Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes.

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers. Univariate MiXeR was used to contrast the genetic architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) was performed using independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted and weighted median MR estimates were evaluated. Sensitivity analyses for uncorrelated (MR PRESSO) and correlated horizontal pleiotropy (CAUSE) were also performed. PTSD was considerably more polygenic (10,863 influential variants) than autoimmune diseases (median 255 influential variants). However, PTSD evidenced significant genetic correlation with nine autoimmune diseases and three inflammatory biomarkers. PTSD had putative causal effects on autoimmune thyroid disease (p = 0.00009) and C-reactive protein (CRP) (p = 4.3 × 10-7). Inferences were not substantially altered by sensitivity analyses. Additionally, the PTSD-autoimmune thyroid disease association remained significant in multivariable MR analysis adjusted for genetically predicted inflammatory biomarkers as potential mechanistic pathway variables. No autoimmune disease had a significant causal effect on PTSD (all p values > 0.05). Although causal effect models were supported for associations of PTSD with CRP, shared pleiotropy was adequate to explain a putative causal effect of CRP on PTSD (p = 0.18). In summary, our results suggest a significant genetic overlap between PTSD, autoimmune diseases, and biomarkers of inflammation. PTSD has a putative causal effect on autoimmune thyroid disease, consistent with existing epidemiologic evidence. A previously reported causal effect of CRP on PTSD is potentially confounded by shared genetics. Together, results highlight the nuanced links between PTSD, autoimmune disorders, and associated inflammatory signatures, and suggest the importance of targeting related pathways to protect against disease and disability.

Posttraumatic Stress Disorder After Spontaneous Coronary Artery Dissection: A Report of the International Spontaneous Coronary Artery Dissection Registry.

BACKGROUND: Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry-based cohort, we documented prevalence of lifetime and past-month SCAD-induced PTSD, as well as related treatment seeking, and examined a range of health-relevant correlates of SCAD-induced PTSD. METHODS AND RESULTS: Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD-induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD-induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD-induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past-month PTSD. Of 811 patients ever reporting any SCAD-induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD-induced PTSD diagnoses reported never receiving trauma-related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past-month PTSD symptom severity in multivariable regression models. Greater past-month SCAD-induced PTSD symptoms were associated with greater past-week sleep disturbance and worse past-month disease-specific health status when adjusting for various risk factors. CONCLUSIONS: Given the high prevalence of SCAD-induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496687.

A physicochemical-sensing electronic skin for stress response monitoring.

Approaches to quantify stress responses typically rely on subjective surveys and questionnaires. Wearable sensors can potentially be used to continuously monitor stress-relevant biomarkers. However, the biological stress response is spread across the nervous, endocrine, and immune systems, and the capabilities of current sensors are not sufficient for condition-specific stress response evaluation. Here we report an electronic skin for stress response assessment that non-invasively monitors three vital signs (pulse waveform, galvanic skin response and skin temperature) and six molecular biomarkers in human sweat (glucose, lactate, uric acid, sodium ions, potassium ions and ammonium). We develop a general approach to prepare electrochemical sensors that relies on analogous composite materials for stabilizing and conserving sensor interfaces. The resulting sensors offer long-term sweat biomarker analysis of over 100 hours with high stability. We show that the electronic skin can provide continuous multimodal physicochemical monitoring over a 24-hour period and during different daily activities. With the help of a machine learning pipeline, we also show that the platform can differentiate three stressors with an accuracy of 98.0%, and quantify psychological stress responses with a confidence level of 98.7%.

