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Objective: Natural variation in ovarian steroid hormones across the female lifespan contributes to an increased risk for depressive and posttraumatic stress disorder (PTSD) symptoms in women. However, minimal work has focused on understanding the impacts of reproductive aging on the brain and behavioral health of trauma-exposed women. This systematic review examines the bidirectional relationship between trauma-related psychopathology and reproductive aging. Method: Following PRISMA guidelines, a systematic review of PubMed, PsychInfo, and Medline databases was undertaken to identify controlled studies on how trauma history impacts psychopathology and menopause symptoms during reproductive aging. Results: Twenty-one studies met the eligibility criteria, with only four utilizing the gold standard STRAW+ 10 criteria for defining reproductive aging stages. The peri and postmenopausal periods appear to be particularly vulnerable phases for individuals with trauma exposure. Menopause symptoms and trauma-related psychopathology symptom severity increase during reproductive aging with increases in the degree of trauma exposure. However, mechanistic insights that may explain this interaction are currently neglected in this area of research. Conclusion: There is a significant lack of understanding regarding how reproductive aging and its related neuroendocrine changes impact the brain to influence PTSD and depression symptoms related to trauma exposure. This lack of basic understanding impedes the ability to identify, assess, and treat PTSD and depressive symptoms in trauma-exposed women most effectively, and mitigate the long-term consequences of these behavioral health symptoms on morbidity and mortality in aging women.

Although there is an established link between smaller hippocampal volume and anxiety, the longitudinal relations between hippocampus structure and anxiety in diverse youth are not well understood. The present longitudinal study investigated hippocampal volumes related to anxiety symptoms in a sample of Black 8–14-year-old youth (N = 64), a population historically underrepresented in neuroimaging research. Smaller hippocampal volumes were associated with greater anxiety symptoms independent of age, sex, intracranial volume and trauma exposure. Exploratory longitudinal analyses showed smaller hippocampal volume as a predictor for anxiety symptoms (n = 37) and not a consequence of anxiety symptoms (n = 32), however results were inconclusive as this finding was no longer significant after correcting for baseline anxiety symptoms. Overall, this data increases our understanding of potential neurobiological mechanisms for anxiety in a high-risk sample of Black youth and suggests future directions into studying trajectories of developmental risk.

Abstract Individuals living in areas with high rates of poverty are disproportionately affected by posttraumatic stress disorder (PTSD). Despite this association, little is known about how neighborhood poverty rates impact risk for PTSD development. In the current prospective study, we determined the relationship between neighborhood poverty rate and PTSD symptoms 6‐months after experiencing a traumatic event in a sample of varied race, gender, and socioeconomic status. Participants (N = 252) were enrolled in a hospital emergency department after experiencing a traumatic event. Demographic information (including zip code of residence), baseline PTSD symptoms, and baseline trauma history was assessed in the emergency department. PTSD symptoms were again assessed 6‐months posttrauma. Neighborhood poverty rate was determined using the American Community Survey. Correlation analyses revealed that neighborhood poverty was significantly associated with baseline PTSD symptoms (r = 0.181, p = 0.004) and PTSD symptoms 6‐months posttrauma (r = 0.163, p = 0.009). A regression analysis controlling for baseline trauma exposure, clinician‐rated trauma severity, and individual socioeconomic status demonstrated that neighborhood poverty predicted PTSD symptoms six‐months posttrauma (R2 = 0.099, B = 0.15, p = 0.04), but this relationship was no longer significant when baseline PTSD symptoms was added as an additional covariate (R2 = 0.304, B = 0.07, p > 0.05). Overall, results suggest that neighborhood poverty generally increases PTSD symptom severity, and the context in which an individual lives should be considered when conceptualizing risk for PTSD.

Abstract 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.

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Abstract The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored.

