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.

Loneliness and depression: bidirectional mendelian randomization analyses using data from three large genome-wide association studies.

Major depression (MD) is a serious psychiatric illness afflicting nearly 5% of the world's population. A large correlational literature suggests that loneliness is a prospective risk factor for MD; correlational assocations of this nature may be confounded for a variety of reasons. This report uses Mendelian Randomization (MR) to examine potentially causal associations between loneliness and MD. We report on analyses using summary statistics from three large genome wide association studies (GWAS). MR analyses were conducted using three independent sources of GWAS summary statistics. In the first set of analyses, we used available summary statistics from an extant GWAS of loneliness to predict MD risk. We used two sources of outcome data: the Psychiatric Genomics Consortium (PGC) meta-analysis of MD (PGC-MD; N = 142,646) and the Million Veteran Program (MVP-MD; N = 250,215). Finally, we reversed analyses using data from the MVP and PGC samples to identify risk variants for MD and used loneliness outcome data from UK Biobank. We find robust evidence for a bidirectional causal relationship between loneliness and MD, including between loneliness, depression cases status, and a continuous measure of depressive symptoms. The estimates remained significant across several sensitivity analyses, including models that account for horizontal pleiotropy. This paper provides the first genetically-informed evidence that reducing loneliness may play a causal role in decreasing risk for depressive illness, and these findings support efforts to reduce loneliness in order to prevent or ameliorate MD. Discussion focuses on the public health significance of these findings, especially in light of the SARS-CoV-2 pandemic.

Design and Implementation of the All of Us Research Program COVID-19 Participant Experience (COPE) Survey.

In response to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic, the All of Us Research Program longitudinal cohort study developed the COVID-19 Participant Experience (COPE) survey to better understand the pandemic experiences and health impacts of COVID-19 on diverse populations within the United States. Six survey versions were deployed between May 2020 and March 2021, covering mental health, loneliness, activity, substance use, and discrimination, as well as COVID-19 symptoms, testing, treatment, and vaccination. A total of 104,910 All of Us Research Program participants, of whom over 73% were from communities traditionally underrepresented in biomedical research, completed 275,201 surveys; 9,693 completed all 6 surveys. Response rates varied widely among demographic groups and were lower among participants from certain racial and ethnic minority populations, participants with low income or educational attainment, and participants with a Spanish language preference. Survey modifications improved participant response rates between the first and last surveys (13.9% to 16.1%, P < 0.001). This paper describes a data set with longitudinal COVID-19 survey data in a large, diverse population that will enable researchers to address important questions related to the pandemic, a data set that is of additional scientific value when combined with the program's other data sources.

Psychological Resilience to Trauma and Risk of COVID-19 Infection and Somatic Symptoms Across 2 Years.

OBJECTIVE: Exposure to trauma increases the risk of somatic symptoms, as well as acute and chronic physical diseases. However, many individuals display psychological resilience, showing positive psychological adaptation despite trauma exposure. Resilience to prior trauma may be a protective factor for physical health during subsequent stressors, including the COVID-19 pandemic. METHODS: Using data from 528 US adults in a longitudinal cohort study, we examined psychological resilience to lifetime potentially traumatic events early in the pandemic and the risk of COVID-19 infection and somatic symptoms across 2 years of follow-up. Resilience was defined as level of psychological functioning relative to lifetime trauma burden, assessed in August 2020. Outcomes included COVID-19 infection and symptom severity, long COVID, and somatic symptoms assessed every 6 months for 24 months. Using regression models, we examined associations between resilience and each outcome adjusting for covariates. RESULTS: Higher psychological resilience to trauma was associated with a lower likelihood of COVID-19 infection over time, with one standard deviation higher resilience score associated with a 31% lower likelihood of COVID-19 infection, adjusting for sociodemographics and vaccination status. Furthermore, higher resilience was associated with lower levels of somatic symptoms during the pandemic, adjusting for COVID-19 infection and long COVID status. In contrast, resilience was not associated with COVID-19 disease severity or long COVID. CONCLUSIONS: Psychological resilience to prior trauma is associated with lower risk of COVID-19 infection and lower somatic symptoms during the pandemic. Promoting psychological resilience to trauma may benefit not only mental but also physical health.