Posttraumatic Stress Disorder Is Associated With Elevated Risk of Incident Stroke and Transient Ischemic Attack in Women Veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans, but evidence for associations with other cardiovascular disorders remains limited in this population. This retrospective longitudinal cohort study evaluated the association of PTSD with incident stroke/transient ischemic attack (TIA) in women veterans. METHODS AND RESULTS: Veterans Health Administration electronic health records were used to identify women veterans aged ≥18 years engaged with Veterans Health Administration health care from January 1, 2000 to December 31, 2019. We identified women veterans with and without PTSD without a history of stroke or TIA at start of follow-up. Propensity score matching was used to match groups on age, race or ethnicity, traditional cardiovascular risk factors, female-specific risk factors, a range of mental and physical health conditions, and number of prior health care visits. PTSD, stroke, TIA, and risk factors used in propensity score matching were based on diagnostic codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of PTSD with an incident stroke/TIA composite. Subanalyses considered stroke and TIA separately, plus age- and race- or ethnicity-stratified analyses were carried out. The analytic sample included 208 092 women veterans (104 046 with and 104 046 without PTSD). PTSD was associated with a greater rate of developing stroke/TIA (HR, 1.33 [95% CI, 1.25-1.42], P<0.001). This elevated risk was especially pronounced in women <50 years old and in Hispanic/Latina women. CONCLUSIONS: Findings indicate a strong association of PTSD with incident stroke/TIA in women veterans. Research is needed to determine whether addressing PTSD and its downstream consequences can offset this risk.

Sex Differences in Psychopathology Following Potentially Traumatic Experiences.

Importance: Various psychopathology may follow trauma; however, sex differences in these ranging manifestations of posttraumatic psychopathology remain understudied. Objective: To investigate sex-specific incidence of posttraumatic psychopathology. Design, Setting, and Participants: This population-based cohort study of Danish national health registries included a cohort of individuals who experienced a potentially traumatic event (PTE) from 1994 to 2016. Individuals were further categorized by presence of any pretrauma psychopathology. A comparison group of individuals who experienced a nontraumatic stressor (nonsuicide death of a first-degree relative) was examined as a reference cohort. Exposures: At least 1 of 8 PTEs (eg, physical assault, transportation accident) derived through health registry International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, with additional qualifiers to improve classification accuracy. Main Outcomes and Measures: Incidence of 9 categories of ICD-10 psychiatric disorders recorded in registries within 5 years of PTEs. The standardized morbidity ratios (SMRs) for psychopathology outcomes were also calculated to compare individuals experiencing PTEs with those experiencing a nontraumatic stressor. Results: This study included 1 398 026 individuals who had been exposed to trauma (475 280 males [34.0%]; 922 750 females [66.0%]). The group of males who had been exposed to trauma were evenly distributed across age, while most females in the trauma-exposed group were aged 16 to 39 years (592 385 [64.2%]). Males and females were equally distributed across income quartiles and predominantly single. Following PTEs, the most common diagnosis was substance use disorders for males (35 160 [7.4%]) and depressive disorders for females (29 255 [3.2%]); incidence proportions for these and other disorders were higher among males and females with any pretrauma psychopathology. Certain PTEs had elevated onset of various psychiatric disorders and some sex differences emerged. Following physical assault, associations were found with schizophrenia or psychotic disorders for males (SMR, 17.5; 95% CI, 15.9-19.3) and adult personality disorders for females (SMR, 16.3; 95% CI, 14.6-18.3). For noninterpersonal PTEs, males had larger SMRs for substance use, schizophrenia or psychotic disorders, and adult personality disorders (SMR, 43.4; 95% CI, 41.9-45.0), and females had larger SMRs for depressive disorders (SMR, 19.0; 95% CI, 18.6-19.4). Sex differences were also observed, particularly when considering pretrauma psychopathology. For example, among interpersonal PTEs, males were most likely to develop substance use disorders after physical assault, whereas females were more likely to develop various disorders, with stronger associations seen for females without pretrauma psychiatric diagnoses. Among noninterpersonal PTEs, exposure to toxic substance showed robust associations with psychopathology, particularly in those without pretrauma psychopathology, with sex-specific differences across psychiatric categories. Conclusions and Relevance: Mental disorders after trauma were wide-ranging for males and females, and sex differences in patterns of posttraumatic psychopathology were more pronounced when accounting for pretrauma psychopathology. Findings provide new insights for sex-relevant PTEs and their mental health consequences. It also outlines future directions for advancing understanding of a constellation of posttraumatic psychopathology in males and females.

