W. Thomas Boyce

Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities: Building a New Framework for Health Promotion and Disease Prevention

A scientific consensus is emerging that the origins of adult disease are often found among developmental and biological disruptions occurring during the early years of life. These early experiences can affect adult health in 2 ways--either by cumulative damage over time or by the biological embedding of adversities during sensitive developmental periods. In both cases, there can be a lag of many years, even decades, before early adverse experiences are expressed in the form of disease. From both basic research and policy perspectives, confronting the origins of disparities in physical and mental health early in life may produce greater effects than attempting to modify health-related behaviors or improve access to health care in adulthood.

Biological sensitivity to context: I. An evolutionary–developmental theory of the origins and functions of stress reactivity

Biological reactivity to psychological stressors comprises a complex, integrated, and highly conserved repertoire of central neural and peripheral neuroendocrine responses designed to prepare the organism for challenge or threat. Developmental experience plays a role, along with heritable, polygenic variation, in calibrating the response dynamics of these systems, with early adversity biasing their combined effects toward a profile of heightened or prolonged reactivity. Conventional views of such high reactivity suggest that it is an atavistic and pathogenic legacy of an evolutionary past in which threats to survival were more prevalent and severe. Recent evidence, however, indicates that (a) stress reactivity is not a unitary process, but rather incorporates counterregulatory circuits serving to modify or temper physiological arousal, and (b) the effects of high reactivity phenotypes on psychiatric and biomedical outcomes are bivalent, rather than univalent, in character, exerting both risk-augmenting and risk-protective effects in a context-dependent manner. These observations suggest that heightened stress reactivity may reflect, not simply exaggerated arousal under challenge, but rather an increased biological sensitivity to context, with potential for negative health effects under conditions of adversity and positive effects under conditions of support and protection. From an evolutionary perspective, the developmental plasticity of the stress response systems, along with their structured, context-dependent effects, suggests that these systems may constitute conditional adaptations: evolved psychobiological mechanisms that monitor specific features of childhood environments as a basis for calibrating the development of stress response systems to adaptively match those environments. Taken together, these theoretical perspectives generate a novel hypothesis: that there is a curvilinear, U-shaped relation between early exposures to adversity and the development of stress-reactive profiles, with high reactivity phenotypes disproportionately emerging within both highly stressful and highly protected early social environments.

Differential susceptibility to the environment: an evolutionary--neurodevelopmental theory.

Two extant evolutionary models, biological sensitivity to context theory (BSCT) and differential susceptibility theory (DST), converge on the hypothesis that some individuals are more susceptible than others to both negative (risk-promoting) and positive (development-enhancing) environmental conditions. These models contrast with the currently dominant perspective on personal vulnerability and environmental risk: diathesis stress/dual risk. We review challenges to this perspective based on emerging theory and data from the evolutionary, developmental, and health sciences. These challenges signify the need for a paradigm shift in conceptualizing Person x Environment interactions in development. In this context we advance an evolutionary--neurodevelopmental theory, based on DST and BSCT, of the role of neurobiological susceptibility to the environment in regulating environmental effects on adaptation, development, and health. We then outline current thinking about neurogenomic and endophenotypic mechanisms that may underpin neurobiological susceptibility, summarize extant empirical research on differential susceptibility, and evaluate the evolutionary bases and implications of BSCT and DST. Finally, we discuss applied issues including methodological and statistical considerations in conducting differential susceptibility research; issues of ecological, cultural, and racial--ethnic variation in neurobiological susceptibility; and implications of differential susceptibility for designing social programs. We conclude that the differential susceptibility paradigm has far-reaching implications for understanding whether and how much child and adult development responds, for better and for worse, to the gamut of species-typical environmental conditions.

Socioeconomic differences in children's health: how and why do these relationships change with age?

The effects of socioeconomic status (SES) on health are well documented in adulthood, but far less is known about its effects in childhood. The authors reviewed the literature and found support for a childhood SES effect, whereby each decrease in SES was associated with an increased health risk. The authors explored how this relationship changed as children underwent normal developmental changes and proposed 3 models to describe the temporal patterns. The authors found that a models capacity to explain SES-health relationships varied across health outcomes. Childhood injury showed stronger relationships with SES at younger ages, whereas smoking showed stronger relationships with SES in adolescence. Finally, the authors proposed a developmental approach to exploring mechanisms that link SES and child health.

Biological Sensitivity to Context

Conventional views suggest that exaggerated biological reactivity to stress is a harmful vestige of an evolutionary past in which threats to survival were more prevalent and severe. Recent evidence, however, indicates that effects of high reactivity on behavior and health are bivalent rather than univalent in character, exerting both risk-augmenting and risk-protective effects depending on the context. These observations suggest that heightened stress reactivity may reflect increased biological sensitivity to context, with potential for negative health effects under conditions of adversity and for positive effects under conditions of support. From an evolutionary perspective, the developmental plasticity of the stress-response systems, along with their structured, context-dependent effects, suggests that variation in these systems has been adaptively patterned to increase the capacity of children to match their stress-response profiles to anticipated developmental environments. Taken together, these theoretical perspectives generate a novel hypothesis: that there is a curvilinear, U-shaped relation between early exposures to adversity and the development of stress-reactive profiles, with high-reactivity phenotypes disproportionately emerging within both highly stressful and highly protected early social environments.