Effects of prior deployments and perceived resilience on anger trajectories of combat-deployed soldiers.

BACKGROUND: Problematic anger is frequently reported by soldiers who have deployed to combat zones. However, evidence is lacking with respect to how anger changes over a deployment cycle, and which factors prospectively influence change in anger among combat-deployed soldiers. METHODS: Reports of problematic anger were obtained from 7298 US Army soldiers who deployed to Afghanistan in 2012. A series of mixed-effects growth models estimated linear trajectories of anger over a period of 1-2 months before deployment to 9 months post-deployment, and evaluated the effects of pre-deployment factors (prior deployments and perceived resilience) on average levels and growth of problematic anger. RESULTS: A model with random intercepts and slopes provided the best fit, indicating heterogeneity in soldiers' levels and trajectories of anger. First-time deployers reported the lowest anger overall, but the most growth in anger over time. Soldiers with multiple prior deployments displayed the highest anger overall, which remained relatively stable over time. Higher pre-deployment resilience was associated with lower reports of anger, but its protective effect diminished over time. First- and second-time deployers reporting low resilience displayed different anger trajectories (stable v. decreasing, respectively). CONCLUSIONS: Change in anger from pre- to post-deployment varies based on pre-deployment factors. The observed differences in anger trajectories suggest that efforts to detect and reduce problematic anger should be tailored for first-time v. repeat deployers. Ongoing screening is needed even for soldiers reporting high resilience before deployment, as the protective effect of pre-deployment resilience on anger erodes over time.

Associations of polygenic risk scores with posttraumatic stress symptom trajectories following combat deployment.

BACKGROUND: Identification of genetic risk factors may inform the prevention and treatment of posttraumatic stress disorder (PTSD). This study evaluates the associations of polygenic risk scores (PRS) with patterns of posttraumatic stress symptoms following combat deployment. METHOD: US Army soldiers of European ancestry (n = 4900) provided genomic data and ratings of posttraumatic stress symptoms before and after deployment to Afghanistan in 2012. Latent growth mixture modeling was used to model posttraumatic stress symptom trajectories among participants who provided post-deployment data (n = 4353). Multinomial logistic regression models tested independent associations between trajectory membership and PRS for PTSD, major depressive disorder (MDD), schizophrenia, neuroticism, alcohol use disorder, and suicide attempt, controlling for age, sex, ancestry, and exposure to potentially traumatic events, and weighted to account for uncertainty in trajectory classification and missing data. RESULTS: Participants were classified into low-severity (77.2%), increasing-severity (10.5%), decreasing-severity (8.0%), and high-severity (4.3%) posttraumatic stress symptom trajectories. Standardized PTSD-PRS and MDD-PRS were associated with greater odds of membership in the high-severity v. low-severity trajectory [adjusted odds ratios and 95% confidence intervals, 1.23 (1.06-1.43) and 1.18 (1.02-1.37), respectively] and the increasing-severity v. low-severity trajectory [1.12 (1.01-1.25) and 1.16 (1.04-1.28), respectively]. Additionally, MDD-PRS was associated with greater odds of membership in the decreasing-severity v. low-severity trajectory [1.16 (1.03-1.31)]. No other associations were statistically significant. CONCLUSIONS: Higher polygenic risk for PTSD or MDD is associated with more severe posttraumatic stress symptom trajectories following combat deployment. PRS may help stratify at-risk individuals, enabling more precise targeting of treatment and prevention programs.

The genetic contribution to the comorbidity of depression and anxiety: a multi-site electronic health records study of almost 178 000 people.

BACKGROUND: Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation. METHODS: Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry. RESULTS: In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18-1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05-1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06-1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11-1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02-1.09), showing a genetic risk gradient across the conditions and the comorbidity. CONCLUSIONS: This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.

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.

Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies.

