Pre-Pandemic Resilience to Trauma & COVID-19 Infection in Older Women.

OBJECTIVE: Prior work suggests psychological resilience to trauma may protect not only mental but also physical health. This study examined the relationship of pre-pandemic psychological resilience to lifetime trauma with self-reported COVID-19 infection and symptoms during the early years of the COVID-19 pandemic. METHODS: Data are from 18,670 longitudinal cohort participants in the Nurses' Health Study II. Based on prior evidence that trauma and subsequent distress can increase infection risk and severity, and that psychological assets may offset this risk, we hypothesized higher versus lower psychological resilience to prior trauma would be associated with lower risk for COVID-19 infection. Pre-pandemic resilience was assessed via self-report between 2017-2019 based on self-reported lifetime trauma exposure and psychological health. COVID-19 infection and symptoms were self-reported on 7 questionnaires administered between May 2020 - October 2021, from which we derived a composite outcome measure of probable COVID-19 infection, defined as having 3+ COVID-19 symptoms (out of 9) and/or a positive COVID-19 test result at any single assessment. RESULTS: Multivariable regression revealed significant associations between higher pre-pandemic resilience scores and lower risk for probable COVID-19 infection, adjusting for socio-demographic and COVID-19-related risk factors (RR = 0.90 [95% CI 0.87, 0.93]). Considering subcomponents of the composite COVID-19 infection measure separately, pre-pandemic resilience was significantly associated with lower risk of reported symptoms (RR = 0.83 [95% CI 0.79, 0.88]), but not with a positive test result alone (RR = 0.96 (95% CI 0.91, 1.01]). CONCLUSION: Identifying protective factors for infection risk may help inform psychosocial interventions to improve health outcomes.

Childhood maltreatment and health in the UK Biobank: triangulation of outcome-wide and polygenic risk score analyses.

BACKGROUND: Childhood maltreatment is common globally and impacts morbidity, mortality, and well-being. Our understanding of its impact is constrained by key substantive and methodological limitations of extant research, including understudied physical health outcomes and bias due to unmeasured confounding. We address these limitations through a large-scale outcome-wide triangulation study. METHODS: We performed two outcome-wide analyses (OWAs) in the UK Biobank. First, we examined the relationship between self-reported maltreatment exposure (number of maltreatment types, via Childhood Trauma Screener) and 414 outcomes in a sub-sample of 157,316 individuals using generalized linear models ("observational OWA"). Outcomes covered a broad range of health themes including health behaviors, cardiovascular disease, digestive health, socioeconomic status, and pain. Second, we examined the relationship between a polygenic risk score for maltreatment and 298 outcomes in a non-overlapping sample of 243,006 individuals ("genetic OWA"). We triangulated results across OWAs based on differing sources of bias. RESULTS: Overall, 23.8% of the analytic sample for the observational OWA reported at least one maltreatment type. Of 298 outcomes examined in both OWAs, 25% were significant in both OWAs and concordant in the direction of association. Most of these were considered robust in the observational OWA according to sensitivity analyses and included outcomes such as marital separation (OR from observational OWA, ORo = 1.25 (95% CI: 1.21, 1.29); OR from genetic OWA, ORg = 1.06 (1.03, 1.08)), major diet changes due to illness (ORo = 1.27 (1.24, 1.29); ORg = 1.01 (1.00, 1.03)), certain intestinal diseases (ORo = 1.14 (1.10, 1.18); ORg = 1.03 (1.01, 1.06)), hearing difficulty with background noise (ORo = 1.11 (1.11, 1.12); ORg = 1.01 (1.00, 1.01)), knee arthrosis (ORo = 1.13 (1.09, 1.18); ORg = 1.03 (1.01, 1.05)), frequent sleeplessness (ORo = 1.21 (1.20, 1.23); ORg = 1.02 (1.01, 1.03)), and low household income (ORo = 1.28 (1.26, 1.31); ORg = 1.02 (1.01, 1.03)). Approximately 62% of results were significant in the observational OWA but not the genetic OWA, including numerous cardiovascular outcomes. Only 6 outcomes were significant in the genetic OWA and null in the observational OWA; these included diastolic blood pressure and glaucoma. No outcomes were statistically significant in opposite directions in the two analyses, and 11% were not significant in either OWA. CONCLUSIONS: Our findings underscore the far-reaching negative effects of childhood maltreatment in later life and the utility of an outcome-wide triangulation design with sensitivity analyses for improving causal inference.

