Adverse Exposures Research Articles

Dietary Inflammatory Index Is Differentially Associated With Cardiometabolic Health After Pregnancy on the Basis of Adverse Pregnancy Outcome Exposure.

Inflammatory diets may influence risk of cardiovascular disease. Subsequent cardiovascular disease is also influenced by adverse pregnancy outcomes (APOs) such as preterm birth, small-for-gestational-age birth, gestational diabetes, and hypertensive disorders of pregnancy. However, the associations between inflammatory diet, APOs, and cardiometabolic health remain unclear. We used data from the nuMoM2b (Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-Be) HHS (Heart Health Study) to assess the relationship between dietary quality and cardiometabolic health. We calculated Energy-Adjusted Dietary Inflammatory Index scores representing the inflammatory burden in a person's diet. We used linear regression to determine the association between Energy-Adjusted Dietary Inflammatory Index score and cardiometabolic outcomes. We performed stratified analyses for outcomes with a significant interaction between Energy-Adjusted Dietary Inflammatory Index and APO. Data were available from 3249 participants at a median of 3.1 years after delivery. Higher Energy-Adjusted Dietary Inflammatory Index scores were associated with higher body mass index (B=0.29 kg/m2 [95% CI, 0.16-0.42]), waist circumference (0.66 cm [95% CI, 0.39-0.93]), diastolic blood pressure (0.26 mm Hg [95% CI, 0.09-0.44]), mean arterial pressure (0.23 mm Hg [95% CI, 0.06-0.40]), triglycerides (2.11 mg/dL [95% CI, 1.05-3.18]), creatinine (2.78 mg/dL [95% CI, 1.13-4.44]), insulin (exp[B]=1.04 [95% CI, 1.03-1.05]) and C-reactive protein (exp[B]=1.07 [95% CI, 1.04-1.10]), and lower high-density lipoprotein cholesterol (-0.41 mg/dL [95% CI, -0.66 to -0.37]) (all P<0.01). Significant interactions with APO (P<0.05) were identified for body mass index and waist circumference, with stratified analysis revealing stronger associations for individuals with APOs. A more proinflammatory diet was associated with worse cardiometabolic health measures, and these relationships differed by a person's APO history. Further investigation should establish how dietary modifications after pregnancy may potentially mitigate cardiovascular disease risk.

Time-out under scrutiny: examining the relationships among the discipline strategy time-out, child well-being and attachment and exposure to adversity.

Discipline is a crucial aspect of parenting, shaping child development and behaviour. Time-out, a widely used disciplinary strategy with a strong evidence-base, has recently come under scrutiny with concerns about potential adverse effects on children's emotional development and attachment, particularly for those with a history of adversity. To contribute critical empirical insights to the current controversy surrounding time-out by exploring the associations among time-out implementation, parent-child attachment and child mental health, and whether adversity exposure moderated these associations. This cross-sectional study utilised a nationally representative sample of 474 primary caregivers in Australia, with children aged 6-8 years, who completed an online survey. Measures included the Implementation of Time-out Scale, Adverse Life Experiences Scale, Primary Attachment Style Questionnaire, Strengths and Difficulties Questionnaire and Spence Child Anxiety Scale. Appropriately implemented time-out was associated with enhanced mental health and attachment, while inappropriate time-out correlated with adverse child outcomes. Exposure to adversity moderated the relationship between time-out implementation and child well-being, such that children exposed to adversity were most likely to experience attachment enhancement from appropriately implemented time-out. Despite recent concerns of harm caused by time-out, particularly for children with a history of adversity, findings support the beneficial impact of time-out on child well-being and attachment when implemented in accordance with evidence-based parameters. Combatting misinformation and disseminating evidence-based time-out guidelines is crucial for promoting child well-being and attachment, especially for children who have experienced adversity.

