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.

Mental health among bereaved youth in the ALSPAC birth cohort: Consideration of early sociodemographic precursors, cognitive ability, and type of loss.

BACKGROUND: Bereaved youth are at greater risk for adverse mental health outcomes, yet less is known about how social context shapes health for bereaved children. Ecosocial theory is employed to conceptualize bereavement in the context of sociodemographic factors. METHOD: This longitudinal study used data from the Avon Longitudinal Study of Parents and Children. Of the 15,454 pregnancies enrolled, 5050 youth were still enrolled at age 16.5 and completed self-report questionnaires on life events and emotional/behavioral symptoms. RESULTS: Sociodemographic precursors associated with parent, sibling, or close friend bereavement included maternal smoking, parental education levels, and financial difficulties. The significant yet small main effect of higher cognitive ability, assessed at age 8, on reduced emotional/behavioral symptoms at age 16.5 (ß = -0.01, SE = 0.00, p < 0.001) did not interact with bereavement. Bereavement of a parent, sibling, or close friend was associated with a 0.19 point higher emotional/behavioral symptom log score compared to non-bereaved youth (95% CI: 0.10-0.28), across emotional, conduct, and hyperactivity subscales. CONCLUSIONS: Descriptive findings suggest sociodemographic precursors are associated with bereavement. While there was an association between the bereavement of a parent, sibling, or close friend and elevated emotional/behavioral symptoms, cognitive ability did not moderate that effect.

Association between trauma exposure and glucocorticosteroid concentration in hair during pregnancy.

BACKGROUND: Traumatic events, including child abuse and intimate partner violence, are highly prevalent among women of child-bearing age. These traumatic experiences may impact maternal and offspring physical and mental health. A proposed mechanism for these effects is maternal hypothalamic-pituitary-adrenal (HPA) axis dysregulation which can be measured using hair corticosteroid levels. AIMS: This study aims to examine the association of child abuse and intimate partner violence exposure with HPA axis functioning, as measured by hair corticosteroid levels in a cohort of pregnant women. METHODS: We included data from 1822 pregnant women (mean gestational age 17 weeks) attending a prenatal clinic in Lima, Peru. We extracted cortisol and cortisone concentrations from hair samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Each participant provided 6-cm hair samples: 3 cm hair segment closest to the scalp reflecting HCC in early pregnancy (first three months), and 3-6 cm from the scalp reflecting HCC in pre-pregnancy (three months prior to conception). Multivariable linear regression procedures were used to assess the association between maternal trauma exposure and hair corticosteroid levels. RESULTS: Overall, women who experienced child abuse on average had higher levels of cortisol (p < 0.01) and cortisone (p < 0.0001) after adjustment for age, race, adult access to basic foods and hair treatments. For the hair segment reflecting early pregnancy, presence of child abuse was associated with a 0.120 log unit increase in cortisol and a 0.260 log unit increase in cortisone (p < 0.001). For the hair segment reflecting pre-pregnancy, a history of child abuse was associated with a 0.100 log unit increase in cortisol and a 0.180 log unit increase in cortisone (p < 0.01). Results also suggested an impact of intimate partner violence on HPA regulation; however, associations were not statistically significant after controlling for child abuse. CONCLUSIONS: These results underscore the long-lasting impacts of exposure to adversity and trauma during early life. Our study findings will have implications for research investigating HPA axis function and long-term effects of violence on corticosteroid regulation.

Posttraumatic Stress Disorder and Risk of Systemic Lupus Erythematosus Among Medicaid Recipients.

OBJECTIVE: We studied posttraumatic stress disorder (PTSD), a severe trauma-related mental disorder, and systemic lupus erythematosus (SLE) risk in a large, diverse population enrolled in Medicaid, a US government-sponsored health insurance program for low-income individuals. METHODS: We identified SLE cases and controls among patients ages 18-65 years enrolled in Medicaid for ≥12 months in the 29 most populated US states from 2007 to 2010. SLE and PTSD case statuses were defined based on validated patterns of International Classification of Diseases, Ninth Revision codes. Index date was the date of the first SLE code. Controls had no SLE codes but had another inpatient or outpatient code on the index date and were matched 1:10 to cases by age, sex, and race. Conditional logistic regressions calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of PTSD with incident SLE, adjusting for smoking, obesity, oral contraceptive use, and other covariates. RESULTS: A total of 10,942 incident SLE cases were matched to 109,420 controls. The prevalence of PTSD was higher in SLE cases, at 10.74 cases of PTSD per 1,000 person-years (95% CI 9.37-12.31) versus 7.83 cases (95% CI 7.42-8.27) in controls. The multivariable-adjusted OR for SLE among those with PTSD was 2.00 (95% CI 1.64-2.46). CONCLUSION: In this large, racially and sociodemographically diverse US population, we found patients with a prior PTSD diagnosis had twice the odds of a subsequent diagnosis of SLE. Studies are necessary to clarify the mechanisms driving the observed association and to inform possible interventions.

