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The development of child mental health problems has been associated with experiences of adversity and dysregulation of stress response systems; however, past research has largely focused on externalizing or internalizing problems (rather than their co-occurrence) and single physiological systems in high-risk adolescent samples. The present study examined whether cumulative family adversity, functioning in the hypothalamic-pituitary-adrenal axis (i.e., cortisol) and the parasympathetic nervous system (i.e., respiratory sinus arrhythmia [RSA]), and their interactions, predicted trajectories of co-occurring externalizing and internalizing problems among young children. Participants included 338 socioeconomically and racially diverse children (M age = 5.32 years, SD = .32; male = 51.8%) from a community sample. Family adversity (assessed with six measures) and child daily cortisol output and resting RSA were assessed in kindergarten. Parents, teachers, and children reported on children's externalizing and internalizing psychopathology up to three times from kindergarten to grade 1. Latent class growth analyses identified stable trajectories of externalizing and internalizing psychopathology. Trajectories were combined to create groups: co-occurring externalizing and internalizing (13.1%), externalizing-only (14.0%), internalizing-only (11.3%), and low problems (61.3%). Family adversity and resting RSA significantly positively predicted co-occurring group membership. Tests for interactions showed adversity did not significantly interact with physiological indicators to predict group membership. However, the two physiological systems interacted, such that higher and lower daily cortisol predicted internalizing group membership for children with lower and higher resting RSA, respectively. Findings support the importance of considering family context and multiple physiological systems to inform understanding of the development of mental health problems, and their co-occurrence, in early childhood.

There is emerging evidence that the development of problematic aggression in childhood may be associated with specific physiological stress response patterns, with both biological overactivation and underactivation implicated. This study tested associations between sex-specific patterns of stress responses across the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis and peer nominations of aggression among 271 kindergarten children (Mean age = 5.32 years; 52% Female; 44% White). Upon entry to kindergarten, children participated in a multidomain standardized stress paradigm. Changes in pre-ejection period (PEP) and salivary cortisol were assessed. On a separate day, children provided peer ratings of physical and relational aggression in a standardized interview. As expected, there was a significant three-way interaction between PEP, cortisol reactivity, and sex, but only for physical aggression. Among boys, cortisol reactivity was positively associated with physical aggression only for those with higher SNS reactivity. Findings suggest that for boys, asymmetrical and symmetrical HPA/SNS reactivity may be associated with lower and higher risk for peer-directed physical aggression, respectively. Understanding the complex associations between multisystem physiology, child sex and peer-directed aggression in early childhood may offer insight into individual differences underlying the emergence of behavioral dysregulation in early peer contexts.

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

Classrooms are key social settings that impact children's mental health, though individual differences in physiological reactivity may render children more or less susceptible to classroom environments. In a diverse sample of children from 19 kindergarten classrooms (N = 338, 48% female, M age = 5.32 years), we examined whether children's parasympathetic reactivity moderated the association between classroom climate and externalizing symptoms. Independent observers coded teachers' use of child-centered and teacher-directed instructional practices across classroom social and management domains. Children's respiratory sinus arrhythmia reactivity to challenge tasks was assessed in fall and a multi-informant measure of externalizing was collected in fall and spring. Both the social and the management domains of classroom climate significantly interacted with children's respiratory sinus arrhythmia reactivity to predict spring externalizing symptoms, controlling for fall symptoms. For more reactive children, as classrooms shifted toward greater proportional use of child-centered methods, externalizing symptoms declined, whereas greater use of teacher-dominated practices was associated with increased symptoms. Conversely, among less reactive children, exposure to more teacher-dominated classroom management practices was associated with lower externalizing. Consistent with the theory of biological sensitivity to context, considering variability in children's physiological reactivity aids understanding of the salience of the classroom environment for children's mental health.