Prenatal social disadvantage is associated with alterations in functional networks at birth

Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood-brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated with alterations in functional brain networks as early as birth. As part of the Early Life Adversity and Biological Embedding study, mothers were recruited during pregnancy, prenatal social disadvantage was assessed across trimesters, and their healthy, full-term offspring were imaged using resting-state functional magnetic resonance imaging during the first weeks of life. Multivariate machine learning methods revealed that neonatal functional connectivity (FC) varied as a function of prenatal exposure to social disadvantage (n = 261, R = 0.43, R2 = 0.18), with validation in an independent sample. Alterations in FC associated with prenatal social disadvantage occurred brain-wide and were most pronounced in association networks (fronto-parietal, ventral attention, dorsal attention) and the somatomotor network. Amygdala FC was altered at birth, with a pattern shared across subcortical structures. These findings provide critical insights into how early in development functional networks begin to diverge in the context of social disadvantage and elucidate the functional networks that are most impacted.

Rumination as a Moderator of the Relation between Childhood Adversity Exposure and College Students’ Psychological Distress

American college students (N = 598) completed self-report questionnaires assessing rumination, psychological distress while attending college (general distress, anhedonic depression, anxious arousal), and exposure to specific types of childhood adversity (i.e., emotional abuse, sexual abuse, physical abuse, emotional neglect, and physical neglect). Latent Moderated Structural Equation Modeling indicated that 1) rumination was associated with all three indicators of psychological distress and 2) rumination moderated associations between childhood adversity exposure and college students’ reports of general distress and anxious arousal such that associations were strongest at higher levels of rumination and weaker at lower levels of rumination. Implications regarding higher education professionals’ efforts to support college student well-being are discussed.

A mesocorticolimbic insulin receptor gene co-expression network moderates the association between early life adversity and food approach eating behaviour style in childhood

Insulin receptors, located in brain regions associated with reward sensitivity and decision-making, facilitate insulin action in the brain, modulating intracellular signaling cascades, gene expression, and neural activity. Here, we tested if variations in the expression of the insulin receptor gene network in the prefrontal cortex (PFC) and striatum (STR) moderate the association between early life adversity and eating behaviour in childhood and if this moderation is sex-specific. Participants from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and Basal Influences on the Baby's Development (BIBO) were included as two independent cohorts. A biologically-informed polygenic score reflecting functional variation of the mesocorticolimbic insulin receptor gene network was created by using insulin receptor co-expression data from the PFC and STR in mice, and validated in humans through filtering by homologous expression in PFC using well-known databases. Early life adversity exposure was measured as a composite score. Eating behaviour was characterized using the Child Eating Behaviour Questionnaire administered to mothers of children aged 4 and 6 years in MAVAN, and 6 years in BIBO. We found that only in those with high expression of the mesocorticolimbic insulin receptor gene network a higher early adversity score associated with a higher desire to drink in 4-year boys and 6-year girls, as well as a higher food approach score and food approach/food avoidance ratio in 4-year girls. Also, a higher early life adversity was associated with higher food responsiveness, food approach score and food approach/food avoidance ratio at 6 years in the MAVAN full sample. The moderation observed on desire to drink was partially replicated in BIBO children aged 6 years. Identifying individual differences in response to early adversity may help to prioritize individuals at high risk for long-term disease and design suitable interventions.

From Globalization to Isolation: Exposure to the 2008 Financial Crisis and Three Dimensions of Liberal Attitudes in a Swedish Twin Design

Abstract This study investigates the link between non-liberal attitudes and adverse exposure to market disturbances during the 2008 global financial crisis, drawing from the premise that anti-liberal sentiments among Western voters stem from economic distress. We delve into three facets of liberal ideology in a Swedish sample: economic liberalism, liberal multiculturalism and liberal internationalism. Using variation in crisis exposure within identical twin pairs, comprehensive longitudinal economic data and detailed survey responses, we find no significant shift in economic or multicultural liberal attitudes with different crisis exposures. However, exposure to increased unemployment risk significantly lowered support for liberal internationalism, increasing scepticism towards global governance and multilateral cooperation.

