Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

HIV status affects PTSD symptom severity, psychophysiology, and heart rate variability in women with low but not high exposure to childhood maltreatment.

Objective: People living with HIV (PLWH) experience high rates of childhood trauma exposure, which is a significant risk factor for the development of posttraumatic stress disorder (PTSD). Because Black Americans living in urban environments are exposed to high levels of trauma, suffer from chronic PTSD, and are at increased risk for HIV infection, it is important to understand how HIV status interacts with childhood maltreatment to influence PTSD symptom severity and underlying psychophysiology. Methods: The current cross-sectional study assessed whether HIV status interacts with childhood maltreatment to influence PTSD symptom severity and heart rate variability during a dark-enhanced startle (DES) task in 88 Black women with (n=30) and without HIV (n=58). Results: HIV was associated with greater PTSD symptom severity only in women with low levels of childhood maltreatment (p=.024). Startle potentiation during DES was highest in women living without HIV and with high childhood maltreatment (p=.018). In women who had experienced low levels of childhood maltreatment, respiratory sinus arrhythmia (RSA) was lower during the dark phase of DES in women living without HIV than women living with HIV (WLWH), (p=.046). RSA during the light phase of DES was lower in WLWH than in women living without HIV (p=.042). Conclusion: In the current sample of Black women, HIV status was associated with PTSD symptom severity in a manner dependent on level of childhood maltreatment, suggesting that HIV status may be an important factor to consider for behavioral and pharmacological treatment strategies for PTSD. Additionally, HIV status is associated with lower percent potentiation to darkness and lower RSA during the light phase of DES, suggesting physiological mechanisms by which HIV may contribute to PTSD symptoms in individuals exposed to low levels of childhood maltreatment.

Higher arterial stiffness and blunted vagal control of the heart in young women with compared to without a clinical diagnosis of PTSD.

PURPOSE: Young women are typically thought to be protected from cardiovascular disease (CVD) before menopause. However, posttraumatic stress disorder (PTSD) increases CVD risk in women by up to threefold. Data in predominantly male cohorts point to physiological mechanisms such as vascular and autonomic derangements as contributing to increased CVD risk. The purpose of the study reported here was to determine whether young women diagnosed with PTSD, compared to those without, present with arterial stiffness and impaired autonomic control of the heart. METHODS: A total of 73 healthy young women, ranging in age from 18 to 40 years, with a history of trauma exposure were included in this study, 32 with and 41 without a clinical PTSD diagnosis. We measured resting pulse wave velocity (PWV), central hemodynamics, augmentation pressure and augmentation index (AI) via pulse wave analysis using applanation tonometry. Heart rate variability was also assessed via peripheral arterial tone. RESULTS: In comparison to controls, women with PTSD showed higher central arterial pressure (mean ± standard deviation: systolic blood pressure 104 ± 8 vs. 97 ± 8 mmHg, p < 0.001; diastolic blood pressure 72 ± 7 vs. 67 ± 7 mmHg, p = 0.003), PWV (6 ± 0.3 vs. 5 ± 0.6 m/s, p < 0.001) and AI (22 ± 13 vs. 15 ± 12%, p = 0.007) but lower standard deviation of normal-to-normal intervals (SDNN; 44 ± 17 vs. 54 ± 18 ms, p = 0.005) and root mean square of successive differences between normal heartbeats (RMSSD; 37 ± 17 vs. 51 ± 22 ms, p = 0.002). CONCLUSION: PTSD in young women is associated with higher brachial and central pressures, increased arterial stiffness and blunted parasympathetic control of the heart. These findings illustrate potential mechanisms underlying high risk for CVD in young women with PTSD, suggesting possible treatment targets for this at-risk group.

Conceptualizing disparities and differences in the psychobiology of traumatic stress.

Understanding biological pathways that mediate trauma-related psychopathology is a major goal for traumatic stress studies. There is growing interest in studying differences in neural, physiological, and behavioral correlates of traumatic stress across demographic groups (e.g., sex/gender, race/ethnicity). However, challenges remain in how to appropriately conceptualize the source, mechanisms, and practical utility of between-group variation. The present brief conceptual review discusses ethnicity, race, and sex/gender-related variability relevant to understanding the psychobiology of traumatic stress in the context of traumatic stress studies. We discuss recent evidence related to socioenvironmental influences on ethnoracial variability in the brain and behavior relevant to traumatic stress, as well as sex/gender associations in neurophysiology that may contribute to the development of adverse posttraumatic sequelae. We further synthesize these findings by discussing intersectional influences of sex/gender- and race/ethnicity-related factors on trauma-related physical and mental health outcomes. The present review provides an important foundation for future research on disparities and individual differences in traumatic stress to move the field toward more effective assessment and treatment approaches.

