Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood.

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.

Putting the concept of biological embedding in historical perspective.

This paper describes evidence that led to the concept of biological embedding and research approaches designed to elucidates its mechanisms. Biological embedding occurs when experience gets under the skin and alters human biological and developmental processes; when systematic differences in experience in different social environments in society lead to systematically different biological and developmental states; when these differences are stable and long term; and, finally, when they have the capacity to influence health, well-being, learning, or behavior over the life course. Biological embedding emerged from insights in population health on the unique characteristics of socioeconomic gradients: Ubiquity in poor and postscarcity societies alike; gradient seen regardless of whether socioeconomic status is measured by income, education, or occupation; cutting widely across health, well-being, learning, and behavior outcomes; replicating itself on new conditions entering society; and, often, showing that flatter gradients mean better overall societal outcomes. Most important, the gradient begins the life course as a gradient in developmental health, suggesting that the emergence of a multifaceted resilience/vulnerability early in life is the best place to look for evidence of biological embedding. To understand its character, the metaphor of the "archeology of biological embedding" has been used, wherein the surficial stratum of the "dig" is experience and behavior, the shallow stratum is organ system and cellular function, and the deep stratum is gene function. We are now ready to address the fundamental question of biological embedding: How do early childhood environments work together with genetic variation and epigenetic regulation to generate gradients in health and human development across the life course?

Commentary on the symposium: biological embedding, life course development, and the emergence of a new science.

A new science of human development is emerging, which has the capacity to transform the way we understand the origins of health and disease; to increase the public health significance of early child development; and to call into question how and when society should act on a range of health problems. It builds on the multidisciplinary evidence that social environments and experiences during sensitive periods in brain and biological development affect health for the balance of the life course through a process called biological embedding. Despite the fact that biological embedding has established credibility in the scientific literature, the transformative power of the new science has yet to be fully realized in policy and practice. To further this transformation, this symposium offers a public health perspective on biological embedding.

Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence.

Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children's early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children's gender. To the authors' knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents' genomic DNA.

A comparative study of population health in the United States and Canada during the neoliberal era, 1980-2008.

This article draws on the vast evidence that suggests, on one hand, that socioeconomic inequalities in health are present in every society in which they have been measured and, on the other hand, that the size of inequalities varies substantially across societies. We conduct a comparative case study of the United States and Canada to explore the role of neoliberalism as a force that has created inequalities in socioeconomic resources (and thus in health) in both societies and the roles of other societal forces (political, economic, and social) that have provided a buffer, thereby lessening socioeconomic inequalities or their effects on health. Our findings suggest that, from 1980 to 2008, while both the United States and Canada underwent significant neoliberal reforms, Canada showed more resilience in terms of health inequalities as a result of differences in: (a) the degree of income inequality, itself resulting from differences in features of the labor market and tax and transfer policies, (b) equality in the provision of social goods such as health care and education, and (c) the extent of social cohesiveness across race/ethnic- and class-based groups. Our study suggests that further attention must be given to both causes and buffers of health inequalities.

How society shapes the health gradient: work-related health inequalities in a comparative perspective.

Analyses in comparative political economy have the potential to contribute to understanding health inequalities within and between societies. This article uses a varieties of capitalism approach that groups high-income countries into coordinated market economies (CME) and liberal market economies (LME) with different labor market institutions and degrees of employment and unemployment protection that may give rise to or mediate work-related health inequalities. We illustrate this approach by presenting two longitudinal comparative studies of unemployment and health in Germany and the United States, an archetypical CME and LME. We find large differences in the relationship between unemployment and health across labor-market and institutional contexts, and these also vary by educational status. Unemployed Americans, especially of low education or not in receipt of unemployment benefits, have the poorest health outcomes. We argue for the development of a broader comparative research agenda on work-related health inequalities that incorporates life course perspectives.

Childhood psychosocial adversity and adult cortisol patterns.

BACKGROUND: Cortisol levels may be altered in childhood in association with maltreatment (neglect, abuse and witnessing abuse) and other adversities, yet little is known about whether effects on cortisol persist into later life. AIMS: To establish whether childhood psychosocial adversities predict cortisol levels in mid-adulthood. METHOD: Childhood psychosocial adversities were ascertained in the 1958 British birth cohort and cortisol was measured in two saliva samples, one 45 min after awaking (T(1)) and the other 3 h later the same day (T(2)), from 6524 participants aged 45 years. RESULTS: No association was seen for abuse or household dysfunction in childhood and adult cortisol levels. In women but not men, T(1) cortisol was lowered by 7.9% per unit increase in childhood neglect score (range 0-3); T(1) to T(2) cortisol decline was less steep. High levels of maltreatment (abuse, neglect, witnessed abuse) were associated with >25% lower T(1) cortisol in both men and women, and 24% higher T(2) cortisol for men after adjustment for concurrent depressive/anxiety symptoms. CONCLUSIONS: In a non-clinical population, cumulative maltreatments in childhood were associated with flattened morning cortisol secretion in mid-adult life.