With progress in genome-wide association studies of depression, from identifying zero hits in ~16 000 individuals in 2013 to 223 hits in more than a million individuals in 2020, understanding the genetic architecture of this debilitating condition no longer appears to be an impossible task. The pressing question now is whether recently discovered variants describe the etiology of a single disease entity. There are a myriad of ways to measure and operationalize depression severity, and major depressive disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders-5 can manifest in more than 10 000 ways based on symptom profiles alone. Variations in developmental timing, comorbidity and environmental contexts across individuals and samples further add to the heterogeneity. With big data increasingly enabling genomic discovery in psychiatry, it is more timely than ever to explicitly disentangle genetic contributions to what is likely 'depressions' rather than depression. Here, we introduce three sources of heterogeneity: operationalization, manifestation and etiology. We review recent efforts to identify depression subtypes using clinical and data-driven approaches, examine differences in genetic architecture of depression across contexts, and argue that heterogeneity in operationalizations of depression is likely a considerable source of inconsistency. Finally, we offer recommendations and considerations for the field going forward.

Unit cohesion during deployment and post-deployment mental health: is cohesion an individual- or unit-level buffer for combat-exposed soldiers?

BACKGROUND: Unit cohesion may protect service member mental health by mitigating effects of combat exposure; however, questions remain about the origins of potential stress-buffering effects. We examined buffering effects associated with two forms of unit cohesion (peer-oriented horizontal cohesion and subordinate-leader vertical cohesion) defined as either individual-level or aggregated unit-level variables. METHODS: Longitudinal survey data from US Army soldiers who deployed to Afghanistan in 2012 were analyzed using mixed-effects regression. Models evaluated individual- and unit-level interaction effects of combat exposure and cohesion during deployment on symptoms of post-traumatic stress disorder (PTSD), depression, and suicidal ideation reported at 3 months post-deployment (model n's = 6684 to 6826). Given the small effective sample size (k = 89), the significance of unit-level interactions was evaluated at a 90% confidence level. RESULTS: At the individual-level, buffering effects of horizontal cohesion were found for PTSD symptoms [B = -0.11, 95% CI (-0.18 to -0.04), p < 0.01] and depressive symptoms [B = -0.06, 95% CI (-0.10 to -0.01), p < 0.05]; while a buffering effect of vertical cohesion was observed for PTSD symptoms only [B = -0.03, 95% CI (-0.06 to -0.0001), p < 0.05]. At the unit-level, buffering effects of horizontal (but not vertical) cohesion were observed for PTSD symptoms [B = -0.91, 90% CI (-1.70 to -0.11), p = 0.06], depressive symptoms [B = -0.83, 90% CI (-1.24 to -0.41), p < 0.01], and suicidal ideation [B = -0.32, 90% CI (-0.62 to -0.01), p = 0.08]. CONCLUSIONS: Policies and interventions that enhance horizontal cohesion may protect combat-exposed units against post-deployment mental health problems. Efforts to support individual soldiers who report low levels of horizontal or vertical cohesion may also yield mental health benefits.

Integrative analysis of genomic and exposomic influences on youth mental health.

BACKGROUND: Understanding complex influences on mental health problems in young people is needed to inform early prevention strategies. Both genetic and environmental factors are known to influence youth mental health, but a more comprehensive picture of their interplay, including wide-ranging environmental exposures - that is, the exposome - is needed. We perform an integrative analysis of genomic and exposomic data in relation to internalizing and externalizing symptoms in a cohort of 4,314 unrelated youth from the Adolescent Brain and Cognitive Development (ABCD) Study. METHODS: Using novel GREML-based approaches, we model the variance in internalizing and externalizing symptoms explained by additive and interactive influences from the genome (G) and modeled exposome (E) consisting of up to 133 variables at the family, peer, school, neighborhood, life event, and broader environmental levels, including genome-by-exposome (G × E) and exposome-by-exposome (E × E) effects. RESULTS: A best-fitting integrative model with G, E, and G × E components explained 35% and 63% of variance in youth internalizing and externalizing symptoms, respectively. Youth in the top quintile of model-predicted risk accounted for the majority of individuals with clinically elevated symptoms at follow-up (60% for internalizing; 72% for externalizing). Of note, different domains of environmental exposures were most impactful for internalizing (life events) and externalizing (contextual including family, school, and peer-level factors) symptoms. In addition, variance explained by G × E contributions was substantially larger for externalizing (33%) than internalizing (13%) symptoms. CONCLUSIONS: Advanced statistical genetic methods in a longitudinal cohort of youth can be leveraged to address fundamental questions about the role of 'nature and nurture' in developmental psychopathology.

Influence of Maternal Childhood Trauma on Perinatal Depression, Observed Mother-Infant Interactions, and Child Growth.