Ambient air pollution, urban green space and childhood overweight and obesity: A health impact assessment for Barcelona, Spain

BackgroundThe burden of childhood overweight and obesity attributable to ambient air pollution and a lack of urban green spaces (UGS) remains unknown. This study aimed to estimate the attributable cases of childhood overweight and obesity due to air pollution and insufficient UGS exposure in Barcelona, Spain. MethodsWe applied a quantitative health impact assessment approach. We collected childhood overweight and obesity prevalence levels and exposure data from 69 spatial basic health zones in Barcelona. We estimated particulate matter (PM2.5) and nitrogen dioxide (NO2) levels using land use regression models, normalized difference vegetation index (NDVI) levels using remote sensing and percentage of green area (%GA) using land use. We estimated relative risks, population attributable fractions, and preventable overweight/obesity cases in children under following scenarios: Compliance of World Health Organization (WHO) air quality guidelines (AQGs) for (1) PM2.5 and (2) NO2; achieving (3) city-target NDVI levels and (4) 25% green area (%GA) recommendations. The analyses were stratified by socioeconomic deprivation index (in quintiles). Uncertainty was quantified using Monte Carlos simulations. ResultsCompliance of WHO AQGs could prevent 0.4% [253 (95%CI, −604; 1086)] and 4.2% [3000 (95%CI, 1009; 4943)] of childhood overweight/obesity cases due to excess PM2.5 and NO2 levels in Barcelona, respectively. Compliance of NDVI and %GA targeted levels could prevent 6% [4094 (95%CI, 1698; 6379)] and 10% [6853 (95%CI, 1440; 12779)] of childhood overweight/obesity cases respectively. The preventable burdens of childhood overweight/obesity cases were slightly higher in middle-class socioeconomic areas due to the higher adverse exposure levels at baseline (high air pollution, less UGS). DiscussionCompliance with WHO AQGs and achieving UGS targets can reduce childhood overweight and obesity levels in Barcelona, and potentially in other locations as well. This underscores the need for policies that foster healthier urban environments of high environmental quality in order to protect child health.

Functional brain network organization and multidomain resilience to neighborhood disadvantage in youth.

Though youth living in disadvantaged neighborhoods experience greater risk for poor behavioral and mental health outcomes, many go on to show resilience in the face of adversity. A few recent studies have identified neural markers of resilience in cognitive and affective brain networks, yet the broader network organization supporting resilience in youth remains unknown, particularly in relation to neighborhood disadvantage. Moreover, most studies have defined resilience as the absence of psychopathology, which does not consider growing evidence that resilience also includes positive outcomes across multiple domains (e.g., social, academic). We examined associations between brain network organization and multiple resilience domains in a sample of 708 twins (7-19 years old) recruited from neighborhoods with above-average poverty levels. Graph analysis on functional connectivity data from resting-state and task-based functional magnetic resonance imaging was used to characterize features of intrinsic whole-brain and network-level organization, from which we explored associations with resilience in three domains: psychological, social, and academic. Fewer connections between a brain network involved in self-referential processing (i.e., default mode network) and the subcortical system were associated with greater social resilience. Further, greater whole-brain functional integration (i.e., efficiency) was associated with better psychological resilience among youth with relatively lower levels of cumulative adversity exposure. Alternatively, lower whole-brain efficiency and higher whole-brain robustness to disruption (i.e., assortativity) were associated with greater psychological and social resilience among youth with relatively higher levels of cumulative adversity. These findings advance support for multidimensional resilience models and reveal distinct neural mechanisms supporting resilience to neighborhood disadvantage across specific domains in youth. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Association of adverse childhood experiences with adult-onset cardiometabolic conditions and prescription medicine use

