Person:

Koenen, Karestan

Background: Shorter stature is associated with greater all cause and heart disease mortality, but taller stature with increased risk of cancer mortality. Though childhood environment is important in determining height, limited data address how maternal depression affects linear growth in children. We examined the relationships between antenatal and postpartum depressive symptoms and child height and linear growth from birth to age 3 years in a U.S. sample. Methods: Subjects were 872 mother-child pairs in Project Viva, a prospective pre-birth cohort study. The study population is relatively advantaged with high levels of income and education and low risk of food insecurity. We assessed maternal depression at mid-pregnancy (mean 28 weeks' gestation) and 6 months postpartum with the Edinburgh Postnatal Depression Scale (score > = 13 on 0–30 scale indicating probable depression). Child outcomes at age 3 were height-for-age z-score (HAZ) and leg length. HAZ was also available at birth and ages 6 months, 1, 2, and 3 years. Findings: Seventy (8.0%) women experienced antenatal depression and 64 (7.3%) experienced postpartum depression. The mean (SD) height for children age 3 was 97.2 cm (4.2), with leg length of 41.6 cm (2.6). In multivariable linear regression models, exposure to postpartum depression was associated with greater HAZ (0.37 [95% confidence interval: 0.16, 0.58]) and longer leg length (0.88 cm [0.35, 1.41]). The relationship between postpartum depression and greater HAZ was evident starting at 6 months and continued to age 3. We found minimal relationships between antenatal depression and child height outcomes. Conclusion: Our findings do not support the hypothesis that maternal depression is associated with reduced height in children in this relatively advantaged sample in a high-income country.

Background: One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder. Methods and design: We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD. The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach. Discussion: Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.

Background: This study examined the association between the type, and cumulative number of lifetime potentially traumatic events (PTEs), and chronic physical conditions, in a South African sample. PTE exposures have been associated with an increased risk for a wide range of chronic physical conditions, but it is unclear whether psychiatric disorders mediate this association. Given the established differences in trauma occurrence, and the epidemiology of posttraumatic stress disorder (PTSD) in South Africa relative to other countries, examining associations between PTEs and chronic physical conditions, particularly while accounting for psychiatric comorbidity is important. Methods: Data were drawn from the South African Stress and Health Study, a cross-sectional population-representative study of psychological and physical health of South African adults. Twenty-seven PTEs, based on the World Health Organization Composite International Diagnostic Interview Version 3.0, DSM-IV PTSD module were grouped into seven PTE types (war events, physical violence, sexual violence, accidents, unexpected death of a loved one, network events, and witnessing PTEs). Five clusters of physical conditions (cardiovascular, arthritis, respiratory, chronic pain, and other health conditions) were examined. Logistic regressions assessed the odds of reporting a physical condition in relation to type and cumulative number of PTEs. Cochran-Armitage test for trend was used to examine dose-response effect of cumulative PTEs on physical conditions. Results: After adjusting for sociodemographic variables and psychiatric disorders, respondents with any PTE had increased odds of all assessed physical conditions, ranging between 1.48 (95 % CI: 1.06–2.07) for arthritis and 2.07 (95 % CI: 1.57–2.73) for respiratory conditions, compared to those without PTE exposure. Sexual violence, physical violence, unexpected death of a loved one, and network PTEs significantly increased the odds of all or nearly all the physical conditions assessed. There was a dose-response relationship between number of PTEs and increased odds of all physical conditions. Conclusions: Results from this study, the first in an African general population, are consistent with other population-based studies; PTEs confer a broad-spectrum risk for chronic physical conditions, independent of psychiatric disorders. These risks increase with each cumulative PTE exposure. Clinically, comprehensive evaluations for risk of mental and physical health morbidities should be considered among PTE survivors.

Because environmental exposure to trauma is the sine qua non for the development of Post Traumatic Stress Disorder (PTSD), the recent focus on genetic studies has been noteworthy. The main catalyst for such studies is the observation from epidemiological studies that not all trauma survivors develop this disorder. Furthermore, neuroendocrine findings suggest pre-existing hormonal alterations that confer risk for PTSD. This paper presents the rationale for examining genetic factors in PTSD and trauma exposure, but suggests that studies of genotype may only present a limited picture of the molecular biology of this disorder. We describe the type of information that can be obtained from candidate gene and genomic studies that incorporate environmental factors in the design (i.e., gene – environment interaction and gene-environment correlation studies) and studies that capitalize on the idea that environment modifies gene expression, via epigenetic or other molecular mechanisms. The examination of epigenetic mechanisms in tandem with gene expression will help refine models that explain how PTSD risk, pathophysiology, and recovery is mediated by the environment. Since inherited genetic variation may also influence the extent of epigenetic or gene expression changes resulting from the environment, such studies should optimally be followed up by studies of genotype.

