Clyde Hertzman

The Biological Embedding of Early Experience and Its Effects on Health in Adulthood

Abstract: Explanations of the socioeconomic gradient in health status must account for the observations that the gradient cuts across a wide range of disease processes and is capable of replicating itself on new disease processes as they emerge in society. Understanding this pattern requires an understanding of how human organisms can become generally vulnerable or resilient to disease over time: a huge collation task across different disciplines. The hypothesis that best fits current evidence is that the gradient is an “emergent property” of the interaction between the developmental status of people and the material and psychosocial conditions they encounter over their life course. Within this broad formulation, special attention is given to child development, and the prospect that socioeconomic differences in the quality of early life experiences contribute to subsequent gradients in health status through socioeconomic differences in brain sculpting and the conditioning of host defense systems that depend on communication with the developing brain. The contribution to the gradient in health is theorized to occur through a combination of latent effects, pathway effects, and cumulative disadvantage.

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.

Socioeconomic factors, perceived control and self-reported health in Russia. A cross-sectional survey

Russia has the lowest life expectancy among industrialised countries, but little is known about other health outcomes and determinants of health in the Russian population. Here we report a cross-sectional study in a national sample of the Russian population of social and psychosocial determinants of two self-reported health indicators: self-rated health (shown to predict mortality in prospective studies) and physical functioning (validated against more objective health measures). A multi-stage sample of the Russian population aged 18 years and more was interviewed (n=1599, response rate 66%). The questionnaire included political attitudes, social and economic circumstances, psychosocial factors, smoking, alcohol consumption, self-rated health and physical functioning (from the SF36 instrument). Scores of perceived control over life and over ones health were calculated from 6 and 3 questions, respectively. Data were analysed in logistic regression for two dichotomised outcomes: poor self-rated health (worse than average) and low physical functioning (less than 60% of maximum). Overall, 25% of subjects rated their health as worse than average; this is substantially more than in western countries. Perceived control over life was strongly related to both outcomes; age- and sex-adjusted OR for 1 standard deviation increase in control were 0.60 (95% CI 0.52-0.69) for poor self-rated health and 0.67 (0.57-0.81) for low physical functioning. Adjustment for a battery of other factors reduced these estimates only slightly. Associations between control over ones health and both outcomes were also significant, but weaker and attenuated in multivariate models. Material deprivation was also strongly related to both outcomes. Education was inversely related to self-rated health, and unmarried men reported poor physical functioning substantially more often. Subjects not approving the economic changes reported poorer health but this association was removed by adjustment for socioeconomic factors and control. Subjects who could not rely on informal social structures when in problems reported worse health; this effect largely persisted in multivariate analyses. These results are consistent with the hypothesis that poor health status in Russia is related to dysfunction of social structures, socioeconomic deprivation, and lack of perceived control. The absence of informal social networks, vital for maintaining general welfare, seems to affect adversely self-rated health. Deprivation and low perceived control may be important mediators between the broad social environment and health in populations undergoing transition and can provide a useful framework for many biological and behavioural factors. Prospective studies are needed to address the issue of temporality and reporting bias, the major problems in interpreting these findings.