Abstract Association of adverse childhood experiences with adult-onset cardiometabolic conditions and prescription medicine use Background and importance Adverse childhood experiences are potentially preventable and traumatic events that occur during childhood. Childhood exposure to trauma is highly prevalent and adults who had adverse childhood experiences are at increased risk of developing physical conditions. However, effect of adverse childhood experiences on health outcomes remains underrecognized. Aim Here, we aimed to measure the association of cumulative adverse childhood experience with adult physical condition and use of prescription medicines in general population. Methods We conducted a cross-sectional analysis using the population-based health study including 21083 participants at age 40 years or older. Self-reported adverse childhood experiences before age at 18 years, present or previous cardiometabolic conditions, and present or previous use of medications prescribed for cardiometabolic conditions were used in our analysis. Cox proportional hazards regression was used to estimate age, sex, smoking, education, and income-adjusted risk of cardiometabolic condition and prescription medicine use after adverse childhood experiences. Association of multimorbidity and using multiple prescription medicines with adverse childhood experience was analyzed using generalized linear model with ordinal classification. Results We found that having a history of adverse childhood experience was associated with increased risk of subsequent cardiometabolic conditions; hazard ratios ranged from 1.117 (95% CI, 1.054 – 1.185) to 1.341 (95% CI, 1.181 – 1.522). Furthermore, adverse childhood experience was associated with multimorbidity of cardiometabolic conditions (odds ratio [OR], 1.195; 95% CI, 1.117 – 1.279) and increased risk of using multiple prescription medicines (OR, 1.131; 95% CI, 1.057 – 1.210). Notably, we observed the dose – effect relationships of cumulative adverse childhood experience to the increased risk of 5 among 6 cardiometabolic conditions and to the increased risk of using 4 among 6 prescription medicines. Furthermore, cumulative adverse childhood experience had the dose – effect associations with multimorbidity of cardiometabolic conditions (ORs ranged from 1.120 [95% CI, 1.033 – 1.214] to 1.526 [95% CI, 1.276 – 1.825]) and using multiple prescription medicines (ORs are 1.393 [95% CI, 1.195 – 1.624] and 1.572 [95% CI 1.315 1.879]). Conclusions and relevance: Our findings implicate cumulative adverse childhood experience as a risk factor for later cardiometabolic conditions and use of medicines prescribed for cardiometabolic conditions. Our results are significant by suggesting inquiry into adverse childhood experience exposure during clinical consultations, services to alleviate the burden and increasing resilience in addition to strategies aimed at prevention of cardiometabolic conditions might improve health outcomes.

Neonatal multimorbidity and the phenotype of premature aging in preterm infants.

Multimorbidity is the co-occurrence of multiple chronic health problems, associated with aging, frailty, and poor functioning. Children born preterm experience more multimorbid conditions in early life compared to term-born peers. Though neonatal multimorbidity is linked to poor health-related quality of life, functional outcomes, and peer group participation, gaps in our theoretical understanding and conceptualization remain. Drawing from life course epidemiology and the Developmental Origins of Heath and Disease models, we offer a framework that neonatal multimorbidity reflects maturational vulnerability posed by preterm birth. The impact of such vulnerability on health and development may be further amplified by adverse exposures and interventions within the environment of the neonatal intensive care unit. This can be exacerbated by disadvantaged home or community contexts after discharge. Uncovering the physiologic and social antecedents of multiple morbid conditions in the neonatal period and their biological underpinnings will allow for more accurate risk-prediction, counseling, and care planning for preterm infants and their families. According to this framework, the maturational vulnerability to multimorbidity imparted by preterm birth and its negative effects on health and development are not predetermined or static. Elucidating pathways of early biologic and physical aging will lead to improvements in care and outcomes. IMPACT: Multimorbidity is associated with significant frailty and dysfunction among older adults and is indicative of early physiologic aging. Preterm infants commonly experience multimorbidities in the newborn period, an underrecognized threat to long-term health and development. We offer a novel framework incorporating multimorbidity, early cellular aging, and life course health development to innovate risk-prediction, care-planning, and therapeutics.