Shared genetic influences on depression and menopause symptoms.

BACKGROUND: Women experience major depression and post-traumatic stress disorder (PTSD) approximately twice as often as men. Estrogen is thought to contribute to sex differences in these disorders, and reduced estrogen is also known to be a key driver of menopause symptoms such as hot flashes. Moreover, estrogen is used to treat menopause symptoms. In order to test for potential shared genetic influences between menopause symptoms and psychiatric disorders, we conducted a genome-wide association study (GWAS) of estrogen medication use (as a proxy for menopause symptoms) in the UK Biobank. METHODS: The analysis included 232 993 women aged 39-71 in the UK Biobank. The outcome variable for genetic analyses was estrogen medication use, excluding women using hormonal contraceptives. Trans-ancestry GWAS meta-analyses were conducted along with genetic correlation analyses on the European ancestry GWAS results. Hormone usage was also tested for association with depression and PTSD. RESULTS: GWAS of estrogen medication use (compared to non-use) identified a locus in the TACR3 gene, which was previously linked to hot flashes in menopause [top rs77322567, odds ratio (OR) = 0.78, p = 7.7 × 10-15]. Genetic correlation analyses revealed shared genetic influences on menopause symptoms and depression (rg = 0.231, s.e.= 0.055, p = 2.8 × 10-5). Non-genetic analyses revealed higher psychiatric symptoms scores among women using estrogen medications. CONCLUSIONS: These results suggest that menopause symptoms have a complex genetic etiology which is partially shared with genetic influences on depression. Moreover, the TACR3 gene identified here has direct clinical relevance; antagonists for the neurokinin 3 receptor (coded for by TACR3) are effective treatments for hot flashes.

Association of maternal polygenic risk scores for mental illness with perinatal risk factors for offspring mental illness.

We examined whether genetic risk for mental illness is associated with known perinatal risk factors for offspring mental illness to determine whether gene-environmental correlation might account for the associations of perinatal factors with mental illness. Among 8983 women with 19,733 pregnancies, we found that genetic risk for mental illness was associated with any smoking during pregnancy [attention-deficit hyperactivity disorder (ADHD) and overall genetic risk], breast-feeding for less than 1 month (ADHD, depression, and overall genetic risk), experience of intimate partner violence in the year before the birth (depression and overall genetic risk), and pregestational overweight or obesity (bipolar disorder). These results indicate that genetic risk may partly account for the association between perinatal conditions and mental illness in offspring.

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.

Genome-wide association study of posttraumatic stress disorder among childhood cancer survivors: results from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

Genetic influence shapes who develops posttraumatic stress disorder (PTSD) after traumatic events. However, the genetic variants identified for PTSD may in fact be associated with traumatic exposures (e.g., interpersonal violence), which appear heritable as well. Childhood cancer survivors (CCS) are at risk for PTSD, but genetic influences affecting cancer are unlikely to overlap with those affecting PTSD. This offers a unique opportunity to identify variants specific to PTSD risk. In a genome-wide association study (GWAS), 3984 5-year survivors of childhood cancer of European-ancestry from the Childhood Cancer Survivor Study (CCSS) were evaluated for discovery and 1467 survivors from the St. Jude Lifetime (SJLIFE) cohort for replication. Childhood cancer-related PTSD symptoms were assessed using the Posttraumatic Stress Diagnostic Scale in CCSS. GWAS was performed in CCSS using logistic regression and lead markers were replicated/meta-analyzed using SJLIFE. Cross-associations of identified loci were examined between CCS and the general population. PTSD criteria were met for 671 participants in CCSS and 161 in SJLIFE. Locus 10q26.3 was significantly associated with PTSD (rs34713356, functionally mapped to ECHS1, P = 1.36 × 10-8, OR 1.57), and was replicated in SJLIFE (P = 0.047, OR 1.37). Variants in locus 6q24.3-q25.1 reached marginal significance (rs9390543, SASH1, P = 3.56 × 10-6, OR 0.75) in CCSS and significance when meta-analyzing with SJLIFE (P = 2.02 × 10-8, OR 0.75). Both loci were exclusively associated with PTSD in CCS rather than PTSD/stress-related disorders in general population (P-for-heterogeneity < 5 × 10-6). Our CCS findings support the role of genetic variation in PTSD development and may provide implications for understanding PTSD heterogeneity.

