Different concepts of neighborhood safety and child internalizing and externalizing behaviors.

Neighborhood safety is defined inconsistently across epidemiologic studies - a conceptual problem that results in incomparable measurements, hampering the design of health interventions. Using child behavior problems (measured via the Child Behavior Checklist) as the outcome of interest, this study directly compared four measures of neighborhood safety: two of experienced safety and two of perceived safety, with each one measured at family and community levels. These included children's direct experience of harm, parental perceptions, community crime statistics, and community perceptions. In a sample of 3291 ten-year-olds from the Generation R cohort (living in municipal Rotterdam, Netherlands, 2013), all four measures were correlated (χ2 ≥ 9.2, P < 0.002 in pairwise chi-square comparisons), but ultimately identified different levels of risk for behavioral health. Direct experiences of harm, parental perceptions, and community crime statistics were all associated with increased child internalizing behaviors (ß = 3.12, ß = 2.10, and ß = 1.77, respectively), while only experiences of harm and parental perceptions were associated with increased externalizing behaviors (ß = 2.75 and ß = 1.31, respectively). These results provide novel evidence that the conceptual distinctions underlying different measures of neighborhood safety are meaningful for child mental health and should be considered in intervention design.

Policy-induced air pollution health disparities: Statistical and data science considerations.

Air pollution causes premature death and disease and disproportionately harms non-white and lower-income groups in the United States. Government policies are responsible for the racial disparity in air pollution exposure and related health outcomes. Investigating complex relationships between policies, air pollution, and health requires (i) harmonized data connecting policies, environmental exposures, socioeconomic characteristics, and health at the individual and area level; (ii) interpretable estimands accounting for the complex interplay between policies and disparities in exposures and health outcomes; and (iii) data science approaches that can elucidate direct and indirect policy effects on disparities to identify effective interventions. We review statistical considerations and new data science approaches needed to scrutinize the policy impacts on disparities in air pollution exposure and health outcomes.

Associations of street-view greenspace with Parkinson's disease hospitalizations in an open cohort of elderly US Medicare beneficiaries.

INTRODUCTION: Protective associations of greenspace with Parkinson's disease (PD) have been observed in some studies. Visual exposure to greenspace seems to be important for some of the proposed pathways underlying these associations. However, most studies use overhead-view measures (e.g., satellite imagery, land-classification data) that do not capture street-view greenspace and cannot distinguish between specific greenspace types. We aimed to evaluate associations of street-view greenspace measures with hospitalizations with a PD diagnosis code (PD-involved hospitalization). METHODS: We created an open cohort of about 45.6 million Medicare fee-for-service beneficiaries aged 65 + years living in core based statistical areas (i.e. non-rural areas) in the contiguous US (2007-2016). We obtained 350 million Google Street View images across the US and applied deep learning algorithms to identify percentages of specific greenspace features in each image, including trees, grass, and other green features (i.e., plants, flowers, fields). We assessed yearly average street-view greenspace features for each ZIP code. A Cox-equivalent re-parameterized Poisson model adjusted for potential confounders (i.e. age, race/ethnicity, socioeconomic status) was used to evaluate associations with first PD-involved hospitalization. RESULTS: There were 506,899 first PD-involved hospitalizations over 254,917,192 person-years of follow-up. We found a hazard ratio (95% confidence interval) of 0.96 (0.95, 0.96) per interquartile range (IQR) increase for trees and a HR of 0.97 (0.96, 0.97) per IQR increase for other green features. In contrast, we found a HR of 1.06 (1.04, 1.07) per IQR increase for grass. Associations of trees were generally stronger for low-income (i.e. Medicaid eligible) individuals, Black individuals, and in areas with a lower median household income and a higher population density. CONCLUSION: Increasing exposure to trees and other green features may reduce PD-involved hospitalizations, while increasing exposure to grass may increase hospitalizations. The protective associations may be stronger for marginalized individuals and individuals living in densely populated areas.

Ambient air temperature exposure and foetal size and growth in three European birth cohorts.