Post-traumatic stress disorder symptom remission and cognition in a large cohort of civilian women.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit. METHODS: Data came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively. RESULTS: Compared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved PTSD symptoms had worse psychomotor speed/attention and learning/working memory. In women with unresolved PTSD symptoms, past-month PTSD symptom severity was inversely associated with baseline cognition. Over follow-up, both women with remitted and unresolved PTSD symptoms in 2008, especially those with high levels of symptoms, had a faster decline in learning/working memory than women with trauma/no PTSD. In women with remitted PTSD symptoms, higher lifetime PTSD symptom severity was associated with a faster decline in learning/working memory. Results were robust to the adjustment for sociodemographic, biobehavioral, and health factors and were partially attenuated when adjusted for depression. CONCLUSION: Unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later. Accelerated cognitive decline was observed among women with either unresolved or remitted PTSD symptoms.

Trends in Cardiovascular Disease Mortality in US Women Veterans vs Civilians.

Importance: Cardiovascular disease (CVD) remains the leading cause of death in the US. Women veterans have higher rates of CVD compared with civilian US women; however, analyses of recent trends in mortality from cardiac disease for women veterans are lacking. Objective: To investigate trends in cardiac disease mortality among women veterans over approximately the past 2 decades and compare rates with those for civilian women. Design, Setting, and Participants: In this retrospective longitudinal cohort study, US Veterans Health Administration (VHA) electronic health record data, linked with the National Death Index, were analyzed for CVD trends and rates of cardiac disease mortality among women veterans (aged 18 years or older) with VHA health care encounters from January 1, 2000, to December 31, 2017. These data were compared with a national cohort of civilian women (aged 15 years or older) in the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, which provides cause-of-death data using death certificates for all US residents. The data analysis was performed between March 10, 2021, and November 28, 2022. Exposure: Cardiac disease mortality among women veterans and civilian women. Main Outcomes and Measures: Cardiac disease mortality was based on International Classification of Diseases, Tenth Revision diagnostic codes (I00-I09, I11, I13, and I20-I51 as defined by CDC WONDER). For women veterans and civilian women, crude and age-adjusted cardiac disease mortality rates (per 100 000 life-years) and 95% CIs were calculated, with the 2000 US general population as the reference for age-adjusted rates. Results: From 2000 to 2017, 817 912 women veterans engaged with VHA health care (mean [SD] age, 45.7 [17.1] years), and 19 022 cardiac disease deaths were identified (22.4% of total deaths). The crude and age-adjusted cardiac disease mortality rates, respectively, per 100 000 life-years were 200.2 (95% CI, 181.0-221.0) and 197.6 (95% CI, 175.2-222.0) in 2000 and 196.0 (95% CI, 186.1-206.4) and 208.1 (95% CI, 196.4-220.4) in 2017, reflecting stable crude rates and a 5.3% increase in age-adjusted rates. For civilian women, the crude and age-adjusted rates decreased over time from 320.7 (95% CI, 319.7-321.8) and 268.1 (95% CI, 267.3-269.0) in 2000 to 220.9 (95% CI, 220.1-221.7) and 164.7 (95% CI, 164.1-165.3) in 2017. Conclusions and Relevance: In this cohort study comparing women veterans and civilian women, cardiac disease mortality rates for women veterans did not exhibit the improvements seen for civilian women during the nearly 2-decade study period. Further research and actionable clinical interventions are warranted to improve cardiovascular care for women veterans, who represent the fastest growing group of patients within the VHA health care system.

Antihypertensive Medications and PTSD Incidence in a Trauma Cohort.