Posttraumatic stress disorder symptoms and timing of menopause and gynecological surgery in the Nurses' Health Study II.

BACKGROUND: Earlier menopause, either natural or through gynecologic surgeries, has been associated with various negative health sequelae. While posttraumatic stress disorder (PTSD) has been linked to dysregulated biological processes, including reproductive system changes that could alter menopausal timing, little work has examined whether trauma and PTSD are associated with greater risk of early cessation of menses. METHODS: Data are from 46,639 women in the Nurses' Health Study II, a prospective cohort study of women followed for up to 26 years. Lifetime trauma and PTSD symptoms were assessed with the Brief Trauma Questionnaire and a PTSD symptom screener in 2008. Age at cessation of menses and reason for cessation of menses (i.e., natural menopause, gynecologic surgery including hysterectomy and/or bilateral salpingo-oophorectomy [BSO]) were assessed. Cox proportional hazards models estimated hazards ratios (HR) of cessation of menses (separately for naturally or surgically) associated with trauma alone or PTSD symptoms, relative to no trauma, adjusting for covariates. RESULTS: Trauma/PTSD status was associated with earlier cessation of menses due to surgery, but not natural menopause. Women with trauma exposure, low, and high PTSD symptoms had higher hazard of cessation of menses due to surgery relative to those with no trauma exposure (HRtrauma = 1.16, 95%CI 1.07-1.26; HRlow PTSD = 1.25, 95%CI 1.15-1.36; HRhigh PTSD = 1.29, 95%CI 1.17-1.42). Trauma exposure and PTSD symptoms were associated with similarly increased risk of hysterectomy and BSO surgeries. CONCLUSIONS: Women who experienced trauma and PTSD may be at elevated risk for common gynecological surgeries premenopausally, potentially due to increased clinical indications or gynecological conditions.

Suicide attempt, impulsivity, and exposure to trauma in college students

Objectives: Past suicide attempt (SA) is one of the most important risk factors for suicide death. An ideation-to-action framework posits that impulsivity, potentially traumatic events, and mental disorders also play a role in increasing suicide risk. This study aimed to assess the association between trait impulsivity, lifetime exposure to trauma, and post-traumatic stress disorder (PTSD) with SA in a sample of Brazilian college students. Methods: A total of 2,137 participants filled self-reported questionnaires consisting of a sociodemographic and clinical questionnaire, Trauma History Questionnaire, Post-Traumatic Stress Disorder Checklist - Civilian version, and Barratt Impulsiveness Scale. Results: Our findings suggest that trait impulsivity may be interpreted as exerting a distal effect on SA, even in the presence of other variables - such as trauma history, psychological neglect, and PTSD - which also increase the odds of SA. High and medium levels of impulsivity, history of trauma, and PTSD increased the likelihood of SA. Conclusions: Intervention strategies to prevent SA may target trait impulsivity and exposure to traumatic experiences.

Childhood Abuse and Cognitive Function in a Large Cohort of Middle-Aged Women.

Cognitive function at middle age is of particular public health interest, as it strongly predicts later dementia. Children who have experienced abuse subsequently have worse cognitive function than those who have not. However, it remains unclear whether the association of abuse with cognitive function persists into middle age. In 2014-2016, 14,151 women ages 49-69 years who had previously responded to a childhood abuse questionnaire completed a cognitive battery. In models adjusted for childhood socioeconomic status and head trauma, combined physical, emotional, and sexual abuse was associated with lower scores on both Learning/Working Memory (severe abuse, lower scores similar to that observed in women 4.8 years older in our data) and Psychomotor Speed/Attention (severe abuse, lower scores similar to that observed in women to 2.9 years older in our data). Adjustment for adulthood socioeconomic status and health factors (e.g., smoking, hypertension) slightly attenuated associations. In exploratory analyses further adjusted for psychological distress, associations were attenuated. Women exposed versus unexposed to childhood abuse had poorer cognitive function at mid-life. Associations were particularly strong for learning and working memory and were not accounted for by adulthood health factors. Childhood abuse should be investigated as a potential risk factor for cognitive decline and dementia in old age.

