early human development as a social determinant of health clyde hertzman
TRANSCRIPT
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Early Human Development as a Social Determinant of Health
Clyde Hertzman
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Gradient in all Cause Mortality: UK Whitehall Study
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CHD Mortality - UK Whitehall Study
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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’
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Canada: % vulnerable by SES
Source: NLSCY/UEY 1999-2000; EDI 1999-2000
% V
ulne
rabl
e
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Sensitive Periods in Early Brain Development
VisionVision
0 1 2 3 7654
High
Low
Years
Habitual ways of Habitual ways of respondingrespondingEmotional Emotional
controlcontrol
SymboSymboll
Peer social skillsPeer social skillsNumbersNumbers
HearingHearing
Graph developed by Council for Early Child Development (ref: Nash, 1997; Early Years Study, 1999; Shonkoff, 2000.)
Pre-school years School years
LanguaLanguagege
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What Influences Early Child Development?
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The experienceschildren have in
the environmentswhere they grow up, live
and learn.
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Life Course Problems Related to Early Life
2nd Decade
3rd/4th Decade
5th/6th
DecadeOld Age
• School Failure
• Teen Pregnancy
• Criminality
• Obesity
• Elevated BloodPressure
• Depression
• Coronary Heart Disease
• Diabetes
• Premature Aging
• Memory Loss
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Two responses
• understanding ECD at the level of the population
• understanding the developmental biology of the gradient
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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
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What Does the EDI Measure?
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EDI is:-a population-based tool -a mobilisation tool-a monitoring tool
EDI is not:-an individual assessment-a prescription for action-perfect
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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
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Two responses
• understanding ECD at the level of the population
• understanding the developmental biology of the gradient
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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
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Archeology of Biological EmbeddingArcheology of Biological EmbeddingArcheology of Biological EmbeddingArcheology of Biological Embedding
Experience/BehaviorExperience/BehaviorExperience/BehaviorExperience/Behavior
Gene ExpressionGene ExpressionGene ExpressionGene Expression
Cell/SynapseCell/SynapseCell/SynapseCell/Synapse
Neural CircuitryNeural CircuitryNeural CircuitryNeural Circuitry
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Shallow Archeology
Candidate Systems• HPA axis --- cortisol
• ANS system --- epinephrine/ne
• Prefrontal cortex
• Social affiliation --- amygdala/locus cereleus
• Immune function -- the ‘peripheral brain’
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Candidate System: Prefrontal Cortex SES Differences by School Age
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Deep Archeology
‘Social Epigenesis’ and other processes that can influence
gene expression.
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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
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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)
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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.
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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.
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So far:
• 1252 loci differentially methylated according to childhood SES
• Approx. 4000 loci differentially methylated according to retrospective reports of abuse in childhood
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Mid- Brain affiliation/attachment
PFC executive function/
impulsivity
HPA stress response
Abuse
Chronic diseases
Health behaviors Mental health
Epigenome
Exposure
Endophenotype
Phenotype
Hypothetical Patterns of Influence
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Exposure
Epigenome
Biochemical/Biophysical Pathway
Phenotype
(Prenatal)Maternal Smoking
Childhood Abuse
Childhood SES
Exposure Specific Pathways
Common Pathways
Exposure Specific Pathways
Exposure Specific Pathways
Outcome(s)Outcome(s)
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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
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www.earlylearning.ubc.ca