Objective: Antihypertensive medications have been examined as agents for posttraumatic stress disorder (PTSD) prevention in trauma-exposed individuals, given well-documented associations between PTSD and increased risk of cardiovascular disease and purported trauma-relevant mechanisms of action for these medications. Evidence regarding the effectiveness of such drugs for this purpose remains mixed.Methods: We conducted a national population-based cohort study using data from Danish national registries to assess whether 4 classes of antihypertensive drugs (beta-adrenoceptor blockers [beta blockers], angiotensin II receptor blockers [ARBs], angiotensin-converting enzyme [ACE] inhibitors, and calcium channel blockers) were associated with a decreased incidence of PTSD (diagnosed according to ICD-10) over a 22-year study period. Data for this study originated from a population-based cohort of over 1.4 million persons who experienced a traumatic event between 1994 and 2016 in Denmark. We calculated the incidence rate of PTSD per 100,000 person-years among persons who filled a prescription for each class of drug in the 60 days prior to a traumatic event and for corresponding unexposed comparison groups. We then used Cox proportional hazards regression to compare the rate of PTSD among persons who filled an antihypertensive medication prescription within 60 days before their trauma to the rate among persons who did not.Results: We found evidence that calcium channel blockers were associated with a decreased incidence of PTSD (adjusted hazard ratio = 0.63, 95% confidence interval [CI] = 0.34, 1.2); all other antihypertensive medication classes had null or near null associations.Conclusions: These findings lay a foundation for additional research focusing on antihypertensive medications that appear most effective in reducing PTSD incidence following trauma and for additional replication work aimed at continuing to clarify the disparate findings reported in the literature to date.

Introduction to the Special Section on the International Society for Traumatic Stress Studies 38th Annual Meeting: Trauma as a transdiagnostic risk factor across the lifespan.

This article serves as an introduction to the special section in the Journal of Traumatic Stress related to the 38th annual meeting of the International Society for Traumatic Stress Studies, held in Atlanta, Georgia (USA) in November 2022. The theme of this meeting, "Trauma as a Transdiagnostic Risk Factor Across the Lifespan," provided an opportunity to recognize the far-reaching impact of trauma and how traumatic experiences can become embedded into the mind, body, and societal spirit. This introductory article outlines the importance of harnessing multiple perspectives to address these wide-ranging sequelae of trauma and provides an overview of the series of contributions to the special section.

Posttraumatic Stress Disorder, Depression, and Accelerated Aging: Leukocyte Telomere Length in the Nurses' Health Study II.

Background: Exposure to trauma, posttraumatic stress disorder (PTSD), and depression have been independently associated with leukocyte telomere length (LTL), a cellular marker of aging associated with mortality and age-related diseases. However, the joint contributions of trauma and its psychological sequelae on LTL have not been examined. Methods: We conducted an analysis of LTL in a subset of women from the Nurses' Health Study II (N = 1868). Lifetime exposure to traumatic events, PTSD, and depression was assessed with validated measures. DNA was extracted from peripheral blood leukocytes and telomere repeat copy number to single gene copy number was determined by quantitative real-time polymerase chain reaction telomere assay. Linear regression models assessed the association of trauma, PTSD, and depression with LTL after adjustment for health behaviors and medical conditions. Results: Trauma, PTSD, and depression were not independently associated with LTL in mutually adjusted models. However, individuals with severe psychological distress-characterized by comorbid PTSD and depression-had shorter LTL equivalent to being 7.62 years older (95% CI, 0.02 to 17.97) than participants who had never experienced a traumatic event and were not depressed. Further examination found only an association among individuals with the highest number of PTSD symptoms and comorbid depression equivalent to 9.71 additional years of aging (95% CI, 1.36 to 20.49). No effect was found among individuals meeting the minimum threshold for probable PTSD with comorbid depression. Conclusions: Severe psychological distress, as indicated by the presence of comorbid PTSD and depression, may be associated with shorter LTL.

Exercise Mitigates Flow Recirculation and Activates Mechanosensitive Transcriptome to Uncover Endothelial SCD1-Catalyzed Anti-Inflammatory Metabolites.