INTRODUCTION: Ambient air temperature may affect birth outcomes adversely, but little is known about their impact on foetal growth throughout pregnancy. We evaluated the association between temperature exposure during pregnancy and foetal size and growth in three European birth cohorts. METHODS: We studied 23,408 pregnant women from the English Born in Bradford cohort, Dutch Generation R Study, and Spanish INMA Project. Using the UrbClimTM model, weekly ambient air temperature exposure at 100x100m resolution at the mothers' residences during pregnancy was calculated. Estimated foetal weight, head circumference, and femur length at mid and late pregnancy and weight, head circumference, and length at birth were converted into standard deviation scores (SDS). Foetal growth from mid to late pregnancy was calculated (grams or centimetres/week). Cohort/region-specific distributed lag non-linear models were combined using a random-effects meta-analysis and results presented in reference to the median percentile of temperature (14 °C). RESULTS: Weekly temperatures ranged from -5.6 (Bradford) to 30.3 °C (INMA-Sabadell). Cold and heat exposure during weeks 1-28 were associated with a smaller and larger head circumference in late pregnancy, respectively (e.g., for 9.5 °C: -1.6 SDS [95 %CI -2.0; -0.4] and for 20.0 °C: 1.8 SDS [0.7; 2.9]). A susceptibility period from weeks 1-7 was identified for cold exposure and a smaller head circumference at late pregnancy. Cold exposure was associated with a slower head circumference growth from mid to late pregnancy (for 5.5 °C: -0.1 cm/week [-0.2; -0.04]), with a susceptibility period from weeks 4-12. No associations that survived multiple testing correction were found for other foetal or any birth outcomes. CONCLUSIONS: Cumulative exposure to cold and heat during pregnancy was associated with changes in foetal head circumference throughout gestation, with susceptibility periods for cold during the first pregnancy trimester. No associations were found at birth, suggesting potential recovery. Future research should replicate this study across different climatic regions including varying temperature profiles.

Association of Environmental Injustice and Cardiovascular Diseases and Risk Factors in the United States.

BACKGROUND: While the impacts of social and environmental exposure on cardiovascular risks are often reported individually, the combined effect is poorly understood. METHODS AND RESULTS: Using the 2022 Environmental Justice Index, socio-environmental justice index and environmental burden module ranks of census tracts were divided into quartiles (quartile 1, the least vulnerable census tracts; quartile 4, the most vulnerable census tracts). Age-adjusted rate ratios (RRs) of coronary artery disease, strokes, and various health measures reported in the Prevention Population-Level Analysis and Community Estimates data were compared between quartiles using multivariable Poisson regression. The quartile 4 Environmental Justice Index was associated with a higher rate of coronary artery disease (RR, 1.684 [95% CI, 1.660-1.708]) and stroke (RR, 2.112 [95% CI, 2.078-2.147]) compared with the quartile 1 Environmental Justice Index. Similarly, coronary artery disease 1.057 [95% CI,1.043-1.0716] and stroke (RR, 1.118 [95% CI, 1.102-1.135]) were significantly higher in the quartile 4 than in the quartile 1 environmental burden module. Similar results were observed for chronic kidney disease, hypertension, diabetes, obesity, high cholesterol, lack of health insurance, sleep <7 hours per night, no leisure time physical activity, and impaired mental and physical health >14 days. CONCLUSIONS: The prevalence of CVD and its risk factors is highly associated with increased social and environmental adversities, and environmental exposure plays an important role independent of social factors.

Who Benefits and How: Five Dimensions of Adolescent Psychological Well-Being and Their Relative Impact on Cardiometabolic Health in Adulthood.