INTRODUCTION: Mothers who have experienced childhood trauma may be at increased risk for disruptions in caregiving behavior, with potential consequences for early child development. However, assessments of caregiving behavior tend to be self-reported, which may bias results, and have been limited in lower-resource settings. METHODS: In an overall sample of 256 South African mothers followed across the perinatal period, this longitudinal study used structural equation modeling to test pathways of association between maternal childhood trauma and depressive symptoms on observed mother-infant interactions at 3.5 months and subsequent child growth outcomes at 1 year. RESULTS: On average, mothers with childhood trauma histories tended to show lower rated overall interactions with their infants (B = - 0.16, p = .013), which in turn was associated with reduced child growth at 1 year (B = 0.17, p = .046). When this model was adjusted for maternal age and relative socioeconomic status (SES), maternal SES strongly explained child growth (B = 0.31, p < .001) such that the direct effect of mother-infant interactions was no longer significant. DISCUSSION: For child growth in a lower-resource setting, quality of mother-infant interactions could be a relevant predictor but more strongly explained by maternal SES factors, suggesting a need for broader approaches that not only improve dyadic relationships but also address maternal ecological resources.

Indirect effects of dissociation on the relationship between lifetime PTSD symptoms and condomless sex among men who have sex with men with a history of childhood sexual abuse.

Posttraumatic stress disorder (PTSD) symptoms may interfere with gay, bisexual and other men who have sex with men's (MSM) ability to engage in safe sex practices. An indirect relationship with dissociation may help to elucidate the relationship between PTSD symptom severity and condomless sex among MSM with childhood sexual abuse (CSA) histories. These relationships have not previously been examined in this group, which has a unique vulnerability for HIV acquisition. A cross-sectional sample of MSM with histories of CSA (N=290) was recruited at study sites in Boston, MA, and Miami, FL. Participants had a mean age of 37.95 years (SD=11.68), 22% were African American and 29.4% identified as Latino. The sample reported a mean of 10.47 (SD=4.38) lifetime PTSD symptoms and 26.4% met the clinical threshold for dissociation. Logistic regression models (adjusted for age, education, and substance use disorder) were used to assess indirect effects of dissociation on the relationship between lifetime PTSD symptoms and condomless anal/vaginal sex episodes with serodiscordant or unknown status partners in the past 3 months. Dissociation accounted for the association between lifetime PTSD symptom severity and condomless sex episodes. The Sobel test (Sobel = 2.04, p= .042; CI 95% bias-corrected bootstrap) suggested significant indirect effects for dissociation. Dissociation among MSM with CSA histories may compromise accurate appraisals of sexual risk and safety and increase vulnerability for HIV acquisition. Further research is warranted to address HIV prevention in the context of PTSD symptom severity to improve the mental health of MSM and increase the effectiveness of HIV prevention interventions.

Measures of adult psychological resilience following early-life adversity: how congruent are different measures?

BACKGROUND: Psychological resilience - positive psychological adaptation in the context of adversity - is defined and measured in multiple ways across disciplines. However, little is known about whether definitions capture the same underlying construct and/or share similar correlates. This study examined the congruence of different resilience measures and associations with sociodemographic factors and body mass index (BMI), a key health indicator. METHODS: In a cross-sectional sample of 1429 African American adults exposed to child maltreatment, we derived four resilience measures: a self-report scale assessing resiliency (perceived trait resilience); a binary variable defining resilience as low depression and posttraumatic stress (absence of distress); a binary variable defining resilience as low distress and high positive affect (absence of distress plus positive functioning); and a continuous variable reflecting individuals' deviation from distress levels predicted by maltreatment severity (relative resilience). Associations between resilience measures, sociodemographic factors, and BMI were assessed using correlations and regressions. RESULTS: Resilience measures were weakly-to-moderately correlated (0.27-0.69), though similarly patterned across sociodemographic factors. Women showed higher relative resilience, but lower perceived trait resilience than men. Only measures incorporating positive affect or resiliency perceptions were associated with BMI: individuals classified as resilient by absence of distress plus positive functioning had lower BMI than non-resilient (ß = -2.10, p = 0.026), as did those with higher perceived trait resilience (ß = -0.63, p = 0.046). CONCLUSION: Relatively low congruence between resilience measures suggests studies will yield divergent findings about predictors, prevalence, and consequences of resilience. Efforts to clearly define resilience are needed to better understand resilience and inform intervention and prevention efforts.