Polygenic risk for major depression, attention deficit hyperactivity disorder, neuroticism, and schizophrenia are correlated with experience of intimate partner violence.

Research has suggested that mental illness may be a risk factor for, as well as a sequela of, experiencing intimate partner violence (IPV). The association between IPV and mental illness may also be due in part to gene-environment correlations. Using polygenic risk scores for six psychiatric disorders - attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), neuroticism, and schizophrenia-and a combined measure of overall genetic risk for mental illness, we tested whether women's genetic risk for mental illness was associated with the experience of three types of intimate partner violence. In this cohort of women of European ancestry (N = 11,095), participants in the highest quintile of genetic risk for ADHD (OR range: 1.38-1.49), MDD (OR range: 1.28-1.43), neuroticism (OR range: (1.18-1.25), schizophrenia (OR range: 1.30-1.34), and overall genetic risk (OR range: 1.30-1.41) were at higher risk for experiencing more severe emotional and physical abuse, and, except schizophrenia, more severe sexual abuse, as well as more types of abuse and chronic abuse. In addition, participants in the highest quintile of genetic risk for neuroticism (OR = 1.43 95% CI: 1.18, 1.72), schizophrenia (OR = 1.33 95% CI: 1.10, 1.62), and the overall genetic risk (OR = 1.40 95% CI: 1.15, 1.71) were at higher risk for experiencing intimate partner intimidation and control. Participants in the highest quintile of genetic risk for ADHD, ASD, MDD, schizophrenia, and overall genetic risk, compared to the lowest quintile, were at increased risk for experiencing harassment from a partner (OR range: 1.22-1.92). No associations were found between genetic risk for BPD with IPV. A better understanding of the salience of the multiple possible pathways linking genetic risk for mental illness with risk for IPV may aid in preventing IPV victimization or re-victimization.

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.

Posttraumatic Stress Disorder, Depression, and Accelerated Aging: Leukocyte Telomere Length in the Nurses' Health Study II.

Background: Exposure to trauma, posttraumatic stress disorder (PTSD), and depression have been independently associated with leukocyte telomere length (LTL), a cellular marker of aging associated with mortality and age-related diseases. However, the joint contributions of trauma and its psychological sequelae on LTL have not been examined. Methods: We conducted an analysis of LTL in a subset of women from the Nurses' Health Study II (N = 1868). Lifetime exposure to traumatic events, PTSD, and depression was assessed with validated measures. DNA was extracted from peripheral blood leukocytes and telomere repeat copy number to single gene copy number was determined by quantitative real-time polymerase chain reaction telomere assay. Linear regression models assessed the association of trauma, PTSD, and depression with LTL after adjustment for health behaviors and medical conditions. Results: Trauma, PTSD, and depression were not independently associated with LTL in mutually adjusted models. However, individuals with severe psychological distress-characterized by comorbid PTSD and depression-had shorter LTL equivalent to being 7.62 years older (95% CI, 0.02 to 17.97) than participants who had never experienced a traumatic event and were not depressed. Further examination found only an association among individuals with the highest number of PTSD symptoms and comorbid depression equivalent to 9.71 additional years of aging (95% CI, 1.36 to 20.49). No effect was found among individuals meeting the minimum threshold for probable PTSD with comorbid depression. Conclusions: Severe psychological distress, as indicated by the presence of comorbid PTSD and depression, may be associated with shorter LTL.

Multiple types of distress are prospectively associated with increased risk of ovarian cancer.