Unemployment and mortality: a comparative study of Germany and the United States.

OBJECTIVES: We examined the relationship between unemployment and mortality in Germany, a coordinated market economy, and the United States, a liberal market economy. METHODS: We followed 2 working-age cohorts from the German Socio-economic Panel and the US Panel Study of Income Dynamics from 1984 to 2005. We defined unemployment as unemployed at the time of survey. We used discrete-time survival analysis, adjusting for potential confounders. RESULTS: There was an unemployment-mortality association among Americans (relative risk [RR]=2.4; 95% confidence interval [CI]=1.7, 3.4), but not among Germans (RR=1.4; 95% CI=1.0, 2.0). In education-stratified models, there was an association among minimum-skilled (RR=2.6; 95% CI=1.4, 4.7) and medium-skilled (RR=2.4; 95% CI=1.5, 3.8) Americans, but not among minimum- and medium-skilled Germans. There was no association among high-skilled Americans, but an association among high-skilled Germans (RR=3.0; 95% CI=1.3, 7.0), although this was limited to those educated in East Germany. Minimum- and medium-skilled unemployed Americans had the highest absolute risks of dying. CONCLUSIONS: The higher risk of dying for minimum- and medium-skilled unemployed Americans, not found among Germans, suggests that the unemployment-mortality relationship may be mediated by the institutional and economic environment.

Prevalence and frequency of mental health care provided by general practitioners: differences between 2 national data sources for the same population.

OBJECTIVE: Estimates from Canada's first national mental health surveillance initiative-which is based on diagnostic codes in administrative health care utilization databases-indicate that the proportion of Canadians who receive mental health care is more than twice as high as reported in Canada's national mental health survey. Our study examines and clarifies the nature and extent of differences between 2 predominant types of data that are used for mental health services research and planning. METHOD: A person-by-person data linkage was conducted between the Canadian Community Health Survey: Mental Health and Well-Being and administrative health care utilization records (British Columbia Ministry of Health Services-Medical Services Plan, and Hospital Discharge Abstract Database) within a universal-access, publically funded health care system, to examine the level of agreement between the data sources and respondent characteristics associated with agreement (N = 2378). RESULTS: The prevalence of mental health care from general practitioners (GPs) was higher in administrative data (19.3%; 95% CI 17.7% to 20.9%) than survey data (8.5%; 95% CI 7.5% to 9.8%). Agreement between prevalence estimates from the 2 data sources was associated with age, mental health characteristics, and the number of GP visits. The median number of visits per person was significantly higher in the survey data. CONCLUSIONS: GPs saw more than twice as many patients for mental health issues according to administrative data, compared with survey data; however, the number of visits per patient was higher in survey data.

How experience gets under the skin to create gradients in developmental health.

Social environments and experiences get under the skin early in life in ways that affect the course of human development. Because most factors associated with early child development are a function of socio-economic status, differences in early child development form a socio-economic gradient. We are now learning how, when, and by what means early experiences influence key biological systems over the long term to produce gradients: a process known as biological embedding. Opportunities for biological embedding are tethered closely to sensitive periods in the development of neural circuitry. Epigenetic regulation is the best example of operating principles relevant to biological embedding. We are now in a position to ask how early childhood environments work together with genetic variation and epigenetic regulation to generate socially partitioned developmental trajectories with impact on health across the life course.

The social determinants of early child development: an overview.

AIM: This paper offers an overview of the current state of knowledge of the critical social determinants of child development and the complex ways in which these can influence health trajectories. METHODS: We conducted an overview of the research conducted by medical and social scientists in the attempt to uncover the conditions under which children reach optimal health and developmental. RESULTS: The first years of life represent a critical period during which trajectories of health vulnerability are determined by the complex interplay between biological, genetic, and environmental conditions. CONCLUSIONS: There are fundamental principles of optimal child development that apply to all human beings, regardless of language and culture.

Why are some books important (and others not)?