Trauma and Posttraumatic Stress Disorder as Important Risk Factors for Gestational Metabolic Dysfunction.

Gestational metabolic diseases adversely impact the health of pregnant persons and their offspring. Pregnant persons of color are impacted disproportionately by gestational metabolic disease, highlighting the need to identify additional risk factors contributing to racial-ethnic pregnancy-related health disparities. Trauma exposure and posttraumatic stress disorder (PTSD) are associated with increased risk for cardiometabolic disorders in nonpregnant persons, making them important factors to consider when identifying contributors to gestational metabolic morbidity and mortality health disparities. Here, we review current literature investigating trauma exposure and posttraumatic stress disorder as psychosocial risk factors for gestational metabolic disorders, inclusive of gestational diabetes, low birth weight and fetal growth restriction, gestational hypertension, and preeclampsia. We also discuss the physiological mechanisms by which trauma and PTSD may contribute to gestational metabolic disorders. Ultimately, understanding the biological underpinnings of how trauma and PTSD, which disproportionately impact people of color, influence risk for gestational metabolic dysfunction is critical to developing therapeutic interventions that reduce complications arising from gestational metabolic disease. KEY POINTS: · Gestational metabolic diseases disproportionately impact the health of pregnant persons of color.. · Trauma and PTSD are associated with increased risk for cardiometabolic disorders in nonpregnant per.. · Trauma and PTSD impact physiological cardiometabolic mechanisms implicated in gestational metabolic..

Predicting aggressive behaviors: Examining unique and interactive roles of PTSD and emotion dysregulation in a minority sample.

Aggression is a costly public health problem with severe and multi-faceted negative consequences and thus, identifying factors that contribute to aggression, particularly in understudied populations, is necessary to develop more effective interventions to reduce the public health cost of aggression. The goal this study was to test whether difficulties regulating emotions moderated the association between posttraumatic stress disorder (PTSD) symptoms and aggression in a community sample of predominantly Black females with high levels of trauma exposure. Furthermore, we explored unique relations between PTSD symptom clusters and distinct subscales of difficulties regulating emotions and aggression. The sample included 601 community participants recruited from an urban public hospital. Symptoms were assessed using self-report measures including the Difficulties in Emotion Regulation Scale (DERS) and Behavioral Questionnaire-Short. Regression analyses were conducted using PTSD symptoms and total DERS to test their interaction as predictors for aggression (using BQ-Short). We found that higher levels of PTSD arousal symptoms and difficulty controlling impulses when upset were positively related to aggression. We also conducted an exploratory analysis to examine the association between PTSD symptom clusters using the Alternative Symptom Clusters hybrid model. The results suggest that some PTSD symptoms (externalizing behavior) and some emotion dysregulation processes (difficulties controlling impulses when upset), relate to aggression in independent, rather than multiplicative ways. These results offer insights for new directions of research that focuses on the independent association between specific emotion dysregulation processes and PTSD symptoms on aggression.

Sleep efficiency and PTSD symptom severity predict microvascular endothelial function and arterial stiffness in young, trauma-exposed women.

