Person:

Wright, Rosalind Jo

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.

Purpose

To assess the association between self-reported racial discrimination and prenatal depressive symptoms among black women.

Methods

Our study population consisted of two cohorts of pregnant women: the Asthma Coalition on Community, Environment, and Social Stress project (ACCESS) and Project Viva. We measured self-reported racial discrimination among black women using a modified Experiences of Discrimination scale (score 0–8). We assessed elevated depressive symptoms (EDS) with the Edinburgh Postnatal Depression Scale (≥13 on a 0–30 scale).

Results

Fifty-four percent of ACCESS and 78% of Viva participants reported experiencing racial discrimination. After adjusting for age, marital status, income, education, and nativity, a 1-U increment in Experiences of Discrimination score was associated with 48% increased odds of EDS (odds ratio, 1.48; 95% confidence interval, 1.24–1.76) for ACCESS participants but was not significantly associated among Viva participants (odds ratio, 1.12; 95% confidence interval, 0.92–1.37). In both cohorts, responding to unfair treatment by talking to others was associated with the lowest odds of EDS.

Conclusions

Our findings suggest that higher levels of perceived racial discrimination may increase depressive symptoms during pregnancy among U.S. black women. Interventions involving talking to others may aid in reducing the risk of depressive symptoms among black women experiencing higher levels of racial discrimination.

Background To investigate lifetime history of interpersonal abuse and risk of pre-natal depression in socio-economically distinct populations in the same city.

Methods We examined associations of physical and sexual abuse with the risk of pre-natal depression in two cohorts in the Boston area, including 2128 participants recruited from a large urban- and suburban-managed care organization (Project Viva) and 1509 participants recruited primarily from urban community health centres (Project ACCESS). Protocols for the studies were designed in parallel to allow us to merge data to enhance ethnic and socio-economic diversity in the combined sample. In mid-pregnancy, the Personal Safety Questionnaire and Edinburgh Postnatal Depression Scale (EPDS) were administered in both cohorts. An EPDS score ≥13 indicated probable pre-natal depression. Logistic regression was used to estimate the odds ratio (OR) of pre-natal depression associated with lifetime abuse history.

Results Project ACCESS participants were twice as likely as Project Viva participants to report symptoms consistent with pre-natal depression: 22% of Project ACCESS participants had EPDS scores ≥13, compared with 11% of Project Viva participants. Fifty-seven percent of women in ACCESS and 46% in Viva reported lifetime physical and/or sexual abuse. In merged analysis, women reporting lifetime physical or sexual abuse had an OR for mid-pregnancy depression of 1.63 [95% confidence interval (95% CI): 1.29–2.07], adjusted for age and race/ethnicity. Lifetime histories of physical abuse [OR 1.48 (95% CI 1.15–1.90)] and sexual abuse [OR 1.68 (95% CI 1.24–2.28)] were independently associated with pre-natal depression. When child/teen, pre-pregnancy adult and pregnancy life periods were considered simultaneously, abuse in childhood was independently associated with an OR of 1.23 (95% CI 1.00–1.59), pre-pregnancy adult abuse with an OR of 1.70 (95% CI 1.31–2.21) and abuse during pregnancy with an OR of 1.77 (95% CI 1.14–2.74). Further adjustment for childhood socio-economic position made no material difference, and there were no clear interactions between abuse and adult socio-economic position.

Conclusions Physical and sexual abuse histories were positively associated with pre-natal depression in two economically and ethnically distinct populations. Stronger associations with recent abuse may indicate that the association of abuse with depression wanes with time or may result from less accurate recall of remote events.

Background: Although child abuse is associated with obesity, it is not known whether early abuse increases risk of type 2 diabetes. Purpose: To investigate associations of child and adolescent abuse with adult diabetes. Methods: Proportional hazards models were used to examine associations of lifetime abuse reported in 2001 with risk of diabetes from 1989 to 2005 among 67,853 women in the Nurses' Health Study II. Data were analyzed in 2009. Results: Child or teen physical abuse was reported by 54% and sexual abuse by 34% of participants. Models were adjusted for age, race, body type at age 5 years, and parental education and history of diabetes. Compared to women who reported no physical abuse, the hazards ratio (HR) was 1.03 (95% CI=0.91, 1.17) for mild physical abuse; 1.26 (1.14, 1.40) for moderate physical abuse; and 1.54 (1.34, 1.77) for severe physical abuse. Compared with women reporting no sexual abuse in childhood or adolescence, the HR was 1.16 (95% CI=1.05, 1.29) for unwanted sexual touching; 1.34 (1.13, 1.59) for one episode of forced sexual activity; and 1.69 (1.45, 1.97) for repeated forced sex. Adult BMI accounted for 60% (95% CI=32%, 87%) of the association of child and adolescent physical abuse and 64% (95% CI=38%, 91%) of the association of sexual abuse with diabetes. Conclusions: Moderate to severe physical and sexual abuse in childhood and adolescence have dose–response associations with risk of type 2 diabetes among adult women. This excess risk is partially explained by the higher BMI of women with a history of early abuse.