Age of Emergence of Disparities in Asthma Prevalence and Morbidity among US Children.

Early-life exposures may precipitate asthma, but their contribution to disparities in asthma is less clear. To elucidate racial, ethnic, and socioeconomic status (SES) disparities in the age trajectory of asthma burden among US children. We analyzed three datasets: (1) 2016-2021 National Children's Health Survey (NCHS) (n=223,551); (2) 2015-2017 Child Asthma Call-Back Survey (ACBS) (n=4,289); and (3) 2018-2019 National Inpatient Sample (NIS) (n=23,713 children with asthma). We examined cumulative asthma prevalence by individual-year of age and children's race and ethnicity or SES (NCHS); mean age at asthma diagnosis by race and ethnicity and SES, unadjusted and adjusted for confounders (ACBS); and asthma hospitalization rates overall and per child with asthma by individual year of age and race and ethnicity (NIS). Among White children, cumulative asthma prevalence rises gradually through childhood, to 6.6% at age 5 and 16.1% by age 17. Prevalence rises more sharply in early childhood among Black children, reaching 17.6% at age 5 (RR 2.6;95%CI 1.9,3.8), but plateaus after age 9, with a consequent decline in Black-White relative disparities into adolescence. Disparities according to SES follow a similar trajectory, emerging early and subsequently narrowing. Similarly, Black, Hispanic and low-income children with asthma are diagnosed at an earlier age than White (or high-income) children. The asthma hospitalization rate rises in the first years of life among all children, but most rapidly among Black children, with a peak absolute Black-White gap at age 4; the relative gap remains wide throughout childhood and peaks at age 10. However, per child with asthma, relative disparities in White-Black hospitalizations rise through age 15. Disparities in asthma prevalence emerge in early childhood and then narrow, suggesting that reducing early-life adverse environmental exposures may be key to asthma prevention. Policies to improve the social determinants of health during gestation and childhood, e.g. environmental equity and family income support, are needed.

Health effects of selected environmental Exposomes Across the Life courSe in Indian populations using longitudinal cohort studies: GEOHealth HEALS Study protocol

IntroductionAir pollution presents a major public health threat to India, affecting more than three quarters of the country’s population. In the current project, GEOHealth Health Effects of Selected Environmental Exposomes...

Personalized Food Avoidance Dietary Approach for Psoriasis and Hypertension: A Case Study and Pilot Trial

Background: The comorbidity, coheritability and common immune pathways of the inflammatory ‘chronic’ (non-communicable) diseases, suggest a shared aetiopathogenic mechanism, with phenotypic localization dependent on genetic predisposition, for example, the arteries in hypertension and the skin in psoriasis. Lifelong observation of psoriasis suggests genetically predisposed toxicity of amphiphilic fats, flavor enhancers, and nonsugar sweeteners. Aim: To conduct trials of personalized dietary intervention to abate the phenotypic expression of psoriasis and hypertension. Materials and Methods: The interventional case study of psoriasis was conducted by means of repetitive dietary challenge and avoidance testing. We then conducted an open trial of personalized nutrition on nine consenting recruits with uncomplicated essential hypertension. They were counseled on which foods to avoid or to take based on the experience gained in psoriasis. Study participants with ‘GOOD’ or ‘FAIR/POOR’ dietary compliance were compared with regard to blood pressure (BP) control, antihypertensive drug treatment requirement (ADTR), and anthropometry. Results: Data from four FAIR/POOR diet compliers and three GOOD compliers, as at 29 weeks of dietary intervention, showed mean systolic home BP values of 128.1 (±6.74) mmHg and 122.3 (±2.03) mmHg, respectively; the mean systolic automated office BP values were 139.8 (±8.80) mmHg and 108.3 (±5.55) mmHg, respectively; as at 39 weeks of dietary intervention, the mean ADTR scores were 4.2 (±2.12) and 1.03 (±0.57), respectively. Using data at baseline and from all available timepoints after dietary intervention, two-way ANOVA confirmed highly significant improvement of BP control (P &lt; 0.0001) and reduction of ADTR score (P = 0.0008) in GOOD compliers. GOOD compliers exhibited significantly more reductions in BMI, abdominal circumference, and triceps skinfold thickness than FAIR/POOR compliers (two-way ANOVA and linear regression: P &lt; 0.05). Conclusion: These results support the case for adverse dietary exposure avoidance to abate the phenotypic expression of chronic disease.

Social genomics, cognition, and well-being during the COVID-19 pandemic.

Adverse psychosocial exposure is associated with increased pro-inflammatory gene expression and reduced type-1 interferon gene expression known as the conserved transcriptional response to adversity (CTRA). CTRA is not well-studied in cognitive impairment but may contribute to late-life cognitive decline. We examined perceived stress, loneliness, well-being, and the impact of coronavirus disease 2019 (COVID-19) and the relationship to the expression of genes associated with the CTRA. Mixed-effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression. Eudaimonic well-being (EWB) was inversely associated with CTRA gene expression in participants with both normal cognition (NC) and mild cognitive impairment (MCI). Self-reported coping strategies differed by cognitive status and variably impacted CTRA gene expression. EWB is an important correlate of stress, even in people with MCI. The prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression. Conserved transcriptional response to adversity (CTRA) gene expression is higher with lower eudaimonic well-being.Eudaimonic well-being was important in both participants with normal cognition and those with mild cognitive impairment.Coping strategies and impact on CTRA gene expression differed by cognitive status.Loneliness in a population with relatively low loneliness scores did not impact CTRA gene expression.

Finding benefits during collective stress: A study of health behaviors in a longitudinal representative U.S. sample during the COVID-19 era.

Cognitive strategies like finding benefits during adversity may facilitate coping during collective stressors (like COVID-19) by reducing distress or motivating health protective behaviors. We explored relationships between benefit finding, collective- and individual-level adversity exposure, psychological distress, and health protective behaviors using longitudinal data collected during the COVID-19 era from a representative, probability-based sample of U.S. residents: Wave 1 (N = 6,514, March 18, 2020-April 18, 2020, 58.5% completion rate); Wave 2 (N = 5,661, September 26, 2020-October 16, 2020, 87.1% completion rate); Wave 3 (N = 4,881, November 8, 2021-November 24, 2021, 75.3% completion rate); and Wave 4 (N = 4,859, May 19, 2022-June 16, 2022, 75.1% completion rate). Benefit finding was common; k-means clustering (an exploratory, data-driven approach) yielded five trajectories: always high (15.85%), always low (18.52%), always middle (28.47%), increasing (17.79%), and decreasing (19.37%). Benefit-finding trajectories were generally not strong correlates of psychological distress and functional impairment over time. Rather, benefit finding robustly correlated with health protective behaviors relevant to COVID-19 and the seasonal flu. In covariate-adjusted models, benefit finding positively correlated with more social distancing (β = .24, p < .001) and mask wearing (β = .18, p < .001) at Wave 2 and greater COVID-19 (odds ratio, OR = 1.23, p = .001) and flu (OR = 1.29, p < .001) vaccination at Wave 3. Although benefit finding was not generally associated with lower psychological distress during a collective stressor, it correlated with engagement in stressor-related health protective behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of Social Vulnerability and Environmental Burden on Care Fragmentation and Social Needs Among Individuals With Rheumatic Conditions.

