Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

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

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.

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

Derivation and Validation of a Brief Emergency Department-Based Prediction Tool for Posttraumatic Stress After Motor Vehicle Collision.

STUDY OBJECTIVE: To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department (ED) patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision. METHODS: Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration. RESULTS: Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort. CONCLUSION: This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery.

Prior histories of posttraumatic stress disorder and major depression and their onset and course in the three months after a motor vehicle collision in the AURORA study.

BACKGROUND: A better understanding of the extent to which prior occurrences of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) predict psychopathological reactions to subsequent traumas might be useful in targeting posttraumatic preventive interventions. METHODS: Data come from 1306 patients presenting to 29 U.S. emergency departments (EDs) after a motor vehicle collision (MVC) in the advancing understanding of recovery after trauma study. Patients completed self-reports in the ED and 2-weeks, 8-weeks, and 3-months post-MVC. Associations of pre-MVC probable PTSD and probable MDE histories with subsequent 3-months post-MVC probable PTSD and probable MDE were examined along with mediation through intervening peritraumatic, 2-, and 8-week disorders. RESULTS: 27.6% of patients had 3-month post-MVC probable PTSD and/or MDE. Pre-MVC lifetime histories of these disorders were not only significant (relative risk = 2.6-7.4) but were dominant (63.1% population attributable risk proportion [PARP]) predictors of this 3-month outcome, with 46.6% prevalence of the outcome among patients with pre-MVC disorder histories versus 9.9% among those without such histories. The associations of pre-MVC lifetime disorders with the 3-month outcome were mediated largely by 2- and 8-week probable PTSD and MDE (PARP decreasing to 22.8% with controls for these intervening disorders). Decomposition showed that pre-MVC lifetime histories predicted both onset and persistence of these intervening disorders as well as the higher conditional prevalence of the 3-month outcome in the presence of these intervening disorders. CONCLUSIONS: Assessments of pre-MVC PTSD and MDE histories and follow-ups at 2 and 8 weeks could help target early interventions for psychopathological reactions to MVCs.

The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

Health care utilization by women sexual assault survivors after emergency care: Results of a multisite prospective study.

BACKGROUND: Approximately, 100,000 US women receive emergency care after sexual assault each year, but no large-scale study has examined the incidence of posttraumatic sequelae, receipt of health care, and frequency of assault disclosure to providers. The current study evaluated health outcomes and service utilization among women in the 6 weeks after sexual assault. METHODS: Women ≥18 years of age presenting for emergency care after sexual assault to twelve sites were approached. Among those willing to be contacted for the study (n = 1080), 706 were enrolled. Health outcomes, health care utilization, and assault disclosure were assessed via 6 week survey. RESULTS: Three quarters (76%) of women had posttraumatic stress, depression, or anxiety, and 65% had pain. Less than two in five reported seeing health care provider; receipt of care was not related to substantive differences in symptoms and was less likely among Hispanic women and women with a high school education or less. Nearly one in four who saw a primary care provider did not disclose their assault, often due to shame, embarrassment, or fear of being judged. CONCLUSION: Most women receiving emergency care after sexual assault experience substantial posttraumatic sequelae, but health care in the 6 weeks after assault is uncommon, unrelated to substantive differences in need, and limited in socially disadvantaged groups. Lack of disclosure to primary care providers was common among women who did receive care.

Trajectories of Subjective Health: Testing Longitudinal Models for Self-rated Health From Adolescence to Midlife.

