Unique and interactive effects of threat and deprivation on latent trait cortisol among emerging adults.

Though considerable work supports the Dimensional Model of Adversity and Psychopathology, prior research has not tested whether the dimensions-threat (e.g., abuse) and deprivation (e.g., neglect)-are uniquely related to salivary trait indicators of hypothalamic pituitary adrenal (HPA) axis activity. We examined the unique and interactive effects of threat and deprivation on latent trait cortisol (LTC)-and whether these effects were modified by co-occurring adversities. Emerging adults (n = 90; Mage = 19.36 years; 99.88% cisgender women) provided salivary cortisol samples four times a day (waking, 30 min and 45 min postwaking, bedtime) over three 3-day measurement waves over 13 weeks. Contextual life stress interviews assessed early adversity. Though the effects varied according to the conceptualization of early adversity, overall, threat-but not deprivation, nor other co-occurring adversities-was uniquely associated with the across-wave LTC. Specifically, the incidence and frequency of threat were each negatively related to the across-wave LTC. Threat severity was also associated with the across-wave LTC, but only among those with no deprivation. Finally, the effects of threat were modified by other co-occurring adversities. Findings suggest that threat has unique implications for individual differences in HPA axis activity among emerging adults, and that co-occurring adversities modify such effects.

Early life adversity and psychopathology in preschoolers: mechanisms and moderators.

Developmental theories suggest that exposure to early life adversity (ELA) alters developing emotional response systems, predicting risk for psychopathology across the life span. The present study examines whether negative emotionality (NE), a trait-like measure of emotionality that develops during early childhood, mediates the association between ELA and psychopathology in a representative sample of 917 preschoolers (Mage = 3.84). Additionally, we explored whether cognitive control, which supports attentional focusing and inhibition and has been identified as a transdiagnostic protective factor, moderates the impact of heightened emotionality following adversity on psychopathology risk. We utilized parent report of adversity, psychopathology, and NE and parent report and task-based measures of cognitive control. Structural equation modeling of cross-sectional data revealed that NE partially mediated the link between ELA and psychopathology symptoms. Moreover, parent-reported cognitive control buffered this link such that the effect of ELA on psychopathology through NE was stronger in children with low versus high cognitive control. These results identify elevated NE as one mechanism linking ELA and psychopathology, specifically among children with poorer top-down control, informing our understanding of key risk and protective factors among adversity-exposed children.

Early-Life Critical Windows of Susceptibility to Manganese Exposure and Sex-Specific Changes in Brain Connectivity in Late Adolescence.

Background: Early-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. Methods: We used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15-23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect of sex on the associations between Mn and intrinsic functional connectivity adjusting for age and socioeconomic status. Results: We identified significant sex-specific associations between dentine Mn at all time points and intrinsic functional connectivity in brain regions involved in cognitive and motor function: 1) prenatal: dorsal striatum, occipital/frontal lobes, and middle frontal gyrus; 2) postnatal: right putamen and cerebellum; and 3) early childhood: putamen and occipital, frontal, and temporal lobes. Network associations differed depending on exposure timing, suggesting that different brain networks may present distinctive CWs to Mn. Conclusions: These findings suggest that the developing brain is vulnerable to Mn exposure, with effects lasting through late adolescence, and that females and males are not equally vulnerable to these effects. Future studies should investigate cognitive and motor outcomes related to these associations.

Distinct Associations of Deprivation and Threat With Alterations in Brain Structure in Early Childhood.

OBJECTIVE: The dimensional model of adversity and psychopathology hypothesizes deprivation and threat impact distinct neurobiological pathways, such as brain structure. This hypothesis has not been examined longitudinally or in young children. This study tested longitudinal associations between threat and deprivation measured in preschool and brain structure in childhood. It was hypothesized that threat would be associated with amygdala and hippocampal subcortical volume and deprivation would be associated with cortical thickness in association cortex. METHOD: The study included T1-weighted scans from 72 children (5-10 years old, 54.2% female participants). Threat was measured by the presence of domestic violence, sexual abuse, physical abuse, or neighborhood violence. Deprivation was measured by the presence of neglect. Associations of deprivation or threat with brain structure were examined controlling for other dimension (deprivation or threat) and nuisance covariates using whole-brain vertex-wise analyses. Subcortical volume was extracted, and the same associations were examined using multiple regression. RESULTS: Threat was associated with widespread decreases in cortical surface area across the prefrontal cortex and other regions. Threat was not associated with amygdala or hippocampal volume. Deprivation was associated with increased thickness in occipital cortex, insula, and cingulate. CONCLUSION: Results suggest distinct associations of deprivation and threat on brain structure in early childhood. Threat is associated with widespread differences in surface area, and deprivation is associated with differences in cortical thickness. These observations are consistent with work in adolescence and adulthood and reflect how dimensions of adversity differentially impact neural structure.

