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.

Metabolomic profiles of chronic distress are associated with cardiovascular disease risk and inflammation-related risk factors.

BACKGROUND: Chronic psychological distress is associated with increased risk of cardiovascular disease (CVD) and investigators have posited inflammatory factors may be centrally involved in these relationships. However, mechanistic evidence and molecular underpinnings of these processes remain unclear, and data are particularly sparse among women. This study examined if a metabolite profile linked with distress was associated with increased CVD risk and inflammation-related risk factors. METHODS: A plasma metabolite-based distress score (MDS) of twenty chronic psychological distress-related metabolites was developed in cross-sectional, 1:1 matched case-control data comprised of 558 women from the Nurses' Health Study (NHS; 279 women with distress, 279 controls). This MDS was then evaluated in two other cohorts: the Women's Health Initiative Observational Cohort (WHI-OS) and the Prevención con Dieta Mediterránea (PREDIMED) trial. We tested the MDS's association with risk of future CVD in each sample and with levels of C-reactive protein (CRP) in the WHI-OS. The WHI-OS subsample included 944 postmenopausal women (472 CHD cases; mean time to event = 5.8 years); the PREDIMED subsample included 980 men and women (224 CVD cases, mean time to event = 3.1 years). RESULTS: In the WHI-OS, a 1-SD increase in the plasma MDS was associated with a 20% increased incident CHD risk (odds ratio [OR] = 1.20, 95% CI: 1.04 - 1.38), adjusting for known CVD risk factors excluding total and HDL cholesterol. This association was attenuated after including total and HDL cholesterol. CRP mediated an average 12.9% (95% CI: 4.9% - 28%, p < 10-15) of the total effect of MDS on CHD risk when adjusting for matching factors. This effect was attenuated after adjusting for known CVD risk factors. Of the metabolites in the MDS, tryptophan and threonine were inversely associated with incident CHD risk in univariate models. In PREDIMED, each one SD increase in the MDS was associated with an OR of 1.19 (95% CI: 1.00 - 1.41) for incident CVD risk, after adjusting all risk factors. Similar associations were observed in men and women. Four metabolites in the MDS were associated with incident CVD risk in PREDIMED in univariate models. Biliverdin and C36:5 phosphatidylcholine (PC) plasmalogen had inverse associations; C16:0 ceramide and C18:0 lysophosphatidylethanolamine(LPE) each had positive associations with CVD risk. CONCLUSIONS: Our study points to molecular alterations that may underlie the association between chronic distress and subsequent risk of cardiovascular disease in adults.

Bereavement, Memorial Attendance, and Mental Health During the COVID-19 Pandemic: Longitudinal Results from the Nurses' Health Study.

BACKGROUND: Mortality increased during the COVID-19 pandemic. Many bereaved individuals were not able to gather to memorialize their loved ones, yet it is unknown if this contributed to worsening mental health. OBJECTIVE: Examine the association of bereavement in the early part of the COVID-19 pandemic with subsequent psychological distress and the role of memorial attendance in reducing psychological distress among the bereaved. DESIGN, SETTINGS, SUBJECTS: In May 2020, 39,564 older females from the Nurses' Health Study II enrolled in a longitudinal COVID-19 substudy (meanage = 65.2 years, SD = 4.5). METHODS: Linear regression analyses estimated associations of bereavement reported between March and October, 2020 with subsequent psychological distress between January and October 2021, adjusting for sociodemographic and prepandemic depression symptoms. Secondary models examined associations between memorial attendance and psychological distress. RESULTS: Bereavement during the early part of the COVID-19 pandemic was associated with higher psychological distress (adjusted ß = 0.21, 95% CI: 0.15, 0.26) assessed over the next year. Among the bereaved, memorial attendance was associated with lower psychological distress (in-person: adjusted ß = -0.41, 95% CI: -0.53, -0.29; online: adjusted ß = -0.24, 95% CI: -0.46, --0.02). CONCLUSION: Attending memorials was associated with lower subsequent psychological distress among bereaved older females.

Genetic Influences on Longitudinal Trajectories of Cortical Thickness and Surface Area during the First 2 Years of Life.