Posttraumatic stress disorder (PTSD) is linked to sleep disturbances and significantly higher risk of developing cardiovascular disease (CVD). Furthermore, vascular dysfunction and sleep are independently associated with CVD. Uncovering the link between PTSD symptom severity, sleep disturbances, and vascular function could shine a light on mechanisms of CVD risk in trauma-exposed young women. The purpose of the present study was to investigate the individual and combined effects of sleep efficiency and PTSD symptom severity on vascular function. We recruited 60 otherwise healthy women [age, 26 ± 7 yr and body mass index (BMI), 27.7 ± 6.5 kg/m2] who had been exposed to trauma. We objectively quantified sleep efficiency (SE) using actigraphy, microvascular endothelial function via Framingham reactive hyperemia index (fRHI), and arterial stiffness via pulse-wave velocity (PWV). PTSD symptom severity was assessed using the PTSD checklist for fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (PCL5). PWV was correlated with age (r = 0.490, P < 0.001) and BMI (r = 0.484, P < 0.001). In addition, fRHI was positively correlated with SE (r = 0.409, P = 0.001) and negatively correlated with PTSD symptoms (r = -0.382, P = 0.002). To explore the predictive value of SE and PTSD symptoms on PWV and fRHI, we conducted two multivariate linear regression models. The model predicting PWV was significant (R2 = 0.584, P < 0.001) with age, BMI, blood pressure, and SE emerging as predictors. Likewise, the model predicting fRHI was significant (R2 = 0.360, P < 0.001) with both PTSD symptoms and SE as significant predictors. Our results suggest that although PTSD symptoms mainly impact microvascular endothelial function, sleep efficiency is additionally associated with arterial stiffness in young trauma-exposed women, after controlling for age and BMI.NEW & NOTEWORTHY This is the first study to investigate the individual and combined impacts of objective sleep and PTSD symptoms severity on arterial stiffness and microvascular endothelial function in young premenopausal women. We report that in young trauma-exposed women, although low sleep efficiency is associated with overall vascular function (i.e., microvascular endothelial function and arterial stiffness), the severity of PTSD symptoms is specifically associated with microvascular endothelial function, after accounting for age and body mass index.

Characterization of the inflammatory response to COVID-19 illness in pregnancy.

OBJECTIVE: Pregnant patients face greater morbidity and mortality from COVID-19 related illness than their non-pregnant peers. Previous research in non-pregnant patients established that poor clinical outcomes in SARS-CoV-2 positive patients admitted to the ICU were correlated with a significant increase in the proinflammatory markers interleukin (IL)-1ß, IL-6, IL-8, and IL-10. Importantly, high levels of these inflammatory markers have also been associated with adverse pregnancy outcomes, including spontaneous preterm birth, preeclampsia, and severe respiratory disease. STUDY DESIGN: This was a retrospective cohort study that compared the serum inflammatory cytokine profiles of pregnant patients with acute/post-acute SARS-CoV-2 infection to those with previous exposure. All subjects in both cohorts tested positive for SARS-CoV-2 antibodies; however, those in the acute/post-acute infection cohort had a documented positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result within 30 days of serum sample collection. Serum samples were obtained during prenatal venipuncture from 13 to 39 weeks' gestation and the cohorts were matched by gestational age. The inflammatory cytokines interferon (IFN)-γ, IL-10, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α were assayed from maternal serum using a standard ELISA assay and median cytokine concentrations were compared using the Mann-Whitney test. RESULTS AND DISCUSSION: We enrolled 50 non-Hispanic Black patients with confirmed COVID-19 infection who received prenatal care at Grady Memorial Hospital in Atlanta, Georgia. Those with acute/post-acute infection (n = 22) had significantly higher concentrations of SARS-CoV-2 antibody, IL-10, IL-1ß, and IL-8, while patients with previous exposure (n = 28) had significantly higher concentrations of IL-4. There were no significant inter-group differences in medical comorbidities. Pregnant patients with acute/post-acute SARS-CoV-2 infection had significantly higher serum concentrations of pro-inflammatory cytokines as compared to those with previous exposure, suggesting that, like in the non-pregnant population, SARS-CoV-2 infection alters the levels of circulating proinflammatory markers during pregnancy. The increased levels of cytokines may contribute to the adverse obstetric outcomes observed with COVID-19 illness.

Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques.

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB-dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB- and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history-in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

Indirect effect of race-related stress on traumatic stress and depression symptoms via subjective social status in a Black community sample.

Experiencing racism is linked to lower subjective social status (SSS), defined as one's perception of their position in society. SSS is influenced by power, prestige, and objective socioeconomic status (SES). Previous findings suggest that race-related stress may be related to adverse mental health outcomes through SSS in Black Americans, a population that has been deeply affected by continuing legacies of oppression. The current study examines the indirect association between race-related stress and posttraumatic stress disorder (PTSD) and depression symptoms through SSS in a community sample of largely trauma-exposed Black Americans (N = 173). Hierarchical regression analyses indicated that overall race-related stress significantly predicted lower SSS, higher PTSD symptoms, and higher depression symptoms. Analyses also revealed indirect effects of cultural race-related stress on PTSD and depression symptoms through SSS after controlling for SES. Results suggest that the experience of race-related stress, particularly cultural race-related stress, which involves the degradation and disparagement of one's culture and worldview, is associated with more severe PTSD and depression symptoms potentially due to these experiences decreasing Black Americans' SSS. Findings support the need for systemic intervention strategies to disrupt the cultural oppression of Black Americans and improve the societal value and mental health of this population.