BACKGROUND: Few modifiable risk factors for epithelial ovarian cancer have been identified. We and other investigators have found that individual psychosocial factors related to distress are associated with higher risk of ovarian cancer. The present study examined whether co-occurring distress-related factors are associated with ovarian cancer risk. METHODS: Five distress-related factors were measured repeatedly over 21 years of follow-up: depression, anxiety, social isolation, widowhood, and, in a subset or women, posttraumatic stress disorder (PTSD). Cox proportional hazards models estimate relative risks (RR) and 95% confidence intervals (CI) of ovarian cancer for a time-updated count of distress-related factors, in age-adjusted models, then further adjusted for ovarian cancer risk factors and behavior-related health risk factors. RESULTS: Across 1,193,927 person-years of follow-up, 526 incident ovarian cancers occurred. Women with ≥3 versus no distress-related psychosocial factors demonstrated increased ovarian cancer risk (HRage-adjusted = 1.71; 95% CI = 1.16, 2.52). No significant difference in ovarian cancer risk was observed in women with one or two versus no distress-related psychosocial factors. In the subsample with PTSD assessed, ≥3 versus no distress-related psychosocial factors was associated with twofold greater ovarian cancer risk (HRage-adjusted = 2.08, 95% CI = 1.01, 4.29). Further analysis suggested that women at highest ovarian cancer risk had PTSD co-occurring with any other distress-related factor (HR = 2.19, 95% CI = 1.20, 4.01). Adjusting for cancer risk factors and health behaviors minimally impacted risk estimates. CONCLUSIONS: Presence of multiple indicators of distress was associated with risk of ovarian cancer. When including PTSD as an indicator of distress, the association was strengthened.

Multidimensional Sleep Health Prior to SARS-CoV-2 Infection and Risk of Post-COVID-19 Condition.

Importance: The association of multiple healthy sleep dimensions with post-COVID-19 condition (PCC), also known as long COVID, has not been investigated. Objective: To examine whether multidimensional sleep health before and during the COVID-19 pandemic, prior to SARS-CoV-2 infection, was associated with the risk of PCC. Design, Setting, and Participants: This prospective cohort study (2015-2021) included Nurses' Health Study II participants who reported testing positive (n = 2303) for SARS-CoV-2 infection in a substudy series of COVID-19-related surveys (n = 32 249) between April 2020 and November 2021. After exclusion for incomplete information about sleep health and nonresponse to a question about PCC, 1979 women were included in the analysis. Exposures: Sleep health was measured both before (June 1, 2015, to May 31, 2017) and early (April 1 to August 31, 2020) in the COVID-19 pandemic. Prepandemic sleep score was defined according to 5 dimensions: morning chronotype (assessed in 2015), 7 to 8 hours of sleep per day, low insomnia symptoms, no snoring, and no frequent daytime dysfunction (all assessed in 2017). On the first COVID-19 substudy survey (returned between April and August 2020), average daily sleep duration and sleep quality for the past 7 days were queried. Main Outcomes and Measures: SARS-CoV-2 infection and PCC (≥4 weeks of symptoms) were self-reported during 1 year of follow-up. Comparisons were examined between June 8, 2022, and January 9, 2023, using Poisson regression models. Results: Of the 1979 participants reporting SARS-CoV-2 infection (mean [SD] age, 64.7 [4.6] years; 1979 [100%] female; and 1924 [97.2%] White vs 55 [2.8%] other races and ethnicities), 845 (42.7%) were frontline health care workers, and 870 (44.0%) developed PCC. Compared with women who had a prepandemic sleep score of 0 or 1 (least healthy), those who scored 5 (most healthy) had a 30% lower risk of developing PCC (multivariable-adjusted relative risk, 0.70; 95% CI, 0.52-0.94; P for trend <.001). Associations did not differ by health care worker status. No or little daytime dysfunction prepandemic and good sleep quality during the pandemic were independently associated with a lower risk of PCC (relative risk, 0.83 [95% CI, 0.71-0.98] and 0.82 [95% CI, 0.69-0.99], respectively). Results were similar when PCC was defined as having 8 or more weeks of symptoms or as having ongoing symptoms at the time of PCC assessment. Conclusions and Relevance: The findings indicate that healthy sleep measured prior to SARS-CoV-2 infection, both before and during the COVID-19 pandemic, may be protective against PCC. Future research should investigate whether interventions on sleep health may prevent PCC or improve PCC symptoms.

Association of early life physical and sexual abuse with premature mortality among female nurses: prospective cohort study.

