A general exposome factor explains individual differences in functional brain network topography and cognition in youth.

Childhood environments are critical in shaping cognitive neurodevelopment. With the increasing availability of large-scale neuroimaging datasets with deep phenotyping of childhood environments, we can now build upon prior studies that have considered relationships between one or a handful of environmental and neuroimaging features at a time. Here, we characterize the combined effects of hundreds of inter-connected and co-occurring features of a child's environment ("exposome") and investigate associations with each child's unique, multidimensional pattern of functional brain network organization ("functional topography") and cognition. We apply data-driven computational models to measure the exposome and define personalized functional brain networks in pre-registered analyses. Across matched discovery (n=5139, 48.5% female) and replication (n=5137, 47.1% female) samples from the Adolescent Brain Cognitive Development study, the exposome was associated with current (ages 9-10) and future (ages 11-12) cognition. Changes in the exposome were also associated with changes in cognition after accounting for baseline scores. Cross-validated ridge regressions revealed that the exposome is reflected in functional topography and can predict performance across cognitive domains. Importantly, a single measure capturing a child's exposome could more accurately and parsimoniously predict cognition than a wealth of personalized neuroimaging data, highlighting the importance of children's complex, multidimensional environments in cognitive neurodevelopment.

The Role of Individual Discrimination and Structural Stigma in the Mental Health of Sexual Minority Youth.

OBJECTIVE: Sexual minority (SM) youth experience a greater mental health burden compared with their heterosexual peers. This study aimed to characterize mental health disparities among SM compared with non-SM youth, test main and interactive associations of SM identity and stressors targeting SM youth at the individual level (interpersonal SM discrimination) and structural level (state-level structural SM stigma) with youth mental health, and explore the contribution of interpersonal SM discrimination to the mental health burden of SM youth. METHOD: Participants included 11,622 youth (ages 9-13; 47.6% assigned female at birth) from the Adolescent Brain Cognitive Development (ABCD) Study. Linear mixed-effects models tested main and interactive associations of SM identity, interpersonal SM discrimination, and structural SM stigma with mental health measures (self-reported overall psychopathology, suicidal ideation, and suicide attempts), adjusting for demographics and other interpersonal stressors not specific to SM (other discrimination types, peer victimization, and cyberbullying). Longitudinal mediation models tested whether interpersonal SM discrimination mediated the associations between SM identity and mental health measures. RESULTS: SM youth (n = 1,051) experienced more interpersonal SM discrimination and overall psychopathology compared with their non-SM peers (n = 10,571). Adjusting for demographics, there were significant associations (main effects) of interpersonal SM discrimination and structural SM stigma with overall psychopathology. When further adjusting for other non-SM-related stressors, the main effect of structural SM stigma was no longer significant. Interpersonal SM discrimination was also significantly associated with suicidal ideation and attempt, accounting for demographics, while structural SM stigma was not. Accounting for both demographics and other non-SM stressors, there was a significant interaction between SM identity and structural SM stigma in association with psychopathology (p = .02), such that, compared with their peers, SM youth showed a greater association between structural SM stigma and psychopathology. Longitudinal mediation revealed that interpersonal SM discrimination was a significant mediator explaining approximately 10% to 15% of the variance of the pathways between SM identity and all mental health outcomes. CONCLUSION: Results delineate contributions of interpersonal discrimination and structural stigma targeting SM youth to their heightened mental health burden in early adolescence. These findings underscore the need to address microlevel and macrolevel SM discrimination and structural stigma when caring for this population. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.

Allostatic load in early adolescence: gene / environment contributions and relevance for mental health.