Self-rated health (SRH) is ubiquitous in population health research. It is one of the few consistent health measures in longitudinal studies. Yet, extant research offers little guidance on its longitudinal trajectory. The literature on SRH suggests several possibilities, including SRH as (1) a more fixed, longer-term view of past, present, and anticipated health; (2) a spontaneous assessment at the time of the survey; (3) a result of lagged effects from prior responses; (4) a function of life course processes; and (5) a combination of the preceding. Different perspectives suggest different longitudinal models, but evidence is lacking about which model best captures SRH trajectory. Using data from the National Longitudinal Study of Adolescent to Adult Health and the National Longitudinal Survey of Youth, we employ structural equation modeling to correct for measurement error and identify the best-fitting, theoretically guided models describing SRH trajectories. Results support a hybrid model that combines the lagged effect of SRH with the enduring perspectives, fitted with a type of autoregressive latent trajectory (ALT) model. This model structure consistently outperforms other commonly used models and underscores the importance of accounting for lagged effects combined with time-invariant effects in longitudinal studies of SRH. Interestingly, comparisons of this latent, time-invariant autoregressive model across gender and racial/ethnic groups suggest that there are differences in starting points but less variability in SRH trajectories from early life into adulthood.

Subjective health in adolescence: Comparing the reliability of contemporaneous, retrospective, and proxy reports of overall health.

Self-rated health (SRH) is one of the most important social science measures of health. Yet its measurement properties remain poorly understood. Most studies ignore the measurement error in SRH despite the bias resulting from even random measurement error. Our goal is to estimate the measurement reliability of SRH in contemporaneous, retrospective, and proxy indicators. We use the National Longitudinal Study of Adolescent to Adult Health to estimate the reliability of SRH relative to proxy assessments and respondents' recollections of past health. Even the best indicators - contemporaneous self-reports - have a modest reliability of ~0.6; retrospective and proxy assessments fare much worse, with reliability less than 0.2. Moreover, not correcting for measurement error in SRH leads to a ~20-40% reduction in its correlation with other measures of health. Researchers should be skeptical of analyses that treat these subjective reports as explanatory variables and fail to take account of their substantial measurement error.

Perceived Care Quality Among Women Receiving Sexual Assault Nurse Examiner Care: Results From a 1-Week Postexamination Survey in a Large Multisite Prospective Study.

INTRODUCTION: This study examined the perspectives of female patients who had been sexually assaulted regarding the quality of care provided by sexual assault nurse examiners, including whether the patients' perspectives varied by their demographic characteristics and health status before the assault. METHODS: A total of 695 female patients who received care from sexual assault nurse examiners at 13 United States emergency care centers and community-based programs completed standardized surveys 1 week after receiving sexual assault nurse examiners' care for sexual assault. RESULTS: Most patients strongly agreed that the sexual assault nurse examiners provided high-quality care, including taking patients' needs/concerns seriously, not acting as though the assault was the patient's fault, showing care/compassion, explaining the sexual assault examination, and providing follow-up information. The perceptions did not vary by the patients' demographic characteristics or preassault health status. DISCUSSION: Female patients who had been sexually assaulted and who were evaluated at 13 widely geographically distributed sexual assault nurse examiners' programs consistently reported that the sexual assault nurse examiners provided high-quality, compassionate care.

Model Implied Instrumental Variables (MIIVs): An Alternative Orientation to Structural Equation Modeling.

Few dispute that our models are approximations to reality. Yet when it comes to structural equation models (SEMs), we use estimators that assume true models (e.g. maximum likelihood) and that can create biased estimates when the model is inexact. This article presents an overview of the Model Implied Instrumental Variable (MIIV) approach to SEMs from Bollen (1996). The MIIV estimator using Two Stage Least Squares (2SLS), MIIV-2SLS, has greater robustness to structural misspecifications than system wide estimators. In addition, the MIIV-2SLS estimator is asymptotically distribution free. Furthermore, MIIV-2SLS has equation-based overidentification tests that can help pinpoint misspecifications. Beyond these features, the MIIV approach has other desirable qualities. MIIV methods apply to higher order factor analyses, categorical measures, growth curve models, dynamic factor analysis, and nonlinear latent variables. Finally, MIIV-2SLS permits researchers to estimate and test only the latent variable model or any other subset of equations. In addition, other MIIV estimators beyond 2SLS are available. Despite these promising features, research is needed to better understand its performance under a variety of conditions that represent empirical applications. Empirical and simulation examples in the article illustrate the MIIV orientation to SEMs and highlight an R package MIIVsem that implements MIIV-2SLS.