OBJECTIVE: To explore associations between early life physical and sexual abuse and subsequent risk of premature mortality (death before age 70 years). DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study II (2001-19). PARTICIPANTS: 67 726 female nurses aged 37-54 years when completing a violence victimization questionnaire in 2001. MAIN OUTCOME MEASURES: Hazard ratios and 95% confidence intervals for total and cause specific premature mortality by childhood or adolescent physical and sexual abuse, estimated by multivariable Cox proportional hazard models. RESULTS: 2410 premature deaths were identified over 18 years of follow-up. Nurses who experienced severe physical abuse or forced sexual activity in childhood and adolescence had a higher crude premature mortality rate than nurses without such abuse in childhood or adolescence (3.15 v 1.83 and 4.00 v 1.90 per 1000 person years, respectively). The corresponding age adjusted hazard ratios for premature deaths were 1.65 (95% confidence interval 1.45 to 1.87) and 2.04 (1.71 to 2.44), respectively, which were materially unchanged after further adjusting for personal characteristics and early life socioeconomic status (1.53, 1.35 to 1.74, and 1.80, 1.50 to 2.15, respectively). Cause specific analyses indicated that severe physical abuse was associated with a greater risk of mortality due to external causes of injury and poisoning (multivariable adjusted hazard ratio 2.81, 95% confidence interval 1.62 to 4.89), suicide (3.05, 1.41 to 6.60), and diseases of the digestive system (2.40, 1.01 to 5.68). Forced sexual activity as a child and adolescent was associated with greater risk of mortality due to cardiovascular disease (2.48, 1.37 to 4.46), external injury or poisoning (3.25, 1.53 to 6.91), suicide (4.30, 1.74 to 10.61), respiratory disease (3.74, 1.40 to 9.99), and diseases of the digestive system (4.83, 1.77 to 13.21). The association of sexual abuse with premature mortality was stronger among women who smoked or had higher levels of anxiety during adulthood. Smoking, low physical activity, anxiety, and depression each explained 3.9-22.4% of the association between early life abuse and premature mortality. CONCLUSION: Early life physical and sexual abuse could be associated with a greater risk of adult premature mortality.

Association of Retrospectively Reported Concussion Symptoms with Objective Cognitive Performance in Former American-Style Football Players.

OBJECTIVE: Sustaining concussions has been linked to health issues later in life, yet evidence for associations between contact sports exposure and long-term cognitive performance is mixed. This cross-sectional study of former professional American-style football players tested the association of several measures of football exposure with later life cognitive performance, while also comparing the cognitive performance of former players to nonplayers. METHODS: In total, 353 former professional football players (Mage = 54.3) completed both (1) an online cognitive test battery measuring objective cognitive performance and (2) a survey querying demographic information, current health conditions, and measures of past football exposure, including recollected concussion symptoms playing professional football, diagnosed concussions, years of professional play, and age of first football exposure. Testing occurred an average of 29 years after former players' final season of professional play. In addition, a comparison sample of 5,086 male participants (nonplayers) completed one or more cognitive tests. RESULTS: Former players' cognitive performance was associated with retrospectively reported football concussion symptoms (rp = -0.19, 95% CI -0.09 to -0.29; p < 0.001), but not with diagnosed concussions, years of professional play, or age of first football exposure. This association could be due to differences in pre-concussion cognitive functioning, however, which could not be estimated based on available data. CONCLUSIONS: Future investigations of the long-term outcomes of contact sports exposure should include measures of sports-related concussion symptoms, which were more sensitive to objective cognitive performance than other football exposure measures, including self-reported diagnosed concussions.

Adherence to Healthy Lifestyle Prior to Infection and Risk of Post-COVID-19 Condition.

