods: The participants (N = 89; 93% Black, 86% women, and 56% with obesity; 72% income lower than USD 2000), recruited from a publicly funded hospital in Atlanta, GA, completed the MacArthur Scale, Dutch Eating Behaviors Questionnaire, Yale Food Addiction Scale, Beck Depression Inventory, PTSD Symptom Checklist, and demographics questionnaire. Results: Twentytwo percent of the sample met the criteria for FA; those with FA had significantly higher BMI than those without (p = 0.018). In the hierarchical linear regression, the SSS community (but not in society) predicted higher severity of emotional eating (β = 0.26, p = 0.029) and FA (β = 0.30, p = 0.029), and higher BMI (β = 0.28, p = 0.046), independent from depression and PTSD symptoms. Conclusions: The findings indicate that, among Black individuals with predominantly low income in the U.S., perceived role in their community is associated with eating patterns and body mass. Given the small sample size, the results should be interpreted with caution.

Hippocampal structure is particularly sensitive to trauma and other stressors. However, previous findings linking hippocampal function with trauma-related psychopathology have been mixed. Heterogeneity in psychological responses to trauma has not been considered with respect to hippocampal function and may contribute to mixed findings. To address these issues, we examined associations between data-driven symptom dimensions and episodic memory formation, a key function of the hippocampus, in a trauma-exposed sample. Symptom dimensions were defined using principal components analysis (PCA) in 3881 trauma-exposed African-American women recruited from primary care waiting rooms of a large urban hospital. Hippocampal and amygdala function were subsequently investigated in an fMRI study of episodic memory formation in a subset of 54 women. Participants viewed scenes with neutral, negative, and positive content during fMRI, and completed a delayed cued recall task. PCA analysis produced five symptom dimensions interpreted as reflecting negative affect, somatic symptoms, re-experiencing, hyper-arousal, and numbing. Re-experiencing was the only symptom type associated with hippocampal function, predicting increased memory encoding-related activation in the hippocampus as well as the amygdala. In contrast, the negative affect component predicted lower amygdala activation for subsequently recalled scenes, and lower functional coupling with other important memory-related regions including the precuneus, inferior frontal gyrus, and occipital cortex. Symptom dimensions were not related to hippocampal volume. The fMRI findings for re-experiencing versus negative affect parallel differences in behavioral memory phenomena in PTSD versus MDD, and highlight a need for more complex models of trauma-related pathology.

Women are twice as likely than men to suffer from posttraumatic stress disorder (PTSD). While women have increased exposure to traumatic events of many types and have greater prevalence of comorbid psychiatric disorders compared to men, these differences do not account for the overall sex difference in the prevalence of PTSD. The current review summarizes significant findings that implicate the role of estradiol, progesterone, and allopregnanolone in female risk for PTSD symptoms and dysregulation of fear psychophysiology that is cardinal to PTSD. We also discuss how these steroid hormones influence the stress axis and neural substrates critical for the regulation of fear responses. Understanding the role of ovarian steroid hormones in risk and resilience for trauma-related adverse mental health outcomes across the lifespan in women has important translational, clinical, and intergenerational implications for mitigating the consequences of trauma exposure.

Anhedonia emerges in some people after psychological trauma, reflected by a loss of interest, diminished affect, and detachment. Structural abnormalities in specific neural pathways at the time of trauma may influence the development of these posttraumatic anhedonia (PTA) symptoms. In this prospective study, we determined whether white matter connectivity at around one month post-trauma predicts PTA and other PTSD symptoms at six months post-trauma. Thirty men and women aged 19–62 were recruited from the emergency department of a Level I trauma center. Participants received diffusion tensor imaging at approximately one month post-trauma and clinical assessments at one and six months post-trauma. Probabilistic tractography was used to examine connectivity of select pathways. A replication sample (N = 57) in an independent, cross-sectional dataset of traumatized women was similarly analyzed. Logistic regression results indicated that, after accounting for early PTSD symptoms (at one month) and other clinical risk factors, the integrity of the uncinate fasciculus (UF) uniquely predicted the presence of PTA at six months post-trauma (Beta = −225.6, p < .05). Together, these factors contributed to 76% of the variance in PTA. Integrity of the UF also predicted re-experiencing PTSD symptoms at six months post-trauma. These results were supported in our replication analyses. Our findings indicate that the integrity of the UF around 1 month post-trauma affects vulnerability for the development of anhedonic PTSD symptoms as well as re-experiencing symptoms. Connectivity of this amygdala-ventromedial prefrontal pathway appears to be a salient predictor of anhedonia, above and beyond clinical risk factors.

Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n = 62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n = 37) and PTSD+ (n = 25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p < 0.05). However, only PTSD- control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p's ≤ 0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (p < 0.001). These data suggest that dexamethasone may serve as a pharmacological agent with which to facilitate fear extinction and discrimination in individuals with PTSD.

In this study, we considered connections between the content of immediate trauma narratives and longitudinal trajectories of negative symptoms to address questions about the timing and predictive value of collected trauma narratives. Participants (N = 68) were individuals who were admitted to the emergency department of a metropolitan hospital and provided narrative recollections of the traumatic event that brought them into the hospital that day. They were then assessed at intervals over the next 12 months for depressive and posttraumatic symptom severity. Linguistic analysis identified words involving affect (positive and negative emotions), sensory input (sight, sound, taste, touch, and smell), cognitive processing (thoughts, insights, and reasons), and temporal focus (past, present, and future) within the narrative content. In participants’ same-day narratives of the trauma, past-focused utterances predicted greater decreases in depressive symptom severity over the next year, d = −0.13, whereas cognitive process utterances predicted more severe posttraumatic symptom severity across time points, d = 0.32. Interaction analyses suggested that individuals who used fewer past-focused and more cognitive process utterances within their narratives tended to report more severe depressive and posttraumatic symptom severity across time, ds = 0.31 to 0.34. Overall, these findings suggest that, in addition to other demographics and baseline symptom severity, early narrative content can serve as an informative marker for longitudinal psychological symptoms, even before extensive narrative processing and phenomenological meaning-making have occurred.

Background: Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. Method: Adult subjects (N = 2229; 56.2% male) aged 18–69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA-PGC PTSD sites underwent T1-weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel-wise (brainageR) and region-of-interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age − chronological age) controlling for chronological age, sex, and scan site. Results: BrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three-way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages. Discussion: Differential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age-related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan.

Background: Moral injury (MI) describes emotional, spiritual, and social suffering that can arise following psychological trauma. Prior research in military pop ulations indicates the relevance of MI to adverse psychological outcomes, such as post-traumatic stress disorder (PTSD) and suicidal behaviours, and shows evidence for MI as a unique construct. Minimal studies of MI have been implemented in civilians, usually restricted to small samples with a specific set of traumatic experiences, despite the conceptual relevance of MI to non-military trauma reactions more broadly (e.g. feelings of betrayal towards a perpetrator of sexual abuse). Objective: To address this problem, we assessed MI in trauma-exposed civilians to examine ways in which this construct was related to and distinct from trauma and traumatic stress-related problems, including PTSD and depression. Method: We adapted an existing MI scale, Moral Injury Events Scale (MIES) and administered this measure to 81 men and women along with measures of trauma exposure, PTSD and depression, and also asked participants about past suicide attempts. Results: We observed that both greater exposure and distress related to potentially morally injurious events were associated with higher trauma exposure, particularly childhood maltreatment, as well as post-traumatic and depressive psychopathology. However, even after accounting for current PTSD and depression symptoms, MI exposure (F = 6.05, p = .017) was significantly higher among participants who had previously attempted suicide. Conclusions: These pilot data reveal the ways in which MI is associated with trauma exposure, PTSD and depression and highlight the salience of MI in civilians. Similarly, these data demonstrate the unique relevance of MI to suicide behaviours, independent of post-traumatic psychopathology, indicating that this construct may be an understudied contributor to suicide risk in civilians.