Evaluating the Performance of the Primary Care Posttraumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) in a Trauma-Exposed, Socioeconomically Vulnerable Patient Population.

The properties and utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) remain unstudied in community-based populations. This study evaluates the performance of the PC-PTSD-5 to determine whether it can be used as a brief alternative to the PTSD Checklist for DSM-5 (PCL-5) in a large public hospital in the southeastern United States. Participants (N = 422; 92.7% Black; 85.8% female; Mage = 42.0 years, SDage = 13.4 years) completed the PCL-5 and PC-PTSD-5 after recruitment from medical clinic waiting rooms and admission lists. Using chance-corrected test quality indices and item response theory (IRT) analyses, we determined optimal cut-scores for screening and examined item performance. Approximately 45.0% of the sample screened positive for probable DSM-5 PTSD using the PCL-5. The PC-PTSD-5 demonstrated high internal consistency and strong associations with PCL-5 scores (total, r = .79; items, rs = .51-.61). A cut-score of one was optimally sensitive for screening (κ[1] = .96), and a cut-score of four had the highest quality of probable efficiency (κ[.5] = .66) for detecting self-reported DSM-5 PTSD on the PCL-5. IRT analyses indicated Item 1 (nightmares, intrusive memories) provided the most information, and other items may not be incrementally useful for this sample. Findings provide preliminary support for the use of the PC-PTSD-5 as a brief alternative to the PCL-5 among chronically trauma-exposed patients in the public healthcare setting.

WHEN REPRODUCTION IS NO LONGER AUTONOMOUS: FEELING RESPECTED BY MATERNITY CARE PROVIDERS MODERATES THE ASSOCIATION BETWEEN AUTONOMY IN DECISION MAKING AND BIRTH-RELATED PTSD SYMPTOMS IN A COMMUNITY SAMPLE OF POSTPARTUM BLACK WOMEN.

Black individuals are at particularly high risk for birth-related posttraumatic stress disorder (PTSD) symptoms, in part due to a lack of opportunity to lead maternity care decisions. Maternal care providers need evidence-based ways to reduce pregnant persons' risk for birth-related PTSD symptoms despite reduced autonomy in decision making resulting from heightened restrictions on reproductive rights. We investigated whether a potential relation between autonomy in decision making and birth-related PTSD symptoms would be moderated by being mistreated or feeling respected by maternity care providers in a community sample of Black women (N = 52; Mage = 28.2 years, SDage = 5.7 years) seeking maternity care at a public hospital in the southeastern United States. At six weeks postpartum, participants completed measures assessing autonomy in decision making, current birth-related PTSD symptoms, number of mistreatment events, and feelings of respect from providers during pregnancy, childbirth, and the postpartum period. Autonomy in decision making was negatively correlated with birth-related PTSD symptoms, r=-.43, p < .01. An interaction between autonomy in decision making and mistreatment by providers was trending toward significance, B=-.23, SE=.14, p = .10. Autonomy in decision making and feeling respected by maternity care provider interacted to predict birth-related PTSD symptoms, B = .05, SE=.01, p < .01. Feeling respected by providers may buffer against the negative effects of lack of autonomy in decision making on birth-related PTSD symptoms, highlighting the importance of providers' ability to convey respect to pregnant patients when they cannot lead care decisions.

Inflammation, amygdala-ventromedial prefrontal functional connectivity and symptoms of anxiety and PTSD in African American women recruited from an inner-city hospital: Preliminary results.