Exercise modulates vascular plasticity in multiple organ systems; however, the metabolomic transducers underlying exercise and vascular protection in the disturbed flow-prone vasculature remain under-investigated. We simulated exercise-augmented pulsatile shear stress (PSS) to mitigate flow recirculation in the lesser curvature of the aortic arch. When human aortic endothelial cells (HAECs) were subjected to PSS ( τ ave = 50 dyne·cm -2 , ∂τ/∂t = 71 dyne·cm -2 ·s -1 , 1 Hz), untargeted metabolomic analysis revealed that Stearoyl-CoA Desaturase (SCD1) in the endoplasmic reticulum (ER) catalyzed the fatty acid metabolite, oleic acid (OA), to mitigate inflammatory mediators. Following 24 hours of exercise, wild-type C57BL/6J mice developed elevated SCD1-catalyzed lipid metabolites in the plasma, including OA and palmitoleic acid (PA). Exercise over a 2-week period increased endothelial SCD1 in the ER. Exercise further modulated the time-averaged wall shear stress (TAWSS or τ ave) and oscillatory shear index (OSI ave ), upregulated Scd1 and attenuated VCAM1 expression in the disturbed flow-prone aortic arch in Ldlr -/- mice on high-fat diet but not in Ldlr -/- Scd1 EC-/- mice. Scd1 overexpression via recombinant adenovirus also mitigated ER stress. Single cell transcriptomic analysis of the mouse aorta revealed interconnection of Scd1 with mechanosensitive genes, namely Irs2 , Acox1 and Adipor2 that modulate lipid metabolism pathways. Taken together, exercise modulates PSS ( τ ave and OSI ave ) to activate SCD1 as a metabolomic transducer to ameliorate inflammation in the disturbed flow-prone vasculature.

Stressful life events and accelerated biological aging over time in youths.

Experiencing adversity in childhood and adolescence, including stressful life events (SLEs), may accelerate the pace of development, leading to adverse mental and physical health. However, most research on adverse early experiences and biological aging (BA) in youths relies on cross-sectional designs. In 171 youths followed for approximately 2 years, we examined if SLEs over follow-up predicted rate of change in two BA metrics: epigenetic age and Tanner stage. We also investigated if rate of change in BA was associated with changes in depressive symptoms over time. Youths aged 8-16 years at baseline self-reported Tanner stage and depressive symptoms at baseline and follow-up and provided saliva samples for DNA at both assessments. Horvath epigenetic age estimates were derived from DNA methylation data measured with the Illumina EPIC array. At follow-up, contextual threat interviews were administered to youths and caregivers to assess youths' experiences of past-year SLEs. Interviews were objectively coded by an independent rating team to generate a SLE impact score, reflecting the severity of all SLEs occurring over the prior year. Rate of change in BA metrics was operationalized as change in epigenetic age or Tanner stage as a function of time between assessments. Higher objective SLE impact scores over follow-up were related to a greater rate of change in epigenetic age (ß = 0.21, p = .043). Additionally, among youths with lower-but not higher-Tanner stage at baseline, there was a positive association of SLE impact scores with rate of change in Tanner stage (Baseline Tanner Stage × SLE Impact Score interaction: ß = - 0.21, p = .011). A greater rate of change in epigenetic age was also associated with higher depressive symptom levels at follow-up, adjusting for baseline symptoms (ß = 0.15, p = .043). Associations with epigenetic age were similar, although slightly attenuated, when adjusting for epithelial (buccal) cell proportions. Whereas much research in youths has focused on severe experiences of early adversity, we demonstrate that more commonly experienced SLEs during adolescence may also contribute to accelerated BA. Further research is needed to understand the long-term consequences of changes in BA metrics for health.

Correlates of Skin Conductance Reactivity to Stroke-Related Trauma Reminders During Hospitalization for Stroke.

Objective: Although several risk factors for stroke-induced posttraumatic stress disorder (PTSD) have been identified, objective risk measures that can be detected in the acute aftermath of these events are needed. This study is the first to collect an objective measure of psychophysiological arousal-skin conductance (SC) reactivity to a trauma interview-in patients after stroke or transient ischemic attack (TIA) and investigate correlates of SC reactivity. Methods: Mobile SC measurement during a resting baseline and standardized trauma interview was performed in-hospital in 98 individuals following stroke/TIA. We examined associations between several stroke-induced PTSD risk factors (sociodemographic, psychosocial, and medical characteristics) and SC reactivity to a trauma interview involving a free-response recalling of the stroke/TIA event. Results: Of the sociodemographic, psychosocial, medical characteristics examined as correlates to SC reactivity to recalling the stroke/TIA event, 2 factors reflecting aspects of prior and in-hospital experience were significantly associated with this indicator of sympathetic nervous system activation. A greater cumulative trauma burden was significantly associated with greater SC reactivity (r = .23, P = .04). Additionally, individuals administered benzodiazepines in-hospital had significantly greater SC reactivity to recalling the stroke/TIA event (M = 1.51, SD = 1.52) than those who were not (M = 0.76, SD = 1.16; P = .01). Greater cumulative trauma burden remained significantly associated with greater SC reactivity when adjusting for age and in-hospital benzodiazepine administration (ß=0.22, P = .04). Conclusion: This study demonstrated that SC reactivity was related to both behavioral and psychological risk factors for PTSD after a stroke/TIA event. Additionally, we demonstrated the feasibility of a low-cost, mobile measurement of SC that can be conducted in-hospital in a novel patient population: individuals with a medical trauma. With this measure, we were able to identify those individuals with the greatest trauma-related sympathetic nervous system reactivity in the days following a medical trauma. Future research is needed to determine whether SC reactivity may be leveraged in the development of brief, noninvasive screening measures for enhancing PTSD risk prediction.