Harsh and restrictive parenting are well-established contributors to the development of oppositional defiant disorder (ODD) among children. However, few studies have explored whether interpersonal relationships that develop outside the family environment attenuate the risk for ODD that is associated with harsh parenting. The current study tested multireporter measures of teacher-child closeness and peer acceptance as moderators of the association between harsh parenting and children's ODD as children's social worlds widen during the kindergarten year (N = 338 children, 48% girls, M age = 5.32 years). Harsh parenting interacted with peer nominations of peer acceptance and children's report of teacher-child closeness to predict children's ODD symptoms in the spring, adjusting for fall symptoms. Children exposed to harsh parenting exhibited greater symptom increases when they were less liked/accepted playmates and in the context of lower teacher-child closeness. However, harsh parenting was not associated with symptom change among children with higher levels of peer-nominated acceptance and those who reported closer relationships with teachers. There were no significant interactions using teacher's report of peer acceptance or teacher's report of teacher-child closeness. Findings highlight positive peer and teacher relationships as promising targets of intervention among children exposed to harsh parenting and support the importance of assessing multiple perspectives of children's social functioning.

ObjectiveTo examine the moderating role of restrictive parenting on the relation of socioeconomic status (SES) to febrile illnesses (FIs) and upper respiratory illnesses (URIs) among ethnic minority and non-minority children.MethodsChildren from diverse ethnic backgrounds (Caucasian, African American, Asian, Latino, other, or multiethnic) were followed across the course of the kindergarten year. Parents reported on SES and parenting. A nurse completed 13 physical exams per child over the year to assess FIs and URIs.ResultsDuring the school year, 28% of children (n = 199, 56% ethnic minority) exhibited one or more FIs (range, 0-6) and 90% exhibited one or more URIs (range, 0-10). No main or moderating effects of SES or restrictive parenting on FIs or URIs were found among Caucasian children; however, among ethnic minority children, the relation of SES to FIs was conditional upon restrictive parenting (β = .66; P = .02), as the fewest FIs were found for lower SES minority children whose parents reported more restrictive practices. Additionally, among minority children, more restrictive parenting was marginally associated with fewer URIs (β = -.21; P = .05).ConclusionsUnexpectedly, among minority children the fewest illnesses occurred among lower SES children whose parents endorsed more restrictive parenting. This may be due to unique appraisals of this rearing style among minority children in lower SES environments and its potential to influence immune functioning. Results suggest variability in the effects of parenting on offspring health and support context-specific evaluations of parenting in efforts to ameliorate early health disparities.

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials & methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans.

OBJECTIVE:Children from families with lower socioeconomic status (SES) evidence greater physiological dysregulation and poorer health. Despite recognition of environmental contributors, little is known about the influence of neighborhood characteristics. The present study examined the moderating role of community-level risks and resources on the relation of family SES to children's daily cortisol output and physical health during the kindergarten year. METHODS:In fall and spring of kindergarten, children's (N = 338) daily total cortisol was measured and parents and teachers rated children's global physical health. Parents reported family SES. Neighborhood characteristics were assessed using the Child Opportunity Index, a population-level tool that evaluates the quality of multiple domains of neighborhood attributes. RESULTS:In fall, children reared in lower SES family environments had higher cortisol when residing in lower quality (lower opportunity) neighborhoods (b = -.097, p < .001), but there was no relation between family SES and children's cortisol in more advantaged (higher opportunity) neighborhoods (b = -.023, p = .36). Lower family SES was prospectively associated with poorer physical health in spring (controlling for fall health) only among children living in lower opportunity neighborhoods (b = -.250, p = .018) and was unrelated to physical health among children residing in higher opportunity neighborhoods (b = .042, p = .70). CONCLUSIONS:Higher opportunity neighborhoods may protect against the negative consequences of low family SES on children's stress physiology and physical health. Public health interventions that bolster neighborhood opportunities may benefit young children reared in socioeconomically disadvantaged family environments.