IntroductionExposure to traumatic events and stressful life experiences are associated with a wide range of adverse mental and physical health outcomes. Studies have found post-traumatic stress disorder (PTSD), depression, and anxiety sensitivity occurrence to be common in addition to inflammatory diseases like asthma, especially in women. Moreover, overlapping neurobiological mechanisms have been linked to both PTSD and asthma.MethodsIn the current study, n = 508 women reported on presence of lifetime asthma diagnosis and symptoms of trauma-related psychopathology including PTSD and depression. A separate group of female participants (n = 64) reported on asthma, PTSD, depression and anxiety sensitivity, and underwent functional MRI scans during a fearful faces task, and their anterior insula responses were analyzed.ResultsOverall, PTSD and depression severity were significantly higher in those with asthma versus those without asthma. There was a positive association between anterior insula response to social threat cues and depression symptoms only among individuals without a lifetime presence of asthma.DiscussionThese findings provide continued evidence on the interactions between stress, neural mechanisms involved in interoception and salience detection, and trauma-related psychopathology.

Abstract Visual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant’s loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms.

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

Adverse social exposures (ASEs) such as low income, low educational attainment, and childhood/adult trauma exposure are associated with variability in brain region measurements of gray matter volume (GMV), surface area (SA), and cortical thickness (CT). These CNS morphometries are associated with stress-related psychiatric illnesses and represent endophenotypes of stress-related psychiatric illness development. Epigenetic mechanisms, such as 5-methyl-cytosine (5mC), may contribute to the biological embedding of the environment but are understudied and not well understood. How 5mC relates to CNS endophenotypes of psychiatric illness is also unclear. In 97 female, African American, trauma-exposed participants from the Grady Trauma Project, we examined the associations of childhood trauma burden (CTQ), adult trauma burden, low income, and low education with blood-derived 5mC clusters and variability in brain region measurements in the amygdala, hippocampus, and frontal cortex subregions. To elucidate whether peripheral 5mC indexes central nervous system (CNS) endophenotypes of psychiatric illness, we tested whether 73 brain/blood correlated 5mC clusters, defined by networks of correlated 5mC probes measured on Illumina’s HumanMethylation Epic Beadchip, mediated the relationship between ASEs and brain measurements. CTQ was negatively associated with rostral middle frontal gyrus (RMFG) SA (β =−0.231, p = 0.041). Low income and low education were also associated with SA or CT in a number of brain regions. Seven 5mC clusters were associated with CTQ (pmin = 0.002), two with low education (pmin = 0.010), and three with low income (pmin = 0.007). Two clusters fully mediated the relation between CTQ and RMFG SA, accounting for 47 and 35% of variability, respectively. These clusters were enriched for probes falling in DNA regulatory regions, as well as signal transduction and immune signaling gene ontology functions. Methylome-network analyses showed enrichment of macrophage migration (p = 9 × 10–8), T cell receptor complex (p = 6 × 10–6), and chemokine-mediated signaling (p = 7 × 10–4) pathway enrichment in association with CTQ. Our results support prior work highlighting brain region variability associated with ASEs, while informing a peripheral inflammation-based epigenetic mechanism of biological embedding of such exposures. These findings could also serve to potentiate increased investigation of understudied populations at elevated risk for stress-related psychiatric illness development.

Abstract Resilience in the face of major life stressors is changeable over time and with experience. Accordingly, differing sets of neurobiological factors may contribute to an adaptive stress response before, during, and after the stressor. Longitudinal studies are therefore particularly effective in answering questions about the determinants of resilience. Here we provide an overview of the rapidly-growing body of longitudinal neuroimaging research on stress resilience. Despite lingering gaps and limitations, these studies are beginning to reveal individual differences in neural circuit structure and function that appear protective against the emergence of future psychopathology following a major life stressor. Here we outline a neural circuit model of resilience to trauma. Specifically, pre-trauma biomarkers of resilience show that an ability to modulate activity within threat and salience networks predicts fewer stress-related symptoms. In contrast, early post-trauma biomarkers of subsequent resilience or recovery show a more complex pattern, spanning a number of major circuits including attention and cognitive control networks as well as primary sensory cortices. This novel synthesis suggests stress resilience may be scaffolded by stable individual differences in the processing of threat cues, and further buttressed by post-trauma adaptations to the stressor that encompass multiple mechanisms and circuits. More attention and resources supporting this work will inform the targets and timing of mechanistic resilience-boosting interventions.