Inflammatory stimuli have been shown to impact brain regions involved in threat detection and emotional processing including amygdala and ventromedial prefrontal cortex (vmPFC), and to increase anxiety. Biomarkers of endogenous inflammation, including inflammatory cytokines and C-reactive protein (CRP), are reliably elevated in a subset of patients with depression and anxiety-related disorders such as post-traumatic stress disorder (PTSD), and have been associated with high anxiety in population studies. We previously reported that plasma CRP and cytokines in patients with depression were negatively correlated with resting-state functional connectivity (FC) between right amygdala and vmPFC, as assessed using both ROI to voxel-wise and targeted FC approaches, in association with symptoms of anxiety, particularly in patients with comorbid anxiety disorders or PTSD. To determine whether relationships between inflammation, right amygdala-vmPFC FC, and anxiety are reproducible across patient samples and research settings, we employed an a priori, hypothesis-driven approach to examine relationships between inflammation, targeted right amygdala-vmPFC FC and anxiety in a cohort of African American (AA) women (n = 54) recruited from an inner-city hospital population reliably found to have higher levels of inflammation (median CRP âˆ¼ 4 mg/L) as well as symptoms of anxiety, depression and PTSD. Higher concentrations of plasma CRP were associated with lower right amygdala-vmPFC FC (r = -0.32, p = 0.017), and this relationship remained significant when controlling for age, body mass index and number of lifetime trauma events experienced, as well as severity of PTSD and depression symptoms (all p < 0.05). This amygdala-vmPFC FC was similarly associated with a composite score of three inflammatory cytokines in a subset of women where plasma was available for analysis (n = 33, r = -0.33, p = 0.058; adjusted r = -0.43, p = 0.026 when controlling for covariates including PTSD and depression symptom severity). Lower right amygdala-vmPFC FC was in turn associated with higher levels of anxiety reported to be generally experienced on the State-Trait Anxiety Inventory, trait component (adjusted r = -0.32, p = 0.039 when controlling for covariates). Exploratory analyses also revealed a negative correlation between severity of childhood maltreatment and right amygdala-vmPFC FC (r = -0.32, p = 0.018) that was independent of CRP and its association with FC, as well as an association between low amygdala-vmPFC FC and severity of PTSD symptoms, specifically the re-experiencing/intrusive symptom subscale (adjusted r = -0.32, p = 0.028 when controlling for covariates). While CRP was not linearly associated with either anxiety or PTSD symptoms, CRP concentrations were higher in women reporting clinically significant anxiety or PTSD symptom severity when these symptoms were considered together (both p < 0.05), but with no interaction. These results support our primary hypothesis that higher inflammation was associated with lower amygdala-vmPFC FC, a relationship that was detected using a hypothesis-driven, targeted approach. Findings also support that this phenotype of high CRP and low vmPFC FC was observed in association with anxiety in primary analyses, as well as symptoms of PTSD in exploratory analyses, in a cohort recruited from an inner-city population of AA women enriched for high inflammation, history of trauma exposure, and symptom severity. Larger, longitudinal samples are required to fully tease apart causal relationships between inflammatory biomarkers, FC and PTSD-related symptoms in future studies.

The relations between C-reactive protein and trauma exposure, PTSD and depression symptoms, and PTSD psychotherapy treatment response in treatment seeking veterans and service members.

While inflammatory markers have been implicated in the link between PTSD and poor health outcomes, there is a paucity of research investigating C-reactive protein (CRP) and psychotherapy treatment response for posttraumatic stress disorder (PTSD). The present study utilized a large, well-characterized sample of veterans and service members (N = 493) engaged in intensive psychotherapy to investigate the associations between CRP, trauma exposure, related variables, and PTSD and depression, as well as investigating if CRP was associated with PTSD psychotherapy treatment response. Bivariate correlation results indicate that CRP was significantly associated with BMI (r = 0.48) and severity of experiences of childhood physical and sexual abuse (r = 0.14 and 0.15, respectively) and was not significantly associated with baseline PTSD total symptom severity, PTSD symptom clusters, or depression symptom severity (rs ranging from -0.03 to 0.04). In multivariate regression models investigating if CRP and related variables were associated with PTSD baseline symptom severity, CRP was not a significant predictor (ß = -0.03). Hierarchical linear modeling did not identify CRP as a significant predictor of PTSD psychotherapy outcome. Given that findings indicate that CRP was broadly elevated in this treatment seeking sample but not associated with PTSD and depression symptom severity, results suggest CRP may not be a specific biomarker for PTSD or depression but may be elevated in psychiatric disease more generally.

Associations among civilian mild traumatic brain injury with loss of consciousness, posttraumatic stress disorder symptom trajectories, and structural brain volumetric data.