Dissecting the heterogeneity of posttraumatic stress disorder: differences in polygenic risk, stress exposures, and course of PTSD subtypes.

BACKGROUND: Definition of disorder subtypes may facilitate precision treatment for posttraumatic stress disorder (PTSD). We aimed to identify PTSD subtypes and evaluate their associations with genetic risk factors, types of stress exposures, comorbidity, and course of PTSD. METHODS: Data came from a prospective study of three U.S. Army Brigade Combat Teams that deployed to Afghanistan in 2012. Soldiers with probable PTSD (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition ≥31) at three months postdeployment comprised the sample (N = 423) for latent profile analysis using Gaussian mixture modeling and PTSD symptom ratings as indicators. PTSD profiles were compared on polygenic risk scores (derived from external genomewide association study summary statistics), experiences during deployment, comorbidity at three months postdeployment, and persistence of PTSD at nine months postdeployment. RESULTS: Latent profile analysis revealed profiles characterized by prominent intrusions, avoidance, and hyperarousal (threat-reactivity profile; n = 129), anhedonia and negative affect (dysphoric profile; n = 195), and high levels of all PTSD symptoms (high-symptom profile; n = 99). The threat-reactivity profile had the most combat exposure and the least comorbidity. The dysphoric profile had the highest polygenic risk for major depression, and more personal life stress and co-occurring major depression than the threat-reactivity profile. The high-symptom profile had the highest rates of concurrent mental disorders and persistence of PTSD. CONCLUSIONS: Genetic and trauma-related factors likely contribute to PTSD heterogeneity, which can be parsed into subtypes that differ in symptom expression, comorbidity, and course. Future studies should evaluate whether PTSD typology modifies treatment response and should clarify distinctions between the dysphoric profile and depressive disorders.

Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank.

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

Genetic susceptibility for major depressive disorder associates with trajectories of depressive symptoms across childhood and adolescence.

BACKGROUND: Early-onset depression during childhood and adolescence is associated with a worse course of illness and outcome than adult onset. However, the genetic factors that influence risk for early-onset depression remain mostly unknown. Using data collected over 13 years, we examined whether polygenic risk scores (PRS) that capture genetic risk for depression were associated with depressive symptom trajectories assessed from childhood to adolescence. METHODS: Data came from the Avon Longitudinal Study of Parents and Children, a prospective, longitudinal birth cohort (analytic sample = 7,308 youth). We analyzed the relationship between genetic susceptibility to depression and three time-dependent measures of depressive symptoms trajectories spanning 4-16.5 years of age (class, onset, and cumulative burden). Trajectories were constructed using a growth mixture model with structured residuals. PRS were generated from the summary statistics of a genome-wide association study of depression risk using data from the Psychiatric Genomics Consortium, UK Biobank, and 23andMe, Inc. We used MAGMA to identify gene-level associations with these measures. RESULTS: Youth were classified into six classes of depressive symptom trajectories: high/renitent (27.9% of youth), high/reversing (9.1%), childhood decrease (7.3%), late childhood peak (3.3%), adolescent spike (2.5%), and minimal symptoms (49.9%). PRS discriminated between youth in the late childhood peak, high/reversing, and high/renitent classes compared to the minimal symptoms and childhood decrease classes. No significant associations were detected at the gene level. CONCLUSIONS: This study highlights differences in polygenic loading for depressive symptoms across childhood and adolescence, particularly among youths with high symptoms in early adolescence, regardless of age-independent patterns.

"I did not plan that is what hurts": Pregnancy intentions and contraceptive use among pregnant young women in KwaZulu-Natal, South Africa.