Entry into kindergarten is a developmental milestone that children may differentially experience as stressful, with implications for variability in neurobiological functioning. Guided by the goodness-of-fit framework, this study tested the hypothesis that kindergarten children's (N = 338) daily cortisol would be affected by the "match" or "mismatch" between children's temperament and qualities of the classroom relational context. The robustness of these associations was also explored among a separate sample of children in third grade (N = 165). Results among kindergarten children showed negative affectivity and overcontrolled temperament were positively related to cortisol expression within classrooms characterized by lower levels of teacher motivational support, but there was no relation between temperament and cortisol when motivational support was higher. Among third-grade children, negative affectivity was marginally positively related to cortisol at lower levels of teacher-child closeness and unrelated at higher levels of teacher-child closeness. Findings suggest children's cortisol expression depends on the extent to which specific temperamental characteristics "fit" within the relational and contextual qualities of the classroom environment, particularly as children navigate the new roles and relationships that emerge during the transition to formal schooling. Developmentally informed neurobiological research in classrooms may contribute to tailored programmatic efforts to support children's school adjustment.

The study of autonomic nervous system responses and contextual factors has shed light on the development of children's negative outcomes, but the majority of these studies have not focused on minority populations living under adversity. To address these gaps, the current longitudinal study included a sample of poor, immigrant Latino families to examine whether associations between children's autonomic nervous system reactivity at 6 months and their externalizing behavior problems at 7 years of age were moderated by two risk factors associated with poverty: the interpersonal factor of chronic maternal depression and the environmental factor of chronic overcrowded housing. Multiple linear regression (N = 99) revealed that children who exhibited less parasympathetic nervous system withdrawal in response to challenge during infancy had more externalizing problems during childhood only if they had mothers who experienced chronic depression. Children who exhibited greater sympathetic nervous system reactivity during infancy had the lowest levels of externalizing problems during childhood only if they had mothers who chronic depression. Chronic overcrowded housing did not moderate associations between physiological reactivity and level of externalizing problems. These findings extend our understanding of the interaction of physiology and context on child outcomes to the understudied population of impoverished Latino families.

BackgroundExposure to parental chronic illness is associated with several adverse developmental outcomes.ObjectivesWe examined the association between parental multiple sclerosis (MS) and childhood developmental outcomes.MethodsWe conducted a population-based retrospective cohort study in Manitoba, Canada, using linked databases. The outcome was childhood development at 5 years of age, expressed as vulnerability (absent vs. present) on the Early Development Instrument (EDI). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).ResultsChildren with an MS parent (n=153) were similar to children of unaffected parents (n=876) on all EDI domains. However, mental health morbidity was more common among MS parents compared with non-MS parents 49.5% vs. 35.3%. Among MS parents, mental health morbidity was associated with children's vulnerability on the social competence (OR, 5.73 [95% CI:1.11-29.58]) and emotional maturity (OR, 3.03 [95% CI:1.03-8.94]) domains. The duration of child's exposure to parental MS was associated with vulnerability on the physical health domain (OR, 1.49 [95%CI:1.03-2.15]).ConclusionParental MS was not associated with adverse early childhood developmental outcomes. However, children of parents with mental health morbidity, and those with longer duration of exposure to parental MS, were at higher risk for early childhood developmental vulnerability.

Evolutionary-minded developmentalists studying predictive-adaptive-response processes linking childhood adversity with accelerated female reproductive development and health scientists investigating the developmental origins of health and disease (DOoHaD) may be tapping the same process, whereby longer-term health costs are traded off for increased probability of reproducing before dying via a process of accelerated reproductive maturation. Using data from 73 females, we test the following propositions using path analysis: (a) greater exposure to prenatal stress predicts greater maternal depression and negative parenting in infancy, (b) which predicts elevated basal cortisol at 4.5 years, (c) which predicts accelerated adrenarcheal development, (d) which predicts more physical and mental health problems at age 18. Results prove generally consistent with these propositions, including a direct link from cortisol to mental health problems. DOoHaD investigators should consider including early sexual maturation as a core component linking early adversity and stress physiology with poor health later in life in females.