Background: Life trauma is highly prevalent in the general population and posttraumatic stress disorder is among the most prevalent psychiatric consequences of trauma exposure. Brazil has a unique environment to conduct translational research about psychological trauma and posttraumatic stress disorder, since urban violence became a Brazilian phenomenon, being particularly related to the rapid population growth of its cities. This research involves three case-control studies: a neuropsychological, a structural neuroimaging and a molecular neuroimaging study, each focusing on different objectives but providing complementary information. First, it aims to examine cognitive functioning of PTSD subjects and its relationships with symptomatology. The second objective is to evaluate neurostructural integrity of orbitofrontal cortex and hippocampus in PTSD subjects. The third aim is to evaluate if patients with PTSD have decreased dopamine transporter density in the basal ganglia as compared to resilient controls subjects. This paper shows the research rationale and design for these three case-control studies. Methods and design: Cases and controls will be identified through an epidemiologic survey conducted in the city of São Paulo. Subjects exposed to traumatic life experiences resulting in posttraumatic stress disorder (cases) will be compared to resilient victims of traumatic life experiences without PTSD (controls) aiming to identify biological variables that might protect or predispose to PTSD. In the neuropsychological case-control study, 100 patients with PTSD, will be compared with 100 victims of trauma without posttraumatic stress disorder, age- and sex-matched controls. Similarly, 50 cases and 50 controls will be enrolled for the structural study and 25 cases and 25 controls in the functional neuroimaging study. All individuals from the three studies will complete psychometrics and a structured clinical interview (the Structured Clinical Interview for DSM-IV and the Clinician-Administered PTSD Scale, Beck Anxiety Inventory, Beck Depression Inventory, Global Assessment of Function, The Social Adjustment Scale, Medical Outcomes Study 36-Item Short-Form Health Survey, Early Trauma Inventory, Clinical global Impressions, and Peritraumatic Dissociative Experiences Questionnaire). A broad neuropsychological battery will be administered for all participants of the neuropsychological study. Magnetic resonance scans will be performed to acquire structural neuroimaging data. Single photon emission computerized tomography with [(99m)Tc]-TRODAT-1 brain scans will be performed to evaluate dopamine transporters. Discussion: This study protocol will be informative for researchers and clinicians interested in considering, designing and/or conducting translational research in the field of trauma and posttraumatic stress disorder.

Background: Trauma exposure and posttraumatic stress disorder (PTSD) have been linked to myocardial infarction and stroke in women, with biological and behavioral mechanisms implicated in underlying risk. The third most common cardiovascular illness, venous thromboembolism (VTE), is a specific health risk for women. Given previous associations with other cardiovascular diseases, we hypothesized that high levels of trauma and PTSD symptoms would be associated with higher risk of incident VTE in younger and middle‐aged women. Methods and Results: We used proportional hazards models to estimate hazard ratios (HRs) and 95% CIs for new‐onset VTE (960 events) over 22 years in 49 296 women in the Nurses’ Health Study II. Compared to no trauma exposure, both trauma exposure and PTSD symptoms were significantly associated with increased risk of developing VTE, adjusting for demographics, family history, and childhood adiposity. Women with the most PTSD symptoms exhibited the greatest risk elevation: trauma/6 to 7 symptoms: HR=2.42 (95% CI, 1.83–3.20); trauma/4 to 5 symptoms: HR=2.00 (95% CI, 1.55–2.59); trauma/1 to 3 symptoms: HR=1.44 (95% CI, 1.12–1.84); trauma/no symptoms: HR=1.72 (95% CI, 1.43–2.08). Results were similar, although attenuated, when adjusting for VTE‐relevant medications, medical conditions, and health behaviors. Conclusions: Women with the highest PTSD symptom levels had nearly a 2‐fold increased risk of VTE compared to women without trauma exposure in fully adjusted models. Trauma exposure alone was also associated with elevated VTE risk. Trauma and PTSD symptoms may be associated with a hypercoagulable state. Treatment providers should be aware that women with trauma exposure and PTSD symptoms may be vulnerable to VTE.

