Early Human Development as a Social Determinant of Health
Clyde Hertzman
Gradient in all Cause Mortality: UK Whitehall Study
CHD Mortality - UK Whitehall Study
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’
Canada: % vulnerable by SES
Source: NLSCY/UEY 1999-2000; EDI 1999-2000
% V
ulne
rabl
e
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
What Influences Early Child Development?
The experienceschildren have in
the environmentswhere they grow up, live
and learn.
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
Two responses
• understanding ECD at the level of the population
• understanding the developmental biology of the gradient
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
What Does the EDI Measure?
EDI is:-a population-based tool -a mobilisation tool-a monitoring tool
EDI is not:-an individual assessment-a prescription for action-perfect
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
Two responses
• understanding ECD at the level of the population
• understanding the developmental biology of the gradient
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
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’
Candidate System: Prefrontal Cortex SES Differences by School Age
Deep Archeology
‘Social Epigenesis’ and other processes that can influence
gene expression.
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
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)
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.
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.
So far:
• 1252 loci differentially methylated according to childhood SES
• Approx. 4000 loci differentially methylated according to retrospective reports of abuse in childhood
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
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)
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
www.earlylearning.ubc.ca
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