The book Why Are Some People Healthy and Others Not? The Determinants of Health of Populations represented a milestone in our evolving understanding of the determinants of population health. Building on Marc Lalonde's earlier A New Perspective on the Health of Canadians, it created a theoretical framework that could incorporate emerging evidence from a wide range of disciplines. Central to its authors' approach was the observation of heterogeneity, of the systematic differences in health observed when populations are partitioned on characteristics such as income, education, geographic region, etc. The universal observation of a social gradient, of a strong correlation between socio-economic class and health, led to a focus on how the social environment might influence health. Social position strongly influences both the stresses to which individuals are subject, and the resources available to cope with them. Furthermore, healthy and unhealthy responses to stress become "embedded", learned or conditioned both behaviourally and biologically, thus influencing health over the whole life course. The book's impact has been remarkable, not merely in academic citations but through its authors' subsequent work and strategic positions in Canadian health research organizations. The concept of "Population Health" has become part of our shared intellectual heritage.

The economic costs of early vulnerability in Canada.

OBJECTIVE: The study estimates the economic costs of early vulnerability in the light of population-level data showing that between 25% and 30% of Canadian children do not arrive at kindergarten meeting all of the developmental benchmarks they need to thrive both now and into the future. METHODS: The study examines Early Development Instrument (EDI) data across Canada as of 2008/09, and across time within British Columbia since 2001. We then link the BC EDI data with school achievement results on standardized tests in grades four and seven, along with graduation records and criminal justice information. RESULTS: The result is a synthetic cohort with which we can simulate the impact on economic growth of reducing early vulnerability in BC from its current rate of 29% to 10%, a threshold above which child vulnerability is biologically unnecessary. DISCUSSION: Nearly three times what it should be, a rate of early vulnerability that approaches 30% signals that the country now tolerates an unnecessary brain drain that will dramatically deplete our future stock of human capital. Economic analyses reveal that this depletion will cause Canada to forgo 20% in GDP (gross domestic product) growth over the next 60 years. The economic value of this loss is equivalent to investing $2.2 trillion to $3.4 trillion today at a rate of 3.5% interest, even after paying for the social investment required to reduce vulnerability.

Mental health differences among middle-aged sawmill workers in rural compared to urban British Columbia.

The study sought to determine whether differences in mental health outcomes were observable in a cohort of workers living in rural compared to urban places in the Canadian province of British Columbia. The study was based on a cohort of male sawmill workers. The cohort was probabilistically linked to the BC Linked Health Database in order to yield objective mental health outcomes. A nested case control design was used. Univariate and multivariate models were constructed using conditional logistic regression. While results differed according to the particular mental health outcome, after controlling for socio-economic confounders it was found that workers who remained in or migrated to rural places tended to have better mental health outcomes than workers who remained in or migrated to urban places.

Social geography of developmental health in the early years.

What happens to children in their earliest years is critical for their development throughout the life course. The years from zero to school age are foundational for brain and biological development. Attachment and face recognition; impulse control and regulation of physical aggression; executive function in the prefrontal cortex and focused attention; fine and gross motor functions and coordination; receptive and expressive language; and understandings of quantitative concepts are all established during this time and become embedded in the architecture and function of the brain (Doherty 1997; Kolb 2009; McCain and Mustard 1999). Brain and biological development are in turn expressed through three broad domains of development of the whole child: physical, social-emotional and language-cognitive, which together are the basis of "developmental health" (Keating and Hertzman 1999). Developmental health influences many aspects of well-being, including obesity and stunting, mental health, heart disease, competence in literacy and numeracy, criminality and economic participation throughout life (Irwin et al. 2007). Accordingly, developmental health is the central concern of this article.

From Kindergarten readiness to fourth-grade assessment: longitudinal analysis with linked population data.

Early child development (ECD)--the development of physical, social-emotional, and language-cognitive capacities in the early years--is a foundation of health, well-being, learning, and behaviour across the life course. Consequently, the capacity to monitor ECD is an important facet of a modern society. This capacity is achieved by having in place an ongoing flow of high-quality information on the state of early child development, its determinants, and long-term developmental outcomes. Accordingly, there remains a considerable need for research that merges community-centred, longitudinal, and linked-data approaches to monitoring child development. The current paper addresses this need by introducing one method of summarising and quantifying the developmental trajectories of British Columbian children at the neighbourhood- or district-level: computing the Community Index of Child Development (CICD) for each geographic area. A simple index that describes change in children's developmental trajectories at the aggregate level, the CICD is computable because of our capacity to conduct individual-level linkage of two population data sets: the Early Development Instrument (EDI), a holistic measure of children's readiness for school which is administered at Kindergarten, and the British Columbia Ministry of Education's Foundation Skills Assessment (FSA), a Grade 4 measure of academic skills. In this paper, we demonstrate: (a) wide variation in the CICDs according to the children's district of residence in Kindergarten; (b) an association of the CICDs with an indicator of the socioeconomic character of the neighbourhoods; and (c) contrasting patterns of neighbourhood convergence and divergence in two different school districts--such that, in some areas, children from high vulnerability neighbourhoods tend to catch up between Kindergarten and Grade 4 whereas, in other areas, they tend to fall further behind.