Importance: Few modifiable risk factors for post-COVID-19 condition (PCC) have been identified. Objective: To investigate the association between healthy lifestyle factors prior to SARS-CoV-2 infection and risk of PCC. Design, Setting, and Participants: In this prospective cohort study, 32 249 women in the Nurses' Health Study II cohort reported preinfection lifestyle habits in 2015 and 2017. Healthy lifestyle factors included healthy body mass index (BMI, 18.5-24.9; calculated as weight in kilograms divided by height in meters squared), never smoking, at least 150 minutes per week of moderate to vigorous physical activity, moderate alcohol intake (5 to 15 g/d), high diet quality (upper 40% of Alternate Healthy Eating Index-2010 score), and adequate sleep (7 to 9 h/d). Main Outcomes and Measures: SARS-CoV-2 infection (confirmed by test) and PCC (at least 4 weeks of symptoms) were self-reported on 7 periodic surveys administered from April 2020 to November 2021. Among participants with SARS-CoV-2 infection, the relative risk (RR) of PCC in association with the number of healthy lifestyle factors (0 to 6) was estimated using Poisson regression and adjusting for demographic factors and comorbidities. Results: A total of 1981 women with a positive SARS-CoV-2 test over 19 months of follow-up were documented. Among those participants, mean age was 64.7 years (SD, 4.6; range, 55-75); 97.4% (n = 1929) were White; and 42.8% (n = 848) were active health care workers. Among these, 871 (44.0%) developed PCC. Healthy lifestyle was associated with lower risk of PCC in a dose-dependent manner. Compared with women without any healthy lifestyle factors, those with 5 to 6 had 49% lower risk (RR, 0.51; 95% CI, 0.33-0.78) of PCC. In a model mutually adjusted for all lifestyle factors, BMI and sleep were independently associated with risk of PCC (BMI, 18.5-24.9 vs others, RR, 0.85; 95% CI, 0.73-1.00, P = .046; sleep, 7-9 h/d vs others, RR, 0.83; 95% CI, 0.72-0.95, P = .008). If these associations were causal, 36.0% of PCC cases would have been prevented if all participants had 5 to 6 healthy lifestyle factors (population attributable risk percentage, 36.0%; 95% CI, 14.1%-52.7%). Results were comparable when PCC was defined as symptoms of at least 2-month duration or having ongoing symptoms at the time of PCC assessment. Conclusions and Relevance: In this prospective cohort study, pre-infection healthy lifestyle was associated with a substantially lower risk of PCC. Future research should investigate whether lifestyle interventions may reduce risk of developing PCC or mitigate symptoms among individuals with PCC or possibly other postinfection syndromes.

Depression, worry, and loneliness are associated with subsequent risk of hospitalization for COVID-19: a prospective study.

BACKGROUND: Pre-pandemic psychological distress is associated with increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but associations with the coronavirus disease 2019 (COVID-19) severity are not established. The authors examined the associations between distress prior to SARS-CoV-2 infection and subsequent risk of hospitalization. METHODS: Between April 2020 (baseline) and April 2021, we followed 54 781 participants from three ongoing cohorts: Nurses' Health Study II (NHSII), Nurses' Health Study 3 (NHS3), and the Growing Up Today Study (GUTS) who reported no current or prior SARS-CoV-2 infection at baseline. Chronic depression was assessed during 2010-2019. Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at baseline. SARS-CoV-2 infection and hospitalization due to COVID-19 was self-reported. Relative risks (RRs) were calculated by Poisson regression. RESULTS: 3663 participants reported a positive SARS-CoV-2 test (mean age = 55.0 years, standard deviation = 13.8) during follow-up. Among these participants, chronic depression prior to the pandemic [RR = 1.72; 95% confidence interval (CI) 1.20-2.46], and probable depression (RR = 1.81, 95% CI 1.08-3.03), being very worried about COVID-19 (RR = 1.79; 95% CI 1.12-2.86), and loneliness (RR = 1.81, 95% CI 1.02-3.20) reported at baseline were each associated with subsequent COVID-19 hospitalization, adjusting for demographic factors and healthcare worker status. Anxiety and perceived stress were not associated with hospitalization. Depression, worry about COVID-19, and loneliness were as strongly associated with hospitalization as were high cholesterol and hypertension, established risk factors for COVID-19 severity. CONCLUSIONS: Psychological distress may be a risk factor for hospitalization in patients with SARS-CoV-2 infection. Assessment of psychological distress may identify patients at greater risk of hospitalization. Future work should examine whether addressing distress improves physical health outcomes.

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.

Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post-COVID-19 Conditions.