Drugs age-of-onset as a signal of later post-traumatic stress disorder: Bayesian analysis of a census protocol.

Individuals with PTSD have an increased risk of drug use disorders. Conversely, we aim to evaluate how early onset of alcohol, tobacco and psychoactive drugs use are associated with PTSD later in life. 2,193 brazilian young adults completed modularized assessments: The Trauma History Questionnaire, Post-Traumatic Stress Disorder Checklist-Civilian Version (PCL-C, transformed to PCL-5 through a crosswalk procedure), the Barratt Impulsivity Scale; and a survey on drug use with self-report questions about first use, current use, frequency, quantity, and interpersonal consequences. Bayesian inference and multivariate regression models were used to examine the effects on the risk of PTSD, considering different assumptions of information flow. Raw and unbiased (multivariate) estimates consistently revealed that earlier age of onset of alcohol and tobacco use increased risk for PTSD (Odds-ratios between 2.39 and 3.19 (Alcohol) and 1.82 to 2.05 (Tobacco). Among those who had PTSD (310), 10.3% (32) were very precocious at the onset age (12 to 18 years) of alcohol consumption (No-PTSD: 89 out 1883, 4.7%). Data supports a model in which age of onset effects are partially mediated by the number of trauma exposures. Early intoxication might suggest vulnerability for qualifying trauma events, or it may increase chances of exposure. Also, PTSD may be more likely to occur among trauma-exposed individuals with early intoxicating experiences due to alcohol or drug self-administration. The last possibility resonates with the idea that early intoxication might disrupt adolescent brain development, with a subsequent reduction in resilience when qualifying trauma events occur.

Maternal psychosocial risk factors and child gestational epigenetic age in a South African birth cohort study.

Accelerated epigenetic aging relative to chronological age has been found to be associated with higher risk of mortality in adults. However, little is known about whether and how in utero exposures might shape child gestational epigenetic age (EA) at birth. We aimed to explore associations between maternal psychosocial risk factors and deviation in child gestational EA at birth (i.e., greater or lower EA relative to chronological age) in a South African birth cohort study-the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression; psychological distress; and alcohol/tobacco use. Child gestational EA at birth was calculated using an epigenetic clock previously devised for neonates; and gestational EA deviation was calculated as the residuals of the linear model between EA and chronological gestational age. Bivariate linear regression was then used to explore unadjusted associations between maternal/child risk factors and child gestational EA residuals at birth. Thereafter, a multivariable regression method was used to determine adjusted associations. Data from 271 maternal-child dyads were included in the current analysis. In the multivariable regression model, maternal PTSD was significantly and negatively associated with child gestational EA residuals at birth (ß = -1.95; p = 0.018), controlling for study site, sex of the child, head circumference at birth, birthweight, mode of delivery, maternal estimated household income, body mass index (BMI) at enrolment, HIV status, anaemia, psychological distress, and prenatal tobacco or alcohol use. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA deviation are warranted.

Posttraumatic Stress Disorder and Likelihood of Hormone Therapy Use among Women in the Nurses' Health Study II: A 26-Year Prospective Analysis.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with higher risk of certain chronic diseases, including ovarian cancer, but underlying mechanisms remain unclear. Although prior work has linked menopausal hormone therapy (MHT) use with elevated ovarian cancer risk, little research considers PTSD to likelihood of MHT use. We examined whether PTSD was prospectively associated with greater likelihood of initiating MHT use over 26 years. METHODS: Using data from the Nurses' Health Study II, with trauma and PTSD (symptoms and onset date) assessed by screener in 2008 and MHT assessed via biennial survey (from 1989), we performed Cox proportional regression models with women contributing person-years from age 36 years. Relevant covariates were assessed at biennial surveys. We considered potential effect modification by race/ethnicity, age at baseline, and period (1989-2002 vs. 2003-2015). RESULTS: Over follow-up, 22,352 of 43,025 women reported initiating MHT use. For example, compared with women with no trauma, the HR for initiating MHT was 1.18 for those with trauma/1-3 PTSD symptoms [95% confidence interval (CI), 1.13-1.22] and 1.31 for those with trauma/4-7 PTSD symptoms (95% CI, 1.25-1.36; P trend < 0.001), adjusting for sociodemographic factors. Associations were maintained when adjusting for reproductive factors and health conditions. We found evidence of effect modification by age at baseline. CONCLUSIONS: Trauma and number of PTSD symptoms were associated with greater likelihood of initiating MHT use in a dose-response manner. IMPACT: MHT may be a pathway linking PTSD to altered chronic disease risk. It is important to understand why women with PTSD initiate MHT use.

