Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods and design</p> <p>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.</p> <p>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.</p> <p>Discussion</p> <p>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.</p

Supportive and Stressful Relationships With Teachers, Peers and Family and Their Influence on Students' Social/Emotional and Academic Experience of School

Binghamton, New Yor

Witnessing Community Violence in Residential Neighborhoods: A Mental Health Hazard for Urban Women

We examined the prevalence and psychological correlates of witnessing community violence among women of low socioeconomic status living in urban neighborhoods in the northeastern United States. Three hundred eighty-six women receiving their health care at an urban community health center were sampled to assess their violence exposures. Women were asked to report the location and timing of their exposure to witnessing violent neighborhood events in which they were not participants. The Brief Symptoms Inventory was used to assess anxiety and depressive symptoms. Controlling for marital status, educational attainment, age, and intimate partner violence victimization, women who witnessed violent acts in their neighborhoods were twice as likely to experience depressive and anxiety symptoms compared to women who did not witness community violence. Central American-born women had particularly high exposures. We conclude that witnessing neighborhood violence is a pervasive experience in this urban cohort, and is associated with anxiety and depressive symptoms, even among women who are not direct participants in violence to which they are exposed. Community violence interventions must incorporate efforts to protect the mental health of adult women who witness events in their neighborhoods