Psychological and biological mechanisms linking trauma with cardiovascular disease risk.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and experiences of psychological trauma have been associated with subsequent CVD onset. Identifying key pathways connecting trauma with CVD has the potential to inform more targeted screening and intervention efforts to offset elevated cardiovascular risk. In this narrative review, we summarize the evidence for key psychological and biological mechanisms linking experiences of trauma with CVD risk. Additionally, we describe various methodologies for measuring these mechanisms in an effort to inform future research related to potential pathways. With regard to mechanisms involving posttraumatic psychopathology, the vast majority of research on psychological distress after trauma and CVD has focused on posttraumatic stress disorder (PTSD), even though posttraumatic psychopathology can manifest in other ways as well. Substantial evidence suggests that PTSD predicts the onset of a range of cardiovascular outcomes in trauma-exposed men and women, yet more research is needed to better understand posttraumatic psychopathology more comprehensively and how it may relate to CVD. Further, dysregulation of numerous biological systems may occur after trauma and in the presence of posttraumatic psychopathology; these processes of immune system dysregulation and elevated inflammation, oxidative stress, mitochondrial dysfunction, renin-angiotensin system dysregulation, and accelerated biological aging may all contribute to subsequent cardiovascular risk, although more research on these pathways in the context of traumatic stress is needed. Given that many of these mechanisms are closely intertwined, future research using a systems biology approach may prove fruitful for elucidating how processes unfold to contribute to CVD after trauma.

Anhedonic Depression Is Not Associated With Risk of Recurrent Major Adverse Cardiac Events and All-Cause Mortality in Acute Coronary Syndrome Patients.

BACKGROUND: Depression after acute coronary syndrome (ACS) is common and increases risks of adverse outcomes, but it remains unclear which depression features are most associated with major adverse cardiac events (MACE) and all-cause mortality (ACM). PURPOSE: To examine whether a subtype of depression characterized by anhedonia and major depressive disorder (MDD) predicts 1-year MACE/ACM occurrence in ACS patients compared to no MDD history. We also consider other depression features in the literature as predictors. METHODS: Patients (N = 1,087) presenting to a hospital with ACS completed a self-report measure of current depressive symptoms in-hospital and a diagnostic interview assessing MDD within 1 week post-hospitalization. MACE/ACM events were assessed at 1-, 6-, and 12-month follow-ups. Cox regression models were used to examine the association of the anhedonic depression subtype and MDD without anhedonia with time to MACE/ACM, adjusting for sociodemographic and clinical covariates. RESULTS: There were 142 MACE/ACM events over the 12-month follow-up. The 1-year MACE/ACM in patients with anhedonic depression, compared to those with no MDD, was somewhat higher in an age-adjusted model (hazard ratio [HR] = 1.63, p = .08), but was not significant after further covariate adjustment (HR = 1.24, p = .47). Of the additional depression features, moderate-to-severe self-reported depressive symptoms significantly predicted the risk of MACE/ACM, even in covariate-adjusted models (HR = 1.72, p = .04), but the continuous measure of self-reported depressive symptoms did not. CONCLUSION: The anhedonic depression subtype did not uniquely predict MACE/ACM as hypothesized. Moderate-to-severe levels of total self-reported depressive symptoms, however, may be associated with increased MACE/ACM risk, even after accounting for potential sociodemographic and clinical confounders.