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

The COronavirus Pandemic Epidemiology (COPE) Consortium: A Call to Action.

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

Evaluating a screener to quantify PTSD risk using emergency care information: a proof of concept study.

BACKGROUND: Previous work has indicated that post-traumatic stress disorder (PTSD) symptoms, measured by the Clinician-Administered PTSD Scale (CAPS) within 60 days of trauma exposure, can reliably produce likelihood estimates of chronic PTSD among trauma survivors admitted to acute care centers. Administering the CAPS is burdensome, requires skilled professionals, and relies on symptoms that are not fully expressed upon acute care admission. Predicting chronic PTSD from peritraumatic responses, which are obtainable upon acute care admission, has yielded conflicting results, hence the rationale for a stepwise screening-and-prediction practice. This work explores the ability of peritraumatic responses to produce risk likelihood estimates of early CAPS-based PTSD symptoms indicative of chronic PTSD risk. It specifically evaluates the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) as a risk-likelihood estimator. METHODS: We used individual participant data (IPD) from five acute care studies that used both the PDEQ and the CAPS (n = 647). Logistic regression calculated the probability of having CAPS scores ≥ 40 between 30 and 60 days after trauma exposure across the range of initial PDEQ scores, and evaluated the added contribution of age, sex, trauma type, and prior trauma exposure. Brier scores, area under the receiver-operating characteristic curve (AUC), and the mean slope of the calibration line evaluated the accuracy and precision of the predicted probabilities. RESULTS: Twenty percent of the sample had CAPS ≥ 40. PDEQ severity significantly predicted having CAPS ≥ 40 symptoms (p < 0.001). Incremental PDEQ scores produced a reliable estimator of CAPS ≥ 40 likelihood. An individual risk estimation tool incorporating PDEQ and other significant risk indicators is provided. CONCLUSION: Peritraumatic reactions, measured here by the PDEQ, can reliably quantify the likelihood of acute PTSD symptoms predictive of chronic PTSD and requiring clinical attention. Using them as a screener in a stepwise chronic PTSD prediction strategy may reduce the burden of later CAPS-based assessments. Other peritraumatic metrics may perform similarly and their use requires similar validation. TRIAL REGISTRATION: Jerusalem Trauma Outreach and Prevention Study (J-TOPS): NCT00146900.

A neurobiological mechanism linking transportation noise to cardiovascular disease in humans.

AIMS: Chronic noise exposure associates with increased cardiovascular disease (CVD) risk; however, the role of confounders and the underlying mechanism remain incompletely defined. The amygdala, a limbic centre involved in stress perception, participates in the response to noise. Higher amygdalar metabolic activity (AmygA) associates with increased CVD risk through a mechanism involving heightened arterial inflammation (ArtI). Accordingly, in this retrospective study, we tested whether greater noise exposure associates with higher: (i) AmygA, (ii) ArtI, and (iii) risk for major adverse cardiovascular disease events (MACE). METHODS AND RESULTS: Adults (N = 498) without CVD or active cancer underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Amygdalar metabolic activity and ArtI were measured, and MACE within 5 years was adjudicated. Average 24-h transportation noise and potential confounders were estimated at each individual's home address. Over a median 4.06 years, 40 individuals experienced MACE. Higher noise exposure (per 5 dBA increase) predicted MACE [hazard ratio (95% confidence interval, CI) 1.341 (1.147-1.567), P < 0.001] and remained robust to multivariable adjustments. Higher noise exposure associated with increased AmygA [standardized ß (95% CI) 0.112 (0.051-0.174), P < 0.001] and ArtI [0.045 (0.001-0.090), P = 0.047]. Mediation analysis suggested that higher noise exposure associates with MACE via a serial mechanism involving heightened AmygA and ArtI that accounts for 12-26% of this relationship. CONCLUSION: Our findings suggest that noise exposure associates with MACE via a mechanism that begins with increased stress-associated limbic (amygdalar) activity and includes heightened arterial inflammation. This potential neurobiological mechanism linking noise to CVD merits further evaluation in a prospective population.