A Limited Information Estimator for Dynamic Factor Models.

Structural equation modeling (SEM) is an increasingly popular method for examining multivariate time series data. As in cross-sectional data analysis, structural misspecification of time series models is inevitable, and further complicated by the fact that errors occur in both the time series and measurement components of the model. In this article, we introduce a new limited information estimator and local fit diagnostic for dynamic factor models within the SEM framework. We demonstrate the implementation of this estimator and examine its performance under both correct and incorrect model specifications via a small simulation study. The estimates from this estimator are compared to those from the most common system-wide estimators and are found to be more robust to the structural misspecifications considered.

Evaluating measurement error in readings of blood pressure for adolescents and young adults.

Readings of blood pressure are known to be subject to measurement error, but the optimal method for combining multiple readings is unknown. This study assesses different sources of measurement error in blood pressure readings and assesses methods for combining multiple readings using data from a sample of adolescents/young adults who were part of a longitudinal epidemiological study based in Cebu, Philippines. Three sets of blood pressure readings were collected at 2-year intervals for 2127 adolescents and young adults as part of the Cebu National Longitudinal Health and Nutrition Study. Multi-trait, multi-method (MTMM) structural equation models in different groups were used to decompose measurement error in the blood pressure readings into systematic and random components and to examine patterns in the measurement across males and females and over time. The results reveal differences in the measurement properties of blood pressure readings by sex and over time that suggest the combination of multiple readings should be handled separately for these groups at different time points. The results indicate that an average (mean) of the blood pressure readings has high validity relative to a more complicated factor-score-based linear combination of the readings.

Structural equation models and the quantification of behavior.

Quantifying behavior often involves using variables that contain measurement errors and formulating multiequations to capture the relationship among a set of variables. Structural equation models (SEMs) refer to modeling techniques popular in the social and behavioral sciences that are equipped to handle multiequation models, multiple measures of concepts, and measurement error. This work provides an overview of latent variable SEMs. We present the equations for SEMs and the steps in modeling, and we provide three illustrations of SEMs. We suggest that the general nature of the model is capable of handling a variety of problems in the quantification of behavior, where the researcher has sufficient knowledge to formulate hypotheses.

A Model Implied Instrumental Variable Approach to Exploratory Factor Analysis (MIIV-EFA).

Spearman (Am J Psychol 15(1):201-293, 1904. https://doi.org/10.2307/1412107 ) marks the birth of factor analysis. Many articles and books have extended his landmark paper in permitting multiple factors and determining the number of factors, developing ideas about simple structure and factor rotation, and distinguishing between confirmatory and exploratory factor analysis (CFA and EFA). We propose a new model implied instrumental variable (MIIV) approach to EFA that allows intercepts for the measurement equations, correlated common factors, correlated errors, standard errors of factor loadings and measurement intercepts, overidentification tests of equations, and a procedure for determining the number of factors. We also permit simpler structures by removing nonsignificant loadings. Simulations of factor analysis models with and without cross-loadings demonstrate the impressive performance of the MIIV-EFA procedure in recovering the correct number of factors and in recovering the primary and secondary loadings. For example, in nearly all replications MIIV-EFA finds the correct number of factors when N is 100 or more. Even the primary and secondary loadings of the most complex models were recovered when the sample sizes were at least 500. We discuss limitations and future research areas. Two appendices describe alternative MIIV-EFA algorithms and the sensitivity of the algorithm to cross-loadings.

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Sex Differences in Response Inhibition-Related Neural Predictors of Posttraumatic Stress Disorder in Civilians With Recent Trauma.

BACKGROUND: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma. METHODS: Participants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months. RESULTS: Lower response inhibition-related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition-related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus. CONCLUSIONS: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions.