Nicole R. Bush

Biological Sensitivity to Context: The Interactive Effects of Stress Reactivity and Family Adversity on Socioemotional Behavior and School Readiness

This study examined the direct and interactive effects of stress reactivity and family adversity on socioemotional and cognitive development in three hundred and thirty-eight 5- to 6-year-old children. Neurobiological stress reactivity was measured as respiratory sinus arrhythmia and salivary cortisol responses to social, cognitive, sensory, and emotional challenges. Adaptation was assessed using child, parent, and teacher reports of externalizing symptoms, prosocial behaviors, school engagement, and academic competence. Results revealed significant interactions between reactivity and adversity. High stress reactivity was associated with more maladaptive outcomes in the context of high adversity but with better adaption in the context of low adversity. The findings corroborate a reconceptualization of stress reactivity as biological sensitivity to context by showing that high reactivity can both hinder and promote adaptive functioning.

The interactive effect of marital conflict and stress reactivity on externalizing and internalizing symptoms: The role of laboratory stressors

Growing evidence supports the biological sensitivity to context theory, which posits that physiologically reactive children, as indexed by autonomic nervous system (ANS) reactivity to laboratory stressors, are more susceptible to both negative and positive environmental influences than their low reactive peers. High biological sensitivity is a risk factor for behavioral and health problems in the context of high adversity, whereas in contexts of low adversity it has been found to promote positive adaptation. However, several studies have shown the opposite effect, finding that children who exhibited high ANS reactivity in response to interpersonal stressors were buffered from the deleterious effects of marital conflict, whereas children who showed low ANS reactivity were more vulnerable to high levels of marital conflict. Using an ethnically diverse sample of 260 kindergartners (130 girls, 130 boys), the current study investigated whether the interaction effect of marital conflict and the two branches of ANS reactivity on childrens externalizing and internalizing symptoms differs with the nature of the laboratory challenge task used to measure childrens stress response. As hypothesized, results indicate that the interaction between ANS reactivity and marital conflict significantly predicted childrens behavior problems, but the direction of the effect varied with the nature of the challenge task (i.e., interpersonal or cognitive). This study illustrates the importance of considering the effect of laboratory stimuli when assessing whether childrens ANS reactivity moderates the effects of adversity exposure on adaptation.

Effortful control as a moderator of the relation between contextual risk factors and growth in adjustment problems

Effortful control was examined as a moderator of the relations of three domains of contextual risk factors to growth in internalizing and externalizing problems in a community sample (N = 189) of children (8-12 years at Time 1). Socioeconomic, maternal, and environmental risk factors were examined as predictors of initial levels and growth in childrens adjustment problems across 3 years. The effects of the risk factors depended on childrens level of effortful control. For children lower in effortful control, socioeconomic risk was related to significantly higher initial levels of internalizing and externalizing problems and decreases over time. However, children lower in effortful control had higher levels of problems at all three time points than children higher in effortful control. Maternal risk was associated with increases in internalizing for children lower in effortful control, and environmental risk was related to increases in internalizing and externalizing problems for children lower in effortful control, but not those higher in effortful control. Children who were lower in effortful control appeared to experience more adverse effects of contextual risk than those higher in effortful control, suggesting that interventions aimed at improving childrens effortful control might serve to protect children from increased risk of adjustment problems associated with contextual risk factors.

Rigor, vigor, and the study of health disparities.

Health disparities research spans multiple fields and methods and documents strong links between social disadvantage and poor health. Associations between socioeconomic status (SES) and health are often taken as evidence for the causal impact of SES on health, but alternative explanations, including the impact of health on SES, are plausible. Studies showing the influence of parents’ SES on their children’s health provide evidence for a causal pathway from SES to health, but have limitations. Health disparities researchers face tradeoffs between “rigor” and “vigor” in designing studies that demonstrate how social disadvantage becomes biologically embedded and results in poorer health. Rigorous designs aim to maximize precision in the measurement of SES and health outcomes through methods that provide the greatest control over temporal ordering and causal direction. To achieve precision, many studies use a single SES predictor and single disease. However, doing so oversimplifies the multifaceted, entwined nature of social disadvantage and may overestimate the impact of that one variable and underestimate the true impact of social disadvantage on health. In addition, SES effects on overall health and functioning are likely to be greater than effects on any one disease. Vigorous designs aim to capture this complexity and maximize ecological validity through more complete assessment of social disadvantage and health status, but may provide less-compelling evidence of causality. Newer approaches to both measurement and analysis may enable enhanced vigor as well as rigor. Incorporating both rigor and vigor into studies will provide a fuller understanding of the causes of health disparities.