Background: Allostatic load is the cumulative "wear and tear" on the body due to chronic adversity. We aimed to test poly-environmental (exposomic) and polygenic contributions to allostatic load and their combined contribution to early adolescent mental health. Methods: We analyzed data on N = 5,035 diverse youth (mean age 12) from the Adolescent Brain Cognitive Development Study (ABCD). Using dimensionality reduction method, we calculated and overall allostatic load score (AL) using body mass index [BMI], waist circumference, blood pressure, blood glycemia, blood cholesterol, and salivary DHEA. Childhood exposomic risk was quantified using multi-level environmental exposures before age 11. Genetic risk was quantified using polygenic risk scores (PRS) for metabolic system susceptibility (type 2 diabetes [T2D]) and stress-related psychiatric disease (major depressive disorder [MDD]). We used linear mixed effects models to test main, additive, and interactive effects of exposomic and polygenic risk (independent variables) on AL (dependent variable). Mediation models tested the mediating role of AL on the pathway from exposomic and polygenic risk to youth mental health. Models adjusted for demographics and genetic principal components. Results: We observed disparities in AL with non-Hispanic White youth having significantly lower AL compared to Hispanic and Non-Hispanic Black youth. In the diverse sample, childhood exposomic burden was associated with AL in adolescence (beta=0.25, 95%CI 0.22-0.29, P<.001). In European ancestry participants (n=2,928), polygenic risk of both T2D and depression was associated with AL (T2D-PRS beta=0.11, 95%CI 0.07-0.14, P<.001; MDD-PRS beta=0.05, 95%CI 0.02-0.09, P=.003). Both polygenic scores showed significant interaction with exposomic risk such that, with greater polygenic risk, the association between exposome and AL was stronger. AL partly mediated the pathway to youth mental health from exposomic risk and from MDD-PRS, and fully mediated the pathway from T2D-PRS. Conclusions: AL can be quantified in youth using anthropometric and biological measures and is mapped to exposomic and polygenic risk. Main and interactive environmental and genetic effects support a diathesis-stress model. Findings suggest that both environmental and genetic risk be considered when modeling stress-related health conditions.

COVID-19 Worries and Insomnia: A Follow-Up Study.

The COVID-19 pandemic was associated with significant increases in sleep disorder symptoms and chronic worry. We previously demonstrated that worry about the pandemic was more strongly associated with subsequent insomnia than the converse during the acute (first 6 months) phase of the pandemic. In this report, we evaluated whether that association held over one year of the pandemic. Participants (n = 3560) completed self-reported surveys of worries about the pandemic, exposure to virus risk factors, and the Insomnia Severity Index on five occasions throughout the course of one year. In cross-sectional analyses, insomnia was more consistently associated with worries about the pandemic than exposure to COVID-19 risk factors. In mixed-effects models, changes in worries predicted changes in insomnia and vice versa. This bidirectional relationship was further confirmed in cross-lagged panel models. Clinically, these findings suggest that during a global disaster, patients who report elevations in either worry or insomnia should be considered for evidence-based treatments for these symptoms to prevent secondary symptoms in the future. Future research should evaluate the extent to which dissemination of evidence-based practices for chronic worry (a core feature of generalized anxiety disorder or illness anxiety disorder) or insomnia reduces the development of co-occurring symptoms during a global disaster.

Contribution of risk and resilience factors to anxiety trajectories during the early stages of the COVID-19 pandemic: A longitudinal study.

The COVID-19 pandemic, and the response of governments to mitigate the pandemic's spread, resulted in exceptional circumstances that comprised a major global stressor, with broad implications for mental health. We aimed to delineate anxiety trajectories over three time-points in the first 6 months of the pandemic and identify baseline risk and resilience factors that predicted anxiety trajectories. Within weeks of the pandemic onset, we established a website (covid19resilience.org), and enrolled 1362 participants (n = 1064 from US; n = 222 from Israel) who provided longitudinal data between April-September 2020. We used latent growth mixture modelling to identify anxiety trajectories and ran multivariate regression models to compare characteristics between trajectory classes. A four-class model best fit the data, including a resilient trajectory (stable low anxiety) the most common (n = 961, 75.08%), and chronic anxiety (n = 149, 11.64%), recovery (n = 96, 7.50%) and delayed anxiety (n = 74, 5.78%) trajectories. Resilient participants were older, not living alone, with higher income, more education, and reported fewer COVID-19 worries and better sleep quality. Higher resilience factors' scores, specifically greater emotion regulation and lower conflict relationships, also uniquely distinguished the resilient trajectory. Results are consistent with the pre-pandemic resilience literature suggesting that most individuals show stable mental health in the face of stressful events. Findings can inform preventative interventions for improved mental health.

Association Between State-Level Access to Reproductive Care and Suicide Rates Among Women of Reproductive Age in the United States.