PURPOSE: Positive dimensions of psychological well-being in adolescence may help youth preserve cardiometabolic health (CMH) as they age, but little is known about which aspects of well-being matter most and for whom. This study examines the differential impact of five dimensions of adolescent psychological well-being on CMH maintenance in adulthood and considers social patterning in both their distribution and respective health benefits. METHODS: Data were from the National Longitudinal Study of Adolescent Health (N = 3,464), five dimensions of psychological well-being were identified at baseline (1994-1995; mean age = 15 years): happiness, optimism, self-esteem, belonging, and feeling loved. CMH was measured using seven biomarkers related to chronic disease risk in 2008 (mean age = 28 years) and 2016-2018 (mean age = 38 years): high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, hemoglobin A1c, C-reactive protein, and body mass index. CMH maintenance in adulthood was characterized as having healthy levels of ≥6 biomarkers at each follow-up. RESULTS: Youth who reported higher levels of belonging in the teen years were more likely to maintain CMH across young adulthood than those who reported lower levels, regardless of one's social standing (ORper 1-standard deviation = 1.23, 95% CI = 1.03-1.46). Associations with other dimensions of well-being were heterogeneous by sex and race and ethnicity, while differences by socioeconomic factors were less apparent. DISCUSSION: Fostering belonging through supportive social environments may help set youth on positive health trajectories and prevent chronic disease across the lifespan.

Comparing two measures of neighborhood quality and internalizing and externalizing behaviors in the adolescent brain cognitive development study.

PURPOSE: There is widespread recognition of the importance and complexity of measuring neighborhood contexts within research on child psychopathology. In this study, we assessed the cross-sectional associations between two measures of neighborhood quality and internalizing and externalizing behaviors in preadolescence. METHODS: Drawing on baseline data from the Adolescent Brain Cognitive Development Study (n = 10,577 preadolescents), we examined two multi-component assessments of neighborhood quality in relation to children's internalizing and externalizing symptoms: the Area Deprivation Index (ADI), which measures socioeconomic adversity, and the Child Opportunity Index 2.0 (COI), which measures economic, educational, and environmental opportunity. Both measures were categorized into quintiles. We then used mixed-effects linear regression models to examine bivariate and adjusted associations. RESULTS: The bivariate associations displayed strong inverse associations between the COI and ADI and externalizing symptoms, with a graded pattern of fewer externalizing behaviors with increasing neighborhood quality. Only the ADI was associated with externalizing behaviors in models adjusted for child and family characteristics. We did not observe a clear association between either measure of neighborhood quality and internalizing behaviors in bivariate or adjusted models. CONCLUSIONS: Neighborhood quality, as measured by the COI and ADI, was associated with externalizing behaviors in preadolescent children. The association using the ADI persisted after adjustment for family-level characteristics, including financial strain. Our results indicate that different assessments of neighborhood quality display distinct associations with preadolescent behavioral health. Future research is needed to assess the association between neighborhood quality and behavior trajectories and to identify place-based intervention strategies.

Shared Genetic Risk in the Association of Screen Time With Psychiatric Problems in Children.

Importance: Children's exposure to screen time has been associated with poor mental health outcomes, yet the role of genetic factors remains largely unknown. Objective: To assess the extent of genetic confounding in the associations between screen time and attention problems or internalizing problems in preadolescent children. Design, Setting, and Participants: This cohort study analyzed data obtained between 2016 and 2019 from the Adolescent Brain Cognitive Development Study at 21 sites in the US. The sample included children aged 9 to 11 years of genetically assigned European ancestry with self-reported screen time. Data were analyzed between November 2021 and September 2023. Exposure: Child-reported daily screen time (in hours) was ascertained from questionnaires completed by the children at baseline. Main Outcomes and Measures: Child psychiatric problems, specifically attention and internalizing problems, were measured with the parent-completed Achenbach Child Behavior Checklist at the 1-year follow-up. Genetic sensitivity analyses model (Gsens) was used, which incorporated polygenic risk scores (PRSs) of both exposure and outcomes as well as either single-nucleotide variant (SNV; formerly single-nucleotide polymorphism)-based heritability or twin-based heritability to estimate genetic confounding. Results: The 4262 children in the sample included 2269 males (53.2%) with a mean (SD) age of 9.9 (0.6) years. Child screen time was associated with attention problems (ß = 0.10 SD; 95% CI, 0.07-0.13 SD) and internalizing problems (ß = 0.03 SD; 95% CI, 0.003-0.06 SD). The television time PRS was associated with child screen time (ß = 0.18 SD; 95% CI, 0.14-0.23 SD), the attention-deficit/hyperactivity disorder PRS was associated with attention problems (ß = 0.13 SD; 95% CI, 0.10-0.16 SD), and the depression PRS was associated with internalizing problems (ß = 0.10 SD; 95% CI, 0.07-0.13 SD). These PRSs were associated with cross-traits, suggesting genetic confounding. Estimates using PRSs and SNV-based heritability showed that genetic confounding accounted for most of the association between child screen time and attention problems and for 42.7% of the association between child screen time and internalizing problems. When PRSs and twin-based heritability estimates were used, genetic confounding fully explained both associations. Conclusions and Relevance: Results of this study suggest that genetic confounding may explain a substantial part of the associations between child screen time and psychiatric problems. Genetic confounding should be considered in sociobehavioral studies of modifiable factors for youth mental health.