Dimensions of Early Adversity and Sexual Behavior in a US Population-Based Adolescent Sample.

PURPOSE: Early life adversity (ELA) is associated with sexual risk, but ELA dimensions-and potential mechanisms-have been less examined. We evaluated associations between threat and deprivation-two key ELA dimensions-and sexual behaviors in adolescents. Secondary analyses investigated age at menarche as a mechanism linking ELA with sexual outcomes in girls. We predicted associations between threat and sexual behaviors, with younger age at menarche as a pathway. METHODS: Data were from the National Comorbidity Survey, Adolescent Supplement. Adolescents and caregivers reported on youths' ELA experiences, which were categorized as threat- or deprivation-related. Adolescents reported if they engaged in sex (N = 9,937) and on specific sexual risk indicators, including age at first sex, number of past-year sexual partners, and condom use consistency ("always" vs. "not always" used). Girls reported age at menarche. RESULTS: Threat (odds ratio [OR] = 1.76 [95% confidence interval [CI], 1.62-1.92]) and deprivation (OR = 1.51 [95% CI, 1.24-1.83]) were each linked with engagement in sex, ps<.05. Threat-related experiences were associated with multiple sexual risk markers, even when accounting for deprivation: earlier age at first sex (b = -0.20 [95% CI, -0.27 to 0.13]), greater number of partners (b = 0.17 [95% CI, 0.10-0.25]), and inconsistent condom use (OR = 0.72 [95% CI, 0.64-0.80]), ps <.001. Deprivation was not associated with sexual risk when adjusting for threat. We observed no significant indirect effects through age at menarche. DISCUSSION: Although threat and deprivation were related to engagement in sexual activity, threat-related experiences were uniquely associated with sexual risk. Screening for threat-related ELA may identify adolescents at-risk for poor sexual health.

Posttraumatic Stress Disorder (PTSD) as a Risk Factor for Cardiovascular Disease: Implications for Future Research and Clinical Care.

PURPOSE OF REVIEW: Posttraumatic stress disorder (PTSD) may be an important risk factor for cardiovascular disease (CVD). We explore the literature linking PTSD to CVD, potential mechanisms, interventions, and clinical implications. We outline gaps in current literature and highlight necessary future research. RECENT FINDINGS: PTSD has been independently associated with deleterious effects on cardiovascular health through biological, behavioral, and societal pathways. There are evidence-based psychotherapeutic interventions and pharmacotherapies for PTSD that may mitigate its impact on CVD. However, there are limited studies that rigorously analyze the impact of treating PTSD on cardiovascular outcomes. Trauma-informed CVD risk stratification, education, and treatment offer opportunities to improve patient care. These approaches can include a brief validated screening tool for PTSD identification and treatment. Pragmatic trials are needed to test PTSD interventions among people with CVD and evaluate for improved outcomes.

Trauma, psychological distress and markers of systemic inflammation among US women: A longitudinal study.

BACKGROUND: Prior evidence links posttraumatic stress disorder (PTSD) and depression, separately, with chronic inflammation. However, whether effects are similar across each independently or potentiated when both are present is understudied. We evaluated combined measures of PTSD and depression in relation to inflammatory biomarker concentrations. METHODS: Data are from women (n's ranging 628-2797) in the Nurses' Health Study II. Trauma exposure, PTSD, and depression symptoms were ascertained using validated questionnaires. We examined (a) a continuous combined psychological distress score summing symptoms for PTSD and depression, and (b) a categorical cross-classified measure of trauma/PTSD symptoms/depressed mood status (reference group: no trauma or depressed mood). Three inflammatory biomarkers (C-reactive protein [CRP], interleukin-6 [IL-6], tumor necrosis factor alpha receptor 2 [TNFR2]) were assayed from at least one of two blood samples collected 10-16 years apart. We examined associations of our exposures with levels of each biomarker concentration (log-transformed and batch-corrected) as available across the two time points (cross-sectional analyses; CRP, IL-6 and TNFR2) and with rate of change in biomarkers across time (longitudinal analyses; CRP and IL-6) using separate linear mixed effects models. RESULTS: In sociodemographic-adjusted models accounting for trauma exposure, a one standard deviation increase in the continuous combined psychological distress score was associated with 10.2% (95% confidence interval (CI): 5.2-15.4%) higher CRP and 1.5% (95% CI: 0.5-2.5%) higher TNFR2 concentrations cross-sectionally. For the categorical exposure, women with trauma/PTSD symptoms/ depressed mood versus those with no trauma or depressed mood had 29.5% (95% CI: 13.3-47.9%) higher CRP and 13.1% (95% CI: 5.1-21.7%) higher IL-6 cross-sectionally. In longitudinal analysis, trauma/PTSD symptoms/depressed mood was associated with increasing CRP levels over time. CONCLUSIONS: High psychological distress levels with trauma exposure is associated with elevated inflammation and is a potential biologic pathway by which distress can impact development of inflammatory-related chronic diseases, such as cardiovascular disease. Considering multiple forms of distress in relation to these pathways may provide greater insight into who is at risk for biologic dysregulation and later susceptibility to chronic diseases.