Importance: Many states in the United States enforce restrictions to reproductive care, with access to abortion remaining a highly divisive issue. Denial of abortion is linked with heightened stress and anxiety among reproductive-aged women. However, no studies have tested whether access to reproductive care is linked to suicide. Objective: To evaluate whether state-level restrictions in access to reproductive care in the United States were associated with suicide rates among reproductive-aged women from 1974 to 2016. Design, Setting, and Participants: A longitudinal ecologic study with a difference-in-differences analysis assessed whether annual changes in the enforcement of state-level restrictions to reproductive care were related to annual state-level suicide rates vs rates of death due to motor vehicle crashes. Duration of follow-up varied between different states (range, 4-40 years), contingent on the first year that restrictions were implemented. Models controlled for year and state fixed effects and other relevant demographic and economic factors. Analyses were conducted between December 2021 and January 2022. Exposures: Targeted Regulation of Abortion Providers (TRAP) laws index measuring state-year-level restrictions to reproductive care. Main Outcomes and Measures: Annual state-level suicide rates and motor vehicle crash death rates among reproductive-aged women (ages 20-34 years; target group) vs women of postreproductive age (ages 45-64 years; control group). Results: Twenty-one US states enforced at least 1 TRAP law between 1974 and 2016. Annual rates of death by suicide ranged from 1.4 to 25.6 per 100 000 women of reproductive age to 2.7 to 33.2 per 100 000 women of postreproductive age during the study period (1974-2016). Annual motor vehicle crash death rates among women of reproductive age ranged from 2.4 to 42.9 per 100 000. Enforcement of TRAP laws was associated with higher suicide rates among reproductive-aged women (ß = 0.17; 95% CI, 0.03 to 0.32; P = .02) but not women of postreproductive age (ß = 0.06; 95% CI, -0.11 to 0.24; P = .47) nor to deaths due to motor vehicle crashes (ß = 0.03, 95% CI, -0.04 to 0.11; P = .36). Among reproductive-aged women, the weighted average annual-state level suicide death rate when no TRAP laws were enforced was 5.5 per 100 000. Enforcement of a TRAP law was associated with a 5.81% higher annual rate of suicide than in pre-enforcement years. Findings remained significant when using alternative, broader indices of reproductive care access and different age categorizations. Conclusions and Relevance: In this study with a difference-in-differences analysis of US women, restrictions on access to reproductive care from 1974 to 2016 were associated with suicide rates among reproductive-aged women. Given the limitations of the ecologic design of this study, further research is needed to assess whether current factors affecting access to reproductive care services are related to suicide risk among women of reproductive age and to inform suicide prevention strategies.

Association between Asthma and Suicidality in 9-12-Year-Old Youths.

PURPOSE: Suicidal ideation and attempts in youth are a growing health concern, and more data are needed regarding their biological underpinnings. Asthma is a common chronic inflammatory disorder in youth and has been associated with suicidal ideation and attempts in adolescent and adult populations, but data in younger children and early adolescents are lacking. We wished to study associations of asthma with childhood suicidality considering asthma's potential as a clinically relevant model for childhood chronic immune dysregulation. METHODS: Using data from the Adolescent Brain Cognitive Development (ABCD) Study (n = 11,876, 47.8% female, mean age 9.9 years at baseline assessment and 12.0 years at two-year follow-up), we assessed associations between asthma and suicidal ideation and attempts through baseline to two-year follow-up. RESULTS: Asthma history as defined by parent report (n = 2282, 19.2% of study population) was associated with suicide attempts (SA) (odds ratio (OR) = 1.44, p = 0.01), and this association remained significant even when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.46, p = 0.028). History of asthma attacks was associated with both suicidal ideation (SI) and SA when controlling for demographics, socioeconomic factors, and environmental factors (OR = 1.27, p = 0.042; OR = 1.83, p = 0.004, respectively). The association of asthma attack with SA remained significant when controlling for self-reported psychopathology (OR = 1.92, p = 0.004). The total number of asthma attacks was associated with both SI and SA (OR = 1.03, p = 0.043; OR = 1.06, p = 0.05, respectively). CONCLUSIONS: Findings suggest an association between asthma and suicidality in early adolescence. Further research is needed to investigate mechanisms underlying this relationship.

Estimating the Association Between Exposome and Psychosis as Well as General Psychopathology: Results From the ABCD Study.