Behavioral and neurostructural correlates of childhood physical violence victimization: Interaction with family functioning.

Violence victimization may cause child behavior problems and neurostructural differences associated with them. Healthy family environments may buffer these effects, but neural pathways explaining these associations remain inadequately understood. We used data from 3154 children (x̅age  = 10.1) to test whether healthy family functioning moderated possible associations between violence victimization, behavior problems, and amygdala volume (a threat-responsive brain region). Researchers collected data on childhood violence victimization, family functioning (McMaster Family Assessment Device, range 0-3, higher scores indicate healthier functioning), and behavior problems (Achenbach Child Behavior Checklist [CBCL] total problem score, range 0-117), and they scanned children with magnetic resonance imaging. We standardized amygdala volumes and fit confounder-adjusted models with "victimization × family functioning" interaction terms. Family functioning moderated associations between victimization, behavior problems, and amygdala volume. Among lower functioning families (functioning score = 1.0), victimization was associated with a 26.1 (95% confidence interval [CI]: 9.9, 42.4) unit higher CBCL behavior problem score, yet victimized children from higher functioning families (score = 3.0) exhibited no such association. Unexpectedly, victimization was associated with higher standardized amygdala volume among lower functioning families (y = 0.5; 95% CI: 0.1, 1.0) but lower volume among higher functioning families (y = -0.4; 95% CI: -0.7, -0.2). Thus, healthy family environments may mitigate some neurobehavioral effects of childhood victimization.

Air Pollution and Mortality at the Intersection of Race and Social Class.

BACKGROUND: Black Americans are exposed to higher annual levels of air pollution containing fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) than White Americans and may be more susceptible to its health effects. Low-income Americans may also be more susceptible to PM2.5 pollution than high-income Americans. Because information is lacking on exposure-response curves for PM2.5 exposure and mortality among marginalized subpopulations categorized according to both race and socioeconomic position, the Environmental Protection Agency lacks important evidence to inform its regulatory rulemaking for PM2.5 standards. METHODS: We analyzed 623 million person-years of Medicare data from 73 million persons 65 years of age or older from 2000 through 2016 to estimate associations between annual PM2.5 exposure and mortality in subpopulations defined simultaneously by racial identity (Black vs. White) and income level (Medicaid eligible vs. ineligible). RESULTS: Lower PM2.5 exposure was associated with lower mortality in the full population, but marginalized subpopulations appeared to benefit more as PM2.5 levels decreased. For example, the hazard ratio associated with decreasing PM2.5 from 12 µg per cubic meter to 8 µg per cubic meter for the White higher-income subpopulation was 0.963 (95% confidence interval [CI], 0.955 to 0.970), whereas equivalent hazard ratios for marginalized subpopulations were lower: 0.931 (95% CI, 0.909 to 0.953) for the Black higher-income subpopulation, 0.940 (95% CI, 0.931 to 0.948) for the White low-income subpopulation, and 0.939 (95% CI, 0.921 to 0.957) for the Black low-income subpopulation. CONCLUSIONS: Higher-income Black persons, low-income White persons, and low-income Black persons may benefit more from lower PM2.5 levels than higher-income White persons. These findings underscore the importance of considering racial identity and income together when assessing health inequities. (Funded by the National Institutes of Health and the Alfred P. Sloan Foundation.).