Genetic influences on cortical thickness (CT) and surface area (SA) are known to vary across the life span. Little is known about the extent to which genetic factors influence CT and SA in infancy and toddlerhood. We performed the first longitudinal assessment of genetic influences on variation in CT and SA in 501 twins who were aged 0-2 years. We observed substantial additive genetic influences on both average CT (0.48 in neonates, 0.37 in 1-year-olds, and 0.44 in 2-year-olds) and total SA (0.59 in neonates, 0.74 in 1-year-olds, and 0.73 in 2-year-olds). In addition, we found strong heritability of the change in average CT (0.49) from neonates to 1-year-olds, but not from 1- to 2-year-olds. Moreover, we found strong genetic correlations for average CT (rG = 0.92) between 1- and 2-year-olds and strong genetic correlations for total SA across all timepoints (rG = 0.96 between neonates and 1-year-olds, rG = 1 between 1- and 2-year-olds). In addition, we found CT and SA are strongly genetic correlated at birth, but weaken over time. Overall, results suggest a dynamic genetic relationship between CT and SA during first 2 years of life and provide novel insights into how genetic influences shape the cortical structure during early brain development.

Influence of gonadal steroids on cortical surface area in infancy.

Sex differences in the human brain emerge as early as mid-gestation and have been linked to sex hormones, particularly testosterone. Here, we analyzed the influence of markers of early sex hormone exposure (polygenic risk score (PRS) for testosterone, salivary testosterone, number of CAG repeats, digit ratios, and PRS for estradiol) on the growth pattern of cortical surface area in a longitudinal cohort of 722 infants. We found PRS for testosterone and right-hand digit ratio to be significantly associated with surface area, but only in females. PRS for testosterone at the most stringent P value threshold was positively associated with surface area development over time. Higher right-hand digit ratio, which is indicative of low prenatal testosterone levels, was negatively related to surface area in females. The current work suggests that variation in testosterone levels during both the prenatal and postnatal period may contribute to cortical surface area development in female infants.

Pre-pandemic resilience to trauma and mental health outcomes during COVID-19.

PURPOSE: The stress-sensitization hypothesis posits that individuals with prior trauma are at elevated risk for poor mental health when faced with subsequent stressors. Little work has examined whether those who have demonstrated psychological resilience to prior trauma would show either increased resilience or vulnerability to subsequent stressors. We examined pre-pandemic psychological resilience to lifetime trauma in relation to mental health outcomes amid the coronavirus disease 2019 (COVID-19) pandemic, a major societal stressor. METHODS: The sample included 16,900 trauma-exposed women from the Nurses' Health Study II. Pre-pandemic resilience was defined by psychological health in 2017-2019 (characterized by levels of both distress and positive emotional well-being) relative to lifetime trauma. Resilience was defined categorically by cross-classifying unfavorable, adequate, and favorable psychological health by higher versus lower trauma burden, and continuously as the residual difference in predicted versus actual psychological health regressed on trauma burden. Mental health outcomes as of May-August 2020 included psychological distress symptoms and overall positive emotional well-being. Associations were assessed using covariate-adjusted regression models. RESULTS: Pre-pandemic resilience was associated with lower distress and higher well-being early in the COVID-19 pandemic. Relative to the women showing highest resilience (favorable psychological health despite higher trauma), only those with lower trauma and favorable prior psychological health had significantly lower distress and higher positive emotional well-being during the pandemic. Higher continuous pre-pandemic resilience was also significantly associated with lower distress and higher positive emotional well-being during the pandemic. CONCLUSION: Preventing mental health problems following trauma may contribute to protecting population well-being amid major stressors.

Trauma, Post-Traumatic Stress Disorder, and Treatment Among Middle-Aged and Older Women in the Nurses' Health Study II.

OBJECTIVE: Trauma and post-traumatic stress disorder (PTSD) are common among women and associated with negative health outcomes across the life course. Relatively few studies, however, have examined the epidemiology of trauma, PTSD, and treatment among middle-aged and older civilian women, who are at elevated risk for adverse health outcomes. We aimed to characterize trauma, PTSD, and trauma-related treatment prevalence and correlates in a large cohort of middle-aged and older women. DESIGN: Cross-sectional, nested substudy within the Nurses' Health Study II cohort. SETTING: United States, 2018-2020. PARTICIPANTS: 33,327 current or former nurses, aged 53-74 years. MEASUREMENTS: 16-item modified version of the Brief Trauma Questionnaire; modified PTSD Checklist for the Diagnostic and Statistical Manual, Version 5. RESULTS: The majority (82.2%) of women reported one or more lifetime traumas. The most common trauma types were unexpected death of a loved one (44.9%) and interpersonal violence (43.5%). Almost 30% reported occupational (nursing-related) trauma. Among the trauma-exposed, 10.5% met criteria for lifetime PTSD and 1.5% had past-month PTSD. One-third of lifetime PTSD cases were due to interpersonal violence event types. One-third of women with lifetime PTSD-and nearly half of those with PTSD from a nursing-related trauma-reported never receiving trauma-related treatment. Women aged 65 years and older with PTSD were less likely to be in treatment than those aged less than 65 years. CONCLUSION: History of trauma and PTSD is prevalent in this population, and a treatment gap persists. Addressing this treatment gap is warranted, particularly among older women and those with nursing-related trauma.