Background: The exposome comprises all nongenetic factors an individual is exposed to across their lifespan. Research suggests that exposomic vulnerability for schizophrenia is associated not only with psychosis but also, to a degree, with general psychopathology. Here, we investigated to what degree exposome factors are associated with psychosis and general psychopathology. Methods: Data were retrieved from the 1-year follow-up assessment of a large U.S. adolescent sample (n = 11,235), the Adolescent Brain Cognitive Development (ABCD) Study. Iterative factor analyses of environmental exposures (n = 798) allowed calculation of 6 exposome factors: household adversity, neighborhood environment, day-to-day experiences, state-level environment, family values, pregnancy/birth complications. Bifactor modeling of clinical symptoms (n = 93) allowed calculation of a general psychopathology factor (p-factor) and 6 subdomains, including a psychosis subdomain. We applied linear regression analyses to estimate the association of exposome factors with the p-factor and psychosis subdomain, respectively. Results: Individual analyses showed that 5 exposome factors were significantly associated with the p-factor after multiple-comparison correction. In the mutually adjusted model, all exposome factors were significantly associated with the p-factor. Psychosis was particularly associated with 3 exposome factors, with the mutually adjusted model yielding the following results: household adversity (ß = 0.04, 95% CI, 0.01 to 0.07), day-to-day experiences (ß = 0.10, 95% CI, 0.08 to 0.12), and pregnancy/birth complications (ß = 0.03, 95% CI, 0.01 to 0.05). Conclusions: Our findings demonstrate that multifaceted environmental background is associated with mental disorders. Psychosis was particularly associated with prenatal, perinatal, and childhood (household and school) adversities, although these exposome domains were also associated with psychopathology. The exposome approach can help understand neurodevelopmental psychopathology.

COVID-19-related financial strain and adolescent mental health.

Background: The COVID-19 pandemic and associated responses have induced a host of crises worldwide, including an economic recession and a global mental health crisis. The specific effects of recession on youth mental health are understudied. We aimed to examine the mechanisms by which pandemic-related financial strain may affect mental health in a diverse sample of American adolescents. Methods: We analyzed data from the Adolescent Brain Cognitive Development Study (ABCD Study®), a large, longitudinal study of diverse US adolescents which collected data before and during the pandemic (N = 9,720, mean age 12.9 years, 18.2% Black). Linear mixed-effects models tested associations of financial strain (parent-reported household wage loss and youth-reported financial stress) with depressive symptomatology over time, covarying for multiple confounders including pre-pandemic socioeconomic status and psychopathology, and pandemic-related environmental factors. Longitudinal mediation analyses examined potential mechanisms leading from wage loss to youth mental health. Findings: Financial strain was highly prevalent, especially among low-income participants, with >70% of the total sample reporting lost wages. Both wage loss and subjective financial stress were associated with depressive symptomatology over time (Estimate = 0.04, P = 0.014; Estimate = 0.17, P < 0.001; respectively). The association between financial stress and depressive symptomatology was robust to the addition of multiple environmental confounders (Estimate = 0.16, P < 0.001). Both family-level (family conflict) and individual-level (financial stress) factors mediated the relationship between wage loss and depressive symptomatology. Interpretation: The financial effects of COVID-19 (and worldwide responses to it) have taken a significant toll on youth mental health. In families that lost wages, youth-reported financial stress and familial factors mediated the relationship between wage loss and mental health over time. Findings highlight financial stress as a key driver of youth mental health burden and identify familial factors as critical targets for intervention to mitigate mental health risks in periods of economic crises. Funding: This study was supported by the National Institute of Mental Health [grant numbers K23MH120437 (RB), R01MH117014 (TMM)]; the Lifespan Brain Institute of Children's Hospital of Philadelphia and Penn Medicine, University of Pennsylvania.

Genetic risk, parental history, and suicide attempts in a diverse sample of US adolescents.

Background: Adolescent suicide is a major health problem in the US marked by a recent increase in risk of suicidal behavior among Black/African American youth. While genetic factors partly account for familial transmission of suicidal behavior, it is not clear whether polygenic risk scores of suicide attempt can contribute to suicide risk classification. Objectives: To evaluate the contribution of a polygenic risk score for suicide attempt (PRS-SA) in explaining variance in suicide attempt by early adolescence. Methods: We studied N = 5,214 non-related youth of African and European genetic ancestry from the Adolescent Brain Cognitive Development (ABCD) Study (ages 8.9-13.8 years) who were evaluated between 2016 and 2021. Regression models tested associations between PRS-SA and parental history of suicide attempt/death with youth-reported suicide attempt. Covariates included age and sex. Results: Over three waves of assessments, 182 youth (3.5%) reported a past suicide attempt, with Black youth reporting significantly more suicide attempts than their White counterparts (6.1 vs. 2.8%, p < 0.001). PRS-SA was associated with suicide attempt [odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.1-1.5, p = 0.001]. Parental history of suicide attempt/death was also associated with youth suicide attempt (OR = 3.1, 95% CI, 2.0-4.7, p < 0.001). PRS-SA remained significantly associated with suicide attempt even when accounting for parental history (OR = 1.29, 95% CI = 1.1-1.5, p = 0.002). In European ancestry youth (n = 4,128), inclusion of PRS-SA in models containing parental history explained more variance in suicide attempt compared to models that included only parental history (ΔR 2 = 0.7%, p = 0.009). Conclusions: Findings suggest that PRS-SA may be useful for youth suicide risk classification in addition to established risk factors.