Associations with early-life socio-economic position in adult DNA methylation

BACKGROUND Disadvantaged socio-economic position (SEP) in childhood is associated with increased adult mortality and morbidity. We aimed to establish whether childhood SEP was associated with differential methylation of adult DNA. METHODS Forty adult males from the 1958 British Birth Cohort Study were selected from SEP extremes in both early childhood and mid-adulthood. We performed genome-wide methylation analysis on blood DNA taken at 45 years using MeDIP (methylated DNA immunoprecipitation). We mapped in triplicate the methylation state of promoters of approximately 20,000 genes and 400 microRNAs. Probe methylation scores were averaged across triplicates and differential methylation between groups of individuals was determined. Differentially methylated promoter sites of selected genes were validated using pyrosequencing of bisulfite-converted DNA. RESULTS Variably methylated probes (9112 from n = 223,359 on the microarray) corresponded to 6176 gene promoters with at least one variable probe. Unsupervised hierarchical clustering of probes obtained from the 500 most variable promoters revealed a cluster enriched with high SEP individuals confirming that SEP differences contribute to overall epigenetic variation. Methylation levels for 1252 gene promoters were associated with childhood SEP vs 545 promoters for adulthood SEP. Functionally, associations with childhood SEP appear in promoters of genes enriched in key cell signalling pathways. The differentially methylated promoters associated with SEP cluster in megabase-sized regions of the genome. CONCLUSIONS Adult blood DNA methylation profiles show more associations with childhood SEP than adult SEP. Organization of these associations across the genome suggests a well-defined epigenetic pattern linked to early socio-economic environment.

Birth weight, childhood socioeconomic environment, and cognitive development in the 1958 British birth cohort study.

abstract Objectives: To examine the combined effect of social class and weight at birth on cognitive trajectories during school age and the associations between birth weight and educational outcomes through to 33 years. Design: Longitudinal, population based, birth cohort study. Participants: 10 845 males and females born during 3-9 March 1958 with information on birth weight, social class, and cognitive tests. Main outcome measures: Reading, maths, draw a man, copying designs, verbal and non-verbal ability tests at ages 7, 11, and 16, highest qualifications achieved by 33, and trajectories of maths standardised scores at 7-16 years. Results: The outcome of all childhood cognitive tests and educational achievements improved significantly with increasing birth weight. Analysis of maths scores at 7 and of highest qualifications achieved by 33 showed that the relations were robust to adjustment for potential confounding factors. For each kilogram increase in birth weight, maths z score increased by 0.17 (adjusted estimate 0.15, 95% confidence interval 0.10 to 0.21) for males and 0.21 (0.20, 0.14 to 0.25) for females. Trajectories of maths z scores between 7 and 16 years diverged for different social class groups: participants from classes I and II increased their relative position on the score with increasing age, whereas classes IV and V showed a relative decline with increasing age. Birth weight explained much less of the variation in cognition than did social class (range 0.5-1.5% v 2.9-12.5%). Conclusions: The postnatal environment has an overwhelming influence on cognitive function through to early adulthood, but these strong effects do not explain the weaker but independent association with birth weight.

Child development and long-term outcomes: A population health perspective and summary of successful interventions.

Studies of socioeconomic gradients in mortality in wealthy societies reveal that they have been persist, and included most of the principal causes of death, even during the era when these principal causes of death have entirely changed. This observation has led to an interest in the ways in which the diversity of conditions of life, unfolding over the life cycle, can become embedded in human biology and subsequently affect health status and vitality. There is evidence that childhood experiences affect subsequent health status (as well as well-being and competence) in profound and long-lasting ways. Conflicting explanatory models of the impact of childhood experiences have been advanced, whose conflicts are political in nature, in that the reflect divergent beliefs about how human potential expresses itself, and, also, about the nature of the obligations which members of society have to one another. Notwithstanding these conflicts, a body of evidence derived from intervention studies in the post-neonatal, preschool, and school age periods suggest that performance in two basic domains of child development, the cognitive and the social-emotional, can be modified in ways which improve health, well-being, and competence in the long-term.

Using an interactive framework of society and lifecourse to explain self-rated health in early adulthood.