Posttraumatic stress disorder, cardiovascular disease outcomes and the modifying role of socioeconomic status.

INTRODUCTION: Substantial evidence indicates that post-traumatic stress disorder (PTSD) is associated with an increased incidence of cardiovascular disease (CVD), and differential PTSD-CVD association by socioeconomic status had been suggested. However, there are inadequate evidence on differential association. This study investigated sociodemographic heterogeneity in the association between PTSD and CVD. METHODS: A total of 53,749 patients diagnosed with PTSD in 2004-2018 were recruited from Korean National Health Insurance Database. Date of first diagnosis of PTSD was set as an index date. We recruited 3 controls per each patient, matched by age and sex (N = 161,247). Monthly insurance premiums were used as a surrogate variable for socioeconomic status. Cox proportional hazard model was used to estimate the hazard of incident coronary artery disease, incident stroke, and cardiovascular mortality. We stratified participants by age, sex, and insurance premium to test heterogeneities in the association. RESULTS: PTSD was associated with increased risk for coronary artery disease, hemorrhagic stroke, and cardiovascular mortality. Elevation in risk of cardiovascular disease was more prominent in younger individuals. PTSD increased the risk of coronary artery disease and ischemic stroke more in individuals with lower SES, especially in men. LIMITATIONS: Insurance premium might not fully represent socioeconomic status of individual. Misclassification or misdiagnosis of PTSD by might have introduced biases. CONCLUSIONS: PTSD was associated with increased incidence of CVD, particularly in male patients with low SES. For PTSD patients with lower SES, preventive measures against cardiovascular disease would be able to decrease the disease burden of cardiovascular comorbidity in PTSD.

Posttraumatic stress disorder and coping strategies in the postpartum period: A symptomics approach.

Posttraumatic stress disorder (PTSD) has been increasingly recognized as a potential mental health concern for new mothers. Elevated PTSD symptoms have been associated with maladaptive coping strategies in the postpartum period, a time when women face many challenges, demands, and stressors. However, PTSD symptoms manifest in heterogeneous ways, and focusing only on total symptom scores may obscure more nuanced associations with particular coping styles. In a large, ethnically diverse sample of postpartum women from across the United States (N = 1,315), first we examined associations between total PTSD symptom severity with three distinct coping styles: active-emotional, avoidant-emotional, and problem-focused. In models adjusting for race and educational attainment, total PTSD symptom severity was significantly positively associated with tendencies to use active- and avoidant-emotional, but not problem-focused, coping. We then adopted a novel "symptomics" approach, employing relative importance analyses to examine associations between individual PTSD symptoms with the coping styles. These analyses identified PTSD symptoms that were most strongly associated with each coping style. Notably, whereas several symptoms explained variance in avoidant-emotional coping, only a few symptoms contributed most to active-emotional and problem-focused coping. Moreover, non-specific symptoms of PTSD that are shared with other psychopathology (e.g., difficulty concentrating, loss of interest) explained significant proportions of variance across all coping styles. Collectively, results suggest that a symptomics approach may provide more nuanced insight into how PTSD symptoms are linked to various coping styles in postpartum women, which can help inform potential screening and intervention targets for at-risk women during this period.