Unintended pregnancy impacts many young women in South Africa, and rates of consistent contraceptive use among this population are suboptimal. Limited empirical work has investigated reasons for inconsistency between pregnancy intention and contraceptive use behaviour with data collected during pregnancy. We explored pregnancy intentions and discordance between intentions and contraceptive use prior to conception among young pregnant women in KwaZulu-Natal, South Africa. In-depth qualitative interviews were conducted with 35 women during pregnancy (mean age = 19.3; range = 18-21) in 2011 and 2012. Data were analysed using content analysis. All participants reported unintended pregnancies; almost half were not using contraception near conception. Reasons for not intending to become pregnant spanned personal, social, health, and economic domains. Participants living with HIV (n = 13) expressed specific concerns related to impacts of pregnancy on HIV disease management and fear of transmission of HIV to the infant. Discordance between pregnancy intentions and contraceptive use prior to conception was attributed to personal, social, health and structural domains. Findings indicate a need for interventions that address barriers to contraceptive use in order to minimise unintended pregnancy and support safe, desired pregnancies among young women.

Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression.

Suicide is a major public health problem. The contribution of common genetic variants for major depressive disorder (MDD) independent of personal and parental history of MDD has not been established. Polygenic risk score (using PRS-CS) for MDD was calculated for US Army soldiers of European ancestry. Associations between polygenic risk for MDD and lifetime suicide attempt (SA) were tested in models that also included parental or personal history of MDD. Models were adjusted for age, sex, tranche (where applicable), and 10 principal components reflecting ancestry. In the first cohort, 417 (6.3%) of 6,573 soldiers reported a lifetime history of SA. In a multivariable model that included personal [OR = 3.83, 95% CI:3.09-4.75] and parental history of MDD [OR = 1.43, 95% CI:1.13-1.82 for one parent and OR = 1.64, 95% CI:1.20-2.26 for both parents), MDD PRS was significantly associated with SA (OR = 1.22 [95% CI:1.10-1.36]). In the second cohort, 204 (4.2%) of 4,900 soldiers reported a lifetime history of SA. In a multivariable model that included personal [OR = 3.82, 95% CI:2.77-5.26] and parental history of MDD [OR = 1.42, 95% CI:0.996-2.03 for one parent and OR = 2.21, 95% CI:1.33-3.69 for both parents) MDD PRS continued to be associated (at p = .0601) with SA (OR = 1.15 [95% CI:0.994-1.33]). A soldier's PRS for MDD conveys information about likelihood of a lifetime SA beyond that conveyed by two predictors readily obtainable by interview: personal or parental history of MDD. Results remain to be extended to prospective prediction of incident SA. These findings portend a role for PRS in risk stratification for suicide attempts.

Individual and combined associations between cardiorespiratory fitness and grip strength with common mental disorders: a prospective cohort study in the UK Biobank.

BACKGROUND: Depression and anxiety are common mental disorders that increase physical health risks and are leading causes of global disability. Several forms of physical fitness could be modifiable risk factors for common mental disorders in the population. We examined associations between individual and combined markers of cardiorespiratory fitness and grip strength with the incidence of common mental disorders. METHODS: A 7-year prospective cohort study in 152,978 UK Biobank participants. An exercise test and dynamometer were used to measure cardiorespiratory and grip strength, respectively. We used Patient Health Questionnaire-9 and Generalised Anxiety Disorder-7 scales to estimate the incidence of common mental disorders at follow-up. RESULTS: Fully adjusted, longitudinal models indicated a dose-response relationship. Low and medium cardiorespiratory fitness was associated with 1.485 (95% CIs, 1.301 to 1.694, p <  0.001) and 1.141 (95% CIs, 1.005 to 1.297, p = 0.041) higher odds of depression or anxiety, compared to high cardiorespiratory fitness. Low and medium grip strength was associated with 1.381 (95% CIs, 1.315 to 1.452, p <  0.001) and 1.116 (95% CIs, 1.063 to 1.172, p <  0.001) higher odds of common mental disorder compared to high grip strength. Individuals in the lowest group for both cardiorespiratory fitness and grip strength had 1.981 (95% CIs, 1.553 to 2.527, p <  0.001) higher odds of depression, 1.599 (95% CIs, 1.148 to 2.118, p = 0.004) higher odds of anxiety, and 1.814 (95% CIs, 1.461 to 2.252, p <  0.001) higher odds of either common mental disorder, compared to high for both types of fitness. CONCLUSIONS: Objective cardiorespiratory and muscular fitness markers represent modifiable risk factors for common mental disorders. Public health strategies to reduce common mental disorders could include combinations of aerobic and resistance activities.