Adolescent Psychological Assets and Cardiometabolic Health Maintenance in Adulthood: Implications for Health Equity.

Background Positive cardiometabolic health (CMH) is defined as meeting recommended levels of multiple cardiometabolic risk factors in the absence of manifest disease. Prior work finds that few individuals-particularly members of minoritized racial and ethnic groups-meet these criteria. This study investigated whether psychological assets help adolescents sustain CMH in adulthood and explored interactions by race and ethnicity. Methods and Results Participants were 3478 individuals in the National Longitudinal Study of Adolescent Health (49% female; 67% White, 15% Black, 11% Latinx, 6% other [Native American, Asian, or not specified]). In Wave 1 (1994-1995; mean age=16 years), data on 5 psychological assets (optimism, happiness, self-esteem, belongingness, and feeling loved) were used to create a composite asset index (range=0-5). In Waves 4 (2008; mean age=28 years) and 5 (2016-2018; mean age=38 years), CMH was defined using 7 clinically assessed biomarkers. Participants with healthy levels of ≥6 biomarkers at Waves 4 and 5 were classified as maintaining CMH over time. The prevalence of CMH maintenance was 12%. Having more psychological assets was associated with better health in adulthood (odds ratio [OR]linear trend, 1.12 [95% CI, 1.01-1.25]). Subgroup analyses found substantive associations only among Black participants (OR, 1.35 [95% CI, 1.00-1.82]). Additionally, there was some evidence that racial and ethnic disparities in CMH maintenance may be less pronounced among participants with more assets. Conclusions Youth with more psychological assets were more likely to experience favorable CMH patterns 2 decades later. The strongest associations were observed among Black individuals. Fostering psychological assets in adolescence may help prevent cardiovascular disease and play an underappreciated role in shaping health inequities.

Long-term associations between early-life family functioning and preadolescent white matter microstructure.

BACKGROUND: Causes of childhood behavior problems remain poorly understood. Enriched family environments and corresponding brain development may reduce the risk of their onset, but research investigating white matter neurodevelopmental pathways explaining associations between the family environment and behavior remains limited. We hypothesized that more positive prenatal and mid-childhood family functioning - a measure of a family's problem solving and supportive capacity - would be associated with two markers of preadolescent white matter neurodevelopment related to reduced behavior problems: higher global fractional anisotropy (FA) and lower global mean diffusivity (MD). METHODS: Data are from 2727 families in the Generation R Study, the Netherlands. Mothers reported family functioning (McMaster Family Assessment Device, range 1-4, higher scores indicate healthier functioning) prenatally and in mid-childhood (mean age 6.1 years). In preadolescence (mean age 10.1), the study collected diffusion-weighted scans. We computed standardized global MD and FA values by averaging metrics from 27 white matter tracts, and we fit linear models adjusting for possible confounders to examine global and tract-specific outcomes. RESULTS: Prenatal and mid-childhood family functioning scores were moderately correlated, r = 0.38. However, only prenatal family functioning - and not mid-childhood functioning - was associated with higher global FA and lower global MD in preadolescence in fully adjusted models: ßglobal FA = 0.11 (95% CI 0.00, 0.21) and ßglobal MD = -0.15 (95% CI -0.28, -0.03) per one-unit increase in functioning score. Sensitivity and tract-specific analyses supported these global findings. CONCLUSIONS: These results suggest high-functioning prenatal or perinatal family environments may confer lasting white matter neurodevelopmental benefits into preadolescence.

The social determinants of ideal cardiovascular health: A global systematic review.