Posttraumatic stress disorder (PTSD) is prevalent and associated with significant morbidity. Mild traumatic brain injury (mTBI) concurrent with psychiatric trauma may be associated with PTSD. Prior studies of PTSD-related structural brain alterations have focused on military populations. The current study examined correlations between PTSD, acute mTBI, and structural brain alterations longitudinally in civilian patients (N = 504) who experienced a recent Criterion A traumatic event. Participants who reported loss of consciousness (LOC) were characterized as having mTBI; all others were included in the control group. PTSD symptoms were assessed at enrollment and over the following year; a subset of participants (n = 89) underwent volumetric brain MRI (M = 53 days posttrauma). Classes of PTSD symptom trajectories were modeled using latent growth mixture modeling. Associations between PTSD symptom trajectories and cortical thicknesses or subcortical volumes were assessed using a moderator-based regression. mTBI with LOC during trauma was positively correlated with the likelihood of developing a chronic PTSD symptom trajectory. mTBI showed significant interactions with cortical thickness in the rostral anterior cingulate cortex (rACC) in predicting PTSD symptoms, r = .461-.463. Bilateral rACC thickness positively predicted PTSD symptoms but only among participants who endorsed LOC, p < .001. The results demonstrate positive correlations between mTBI with LOC and PTSD symptom trajectories, and findings related to mTBI with LOC and rACC thickness interactions in predicting subsequent chronic PTSD symptoms suggest the importance of further understanding the role of mTBI in the context of PTSD to inform intervention and risk stratification.

From alcohol to aggression: Examining the structure and nomological network of dysregulated behaviors in a trauma-exposed community sample.

OBJECTIVE: A large body of research has shown that alcohol use, drug use, aggression, and self-harm often co-occur within the same individuals, suggesting the possibility of shared etiologies. Research has yet to determine the factor structure of these dysregulated behaviors. METHODS: Participants (Mage = 40.33; 74% women) completed self-report and interview-based measures of dysregulated behaviors (alcohol use, drug use, aggression, and self-harm), emotion dysregulation, maladaptive personality traits, and symptoms of DSM disorders (e.g., borderline personality disorder [BPD], depression). RESULTS: Results showed support for a bifactor model (i.e., all indicators load on a common dysregulated behavior factor and on unique alcohol, drug, aggression, and self-harm factors), which provided a better fit to the data than other models. In line with our hypotheses, the general dysregulated behavior factor was positively associated with emotion regulation difficulties, negative affect, and BPD symptoms. CONCLUSIONS: These results have implications for several areas of psychopathology and intervention research.

When Anger Remains Unspoken: Anger and Accelerated Epigenetic Aging Among Stress-Exposed Black Americans.

OBJECTIVE: Race-related lifetime stress exposure (LSE) including racial discrimination, trauma, and stressful life events have been shown to contribute to racial health disparities. However, little is known about associations between race-related stressors and premature biological aging that confer the risk of adverse health outcomes. Even less is known about the mechanisms through which race-related stressors may be associated with accelerated aging. Early evidence suggests psychological processes such as anger, and particularly the internalization of anger, may play a role. METHODS: In a community sample of predominantly low-income Black adults (n = 219; age = 45.91 [12.33] years; 64% female), the present study examined the association of race-related LSE (as defined by exposure to racial discrimination, trauma, and stressful life events) and epigenetic age acceleration through anger expression. RESULTS: Internalized and externalized anger expression were each significantly associated with LSE and age acceleration. Although LSE was not directly associated with age acceleration (ΔR2 = 0.001, p = .64), we found that greater LSE was indirectly associated with age acceleration through increases in internalized, but not externalized, anger (indirect effect: ß = 0.03, standard error = 0.02, 95% confidence interval = 0.003 to 0.08; total effect: ß = 0.02, 95% confidence interval = -0.25 to 0.31). CONCLUSIONS: These results suggest race-related LSE may elicit the internalization of anger, which, along with the externalization of anger, may initiate detrimental epigenetic alterations that confer the risk of adverse health outcomes. These findings lay the groundwork for longitudinal studies of the association between race-related stress and racial health disparities.

PTSD is associated with increased DNA methylation across regions of HLA-DPB1 and SPATC1L.

Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, avoidance, negative alterations in cognitions and mood, and arousal symptoms that adversely affect mental and physical health. Recent evidence links changes in DNA methylation of CpG cites to PTSD. Since clusters of proximal CpGs share similar methylation signatures, identification of PTSD-associated differentially methylated regions (DMRs) may elucidate the pathways defining differential risk and resilience of PTSD. Here we aimed to identify epigenetic differences associated with PTSD. DNA methylation data profiled from blood samples using the MethylationEPIC BeadChip were used to perform a DMR analysis in 187 PTSD cases and 367 trauma-exposed controls from the Grady Trauma Project (GTP). DMRs were assessed with R package bumphunter. We identified two regions that associate with PTSD after multiple test correction. These regions were in the gene body of HLA-DPB1 and in the promoter of SPATC1L. The DMR in HLA-DPB1 was associated with PTSD in an independent cohort. Both DMRs included CpGs whose methylation associated with nearby sequence variation (meQTL) and that associated with expression of their respective genes (eQTM). This study supports an emerging literature linking PTSD risk to genetic and epigenetic variation in the HLA region.

Multimodal structural neuroimaging markers of risk and recovery from posttrauma anhedonia: A prospective investigation.

BACKGROUND: Anhedonic symptoms of posttraumatic stress disorder (PTSD) reflect deficits in reward processing that have significant functional consequences. Although recent evidence suggests that disrupted integrity of fronto-limbic circuitry is related to PTSD development, including anhedonic PTSD symptoms (posttrauma anhedonia [PTA]), little is known about potential structural biomarkers of long-term PTA as well as structural changes in fronto-limbic pathways associated with recovery from PTA over time. METHODS: We investigated associations between white matter microstructure, gray matter volume, and PTA in 75 recently traumatized individuals, with a subset of participants (n = 35) completing follow-up assessment 12 months after trauma exposure. Deterministic tractography and voxel-based morphometry were used to assess changes in white and gray matter structure associated with changes in PTA. RESULTS: Reduced fractional anisotropy (FA) of the uncinate fasciculus at around the time of trauma predicted greater PTA at 12-months posttrauma. Further, increased FA of the fornix over time was associated with lower PTA between 1 and 12-months posttrauma. Increased gray matter volume of the ventromedial prefrontal cortex and precuneus over time was also associated with reduced PTA. CONCLUSIONS: The microstructure of the uncinate fasciculus, an amygdala-prefrontal white matter connection, may represent a biomarker of vulnerability for later PTA. Conversely, development and recovery from PTA appear to be facilitated by white and gray matter structural changes in a major hippocampal pathway, the fornix. The present findings shed new light on neuroanatomical substrates of recovery from PTA and characterize white matter biomarkers of risk for posttraumatic dysfunction.

Prior trauma-related experiences predict the development of posttraumatic stress disorder after a new traumatic event.

BACKGROUND: Many reports have documented the relationship between previous traumatic experiences, including childhood trauma, and the development of later life psychopathology, including posttraumatic stress disorder (PTSD). Identification of individuals at greatest risk for the development of PTSD could lead to preventative interventions. The present study examined the developmental course of PTSD after trauma exposure, using histories of previous traumatic experiences and the severity of the reaction to the trauma as predictors. METHODS: Participants (N = 713) were recruited from Emergency Departments in Miami and Atlanta immediately following a traumatic experience. Histories of previous traumatic experiences and the immediate reaction to the new trauma were examined at baseline. Follow-up assessments of PTSD severity were conducted at 1, 3, and 6 months. RESULTS: Histories of child abuse and pre-existing trauma symptoms predicted the immediate response to stress (R2 = .21, p < .001) and the initial trauma reaction (p < .005).) A mixed-model repeated-measures analysis of variance found that immediate stress response and a history of prior trauma (p < .001) significantly predicted the course of PTSD symptoms. Area under the curve (AUC) analyses suggested that the presence of PTSD at each successive assessment was predicted most substantially by the severity of PTSD at the immediately prior follow-up assessment (AUC > 0.86). CONCLUSIONS: The current findings suggest that previous traumatic experiences lead to a greater immediate reaction to trauma and combine to predict the development of PTSD, the maintenance of which is not moderated by these earlier experiences. The identification of people likely to develop PTSD may be aided by the assessment of prior experiences and immediate reactions.