Importance: Few risk factors for long-lasting (≥4 weeks) COVID-19 symptoms have been identified. Objective: To determine whether high levels of psychological distress before SARS-CoV-2 infection, characterized by depression, anxiety, worry, perceived stress, and loneliness, are prospectively associated with increased risk of developing post-COVID-19 conditions (sometimes called long COVID). Design, Setting, and Participants: This prospective cohort study used data from 3 large ongoing, predominantly female cohorts: Nurses' Health Study II, Nurses' Health Study 3, and the Growing Up Today Study. Between April 2020 and November 2021, participants were followed up with periodic surveys. Participants were included if they reported no current or prior SARS-CoV-2 infection at the April 2020 baseline survey when distress was assessed and returned 1 or more follow-up questionnaires. Exposures: Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at study baseline early in the pandemic, before SARS-CoV-2 infection, using validated questionnaires. Main Outcomes and Measures: SARS-CoV-2 infection was self-reported during each of 6 monthly and then quarterly follow-up questionnaires. COVID-19-related symptoms lasting 4 weeks or longer and daily life impairment due to these symptoms were self-reported on the final questionnaire, 1 year after baseline. Results: Of 54 960 participants, 38.0% (n = 20 902) were active health care workers, and 96.6% (n = 53 107) were female; the mean (SD) age was 57.5 (13.8) years. Six percent (3193 participants) reported a positive SARS-CoV-2 test result during follow-up (1-47 weeks after baseline). Among these, probable depression (risk ratio [RR], 1.32; 95% CI = 1.12-1.55), probable anxiety (RR = 1.42; 95% CI, 1.23-1.65), worry about COVID-19 (RR, 1.37; 95% CI, 1.17-1.61), perceived stress (highest vs lowest quartile: RR, 1.46; 95% CI, 1.18-1.81), and loneliness (RR, 1.32; 95% CI, 1.08-1.61) were each associated with post-COVID-19 conditions (1403 cases) in generalized estimating equation models adjusted for sociodemographic factors, health behaviors, and comorbidities. Participants with 2 or more types of distress prior to infection were at nearly 50% increased risk for post-COVID-19 conditions (RR, 1.49; 95% CI, 1.23-1.80). All types of distress were associated with increased risk of daily life impairment (783 cases) among individuals with post-COVID-19 conditions (RR range, 1.15-1.51). Conclusions and Relevance: The findings of this study suggest that preinfection psychological distress may be a risk factor for post-COVID-19 conditions in individuals with SARS-CoV-2 infection. Future work should examine the biobehavioral mechanism linking psychological distress with persistent postinfection symptoms.

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.

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.

Association of Posttraumatic Stress Disorder With Accelerated Cognitive Decline in Middle-aged Women.

Importance: Posttraumatic stress disorder (PTSD) has been hypothesized to lead to impaired cognitive function. However, no large-scale studies have assessed whether PTSD is prospectively associated with cognitive decline in middle-aged adults. Objective: To assess the association between PTSD and decline in cognitive function over time. Design, Setting, and Participants: This cohort study included participants from the Nurses' Health Study II, an ongoing longitudinal cohort study involving community-dwelling middle-aged female nurses residing in the US who had at least a 2-year nursing degree at the time of enrollment in 1989. The present study included 12 270 trauma-exposed women who were enrolled in the PTSD substudy of the Nurses' Health Study II and completed 1 to 5 cognitive assessments. Data were collected from March 1, 2008, to July 30, 2019. Exposures: Lifetime PTSD symptoms, assessed using a validated questionnaire between March 1, 2008, and February 28, 2010. Main Outcomes and Measures: The main outcome was evaluated using the Cogstate Brief Battery, a self-administered online cognitive battery. Cognitive function was measured by a psychomotor speed and attention composite score and a learning and working memory composite score. Women completed the Cogstate Brief Battery every 6 or 12 months (up to 24 months) from October 3, 2014, to July 30, 2019. Linear mixed-effects models were used to evaluate the association of PTSD symptoms with the rate of change in cognition over follow-up, considering a broad range of relevant covariates, including the presence of depression symptoms and history of clinician-diagnosed depression. The rate of cognitive change was adjusted for potential practice effects (ie, potential changes in test results that occur when a test is taken more than once) by including indicators for the number of previous tests taken. Results: Among 12 270 women, the mean (SD) age at the baseline cognitive assessment was 61.1 (4.6) years; 125 women (1.0%) were Asian, 75 (0.6%) were Black, 156 (1.3%) were Hispanic, 11 767 (95.9%) were non-Hispanic White, and 147 (1.2%) were of other race and/or ethnicity. A higher number of PTSD symptoms was associated with worse cognitive trajectories. Compared with women with no PTSD symptoms, women with the highest symptom level (6-7 symptoms) had a significantly worse rate of change in both learning and working memory (ß = -0.08 SD/y; 95% CI, -0.11 to -0.04 SD/y; P < .001) and psychomotor speed and attention (ß = -0.05 SD/y; 95% CI, -0.09 to -0.01 SD/y; P = .02), adjusted for demographic characteristics. Associations were unchanged when additionally adjusted for behavioral factors (eg, 6-7 symptoms in the analysis of learning and working memory: ß = -0.08 SD/y; 95% CI, -0.11 to -0.04 SD/y; P < .001) and health conditions (eg, 6-7 symptoms in the analysis of learning and working memory: ß = -0.08 SD/y; 95% CI, -0.11 to -0.04 SD/y; P < .001) and were partially attenuated but still evident when further adjusted for practice effects (eg, 6-7 symptoms in the analysis of learning and working memory: ß = -0.07 SD/y; 95% CI, -0.10 to -0.03 SD/y; P < .001) and comorbid depression (eg, 6-7 symptoms in the analysis of learning and working memory: ß = -0.07 SD/y; 95% CI, -0.11 to -0.03 SD/y; P < .001). Conclusions and Relevance: In this large-scale prospective cohort study, PTSD was associated with accelerated cognitive decline in middle-aged women, suggesting that earlier cognitive screening among women with PTSD may be warranted. Given that cognitive decline is strongly associated with subsequent Alzheimer disease and related dementias, better understanding of this association may be important to promote healthy aging.

Plasma Metabolomic Signature of Early Abuse in Middle-Aged Women.

OBJECTIVE: Metabolomic profiling may provide insights into biological mechanisms underlying the strong epidemiologic links observed between early abuse and cardiometabolic disorders in later life. METHODS: We examined the associations between early abuse and midlife plasma metabolites in two nonoverlapping subsamples from the Nurses' Health Study II, comprising 803 (mean age = 40 years) and 211 women (mean age = 61 years). Liquid chromatography-tandem mass spectrometry assays were used to measure metabolomic profiles, with 283 metabolites consistently measured in both subsamples. Physical and sexual abuse before age 18 years was retrospectively assessed by validated questions integrating type/frequency of abuse. Analyses were conducted in each sample and pooled using meta-analysis, with multiple testing adjustment using the q value approach for controlling the positive false discovery rate. RESULTS: After adjusting for age, race, menopausal status, body size at age 5 years, and childhood socioeconomic indicators, more severe early abuse was consistently associated with five metabolites at midlife (q value < 0.20 in both samples), including lower levels of serotonin and C38:3 phosphatidylethanolamine plasmalogen and higher levels of alanine, proline, and C40:6 phosphatidylethanolamine. Other metabolites potentially associated with early abuse (q value < 0.05 in the meta-analysis) included triglycerides, phosphatidylcholine plasmalogens, bile acids, tyrosine, glutamate, and cotinine. The association between early abuse and midlife metabolomic profiles was partly mediated by adulthood body mass index (32% mediated) and psychosocial distress (13%-26% mediated), but not by other life-style factors. CONCLUSIONS: Early abuse was associated with distinct metabolomic profiles of multiple amino acids and lipids in middle-aged women. Body mass index and psychosocial factors in adulthood may be important intermediates for the observed association.

Association of Adverse Childhood Experiences With Poor Neuropsychiatric Health and Dementia Among Former Professional US Football Players.

Importance: Childhood adversities, including neglect, abuse, and other indicators of family dysfunction, are associated in adulthood with risk factors for poor cognitive and mental health. However, the extent to which these experiences are associated with adulthood cognition-related quality of life and risk for dementia is unknown. Objective: To determine the association of 10 adverse childhood experiences (ACEs) with neuropsychiatric outcomes among former National Football League (NFL) players. Design, Setting, and Participants: This cross-sectional analysis used data from the Football Player's Health Study at Harvard University, an ongoing longitudinal cohort study from January 30, 2015, to November 19, 2021, of former NFL players. Exposures: Ten ACEs were assessed using the Adverse Childhood Experiences Questionnaire. Main Outcomes and Measures: Dementia symptoms were assessed using the AD8: The Washington University Dementia Screening Test; cognition-related quality of life was assessed with the short form of the Quality of Life in Neurological Disorders; depression was assessed with the Patient Health Questionnaire-9; anxiety was assessed with the Generalized Anxiety Disorder-7; and pain intensity and pain interference in daily life were assessed with the Brief Pain Inventory. Risk ratios (RRs) assessing the association between ACEs and neuropsychiatric outcomes were estimated using generalized estimating equations, adjusted for age, race, and childhood socioeconomic status, and further adjusted for playing position, concussions incurred during football play, and number of seasons played in the NFL. Results: A total of 1755 men (mean [SD] age, 57.2 [13.5] years) who were former professional football players were included in the analysis. Five hundred twenty players (29.6%) identified as Black, 1160 (66.1%) identified as White, and 75 (4.3%) identified as other race or ethnicity. Players with 4 or more ACEs were at 48% greater risk of a positive screen for dementia (RR, 1.48 [95% CI, 1.22-1.79]), and at significantly greater risk of every other neuropsychiatric outcome except anxiety (RR range, 1.62 [95% CI, 1.09-2.39] to 1.74 [95% CI, 1.27-2.40]) compared with players with no ACEs. Further adjustment for concussions incurred during playing years attenuated these associations, although some were still significant (adjusted RR range, 1.32 [95% CI, 1.10-1.58] to 1.56 [95% CI, 1.15-2.11]). ACEs were also associated with concussion symptoms; players with 4 or more ACEs had a 60% increased risk of being in the top quartile of concussion symptoms (RR, 1.60; 95% CI, 1.12-2.28) compared with players with no ACEs. Conclusions and Relevance: These findings suggest that ACEs may be associated with dementia symptoms among former NFL players. Moreover, ACEs should be investigated among professional football players and other populations as a prospective indicator of persons at high risk of concussion. These findings further suggest that treatment of psychological trauma in addition to treatment of physical injury may improve neuropsychiatric health in former NFL players.