This paper presents an integrated model of the determinants of adult health combining lifecourse factors and contemporary circumstances. Using the 1958 British Birth Cohort, it operationalises lifecourse influences in terms of factors from birth to age 33, which might act through latent, pathway, or cumulative effects. Contemporary circumstances are represented by variables at different levels of social aggregation: macro (socio-economic circumstances); meso (involvement in civil society functions); micro (personal social support); and intersecting (job insecurity and life control). Multiple regression models were fitted, using self-rated health at age 33 as the health outcome. To allow for temporal ordering of events, early life factors were entered first in the final model, followed by later childhood factors and, finally current factors. Self-rated health was predicted by variables representing both early and later stage of the lifecourse and also contemporary societal-level factors. The effects of childhood factors were not removed by including contemporary factors, and conversely, contemporary factors contributed to the prediction of self-rated health over and above lifecourse factors. The factors were not collinear; supporting the notion that each dimension was distinct from the others. Although the model accounted for only 9% of the variance in self-rated health, the general conclusion is that both lifecourse and contemporary circumstances should be considered together in explaining adult health.

Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population‐based health data

BACKGROUND To determine a population-based incidence of congenital anomalies following prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants used alone and in combination with a benzodiazepines (BZ). METHODS Population health data, maternal health, and prenatal prescription records were linked to neonatal records, representing all live births (British Columbia, Canada, N=119,547) during a 39-month period (1998-2001). The incidence and risk differences (RD) for major congenital anomalies (CA) and congenital heart disease (CHD), including ventricular and atrial septal defects (VSD, ASD), from infants of mothers treated with an SRI alone, a benzodiazepine (BZ) alone, or SRI+BZ in combinationcompared to outcomesno exposure. RESULTS Risk for a CA or CHD did increase following combined SRI+BZ exposure compared with no exposure. However, using a weighted regression model, controlling for maternal illness characteristics, combination therapy risk remained significantly associated only with CHD. The risk for an ASD was higher following SRI monotherapy compared with no exposure, after adjustment for maternal covariates. Dose/day was not associated with increased risk. CONCLUSIONS Infants exposed to prenatal SRIs in combination with BZs had a higher a incidence of CHD compared to no exposure, even after controlling for maternal illness characteristics. SRI monotherapy was not associated with an increased risk for major CA, but was associated with an increased incidence of ASD. Risk was not associated with first trimester medication dose/day.

Predictors of Low Back Pain Onset in a Prospective British Study

OBJECTIVES This study examined predictors of low back pain onset in a British birth cohort. METHODS Univariate and multivariate analyses focused on individuals who experienced onset of low back pain at 32 to 33 years of age (n= 571) and individuals who were pain free (n = 5210). Participants were members of the 1958 British birth cohort. RESULTS Incident pain was elevated among those with psychological distress at 23 years of age (adjusted odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.65, 3.86) and among persistent moderate or heavy smokers (adjusted OR = 1.63, 95% CI = 1.23, 2.17). Significant univariate associations involving other factors (e.g., social class, childhood emotional status, body mass index, job satisfaction) did not persist in multivariate analyses. CONCLUSIONS This prospectively studied cohort provides evidence that psychological distress more than doubles later risk of low back pain, with smoking having a modest independent effect. Other prospective studies are needed to confirm these findings before implications for low back pain prevention can be assessed.

Children's Event-Related Potentials of Auditory Selective Attention Vary With Their Socioeconomic Status

Past research suggests a link between socioeconomic status (SES) and brain processes in children, but direct evidence from neuroimaging is scarce. The authors investigated the relationships among SES, performance, and the neural correlates of auditory selective attention, by comparing event-related potentials (ERPs) in lower- and higher-SES preadolescent children during a task in which they attended to two types of pure tones but ignored two other types. Our hypothesis was that, at comparable performance levels, higher-SES children ignore distracters (the unattended, irrelevant tones) while lower-SES children attend equally to distracters and to targets (the attended, relevant tones). The authors found that ERP waveform differences between attended and unattended tones (Nd, difference negativity) were significant in the higher-SES but not in the lower-SES group. However, the groups did not differ in reaction times or accuracy. Electroencephalographic power analysis revealed a differential pattern of theta activity concomitant with irrelevant tones for the two groups, indicating that although they performed similarly the children from these groups recruited different neural processes. Lower-SES children, the authors suggest, deployed supplementary resources to also attend to irrelevant information.