Introduction Childhood trauma is strongly associated with fear-related psychopathology, like anxiety and posttraumatic stress disorder (PTSD). Atypical fear extinction and neural responses to social threat (i.e., negative emotional faces) may serve as intermediate phenotypes preceding the emergence of fear-related psychopathology during childhood and adolescence. However, few studies have examined associations among these phenotypes in trauma-exposed youth. Methods 29 9-year-old children with high rates of trauma exposure (Mdn = 4, min = 0, max= 14 total events) completed a fear-potentiated startle paradigm assessing fear conditioning and extinction and an emotional faces functional magnetic resonance imaging (fMRI) task assessing neural responses to fearful and neutral faces. Results Overall amygdala response was positively associated with anxiety (peak coordinates: x = −30, y = −6, z = −24; Z = 3.54; pFWE corrected = 0.011; k = 24 voxels) and fear-potentiated startle during early extinction (peak coordinates x = 28, y = −6, z = −18; Z = 3.50; pFWE corrected = 0.012; k = 19 voxels). Across the session, amygdala reactivity to fearful faces increased (F(1, 29) = 4.427, p = .044) and was positively associated with fear-potentiated startle during early extinction (r = .56, p = .002). Conclusions We found a positive association between increasing amygdala response to threatening faces and fear load, that is, heightened fear-potentiated startle during early extinction, in trauma-exposed children. These fear-based intermediate phenotypes may share underlying amygdala circuits, such that hyperactivity may represent an early marker of anxiety risk in trauma-exposed youth.

It is well-known that morphological features in the brain undergo changes due to traumatic events and associated disorders such as post-traumatic stress disorder (PTSD). However, existing approaches typically offer group-level comparisons, and there are limited predictive approaches for modeling behavioral outcomes based on brain shape features that can account for heterogeneity in PTSD, which is of paramount interest. We propose a comprehensive shape analysis framework representing brain sub-structures, such as the hippocampus, amygdala, and putamen, as parameterized surfaces and quantifying their shape differences using an elastic shape metric. Under this metric, we compute shape summaries (mean, covariance, PCA) of brain sub-structures and represent individual brain shapes by their principal scores under a shape-PCA basis. These representations are rich enough to allow visualizations of full 3D structures and help understand localized changes. In order to validate the elastic shape analysis, we use the principal components (PCs) to reconstruct the brain structures and perform further evaluation by performing a regression analysis to model PTSD and trauma severity using the brain shapes represented via PCs and in conjunction with auxiliary exposure variables. We apply our method to data from the Grady Trauma Project (GTP), where the goal is to predict clinical measures of PTSD. The framework seamlessly integrates accurate morphological features and other clinical covariates to yield superior predictive performance when modeling PTSD outcomes. Compared to vertex-wise analysis and other widely applied shape analysis methods, the elastic shape analysis approach results in considerably higher reconstruction accuracy for the brain shape and reveals significantly greater predictive power. It also helps identify local deformations in brain shapes associated with PTSD severity.

Background Inhibition is a critical executive control process and an established neurobiological phenotype of PTSD, yet to our knowledge, no prospective studies have examined this using a contextual cue task that enables measurement of behavioural response and neural activation patterns across proactive and reactive inhibition. Objective The current longitudinal study utilised functional magnetic resonance imaging (fMRI) to examine whether deficits in proactive and reactive inhibition predicted PTSD symptoms six months after trauma. Method Twenty-three (65% males) medical patients receiving emergency medical care from a level 1 trauma centre were enrolled in the study and invited for an MRI scan 1-2-months post-trauma. PTSD symptoms were measured using self-report at scan and 6-months post-trauma. A stop-signal anticipation task (SSAT) during an fMRI scan was used to test whether impaired behavioural proactive and reactive inhibition, and reduced activation in right inferior frontal gyrus (rIFG), ventromedial prefrontal cortex (vmPFC), and bilateral hippocampus, were related to PTSD symptoms. We predicted that lower activation levels of vmPFC and rIFG during reactive inhibition and lower activation of hippocampus and rIFG during proactive inhibition would relate to higher 6-month PTSD symptoms. Results No significant associations were found between behavioural measures and 6-month PTSD. Separate linear regression analyses showed that reduced rIFG activation (F1,21 = 9.97, R2 = .32, p = .005) and reduced vmPFC activation (F1,21 = 5.19, R2 = .20, p = .03) significantly predicted greater 6-month PTSD symptoms; this result held for rIFG activation controlling for demographic variables and baseline PTSD symptoms (β = −.45, p = .04) and Bonferroni correction. Conclusion Our findings suggest that impaired rIFG and, to a lesser extent, vmPFC activation during response inhibition may predict the development of PTSD symptoms following acute trauma exposure. Given the small sample size, future replication studies are needed. HIGHLIGHTS Impaired inhibition may be an important risk factor for the development of PTSD following trauma, with less right inferior frontal gyrus and ventromedial prefrontal cortex activation during response inhibition predicting PTSD development.

