1. Early Human Development as a Social Determinant of Health Clyde Hertzman

2. Gradient in all Cause Mortality: UK Whitehall Study

3. CHD Mortality - UK Whitehall Study

4. The Challenge of the Gradient ubiquitous in wealthy and majority world countries by income, education, or occupation cuts across a wide range of disease processes not explained by traditional risk factors replicates itself on new conditions as they emerge occurs among males and females ‘flattens up’ begins life as gradient in ‘developmental health’

5. Canada: % vulnerable by SES Source: NLSCY/UEY 1999-2000; EDI 1999-2000 % Vulnerable

6. Sensitive Periods in Early Brain DevelopmentVision 0 1237654 High Low Years Habitual ways of responding Emotional control Symbol Peer social skills Numbers Hearing Graph developed by Council for Early Child Development (ref: Nash, 1997; Early Years Study, 1999; Shonkoff, 2000.) Pre-school yearsSchool years Language

7. What Influences Early Child Development?

8. The experiences children have in the environments where they grow up, live and learn.

10. Life Course Problems Related to Early Life 2 nd Decade 3 rd /4 th Decade 5 th /6 th Decade Old Age School Failure Teen Pregnancy Criminality Obesity Elevated Blood Pressure Depression Coronary Heart Disease Diabetes Premature Aging Memory Loss

11. Two responses understanding ECD at the level of the population understanding the developmental biology of the gradient

12. Early Development Instrument 104 items Extensive validity and reliability data from several countries Not a test Teacher at age 5 is respondent Five developmental domains, with sixteen subdomains A guide with explanations available

13. What Does the EDI Measure?

14. EDI is: -a population-based tool -a mobilisation tool -a monitoring tool EDI is not: -an individual assessment -a prescription for action -perfect

21. What the maps reveal… Large local area differences in the proportion of developmentally vulnerable children The high proportion of avoidable vulnerability The degree to which socioeconomic context explains and does not explain variations in early development Which communities are doing better or worse than predicted…….to set up the study of ‘why’ Change over time Rationale for programs and policies

22. Two responses understanding ECD at the level of the population understanding the developmental biology of the gradient

23. Biological embedding occurs when experience gets under the skin and alters human biodevelopment; systematic differences in experience in different social environments lead to different biodevelopmental states; the differences are stable and long-term; they influence health, well-being, learning, and/or behaviour over the life course. Hypothesis: Biological embedding

24. Archeology of Biological Embedding Experience/BehaviorExperience/Behavior Gene Expression Cell/SynapseCell/Synapse Neural Circuitry

25. Shallow Archeology Candidate Systems HPA axis --- cortisol ANS system --- epinephrine/ne Prefrontal cortex Social affiliation --- amygdala/locus cereleus Immune function -- the ‘peripheral brain’

26. Candidate System: Prefrontal Cortex SES Differences by School Age

27. Deep Archeology ‘Social Epigenesis’ and other processes that can influence gene expression.

28. Biological Embedding: The ‘Meaney- Szyf Paradigm’ rat pups from high and low licking/suckling mothers cross-fostered to remove genetic effect differential qualities of nurturance occurs during sensitive period of brain development differential nurturance leads to epigenetic modification of key DNA regulatory loci through methylation

29. The ‘Meaney-Szyf Paradigm’ (cont’d) epigenetic modification leads to lifelong change in HPA axis response to stress this change affects learning and behaviour across the rat life course inter-generational transmission (high licked female pups become high licking mothers, and vice versa)

30. The Scenario If early experience really does ‘get under the skin’ to influence brain and biological development through epigenetic processes, then: similar environments & experiences should leave a consistent set of epigenetic ‘marks’ on different populations, and/or create great opportunities for understanding gene-environment-epigenetic interplay. the variation in epigenetic marks in children from diverse environments (& experiences) globally should teach us a great deal about biological embedding.

31. SES, Life Course and Epigenesis: An Hypothesis Generating Study The opportunity: a large birth cohort (>17,000 at birth), with >4000 phenotypic variables collected at birth and 7 follow-ups, with fresh lymphocytes collected at age 45. The goal: to identify a full range of gene loci where experience may have become ‘biologically embedded’ through methylation. Done to date: examined >20,000 regulatory regions of 40 cohort members, sampled according to a factorial design, based upon extremes of SES in childhood and adulthood.

32. So far: 1252 loci differentially methylated according to childhood SES Approx. 4000 loci differentially methylated according to retrospective reports of abuse in childhood

33. Mid- Brain affiliation/attachment PFC executive function/ impulsivity HPA stress response Abuse Chronic diseases Health behaviors Mental health Epigenome ExposureEndophenotypePhenotype Hypothetical Patterns of Influence

34. ExposureEpigenomeBiochemical /Biophysical Pathway Phenotype (Prenatal) Maternal Smoking Childhood Abuse Childhood SES Exposure Specific Pathways Common Pathways Exposure Specific Pathways Outcome(s)

35. Where to from there? The Wisconsin Study of Families and Work The BC GECKO Study: ‘On and Off-diagonal children’ in ‘On and Off-diagonal neighbourhoods’ Developing country studies

36. www.earlylearning.ubc.ca