A case control study of differences in non-work injury and accidents among sawmill workers in rural compared to urban British Columbia, Canada.

BACKGROUND: Using a cohort of British Columbian male sawmill workers, we conducted a nested case-control study of the impact of rural compared to urban residence as well as rural/urban migration patterns in relation to hospitalization for non-work injury. We postulate that for many types of non-work injuries, rates will be higher in rural communities than in urban ones and that rates will also be higher for workers who migrate from urban to rural communities. METHODS: Using conditional logistic regression, univariate models were first run with each of five non-work injury outcomes. These outcomes were hospitalizations due to assault, accidental poisoning, medical mis-adventure, motor vehicle trauma, and other non-work injuries. In multivariate models marital status, ethnicity, duration of employment, and occupation were forced into the model and associations with urban, compared to rural, residence and various urban/migration patterns were tested. RESULTS: Urban or rural residence and migration status from urban to other communities, and across rural communities, were not associated with hospitalization for medical misadventure, assault, or accidental poisoning. The likelihood of a rural resident being hospitalized for motor vehicle trauma is higher than for an urban resident. The likelihood that a rural resident is hospitalized for "other" non-work injury is higher than for an urban resident. CONCLUSION: In a relatively homogenous group of workers, and using a rigorous study design, we have demonstrated that the odds of other non-work injury are much higher for workers resident in and migrating to rural regions of Canada than they are for workers resident in or migrating to urban places.

Regions, hospitals and health outcomes over time: A multi-level analysis of repeat prevalence among a cohort of health-care workers.

BACKGROUND: The relative importance of region, workplace, and individual determinants of health burden is debated. OBJECTIVE: To model the contribution of hospital characteristics to employee mental and musculoskeletal disorders. METHODS: We linked employment records of nurses and support services' staff with health records, neighbourhood census, and hospital administrative data. We conducted multi-level logistic regression analyses with three levels: year (I), employee characteristics (II), and hospital characteristics (III). RESULTS: Northern region hospitals experienced lower disorder prevalences (odds ratios (OR) 0.58, 95% confidence intervals (0.40, 0.82) for mental and 0.56 (0.44, 0.73) for musculoskeletal disorders). Hospitals with yearly workloads of the highest versus lowest quintiles of inpatient days/1000 employee hours (>86.0 vs. <42.6) and surgical cases/1000 employee hours (>10.5 vs. <3.9) had greater odds of mental (1.29 (1.05, 1.57); 1.22 (1.05, 1.42)) and musculoskeletal (1.38 (1.21, 1.58); 1.21 (1.09, 1.34)) disorders. CONCLUSION: Opportunities exist for reduction in burden with hospital workload reduction. Further exploration of regional effects is needed.

Cognitive development and cortisol patterns in mid-life: findings from a British birth cohort.

Life-course associations among cortisol, cognitive development and educational attainment in the general population are not well understood. Using the 1958 British birth cohort, our aim was to establish whether cortisol patterns at age 45y are associated with childhood cognition and qualification level by adulthood. We measured salivary cortisol in 6527 individuals, 45min after waking (t(1)) and 3h later (t(2)). To identify lack of morning cortisol peak and diurnal rhythm, we defined groups with: (a) t(1) cortisol in the bottom 5% of the distribution, or (b) 'flat't(1)-t(2) cortisol. Data on cognitive tests at ages 7, 11 and 16y and educational level were used. All childhood cognitive tests (maths, reading, verbal and non-verbal ability) were inversely associated, although not always significantly, with low t(1) and flat t(1)-t(2) cortisol. For example, at age 11 for males, a standard deviation (SD) increase in maths score was associated with a 28% decreased odds for lowest t(1) cortisol, and with a 13% decreased odds of flat t(1)-t(2) cortisol. Associations for lowest t(1) and flat t(1)-t(2) cortisol were attenuated after adjustment for qualification level at 33y among males, although adjustment for childhood socio-economic position had little effect. Weaker associations for lowest t(1) cortisol among females were either unchanged or strengthened after adjustment for qualification level. Our results for males, but less so for females, are compatible with a causal relationship in either direction, namely from cortisol to cognitive ability or vice versa.