Environmental hazards and heightened neighborhood social vulnerability coexist and disproportionately affect minoritized populations. We investigated associations between exposure to adverse environmental burden concentrated in areas with high social vulnerability and care fragmentation (missed appointments, emergency department visits, and hospitalizations) and social needs (eg, food and housing insecurity) among individuals with rheumatic conditions. We identified adults receiving care in a Massachusetts multihospital system with at least two rheumatic disease codes and complete street addresses. Geocoded addresses were linked to the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social-Environmental Ranking (SER), which combines census-tract social vulnerability variables (eg, socioeconomic status) with environmental hazards (eg, air and water pollution). Social needs were obtained from self-reported surveys. Multilevel, multinomial regression models estimated associations between SER quartiles and care fragmentation and social need burden, accounting for demographics and comorbidities. Among 16,856 individuals with rheumatic conditions, 70% were female, 6% were Black, 82% were White, and 7% resided in the highest combined social vulnerability and environmental burden (SER quartile 4) areas. Among 7,083 with social needs data, 19% experienced more than one challenge. Individuals in SER quartile 4 areas (vs quartile 1) had 2.02 (95% confidence interval [CI] 1.67-2.46) times greater odds of at least four care fragmentation occurrences (vs 0) and 2.37 (95% CI 1.73-3.25) times greater odds of at least two social needs (vs 0). Residence in areas of high combined adverse environmental burden and social vulnerability was associated with significantly greater odds of care fragmentation and social needs. Addressing structural factors and emerging environmental threats contributing to these adverse exposures is essential to reduce rheumatic disease care inequities.

The Effects of Adverse Life Events on Brain Development in the ABCD Study®: A Propensity-weighted Analysis.

Longitudinal studies of the effects of adversity on human brain development are complicated by the association of stressful events with confounding variables. To counter this bias, we apply a propensity-weighted analysis of the first two years of The Adolescent Brain Cognitive DevelopmentSM (ABCD) Study® data, employing a machine learning analysis weighted by individuals' propensity to experience adversity. Data included 338 resting-state functional connections from 7190 youth (46% female), divided into a training group (80%) and an independent testing group (20%). Propensity scores were computed using 390 variables to balance across two-year adverse life event exposures. Using elastic net regularization with and without inverse propensity weighting, we developed linear models in which changes in functional connectivity of brain connections during the two-year period served as predictors of the number of adverse events experienced during that same period. Haufe's method was applied to forward-transform the backward prediction models. We also tested whether brain changes associated with adverse events correlated with concomitant changes in internalizing or externalizing behaviors or to academic achievement. In the propensity-weighted analysis, brain development significantly predicted the number of adverse events experienced during that period in both the training group (ρ=0.14, p<0.001) and the independent testing group (ρ=0.10, p<0.001). The predictor indicated a general pattern of decreased functional connectivity between large-scale networks and subcortical brain regions, particularly for cingulo-opercular and sensorimotor networks. These network-to-subcortical functional connectivity decreases inversely associated with the development of internalizing symptoms, suggesting adverse events promoted adaptive brain changes that may buffer against stress-related psychopathology. However, these same functional connections were also associated with poorer grades at the two-year follow-up. Although cortical-subcortical brain developmental responses to adversity potentially shield against stress-induced mood and anxiety disorders, they may be detrimental to other domains such as academic success.

Associations between multiple metals exposure and cognitive function in the middle-aged and older adults from China: A cross-sectional study