The World Trade Center Exposome and Health Effects in 9/11 Rescue and Recovery Workers.

In the aftermath of the World Trade Center (WTC) attack, rescue and recovery workers faced hazardous conditions and toxic agents. Prior research linked these exposures to adverse health effects, but mainly examined individual factors, overlooking complex mixture effects. This study applies an exposomic approach encompassing the totality of responders' experience, defined as the WTC exposome. We analyzed data from 34,096 members of the WTC Health Program General Responder, including mental and physical health, occupational history, traumatic and environmental exposures using generalized weighted quantile sum regression. We find a significant association between the exposure mixture index all investigated health outcomes. Factors identified as risk factors include working in an enclosed heavily contaminated area, construction occupation, and exposure to blood and body fluids. Conversely, full-time employment emerged as a protective factor. This exposomics study emphasizes the importance of considering combined exposures. In an era marked by more frequent and severe natural disasters due to the evolving climate crisis, the exposomic framework holds promise as a valuable tool for disaster preparedness.

Prenatal urinary concentrations of phthalate metabolites and behavioral problems in Mexican children: The Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) study.

BACKGROUND: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. AIM: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. METHODS: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log2-transformed phthalate metabolites and parent-reported 4-6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. RESULTS: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (ß = 0.57, 95% CI = 0.17, 1.13) and in girls (ß = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (ß = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (ß = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = -0.54, 95% CI = -1.08, -0.21). DISCUSSION: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex.

Waist Circumference Is Not Associated with Impaired Fasting Blood Glucose in a Sample of Mexican Children and Teenagers: Results from a State Screening Program.

A high waist circumference (WC) is used as a risk factor for impaired fasting blood glucose (IFG) in adults. This association is less studied in children and teenagers. The purpose of this study was to analyze the association between having a high WC and IFG by sex and age in a sample of Mexican children and teenagers. We analyzed the data of 12979 participants aged 5 to 17 years to calculate percentile references for uncorrected WC, corrected for height (WC/HT) and by height squared (WC/HT2) with quantile regression. A subsample of 2309 participants with fasting blood glucose samples (FBG), WC, WC/HT and WC/HT2 values was analyzed with logistic regression. A high WC, WC/HT, and WC/HT2 were considered at the sex- and age-specific 90th percentile from the subsample. The IFG was considered as FBG ≥100 mg/dL. Having a high WC, WC/HT, nor WC/HT2 was not significantly associated with IFG for either sex and age group (all p > 0.05). A high WC, either on its uncorrected or corrected for height values, was not an important assessment for predicting IFG in a sample of Mexican children and teenagers. This study provides percentile reference values specific for sex and age.

Vital signs assessed in initial clinical encounters predict COVID-19 mortality in an NYC hospital system.

Timely and effective clinical decision-making for COVID-19 requires rapid identification of risk factors for disease outcomes. Our objective was to identify characteristics available immediately upon first clinical evaluation related COVID-19 mortality. We conducted a retrospective study of 8770 laboratory-confirmed cases of SARS-CoV-2 from a network of 53 facilities in New-York City. We analysed 3 classes of variables; demographic, clinical, and comorbid factors, in a two-tiered analysis that included traditional regression strategies and machine learning. COVID-19 mortality was 12.7%. Logistic regression identified older age (OR, 1.69 [95% CI 1.66-1.92]), male sex (OR, 1.57 [95% CI 1.30-1.90]), higher BMI (OR, 1.03 [95% CI 1.102-1.05]), higher heart rate (OR, 1.01 [95% CI 1.00-1.01]), higher respiratory rate (OR, 1.05 [95% CI 1.03-1.07]), lower oxygen saturation (OR, 0.94 [95% CI 0.93-0.96]), and chronic kidney disease (OR, 1.53 [95% CI 1.20-1.95]) were associated with COVID-19 mortality. Using gradient-boosting machine learning, these factors predicted COVID-19 related mortality (AUC = 0.86) following cross-validation in a training set. Immediate, objective and culturally generalizable measures accessible upon clinical presentation are effective predictors of COVID-19 outcome. These findings may inform rapid response strategies to optimize health care delivery in parts of the world who have not yet confronted this epidemic, as well as in those forecasting a possible second outbreak.