Background: The nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear. Methods: We investigated the genetic overlap of PTSD with anthropometric traits and reproductive behaviors and functions in women. The analysis was conducted using female-specific summary statistics from large genome-wide association studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and 2611 trauma-exposed controls). We applied a high-resolution polygenic score approach and Mendelian randomization analysis to investigate genetic correlations and causal relationships. Results: We observed an inverse association of PTSD with genetically determined anthropometric traits related to body shape, independent of body mass index (BMI). The top association was related to BMI-adjusted waist circumference (WCadj; R = –0.079, P < 0.001, Q = 0.011). We estimated a relative decrease of 64.6% (95% confidence interval = 27.5–82.7) in the risk of PTSD per 1-SD increase in WCadj. MR-Egger regression intercept analysis showed no evidence of pleiotropic effects in this association (Ppleiotropy = 0.979). We also observed associations of genetically determined WCadj with age at first sexual intercourse and number of sexual partners (P = 0.013 and P < 0.001, respectively). Conclusions: There is a putative causal relationship between genetically determined female body shape and PTSD, which could be mediated by evolutionary mechanisms involved in human sexual behaviors. Electronic supplementary material The online version of this article (doi:10.1186/s13073-017-0491-4) contains supplementary material, which is available to authorized users.

Although earlier trauma exposure is known to predict post-traumatic stress disorder (PTSD) after subsequent traumas, it is unclear if this association is limited to cases where the earlier trauma led to PTSD. Resolution of this uncertainty has important implications for research on pre-trauma vulnerability to PTSD. We examined this issue in the WHO World Mental Health (WMH) Surveys with 34,676 respondents who reported lifetime trauma exposure. One lifetime trauma was selected randomly for each respondent. DSM-IV PTSD due to that trauma was assessed. We reported in a previous paper that four earlier traumas involving interpersonal violence significantly predicted PTSD after subsequent random traumas (OR=1.3–2.5). We also assessed 14 lifetime DSM-IV mood, anxiety, disruptive behavior, and substance disorders prior to random traumas. We show in the current report that only prior anxiety disorders significantly predicted PTSD in a multivariate model (OR=1.5–4.3) and that these disorders interacted significantly with three of the earlier traumas (witnessing atrocities, physical violence victimization, rape). History of witnessing atrocities significantly predicted PTSD after subsequent random traumas only among respondents with prior PTSD (OR=5.6). Histories of physical violence victimization (OR=1.5) and rape after age 17 (OR=17.6) significantly predicted only among respondents with no history of prior anxiety disorders. Although only preliminary due to reliance on retrospective reports, these results suggest that history of anxiety disorders and history of a limited number of earlier traumas might usefully be targeted in future prospective studies as distinct foci of research on individual differences in vulnerability to PTSD after subsequent traumas.

ABSTRACT Background:: Understanding the development of post-traumatic stress disorder (PTSD) is a precondition for efficient risk assessment and prevention planning. Studies to date have been site and sample specific. Towards developing generalizable models of PTSD development and prediction, the International Consortium to Predict PTSD (ICPP) compiled data from 13 longitudinal, acute-care based PTSD studies performed in six different countries. Objective:: The objectives of this study were to describe the ICPP’s approach to data pooling and harmonization, and present cross-study descriptive results informing the longitudinal course of PTSD after acute trauma. Methods:: Item-level data from 13 longitudinal studies of adult civilian trauma survivors were collected. Constructs (e.g. PTSD, depression), measures (questions or scales), and time variables (days from trauma) were identified and harmonized, and those with inconsistent coding (e.g. education, lifetime trauma exposure) were recoded. Administered in 11 studies, the Clinician Administered PTSD Scale (CAPS) emerged as the main measure of PTSD diagnosis and severity. Results:: The pooled data set included 6254 subjects (39.9% female). Studies’ average retention rate was 87.0% (range 49.1–93.5%). Participants’ baseline assessments took place within 2 months of trauma exposure. Follow-up durations ranged from 188 to 1110 days. Reflecting studies’ inclusion criteria, the prevalence of baseline PTSD differed significantly between studies (range 3.1–61.6%), and similar differences were observed in subsequent assessments (4.3–38.2% and 3.8–27.0% for second and third assessments, respectively). Conclusion:: Pooling data from independently collected studies requires careful curation of individual data sets for extracting and optimizing informative commonalities. However, it is an important step towards developing robust and generalizable prediction models for PTSD and can exceed findings of single studies. The large differences in prevalence of PTSD longitudinally cautions against using any individual study to infer trauma outcome. The multiplicity of instruments used in individual studies emphasizes the need for common data elements in future studies.