Sexual Violence and Risk of Hypertension in Women in the Nurses' Health Study II: A 7-Year Prospective Analysis.

Background Hypertension is a prevalent condition in women and an important modifiable risk factor for cardiovascular disease. Despite women's experiences of sexual violence being common, no prospective studies have examined lifetime sexual assault and workplace sexual harassment in relationship to hypertension in large civilian samples with extended follow-up. Here, we examined whether these experiences were prospectively associated with greater risk of developing hypertension over 7 years. Methods and Results Data are from a substudy of the Nurses' Health Study II and include women free of hypertension at the time of sexual assault and workplace sexual harassment assessment in 2008 (n=33 127). Hypertension was defined as self-reported doctor diagnosis or initiating antihypertensive medication use, assessed biennially through 2015. We performed Cox proportional hazards regression models to predict time to developing hypertension associated with sexual violence exposure, adjusting for relevant covariates. Over follow-up, 7096 women developed hypertension. Sexual assault and workplace sexual harassment were prevalent (23% and 12%, respectively; 6% of women experienced both). Compared with women with no exposure, women who experienced both sexual assault and workplace sexual harassment had the highest risk of developing hypertension (hazard ratio [HR], 1.21; 95% CI, 1.09-1.35), followed by women who experienced workplace sexual harassment (HR, 1.15; 95% CI, 1.05-1.25) and then by women who experienced sexual assault (HR, 1.11; 95% CI, 1.03-1.19), after adjusting for relevant covariates. Conclusions Sexual assault and workplace sexual harassment are prospectively associated with greater risk of hypertension. Reducing such violence is important in its own right and may also improve women's cardiovascular health.

Do levels of posttraumatic growth vary by type of traumatic event experienced? An analysis of the Nurses' Health Study II.

OBJECTIVE: Posttraumatic growth (PTG) has been documented in the aftermath of a range of traumatic events, including bereavement, physical assault, and rape. However, only a handful of studies have examined whether levels of total PTG, as well as the 5 domains of PTG (Appreciation of Life, New Possibilities, Relating to Others, Personal Strength, and Spiritual Change), vary by the type of potentially traumatic event. The current study examined variation in total PTG and PTG domains, as well as posttraumatic stress (PTS), by event type using data from a large epidemiological study. METHOD: Participants were from a substudy of the Nurses' Health Study 2, an epidemiologic study of female nurses in the United States (N = 1,574). RESULTS: Controlling for demographic covariates, we found that rape was consistently associated with lower PTG, both total PTG and all five PTG domains, relative to other event types. Other findings were limited to specific PTG domains; for example, intimate partner violence (IPV) was associated with higher Personal Strength and New Possibilities. In contrast, rape and IPV were associated with higher PTS, and the serious illness or injury of someone close with lower PTS, relative to other event types. CONCLUSION: These results add to the growing literature exploring variation in PTG by event type and suggest that different events could yield markedly different patterns of PTG domains and PTS. (PsycInfo Database Record (c) 2022 APA, all rights reserved).