Abstract 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: Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning. Methods: 192 participants were recruited from emergency departments following trauma exposure (Mean age = 35.88, 68.2% female). Skin conductance was measured in the emergency department; fear conditioning was completed two weeks later and included measures of blood pressure (BP), heart rate (HR), and high frequency heart rate variability (HF-HRV). PTSD symptoms were assessed 8 weeks after trauma. Results: 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR levels. Two-week HF-HRV was significantly lower in women, and a sex by PTSD interaction suggested that women with PTSD demonstrated the lowest HF-HRV levels. Skin conductance response in the emergency department was associated with 2-week HR and HF-HRV only among women who developed PTSD. Conclusions: Our results indicate that there are notable sex differences in autonomic functioning among trauma-exposed individuals. Differences in sympathetic biomarkers (BP and HR) may have implications for cardiovascular disease risk given that sympathetic arousal is a mechanism implicated in this risk among PTSD populations. Future research examining differential pathways between PTSD and cardiovascular risk among men versus women is warranted.

Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex is indirectly associated with the probability of developing nonremitting PTSD through pro-inflammatory markers and whether steroid hormone concentrations influence this effect. Female ( n = 179) and male ( n = 197) trauma survivors were recruited from an emergency department and completed clinical assessment within 24 h and blood samples within ∼three hours of trauma exposure. Pro-inflammatory cytokines (IL-6, IL-1 β , TNF, IFNγ), and steroid hormone (estradiol, testosterone, progesterone, cortisol) concentrations were quantified in plasma. Compared to men, women had a higher probability of developing nonremitting PTSD after trauma ( p = 0.04), had lower pro-inflammatory cytokines and testosterone ( p ’ s

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study – United Kingdom Biobank – PTSD symptoms were negatively associated with SBP levels (β = −1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.

Recent research has linked early life stress (ELS), such as trauma exposure, with early puberty. Early puberty has also been identified as a risk factor for poor mental health outcomes. However, these two paths have primarily been examined independently. In addition, more studies have examined these associations in girls than boys, and findings for boys remain mixed. We hypothesized that early puberty (relative to peers) would be positively associated with both prior trauma exposure and concurrent anxiety symptoms. We anticipated that these associations might differ by sex. We tested these hypotheses within a cross-sectional sample of 133 8- to 13-year-old Black girls and boys with trauma exposure. The association between trauma and accelerated pubertal timing was sex-specific: it was positive for girls and negative for boys. We stratified subsequent analyses by sex. Regression analyses indicated that early puberty relative to peers predicted more anxiety symptoms for girls but not boys, after accounting for trauma exposure. A statistical mediation analysis indicated that, for girls, the positive association between trauma exposure and anxiety was partially mediated by pubertal timing. These results indicate that trauma exposure may have sex-specific effects on pubertal timing and anxiety risk in Black children. We also found that, for girls, trauma may increase risk for adverse outcomes by prompting earlier puberty, which is linked to higher anxiety. These findings are consistent with cascading effects of trauma across development, and highlight the need for further study of sex-specific mechanisms.

Background: Moral injury (MI) describes emotional, spiritual, and social suffering that can arise following psychological trauma. Prior research in military populations 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.