The rapidly rising risk of cognitive decline is a serious challenge for the elderly. As the wide-distributed environmental chemicals, the effects of metals exposure on cognitive function have attracted much attention, but the results remain inclusive. This study aimed to investigate the roles of multiple metals co-exposure on cognition. We included a total of 6112 middle-aged and older participants, detected their plasma levels of 23 metals by using inductively coupled plasma mass spectrometry, and assessed their cognitive function by using the Mini-Mental State Examination (MMSE). The results showed that increased plasma levels of iron (Fe) and zinc (Zn) were positively associated with MMSE score, but the increased levels of nickel (Ni) and lead (Pb) were associated with decreased MMSE score (all FDR < 0.05). Subjects exposed to both high levels of Ni and Pb showed the lowest MMSE score [β (95% CI) = −0.310 (−0.519, −0.100)], suggesting that Ni and Pb had a synergistic toxic effect on cognitive function. In addition, the hazardous roles of Ni and Pb were mainly found among subjects with low plasma level of Zn, but were not significant among those with high-Zn level [Ni: β (95% CI) = −0.281 (−0.546, −0.015) vs. −0.146 (−0.351, 0.058); Pb: β (95% CI) = −0.410 (−0.651, −0.169) vs. −0.060 (−0.275, 0.155)], which suggested that Zn could attenuate the adverse effects of Pb and Ni on cognitive function. The cognitive function was gradually decreased among subjects with increased number of adverse exposures to the above four metals (Ptrend < 0.001). In conclusion, our findings revealed the individual, interactive, and combined effects of Fe, Ni, Pb, and Zn on cognitive function, which may provide new perspectives on cognitive protection, but further prospective cohort studies and biological researches are needed to validate these findings.

Sperm miR-142-3p Reprogramming Mediates Paternal Pre-Pregnancy Caffeine Exposure-Induced Non-Alcoholic Steatohepatitis in Male Offspring Rats.

Numerous studies have suggested a strong association between paternal adverse environmental exposure and increased disease susceptibility in offspring. However, the impact of paternal pre-pregnant caffeine exposure (PPCE) on offspring health remains unexplored. This study elucidates the sperm reprogramming mechanism and potential intervention targets for PPCE-induced non-alcoholic steatohepatitis (NASH) in offspring. Here, male rats are administrated caffeine (15-60mgkg-1/d) by gavage for 8 weeks and then mated with females to produce offspring. This study finds that NASH with transgenerational inheritance occurred in PPCE adult offspring. Mechanistically, a reduction of miR-142-3p is implicated in the occurrence of NASH, characterized by hepatic lipid metabolism dysfunction and chronic inflammation through an increase in ACSL4. Conversely, overexpression of miR-142-3p mitigated these manifestations. The origin of reduced miR-142-3p levels is traced to hypermethylation in the miR-142-3p promoter region of parental sperm, induced by elevated corticosterone levels rather than by caffeine per se. Similar outcomes are confirmed in offspring conceived via in vitro fertilization using miR-142-3pKO sperm. Overall, this study provides the first evidence of transgenerational inheritance of NASH in PPCE offspring and identifies miR-142-3p as a potential therapeutic target for NASH induced by paternal environmental adversities.

Prenatal glucocorticoids exposure and adverse cardiovascular effects in offspring.

Glucocorticoids (GCs) are steroid hormones fundamental to the body's normal physiological functions and are pivotal in fetal growth and development. During gestation, the mother's cortisol concentration (active GCs) escalates to accommodate the requirements of fetal organ development and maturation. A natural placental GCs barrier, primarily facilitated by 11β hydroxysteroid dehydrogenase 2, exists between the mother and fetus. This enzyme transforms biologically active cortisol into biologically inactive corticosterone, thereby mitigating fetal GCs exposure. However, during pregnancy, the mother may be vulnerable to adverse factor exposures such as stress, hypoxia, caffeine, and synthetic GCs use. In these instances, maternal serum GCs levels may surge beyond the protective capacity of the placental GCs barrier. Moreover, these adverse factors could directly compromise the placental GCs barrier, resulting in excessive fetal exposure to GCs. It is well-documented that prenatal GCs exposure can detrimentally impact the offspring's cardiovascular system, particularly in relation to blood pressure, vascular function, and heart function. In this review, we succinctly delineate the alterations in GCs levels during pregnancy and the potential mechanisms driving these changes, and also analyze the possible causes of prenatal GCs exposure. Furthermore, we summarize the current advancements in understanding the adverse effects and mechanisms of prenatal GCs exposure on the offspring's cardiovascular system.