Posttraumatic Stress Disorder Is Associated with Increased Risk of Ovarian Cancer: A Prospective and Retrospective Longitudinal Cohort Study.

Ovarian cancer is the deadliest gynecologic cancer. Chronic stress accelerates tumor growth in animal models of ovarian cancer. We therefore postulated that posttraumatic stress disorder (PTSD) may be associated with increased risk of ovarian cancer. We used data from the Nurses' Health Study II, a longitudinal cohort study with 26 years of follow-up, conducted from 1989 to 2015 with 54,710 subjects. Lifetime PTSD symptoms were measured in 2008. Self-reported ovarian cancer was validated with medical records. Risk of ovarian cancer was estimated with Cox proportional hazards models and further adjusted for known ovarian cancer risk factors (e.g., hormonal factors) and health risk factors (e.g., smoking). Fully prospective secondary analyses examined incident ovarian cancer occurring after PTSD assessment in 2008. In addition, we examined associations by menopausal status. During follow-up, 110 ovarian cancers were identified. Women with high PTSD symptoms had 2-fold greater risk of ovarian cancer versus women with no trauma exposure [age-adjusted HR = 2.10; 95% confidence interval (CI), 1.12-3.95]. Adjustment for health and ovarian cancer risk factors moderately attenuated this association (HR = 1.86; 95% CI, 0.98-3.51). Associations were similar or moderately stronger in fully prospective analyses (age-adjusted HR = 2.38; 95% CI, 0.98-5.76, N cases = 50) and in premenopausal women (HR = 3.42; 95% CI, 1.08-10.85). In conclusion, we show that PTSD symptoms are associated with increased risk of ovarian cancer. Better understanding of the underlying molecular mechanisms could lead to interventions that reduce ovarian cancer risk in women with PTSD and other stress-related mental disorders. SIGNIFICANCE: PTSD is associated with ovarian cancer risk, particularly in premenopausal women. Understanding the underlying molecular mechanisms will aid in formulating ways to reduce ovarian cancer risk associated with chronic stress.

Amygdalar Metabolic Activity Independently Associates With Progression of Visceral Adiposity.

CONTEXT: Epidemiologic data link psychological stress to adiposity. The underlying mechanisms remain uncertain. OBJECTIVES: To test whether (i) higher activity of the amygdala, a neural center involved in the response to stress, associates with greater visceral adipose tissue (VAT) volumes and (ii) this association is mediated by increased bone marrow activity. SETTING: Massachusetts General Hospital, Boston, Massachusetts. PATIENTS: Two hundred forty-six patients without active oncologic, cardiovascular, or inflammatory disease who underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging were studied. VAT imaging was repeated ∼1 year later in 68 subjects. DESIGN: Metabolic activity of the amygdala (AmygA), hematopoietic tissue activity, and adiposity volumes were measured with validated methods. MAIN OUTCOME MEASURE: The relationship between AmygA and baseline and follow-up VAT. RESULTS: AmygA associated with baseline body mass index (standardized ß = 0.15; P = 0.01), VAT (0.19; P = 0.002), and VAT/subcutaneous adipose tissue ratio (0.20; P = 0.002), all remaining significant after adjustment for age and sex. AmygA also associated with bone marrow activity (0.15; P = 0.01), which in turn associated with VAT (0.34; P < 0.001). Furthermore, path analysis showed that 48% of the relationship between AmygA and baseline VAT was mediated by increased bone marrow activity (P = 0.007). Moreover, AmygA associated with achieved VAT after 1 year (P = 0.02) after adjusting for age, sex, and baseline VAT. CONCLUSIONS: These results suggest a neurobiological pathway involving the amygdala and bone marrow linking psychosocial stress to adiposity in humans. Future studies should test whether targeting this mechanism attenuates adiposity and its complications.