The association of posttraumatic stress disorder, depression, and head injury with mid-life cognitive function in civilian women.

BACKGROUND: Despite evidence linking posttraumatic stress disorder (PTSD), depression, and head injury, separately, with worse cognitive performance, investigations of their combined effects on cognition are limited in civilian women. METHODS: The Cogstate Brief Battery assessment was administered in 10,681 women from the Nurses' Health Study II cohort, mean age 64.9 years (SD = 4.6). Psychological trauma, PTSD, depression, and head injury were assessed using online questionnaires. In this cross-sectional analysis, we used linear regression models to estimate mean differences in cognition by PTSD/depression status and stratified by history of head injury. RESULTS: History of head injury was prevalent (36%), and significantly more prevalent among women with PTSD and depression (57% of women with PTSD and depression, 21% of women with no psychological trauma or depression). Compared to having no psychological trauma or depression, having combined PTSD and depression was associated with worse performance on psychomotor speed/attention ( ß = -.15, p = .001) and learning/working memory ( ß = -.15, p < .001). The joint association of PTSD and depression on worse cognitive function was strongest among women with past head injury, particularly among those with multiple head injuries. CONCLUSIONS: Head injury, like PTSD and depression, was highly prevalent in this sample of civilian women. In combination, these factors were associated with poorer performance on cognitive tasks, a possible marker of future cognitive health. Head injury should be further explored in future studies of PTSD, depression and cognition in women.

Cortical Structure and Cognition in Infants and Toddlers.

Cortical structure has been consistently related to cognitive abilities in children and adults, yet we know little about how the cortex develops to support emergent cognition in infancy and toddlerhood when cortical thickness (CT) and surface area (SA) are maturing rapidly. In this report, we assessed how regional and global measures of CT and SA in a sample (N = 487) of healthy neonates, 1-year-olds, and 2-year-olds related to motor, language, visual reception, and general cognitive ability. We report novel findings that thicker cortices at ages 1 and 2 and larger SA at birth, age 1, and age 2 confer a cognitive advantage in infancy and toddlerhood. While several expected brain-cognition relationships were observed, overlapping cortical regions were also implicated across cognitive domains, suggesting that infancy marks a period of plasticity and refinement in cortical structure to support burgeoning motor, language, and cognitive abilities. CT may be a particularly important morphological indicator of ability, but its impact on cognition is relatively weak when compared with gestational age and maternal education. Findings suggest that prenatal and early postnatal cortical developments are important for cognition in infants and toddlers but should be considered in relation to other child and demographic factors.

Environmental Influences on Infant Cortical Thickness and Surface Area.

Cortical thickness (CT) and surface area (SA) vary widely between individuals and are associated with intellectual ability and risk for various psychiatric and neurodevelopmental conditions. Factors influencing this variability remain poorly understood, but the radial unit hypothesis, as well as the more recent supragranular cortex expansion hypothesis, suggests that prenatal and perinatal influences may be particularly important. In this report, we examine the impact of 17 major demographic and obstetric history variables on interindividual variation in CT and SA in a unique sample of 805 neonates who received MRI scans of the brain around 2 weeks of age. Birth weight, postnatal age at MRI, gestational age at birth, and sex emerged as important predictors of SA. Postnatal age at MRI, paternal education, and maternal ethnicity emerged as important predictors of CT. These findings suggest that individual variation in infant CT and SA is explained by different sets of environmental factors with neonatal SA more strongly influenced by sex and obstetric history and CT more strongly influenced by socioeconomic and ethnic disparities. Findings raise the possibility that interventions aimed at reducing disparities and improving obstetric outcomes may alter prenatal/perinatal cortical development.