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