Association of Cyberbullying Experiences and Perpetration With Suicidality in Early Adolescence.

Importance: Adolescent suicidality (ie, suicidal ideation or attempts) is a major public health concern. Cyberbullying experiences and perpetration have become increasingly prevalent and are associated with mental health burden, but their roles as independent suicidality risk factors remain unclear. Data are needed to clarify their contribution to teen suicidality to inform suicide prevention efforts. Objective: To examine whether cyberbullying experiences and perpetration are distinct stressors divergent from other forms of peer aggression experiences in their association with suicidality in early adolescence. Design, Setting, and Participants: This cross-sectional analysis used data collected between July 2018 and January 2021 from the Adolescent Brain Cognitive Development (ABCD) study, a large, diverse sample of US children aged 10 to 13 years. Exposures: Youth reports of cyberbullying experiences or perpetration. Main Outcomes and Measures: The main outcome was youth-reported suicidality (past or present, as reported in the ABCD 2-year follow-up assessment). Covariates included demographics, established environmental risk and protective factors for youth suicidality, psychopathology, and experiences or perpetration of offline peer aggression. Results: A total of 10 414 ABCD participants were included in this study. Participants had a mean (SD) age of 12.0 (0.7) years and 4962 (47.6%) were female; 796 (7.6%) endorsed suicidality. A total of 930 (8.9%) reported experiencing cyberbullying and 96 (0.9%) reported perpetrating cyberbullying. Of the perpetrators, 66 (69.0%) also endorsed experiencing cyberbullying. Controlling for demographics, experiencing cyberbullying was associated with suicidality (odds ratio [OR], 4.2 [95% CI, 3.5-5.1]; P < .001), whereas perpetrating cyberbullying was not (OR, 1.3 [95% CI, 0.8-2.3]; P = .30). Experiencing cyberbullying remained associated with suicidality when accounting for negative life events, family conflict, parental monitoring, school environment, and racial and ethnic discrimination (OR, 2.5 [95% CI, 2.0-3.0]; P < .001) and when further covarying for internalizing and externalizing psychopathology (OR, 1.8 [95% CI, 1.4-2.4]; P < .001). Both being a target and being a perpetrator of offline peer aggression were associated with suicidality (OR, 1.5 [95% CI, 1.1-2.0] for both), controlling for all covariates described earlier. Cyberbullying experiences remained associated with suicidality (OR, 1.7 [95% CI, 1.3-2.2]; P < .001, controlling for all covariates) when included with offline peer aggression experiences and perpetration. Conclusions and Relevance: In this cross-sectional study, experiencing-but not perpetrating-cyberbullying was associated with suicidality in early adolescence. This association was significant over and above other suicidality risk factors, including offline peer aggression experiences or perpetration. These findings can inform adolescent suicide prevention strategies, and they suggest that clinicians and educational staff working with this population should routinely evaluate for adolescents' experience with cyberbullying.

Association between racial/ethnic discrimination and pubertal development in early adolescence.

Racial health disparities in the United States are a major concern, with Black or African Americans experiencing more morbidity and mortality at earlier ages compared to White Americans. More data is needed on the biological underpinnings of this phenomenon. One potential explanation for racial health disparities is that of accelerated aging, which is associated with increased stress exposure. Black Americans face disproportionate levels of environmental stress, specifically racial/ethnic discrimination. Here we investigated associations between self-reported experiences of discrimination and pubertal development (PD) in a diverse sample of young American adolescents (N = 11,235, mean age 10.9 years, 20.5% Black participants) from the Adolescent Brain Cognitive Development (ABCD) Study. Compared to their non-Black counterparts, Black youth experienced more racial/ethnic discrimination in the past year (10.4% vs 3.1%) and had a greater likelihood of being in late/post-pubertal status (3.6% vs 1.5% in boys, 21.3% vs 11.4% in girls). In both sexes, multivariable regression models run in the full sample revealed a cross-sectional association of experiences of racial/ethnic discrimination with pubertal development (boys: standardized beta [ß]=0.123, P < .001; girls: ß = 0.110, P < .001) covarying for demographics, BMI, and dietary habits. Associations remained significant when controlling for multiple other environmental confounders including other forms of (non-racial/ethnic) discrimination and other environmental adversities including poverty and negative life events, and when using parent-reported assessment of pubertal development. Furthermore, racial/ethnic discrimination was associated with elevated estradiol levels in girls (ß = 0.057, P = .002). Findings suggest an association between experiences of discrimination and pubertal development that is independent of multiple environmental stressors. Future longitudinal studies are warranted to establish causal mechanism.