BackgroundRecent research shows that by age 5, children form rigid social hierarchies, with some children consistently subordinated, and then later, bullied. Further, several studies suggest that enduring mental and physical harm follow. It is time to analyze the health burdens posed by early social dominance and to consider the ethical implications of ongoing socially caused harms.MethodsFirst, we reviewed research demonstrating the health impact of early childhood subordination. Second, we used philosophical conceptions of children's rights and social justice to consider whether children have a right to protection and who has an obligation to protect them from social harms.ResultsCollectively, recent studies show that early subordination is instantiated biologically, increasing lifetime physical and mental health problems. The pervasive, and enduring nature of these harms leads us to argue that children have a right to be protected. Further, society has a role responsibility to protect children because society conscripts children into schools. Society's promise to parents that schools will be fiduciaries entails an obligation to safeguard each child's right to a reasonably open future. Importantly, this role responsibility holds independently of bearing any causal responsibility for the harm. This new argument based on protecting from harm is much stronger than previous equality of opportunity arguments, and applies broadly to other social determinants of health.ConclusionsSocial institutions have a role responsibility to protect children that is not dependent on playing a causal role in the harm. Children's rights to protection from social harms can be as strong as their rights to protection from direct bodily harms.

Despite widespread recognition that the physiological systems underlying stress reactivity are well coordinated at a neurobiological level, surprisingly little empirical attention has been given to delineating precisely how the systems actually interact with one another when confronted with stress. We examined cross-system response proclivities in anticipation of and following standardized laboratory challenges in 664 4- to 14-year-olds from four independent studies. In each study, measures of stress reactivity within both the locus coeruleus-norepinephrine system (i.e., the sympathetic and parasympathetic branches of the autonomic nervous system) and the corticotrophin releasing hormone system (i.e., the hypothalamic-pituitary-adrenal axis) were collected. Latent profile analyses revealed six distinctive patterns that recurred across the samples: moderate reactivity (average cross-system activation; 52%-80% of children across samples), parasympathetic-specific reactivity (2%-36%), anticipatory arousal (4%-9%), multisystem reactivity (7%-14%), hypothalamic-pituitary-adrenal axis specific reactivity (6%-7%), and underarousal (0%-2%). Groups meaningfully differed in socioeconomic status, family adversity, and age. Results highlight the sample-level reliability of children's neuroendocrine responses to stress and suggest important cross-system regularities that are linked to development and prior experiences and may have implications for subsequent physical and mental morbidity.

This study investigates the dynamic interplay between teacher-child relationship quality and children's behaviors across kindergarten and first grade to predict academic competence in first grade. Using a sample of 338 ethnically diverse 5-year-old children, nested path analytic models were conducted to examine bidirectional pathways between children's behaviors and teacher-child relationship quality. Low self-regulation in kindergarten fall, as indexed by inattention and impulsive behaviors, predicted more conflict with teachers in kindergarten spring and this effect persisted into first grade. Conflict and low self-regulation jointly predicted decreases in school engagement which in turn predicted first-grade academic competence. Findings illustrate the importance of considering transactions between self-regulation, teacher-child relationship quality, and school engagement in predicting academic competence.

BackgroundTo understand whether the relationship between young children's autonomic nervous system (ANS) responses predicted their BMI, or vice versa, the association between standardized BMI (zBMI) at 2, 3.5, and 5 years of age and ANS reactivity at 3.5-5 years of age, and whether zBMI predicts later ANS reactivity or whether early ANS reactivity predicts later zBMI, was studied.MethodsLow-income, primarily Latino children (n=112) were part of a larger cohort study of mothers recruited during early pregnancy. Study measures included maternal prenatal weight, children's health behaviors (i.e., time watching television, fast food consumption, and time playing outdoors), children's height and weight at 2, 3.5, and 5 years, and children's ANS reactivity at 3.5 and 5 years. ANS measures of sympathetic nervous system (i.e., pre-ejection period) and parasympathetic nervous system (i.e., respiratory sinus arrhythmia) activity were monitored during rest and four challenges. Reactivity was calculated as the difference between mean challenge response and rest. Structural equation models analyzed the relationship between children's zBMI at 2, 3.5, and 5 years and ANS reactivity at 3.5 and 5 years, adjusting for mother's BMI, children's behaviors, and changes in height.ResultsThere was no association between zBMI and ANS cross-sectionally. Children with high zBMI at 2 or 3.5 years or large zBMI increases from 2 to 3.5 years of age had decreased sympathetic activity at 5 years. Neither sympathetic nor parasympathetic reactivity at 3.5 years predicted later zBMI.ConclusionsIncreased zBMI early in childhood may dampen young children's SNS responses later in life.