Autonomic and adrenocortical reactivity and buccal cell telomere length in kindergarten children.

Objective: To examine associations between autonomic nervous system and adrenocortical reactivity to laboratory stressors and buccal cell telomere length (BTL) in children. Methods: The study sample comprised 78 children, aged 5 to 6 years, from a longitudinal cohort study of kindergarten social hierarchies, biologic responses to adversity, and child health. Buccal cell samples and reactivity measures were collected in the spring of the kindergarten year. BTL was measured by real-time polymerase chain reaction, as the telomere-to-single-copy gene ratio. Parents provided demographic information; parents and teachers reported childrens internalizing and externalizing behavior problems. Components of childrens autonomic (heart rate, respiratory sinus arrhythmia [RSA], and preejection period [PEP]) and adrenocortical (salivary cortisol) responses were monitored during standardized laboratory challenges. We examined relationships between reactivity, internalizing and externalizing behaviors, and BTL, adjusted for age, race, and sex. Results: Heart rate and cortisol reactivity were inversely related to BTL, PEP was positively related to BTL, and RSA was unrelated to BTL. Internalizing behaviors were also inversely related to BTL (standardized &bgr; = −0.33, p =.004). Split at the median of reactivity parameters, children with high sympathetic activation (decreasing PEP), and parasympathetic withdrawal (decreasing RSA) did not differ with regard to BTL. However, children with both this profile and high cortisol reactivity (n = 12) had significantly shorter BTL (0.80 versus 1.00; &khgr;2 = 7.6, p =.006), compared with other children. Conclusions: The combination of autonomic and adrenocortical reactivity was associated with shorter BTL in children. These data suggest that psychophysiological processes may influence, and that BTL may be a useful marker of, early biologic aging.DNA = deoxyribonucleic acid; BTL = buccal cell telomere length; ANS = autonomic nervous system; HPA = hypothalamic-pituitary-adrenal; HR = heart rate; SNS = sympathetic nervous system; PNS = parasympathetic nervous system; PEP = preejection period; RSA = respiratory sinus arrhythmia; PAWS = Peers and Wellness Study; BMI = body mass index; T/S = telomere repeat copy number to single-copy gene copy number; ECG = electrocardiograph; SES = socioeconomic status.

An epigenetic clock for gestational age at birth based on blood methylation data

BackgroundGestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth.ResultsWe find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry.ConclusionsDNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.

Kindergarten stressors and cumulative adrenocortical activation: The "first straws" of allostatic load?

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on childrens developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted childrens daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict childrens HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

The symphonic structure of childhood stress reactivity: patterns of sympathetic, parasympathetic, and adrenocortical responses to psychological challenge.

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 childrens 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.

Social stratification, classroom climate, and the behavioral adaptation of kindergarten children

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 childrens 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 childrens 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 Contributions of Early Experience to Biological Development and Sensitivity to Context

Although long a focus of developmental psychopathology, in recent years a variety of professional disciplines and the general public have demonstrated an increased interest in the manner in which early life experience relates to the development of health outcomes. Adding to the already rich empirical evidence of early life experience effects on child development, it is now becoming common for studies of adult mental health to include indices of childhood social context. In tandem with this movement, there has been a remarkable advancement in understanding of human biology and the biological mechanisms underlying psychopathology. In combination, these advancements in the study of early experience and biology illuminate many of the etiologic complexities of mental health. This chapter will review theories and evidence for the biological embedding of early life experience and the manner in which context and biology interact to predict psychopathology. In particular, we approach this work through the lens of Biological Sensitivity to Context Theory, which allows for examination of both phenomena and their integration, across development.