Worry about COVID-19 as a predictor of future insomnia.

The coronavirus disease 2019 (COVID-19) pandemic resulted in significant increases in insomnia, with up to 60% of people reporting increased insomnia. However, it is unclear whether exposure to risk factors for the virus or worries about COVID-19 are more strongly associated with insomnia. Using a three-part survey over the course of the first 6 months of the pandemic, we evaluated associations between COVID-19 exposures, COVID-19 worries, and insomnia. We hypothesised that COVID-19-related worries and exposure to risk of COVID-19 would predict increases in insomnia. Participants (N = 3,560) completed a survey at three time-points indicating their exposures to COVID-19 risk factors, COVID-19-related worries, and insomnia. COVID-19 worry variables were consistently associated with greater insomnia severity, whereas COVID-19 exposure variables were not. COVID-19 worries decreased significantly over time, and there were significant interactions between change in COVID-19 worries and change in insomnia severity over time. Individuals who experienced increases in COVID-19 worries also experienced increases in insomnia severity. Changes in worry during the COVID-19 pandemic were associated with changes in insomnia; worries about COVID-19 were a more consistent predictor of insomnia than COVID-19 exposures. Evidence-based treatments targeting virus-related worries may improve insomnia during this and future calamities.

Association Between Discrimination Stress and Suicidality in Preadolescent Children.

Objective: Youth suicide rates in the United States have been increasing in recent years, especially in Black Americans, the reasons for which are unclear. Environmental adversity is key in youth suicidality; hence there is a need to study stressors that have a disproportionate impact on Black youths. We aimed to disentangle the unique contribution of racial/ethnic discrimination from other adversities associated with childhood suicidal ideation and attempts (suicidality). Method: We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, which included a large, diverse sample of US children (N = 11,235, mean age 10.9 years, 20.2% Black), assessed for multiple environmental adversities including discrimination. Multivariate regression models tested the association of self-reported racial/ethnic discrimination with suicidality, covarying for multiple confounders including other discrimination types (toward non-US-born individuals, sexual orientation-based, and weight-based). Matched analyses contrasted effects of racial/ethnic discrimination and racial identity on suicidality. Results: Black youths reported more discrimination and higher suicidality rates than non-Black youths. High racial/ethnic discrimination was positively and significantly associated with suicidality, adjusting for other discrimination types (odds ratio = 2.6, 95% CI = 2.1-3.2). Findings remained significant after adjusting for multiple suicidality risk factors. Once experienced, racial/ethnic discrimination was similarly associated with suicidality in White, Black, and Hispanic youths. Matched analyses revealed that racial/ethnic discrimination was associated with suicidality (relative risk = 2.7, 95% CI = 2-3.5), whereas Black race was not (relative risk = 0.9, 95% CI = 0.7-1.2). Conclusion: Racial/ethnic discrimination is disproportionately experienced by Black children, and is associated with preadolescent suicidality, over and above other adversities. Findings highlight the need to address discrimination as part of suicide prevention strategies. Cross-sectional design hampers causal inferences.Reprinted from J Am Acad Child Adolesc Psychiatry, Argabright et al., Association Between Discrimination Stress and Suicidality in Preadolescent Children, S0890-8567(21)01355-1, copyright 2021, with permission from Elsevier.

Modeling environment through a general exposome factor in two independent adolescent cohorts.