Behavioural, structural, and functional neuroimaging have implicated the hippocampus as a critical brain region in posttraumatic stress disorder (PTSD) pathogenesis. Recent work in a normative, primarily European, sample identified 15 unique genetic loci contributing to structural variability in six hippocampal subfield volumes. We explored the relevance of these loci in two samples (Mental Illness Research Education and Clinical Centre [MIRECC] and Grady; n = 290) of trauma-exposed individuals enriched for PTSD and of diverse ancestry. Four of the previous loci demonstrated nominal evidence of replication in the MIRECC dataset, primarily within non-Hispanic whites (NHW). One locus replicated in the Grady cohort, which was composed exclusively of non-Hispanic blacks (NHB). Our data supported genetic interactions with diagnosis of lifetime PTSD and genetic interactions with childhood trauma in the MIRECC sample, but not the Grady sample. Given the racial, diagnostic, and trauma-exposure differences with the original genome-wide association study (GWAS) report, we conducted a full GWAS in the MIRECC and Grady datasets. Interactions between genetic variants and lifetime PTSD or childhood trauma were interrogated for single nucleotide polymorphisms (SNPs) with evidence of main effects. Genetic associations surpassed false discovery rate (FDR)-correction within hippocampal subfields in fimbria, subiculum, cornu ammonis-1 (CA1), and hippocampal amygdala transition area (HATA). One association was replicated in the Grady cohort (rs12880795 in TUNAR with left (L)-HATA volume). The most significant association in the MIRECC dataset was between rs6906714 in LINC02571 and right (R)-fimbria volume (p = 5.99×10−8, q = 0.0056). Interestingly, the effect of rs6906714 on R-fimbria volume increased with exposure to childhood trauma (gene*environment [G*E] interaction p = 0.022). These preliminary results argue for G*E interactions between genetic loci with PTSD and childhood trauma on hippocampal phenotypes. Our results underscore the need for larger neuroimaging-genetic studies in PTSD, trauma, and ancestrally diverse populations.

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. Keywords: Trauma, Ptsd, Hippocampus, Amygdala, Episodic memory, Symptom dimensions

Background Exposure to a traumatic event leads to posttraumatic stress disorder in 10% to 20% of exposed individuals. Predictors of risk are needed to target early interventions to those who are most vulnerable. The objective of the study was to test whether a noninvasive mobile device that measures a physiological biomarker of autonomic nervous system activation could predict future posttraumatic stress disorder symptoms. Methods Skin conductance response was collected during a trauma interview in the emergency department within hours of exposure to trauma in 95 individuals. Trajectories of posttraumatic stress disorder symptoms over 12-month posttrauma were identified using latent growth mixture modeling. Results Skin conductance response was significantly correlated with the probability of being in the chronic posttraumatic stress disorder trajectory following trauma exposure in the emergency department (r = 0.489, p

In the adult literature, emotional arousal is regarded as a source of the enhancing effect of emotion on subsequent memory. Here, we used behavioral, electrophysiological, and psychophysiological methods to examine the role of emotional arousal on subsequent memory in school-age children. Five- to 8-year-olds, divided into younger and older groups, viewed emotional scenes as EEG, heart rate, and respiration was recorded, and participated in a memory task 24 hours later where EEG and behavioral responses were recorded; participants provided subjective ratings of the scenes after the memory task. All measures indicated emotion responses in both groups, and in ERP measures the effects were stronger for older children. Emotion responses were more consistent across measures for negative than positive stimuli. Behavioral memory performance was strong but did not differ by emotion condition. Emotion influenced the ERP index of recognition memory in the older group only (enhanced recognition of negative scenes). The findings an increasing interaction of emotion and memory during the school years. Further, the findings impress the value of combining multiple methods to assess emotion and memory in development. Development in the neurophysiology of emotion processing and memory in school-age children.

Nature Communications 6: Article number: 10106 (2015); Published: 3 December 2015; Updated: 3 March 2016 The original version of this Article contained an error in the spelling of the author Jennifer S. Stevens, which was incorrectly given as Jennifer J. Stevens. Furthermore, in Fig. 5, the titles for panels a and b were inadvertently switched.