This systematic review synthesizes research published from January 2010-July 2022 on the social determinants of ideal cardiovascular health (CVH) carried out around the world and compares trends in high-income countries (HICs) to those in low- and middle-income countries (LMICs). 41 studies met inclusion criteria (n = 28 HICs, n = 13 LMICs). Most were from the United States (n = 22) and cross-sectional (n = 33), and nearly all evaluated associations among adults. Among studies conducted in LMICs, nearly all were from middle-income countries and only one was carried out in low-income country. Education (n = 24) and income/wealth (n = 17) were the most frequently examined social determinants in both HICs and LMICs. Although most studies assessed ideal CVH using reliable and valid methods (n = 24), only 7 used criteria pre-defined by the American Heart Association to characterize ideal levels of each CVH metric. Despite heterogeneity in how outcome measures were derived and analyzed, consistent associations were evident between multiple markers of higher social status (i.e. greater education, income/wealth, socioeconomic status, racial/ethnic majority status) and greater levels of ideal CVH across both country contexts. Gaps in the literature include evidence from LMICs and HICs other than the United States, longitudinal research, and investigations of a wider array of social determinants beyond education and income/wealth.

Editorial: Are Neural Biomarkers Valid for All Children?

Poverty-like all life experiences-can change the developing brain. Psychopathology can, too. But how? And when? And why? And what happens to brain development when children face both poverty and pathology at the same time? With 1 in 5 children growing up poor in the United States today-each at higher risk for developing depression-answering these questions remains among public mental health's most important imperatives. Yet doing so is wickedly challenging: investigators must decipher a wide array of interacting social and biological processes.

Pursuing Pharmacoequity: Determinants, Drivers, and Pathways to Progress.

The United States pays more for medical care than any other nation in the world, including for prescription drugs. These costs are inequitably distributed, as individuals from underrepresented racial and ethnic groups in the United States experience the highest costs of care and unequal access to high-quality, evidence-based medication therapy. Pharmacoequity refers to equity in access to pharmacotherapies or ensuring that all patients, regardless of race and ethnicity, socioeconomic status, or availability of resources, have access to the highest quality of pharmacotherapy required to manage their health conditions. Herein the authors describe the urgent need to prioritize pharmacoequity. This goal will require a bold and innovative examination of social policy, research infrastructure, patient and prescriber characteristics, as well as health policy determinants of inequitable medication access. In this article, the authors describe these determinants, identify drivers of ongoing inequities in prescription drug access, and provide a framework for the path toward achieving pharmacoequity.

Harsh Parenting and Child Brain Morphology: A Population-Based Study.

Evidence suggests that maltreatment shapes the child's brain. Little is known, however, about how normal variation in parenting influences the child neurodevelopment. We examined whether harsh parenting is associated with the brain morphology in 2,410 children from a population-based cohort. Mothers and fathers independently reported harsh parenting at child age 3 years. Structural and diffusion-weighted brain morphological measures were acquired with MRI scans at age 10 years. We explored whether associations between parenting and brain morphology were explained by co-occurring adversities, and whether there was a joint effect of both parents' harsh parenting. Maternal harsh parenting was associated with smaller total gray (ß = -0.05 (95%CI = -0.08; -0.01)), cerebral white matter and amygdala volumes (ß = -0.04 (95%CI = -0.07; 0)). These associations were also observed with the combined harsh parenting measure and were robust to the adjustment for multiple confounding factors. Similar associations, although non-significant, were found between paternal parenting and these brain outcomes. Maternal and paternal harsh parenting were not associated with the hippocampus or the white matter microstructural metrics. We found a long-term association between harsh parenting and the global brain and amygdala volumes in preadolescents, suggesting that adverse rearing environments common in the general population are related to child brain morphology.

Are all domains of life satisfaction equal? Differential associations with health and well-being in older adults.