Exposures to perinatal, familial, social, and physical environmental stimuli can have substantial effects on human development. We aimed to generate a single measure that capture's the complex network structure of the environment (ie, exposome) using multi-level data (participant's report, parent report, and geocoded measures) of environmental exposures (primarily from the psychosocial environment) in two independent adolescent cohorts: The Adolescent Brain Cognitive Development Study (ABCD Study, N = 11 235; mean age, 10.9 years; 47.7% females) and an age- and sex-matched sample from the Philadelphia Neurodevelopmental Cohort (PNC, N = 4993). We conducted a series of data-driven iterative factor analyses and bifactor modeling in the ABCD Study, reducing dimensionality from 348 variables tapping to environment to six orthogonal exposome subfactors and a general (adverse) exposome factor. The general exposome factor was associated with overall psychopathology (B = 0.28, 95% CI, 0.26-0.3) and key health-related outcomes: obesity (odds ratio [OR] , 1.4; 95% CI, 1.3-1.5) and advanced pubertal development (OR, 1.3; 95% CI, 1.2-1.5). A similar approach in PNC reduced dimensionality of environment from 29 variables to 4 exposome subfactors and a general exposome factor. PNC analyses yielded consistent associations of the general exposome factor with psychopathology (B = 0.15; 95% CI, 0.13-0.17), obesity (OR, 1.4; 95% CI, 1.3-1.6), and advanced pubertal development (OR, 1.3; 95% CI, 1-1.6). In both cohorts, inclusion of exposome factors greatly increased variance explained in overall psychopathology compared with models relying solely on demographics and parental education (from <4% to >38% in ABCD; from <4% to >18.5% in PNC). Findings suggest that a general exposome factor capturing multi-level environmental exposures can be derived and can consistently explain variance in youth's mental and general health.

Association Between Discrimination Stress and Suicidality in Preadolescent Children.

OBJECTIVE: Youth suicide rates in the United States have been increasing in recent years, especially in Black Americans, the reasons for which are unclear. Environmental adversity is key in youth suicidality; hence there is a need to study stressors that have a disproportionate impact on Black youths. We aimed to disentangle the unique contribution of racial/ethnic discrimination from other adversities associated with childhood suicidal ideation and attempts (suicidality). METHOD: We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, which included a large, diverse sample of US children (N = 11,235, mean age 10.9 years, 20.2% Black), assessed for multiple environmental adversities including discrimination. Multivariate regression models tested the association of self-reported racial/ethnic discrimination with suicidality, covarying for multiple confounders including other discrimination types (toward non-US-born individuals, sexual orientation-based, and weight-based). Matched analyses contrasted effects of racial/ethnic discrimination and racial identity on suicidality. RESULTS: Black youths reported more discrimination and higher suicidality rates than non-Black youths. High racial/ethnic discrimination was positively and significantly associated with suicidality, adjusting for other discrimination types (odds ratio = 2.6, 95% CI = 2.1-3.2). Findings remained significant after adjusting for multiple suicidality risk factors. Once experienced, racial/ethnic discrimination was similarly associated with suicidality in White, Black, and Hispanic youths. Matched analyses revealed that racial/ethnic discrimination was associated with suicidality (relative risk = 2.7, 95% CI = 2-3.5), whereas Black race was not (relative risk = 0.9, 95% CI = 0.7-1.2). CONCLUSION: Racial/ethnic discrimination is disproportionately experienced by Black children, and is associated with preadolescent suicidality, over and above other adversities. Findings highlight the need to address discrimination as part of suicide prevention strategies. Cross-sectional design hampers causal inferences.

Contributions of PTSD polygenic risk and environmental stress to suicidality in preadolescents.

Suicidal ideation and attempts (i.e., suicidality) are complex behaviors driven by environmental stress, genetic susceptibility, and their interaction. Preadolescent suicidality is a major health problem with rising rates, yet its underlying biology is understudied. Here we studied effects of genetic stress susceptibility, approximated by the polygenic risk score (PRS) for post-traumatic-stress-disorder (PTSD), on preadolescent suicidality in participants from the Adolescent Brain Cognitive Development (ABCD) Study®. We further evaluated PTSD-PRS effects on suicidality in the presence of environmental stressors that are established suicide risk factors. Analyses included both European and African ancestry participants using PRS calculated based on summary statistics from ancestry-specific genome-wide association studies. In European ancestry participants (N = 4,619, n = 378 suicidal), PTSD-PRS was associated with preadolescent suicidality (odds ratio [OR] = 1.12, 95%CI 1-1.25, p = 0.038). Results in African ancestry participants (N = 1,334, n = 130 suicidal) showed a similar direction but were not statistically significant (OR = 1.21, 95%CI 0.93-1.57, p = 0.153). Sensitivity analyses using non-psychiatric polygenic score for height and using cross-ancestry PTSD-PRS did not reveal any association with suicidality, supporting the specificity of the association of ancestry-specific PTSD-PRS with suicidality. Environmental stressors were robustly associated with suicidality across ancestries with moderate effect size for negative life events and family conflict (OR 1.27-1.6); and with large effect size (OR âˆ¼ 4) for sexual-orientation discrimination. When combined with environmental factors, PTSD-PRS showed marginal additive effects in explaining variability in suicidality, with no evidence for G × E interaction. Results support use of cross-phenotype PRS, specifically stress-susceptibility, as a genetic marker for suicidality risk early in the lifespan.