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.

Psychobiologic reactivity to stress and childhood respiratory illnesses: results of two prospective studies.

Psychological stress is thought to undermine host resistance to infection through neuroendocrine-mediated changes in immune competence. Associations between stress and infection have been modest in magnitude, however, suggesting individual variability in stress response. We therefore studied environmental stressors, psychobiologic reactivity to stress, and respiratory illness incidence in two studies of 236 preschool children. In Study 1, 137 3- to 5-year-old children from four childcare centers underwent a laboratory-based assessment of cardiovascular reactivity (changes in heart rate and mean arterial pressure) during a series of developmentally challenging tasks. Environmental stress was evaluated with two measures of stressors in the childcare setting. The incidence of respiratory illnesses was ascertained over 6 months using weekly respiratory tract examinations by a nurse. In Study 2, 99 5-year-old children were assessed for immune reactivity (changes in CD4+, CD8+, and CD19+ cell numbers, lymphocyte mitogenesis, and antibody response to pneumococcal vaccine) during the normative stressor of entering school. Blood for immune measures was sampled 1 week before and after kindergarten entry. Environmental stress was indexed with parent reports of family stressors, and a 12-week respiratory illness incidence was measured with biweekly, parent-completed symptom checklists. The two studies produced remarkably similar findings. Although environmental stress was not independently associated with respiratory illnesses in either study, the incidence of illness was related to an interaction between childcare stress and mean arterial pressure reactivity (beta =.35, p <.05) in Study 1 and to an interaction between stressful life events and CD19+ reactivity (beta =.51, p <.05) in Study 2. In both studies, reactive children sustained higher illness rates under high-stress conditions, but lower rates in low-stress conditions, compared with less reactive peers. Stress was associated with increased rates of illnesses, but only among psychobiologically reactive children. Less reactive children experienced no escalation in illness incidence under stressful conditions, suggesting that only a subset of individuals may be susceptible to the health-altering effects of stressors and adversity.

Socioeconomic disparities affect prefrontal function in children

Social inequalities have profound effects on the physical and mental health of children. Children from low socioeconomic status (SES) backgrounds perform below children from higher SES backgrounds on tests of intelligence and academic achievement, and recent findings indicate that low SES (LSES) children are impaired on behavioral measures of prefrontal function. However, the influence of socioeconomic disparity on direct measures of neural activity is unknown. Here, we provide electrophysiological evidence indicating that prefrontal function is altered in LSES children. We found that prefrontal-dependent electrophysiological measures of attention were reduced in LSES compared to high SES (HSES) children in a pattern similar to that observed in patients with lateral prefrontal cortex (PFC) damage. These findings provide neurophysiological evidence that social inequalities are associated with alterations in PFC function in LSES children. There are a number of factors associated with LSES rearing conditions that may have contributed to these results such as greater levels of stress and lack of access to cognitively stimulating materials and experiences. Targeting specific prefrontal processes affected by socioeconomic disparity could be helpful in developing intervention programs for LSES children.

Associations between physiological reactivity and children's behavior: advantages of a multisystem approach.

ABSTRACT. The past decade has seen a notable increase in interest in and research concerning the physiological correlates of behavior problems in childhood. The present article reviews what this growing body of research has revealed. The main tenet is that disruptions in both sympathetic and adrenocortical regulation appear to be common among children with internalizing and externalizing behavior problems. The associations between such neuroendocrine alterations and behavior are discussed and their implications for the fields of stress physiology, neuroendocrinology, and developmental psychopathology are outlined. It is proposed that substantial advances can be made by investigating patterns of physiological responses among multiple, concurrent systems rather than individual response systems.

Family Socioeconomic Status and Child Executive Functions: The Roles of Language, Home Environment, and Single Parenthood

The association between family socioeconomic status (SES) and child executive functions is well-documented. However, few studies have examined the role of potential mediators and moderators. We studied the independent and interactive associations between family SES and single parenthood to predict child executive functions of inhibitory control, cognitive flexibility, and working memory and examined child expressive language abilities and family home environment as potential mediators of these associations. Sixty families from diverse SES backgrounds with a school-age target child (mean [SD] age = 9.9 [0.96] years) were evaluated. Child executive functioning was measured using a brief battery. The quality of the home environment was evaluated using the Home Observation for the Measurement of the Environment inventory. Family SES predicted the three child executive functions under study. Single parent and family SES were interactively associated with childrens inhibitory control and cognitive flexibility; such that children from low SES families who were living with one parent performed less well on executive function tests than children from similarly low SES who were living with two parents. Parental responsivity, enrichment activities and family companionship mediated the association between family SES and child inhibitory control and working memory. This study demonstrates that family SES inequalities are associated with inequalities in home environments and with inequalities in child executive functions. The impact of these disparities as they unfold in the lives of typically developing children merits further investigation and understanding.