PURPOSE: Growing evidence documents strong associations between overall life satisfaction and favorable health and well-being outcomes. However, because most previous studies have assessed satisfaction with one's life as a whole, we know little about whether specific domains of life satisfaction (e.g., satisfaction with family life, income) might be responsible for longitudinally driving better health and well-being. METHODS: Data were from 13,752 participants in the Health and Retirement Study-a prospective and nationally representative cohort of US adults aged > 50. We evaluated if positive changes in seven individual domains of life satisfaction (between t0; 2008/2010 and t1; 2012/2014) were associated with 35 indicators of physical, behavioral, and psychosocial health and well-being (at t2; 2016/2018). RESULTS: Most domains of life satisfaction were associated with psychological outcomes: satisfaction with family and non-work activities showed the largest associations (sometimes double in magnitude) with subsequent psychological factors, followed by satisfaction with financial situation and income. Further, some domains showed associations with specific physical health outcomes (e.g., mortality, number of chronic conditions, physical functioning limitations), health behaviors (e.g., sleep problems), and social factors (e.g., loneliness). CONCLUSIONS: As countries seek innovative and cost-effective methods of enhancing the health and well-being of our rapidly aging populations, findings from our study suggest that some domains of life satisfaction have a substantially larger influence on health and well-being outcomes than others. Individual domains of life satisfaction might be novel targets for interventions and policies seeking to enhance specific facets of health and well-being.

Differences in cortical morphology and child internalizing or externalizing problems: Accounting for the co-occurrence.

Background: Childhood internalizing and externalizing problems frequently co-occur. Many studies report neural correlates of either internalizing or externalizing problems, but few account for their co-occurrence. We aimed to assess specific cortical substrates of these psychiatric problems. Methods: We used data from 9635 children aged 9-11 years in the baseline Adolescent Brain Cognitive Development Study. Internalizing and externalizing problem composite scales scores were derived from the Child Behavior Checklist. We standardized FreeSurfer-derived volumes of 68 cortical regions. We examined internalizing and externalizing problems separately and jointly (covariate-adjustment) in relation to cortical volumes, with and without adjusting for total brain volume (TBV) in multivariate linear regressions adjusted for demographics and multiple comparisons. We fit bifactor models to confirm the consistency of patterns exploring specific internalizing and specific externalizing problems. Sensitivity analyses included a vertex-wide analysis and a replication in another large population-based study. Results: In separate TBV-unadjusted analyses, externalizing and internalizing problems were associated with smaller cortical volumes. If adjusted for externalizing behavior, however, larger cortical volumes were associated with internalizing problems, while smaller cortical volumes remained associated with externalizing problems after adjustment for internalizing problems. The bifactor model produced similar results, which were consistently replicated in another pre-adolescent neuroimaging sample. These associations likely represent global effects: adjusting for TBV rendered most associations non-significant. Vertex-wise analyses confirmed global patterns. Conclusion: Our results suggest that internalizing and externalizing problems have globally opposing, and non-specific associations with cortical morphology in childhood, which are only apparent if analyses account for their co-occurrence.

Are all threats equal? Associations of childhood exposure to physical attack versus threatened violence with preadolescent brain structure.

BACKGROUND: Neurodevelopmental studies of childhood adversity often define threatening experiences as those involving harm or the threat of harm. Whether effects differ between experiences involving harm ("physical attack") versus the threat of harm alone ("threatened violence") remains underexplored. We hypothesized that while both types of experiences would be associated with smaller preadolescent global and corticolimbic brain volumes, associations with physical attack would be greater. METHODS: Generation R Study researchers (the Netherlands) acquired T1-weighted scans from 2905 preadolescent children, computed brain volumes using FreeSurfer, and asked mothers whether their children ever experienced physical attack (n = 202) or threatened violence (n = 335). Using standardized global (cortical, subcortical, white matter) and corticolimbic (amygdala, hippocampus, anterior cingulate cortex, orbitofrontal cortex) volumes, we fit confounder-adjusted models. RESULTS: Physical attack was associated with smaller global volumes (ßcortical=-0.14; 95% CI: -0.26, -0.02); ßwhite matter= -0.16; 95% CI: - 0.28, - 0.03) and possibly some corticolimbic volumes, e.g., ßamygdala/ICV-adjusted= -0.10 (95% CI: -0.21, 0.01). We found no evidence of associations between threatened violence and smaller volumes in any outcome; instead, such estimates were small, highly uncertain, and positive in direction. CONCLUSIONS: Experiences of physical attack and threatened violence may have quantitively different neurodevelopmental effects. Thus, differences between types of threatening experiences may be neurodevelopmentally salient.