The purpose of the study was to determine whether mothers' adversities experienced during early pregnancy are associated with offspring's autonomic nervous system (ANS) reactivity trajectories from 6 months to 5 years of age. This cohort study of primarily Latino families included maternal interviews at 13-14 weeks gestation about their experience of a range of adversities: father's absence, general social support, poverty level, and household density. ANS measures of heart rate, respiratory sinus arrhythmia (parasympathetic nervous system) and preejection period (sympathetic nervous system) were collected during resting and challenging conditions on children at 6 months and 1, 3.5 and 5 years of age. Reactivity measures were calculated as the mean of the responses to challenging conditions minus a resting condition. Fixed effects models were conducted for the 212 children with two or more timepoints of ANS measures. Interactions between maternal prenatal adversity levels and child age at time of ANS protocol were included in the models, allowing the calculation of separate trajectories or slopes for each level of adversity. Results showed no significant relations between mothers' prenatal socioeconomic or social support adversity and offspring's parasympathetic nervous system trajectories, but there was a statistically significant relationship between social support adversity and offspring's heart rate trajectories (p

ObjectiveTo explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status.MethodsData from 38 HIV-positive and 29 HIV-negative children born to seropositive women were obtained. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity, and enumerative and functional changes in peripheral blood immune parameters.ResultsIn comparison with children who were HIV-negative, children who were HIV-positive at baseline had fewer CD4(+) T lymphocytes (mean [M] = 916 versus 1206 cells/mm(3) × 10(3); F = 7.8, p = .007), more CD8(+) cells (M = 1046 versus 720 cells/mm(3) × 10(3); F = 7.98, p = .006), and diminished natural killer cell cytotoxicity (M = -0.29 versus 0.41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters after school entry were associated with family stress and preschool entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8(+) cells after school entry or the greatest decrease, depending on reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity.ConclusionsThese results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV.

Socioeconomic status (SES) is the single most potent determinant of health within human populations, from infancy through old age. Although the social stratification of health is nearly universal, there is persistent uncertainty regarding the dimensions of SES that effect such inequalities and thus little clarity about the principles of intervention by which inequalities might be abated. Guided by animal models of hierarchical organization and the health correlates of subordination, this prospective study examined the partitioning of children's adaptive behavioral development by their positions within kindergarten classroom hierarchies. A sample of 338 5-y-old children was recruited from 29 Berkeley, California public school classrooms. A naturalistic observational measure of social position, parent-reported family SES, and child-reported classroom climate were used in estimating multilevel, random-effects models of children's adaptive behavior at the end of the kindergarten year. Children occupying subordinate positions had significantly more maladaptive behavioral outcomes than their dominant peers. Further, interaction terms revealed that low family SES and female sex magnified, and teachers' child-centered pedagogical practices diminished, the adverse influences of social subordination. Taken together, results suggest that, even within early childhood groups, social stratification is associated with a partitioning of adaptive behavioral outcomes and that the character of larger societal and school structures in which such groups are nested can moderate rank-behavior associations.

The prefrontal cortex (PFC) develops from birth through late adolescence. This extended developmental trajectory provides many opportunities for experience to shape the structure and function of the PFC. To date, a few studies have reported links between parental socioeconomic status (SES) and prefrontal function in childhood, raising the possibility that aspects of environment associated with SES impact prefrontal function. Considering that behavioral measures of prefrontal function are associated with learning across multiple domains, this is an important area of investigation. In this study, we used fMRI to replicate previous findings, demonstrating an association between parental SES and PFC function during childhood. In addition, we present two hypothetical mechanisms by which SES could come to affect PFC function of this association: language environment and stress reactivity. We measured language use in the home environment and change in salivary cortisol before and after fMRI scanning. Complexity of family language, but not the child's own language use, was associated with both parental SES and PFC activation. Change in salivary cortisol was also associated with both SES and PFC activation. These observed associations emphasize the importance of both enrichment and adversity-reduction interventions in creating good developmental environments for all children.