Evaluation of Attention-Deficit/Hyperactivity Disorder Medications, Externalizing Symptoms, and Suicidality in Children.

Importance: Childhood suicidality (ie, suicidal ideation or attempts) rates are increasing, and attention-deficit/hyperactivity disorder (ADHD) and externalizing symptoms are common risk factors associated with suicidality. More data are needed to describe associations of ADHD pharmacotherapy with childhood suicidality. Objective: To investigate the associations of ADHD pharmacotherapy with externalizing symptoms and childhood suicidality. Design, Setting, and Participants: In this cohort study, cross-sectional and 1-year-longitudinal associations were examined using data (collected during 2016-2019) from the Adolescent Brain Cognitive Development (ABCD) Study, a large, diverse US sample of children aged 9 to 11 years. Data analysis was performed from November to December 2020. Exposures: Main and interaction associations of externalizing symptoms (hyperactivity ADHD symptoms, oppositional defiant, and conduct disorder symptoms) and ADHD medication treatment (methylphenidate and amphetamine derivatives, α-2-agonists, and atomoxetine) at baseline assessment. Main Outcomes and Measures: Child-reported suicidality (past and present at baseline; current at longitudinal assessment). Covariates were age, sex, race/ethnicity, parents' education, marital status, and concomitant child psychiatric pharmacotherapy (antidepressants and antipsychotics). Results: Among 11 878 children at baseline assessment (mean [SD] age, 9.9 [0.6] years; 6196 boys [52.2%]; 8805 White [74.1%]), 1006 (8.5%) were treated with ADHD medication and 1040 (8.8%) reported past or current suicidality. Externalizing symptoms (median [range], 1 [0-29] symptom count) were associated with suicidality (for a change of 1 SD in symptoms, odds ratio [OR], 1.34; 95% CI, 1.26-1.42; P < .001), as was ADHD medication treatment (OR, 1.32; 95% CI, 1.06-1.64; P = .01). ADHD medication use was associated with less suicidality in children with more externalizing symptoms (significant symptom-by-medication interaction, B = -0.250; SE = 0.086; P = .004), such that for children who were not receiving ADHD medications, there was an association between more externalizing symptoms and suicidality (for a change of 1 SD in symptoms, OR, 1.42; 95% CI, 1.33-1.52; P < .001); however, for children who were receiving ADHD medication, there was no such association (OR, 1.15; 95% CI, 0.97-1.35; P = .10). The association with medication remained even when covarying for multiple confounders, including risk and protective factors for suicidality in ABCD, and was replicated in 1-year longitudinal follow-up. Sensitivity analyses matching participants with high numbers of externalizing symptoms taking and not taking ADHD medication treatment confirmed its association with less suicidality. Conclusions and Relevance: These findings suggest that ADHD medication treatment is associated with less suicidality in children with substantial externalizing symptoms and may be used to inform childhood suicide prevention strategies.

Association among income loss, financial strain and depressive symptoms during COVID-19: Evidence from two longitudinal studies.

BACKGROUND: COVID-19 pandemic has major ramifications for global health and economy, with growing concerns about economic recession and implications for mental health. Here we investigated the associations between pandemic-related income loss with financial strain and mental health trajectories over a 1-month course, in two independent cohorts. METHODS: Two independent studies were conducted in the U.S and in Israel at the beginning of the outbreak (March-April 2020, T1; study I: N = 2904, study II: N = 1267) and at a 1-month follow-up (T2; study I: N = 1318, study II: N = 241). Mixed-effects models were applied to assess associations among COVID-19-related income loss, financial strain, and pandemic-related worries about health, with anxiety and depression, controlling for multiple covariates including pre-COVID-19 income. RESULTS: In both studies, income loss and financial strain were associated with greater depressive symptoms at T1, above and beyond T1 anxiety, worries about health, and pre-COVID-19 income. Worsening of income loss was associated with exacerbation of depression at T2 in both studies. Worsening of subjective financial strain was associated with exacerbation of depression at T2 in one study (US). CONCLUSIONS: Income loss and financial strain were uniquely associated with depressive symptoms and their exacerbation over time, above and beyond pandemic-related anxiety. In times when a myriad of stressors are affecting mental health worldwide, our findings reveal specific links between the economic impact of COVID-19 and psychiatric outcomes.