biological embedding: implications for neurodevelopment clyde hertzman, md human early learning...
TRANSCRIPT
Biological Embedding: Implications for
Neurodevelopment Clyde Hertzman, MD
Human Early Learning PartnershipUniversity of British Columbia, Vancouver
Gradient in all Cause Mortality: UK Whitehall Study
CHD Mortality - UK Whitehall Study
SEP Gradients in Health: Social Determinants to Early Development
• 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• begins life as gradient in ‘developmental health’
with life course persistence and ‘flattening up’
very poor poor not poor well-off0
10
20
30
40
50
60
31.929.1
23.1
13.7
% vulnerable
Percent vulnerable and SESCanada
very poor poor not poor well-off0
10
20
30
40
50
60
31.929.1
23.1
13.7
% vulnerable
Canada
Q1 Q2 Q3 Q40
10
20
30
40
50
60
56.3
43.240
30.8
% vulnerable
Very poor Poor Not poor Rich0
10
20
30
40
50
60
27.323.9
17.5 16.1
% vulnerable
Mexico
Kosovo
Australia
Canada
Bottom 10%
10-25% 25-50% 50-75% 75-90% Top 90%0
10
20
30
40
50
60
35.3
27.6 26.324
18.7
11.2
% vulnerable
Percent vulnerable and SES
Life Course Problems Related to Early Life
2nd Decad
e
3rd/4th Decad
e
5th/6th
Decade
Old Age
• School Failure
• Teen Pregnancy
• Criminality
• Obesity
• Elevated Blood Pressure
• Depression
• Coronary Heart Disease
• Diabetes
• Premature Aging
• Memory Loss
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.
Biological Embedding
Archeology of Biological Embedding
Gene Function
Cell/Synapse
Neural Circuitry
Experience/Behavior
Surficial Archeology
Gene Function
Cell/Synapse
Neural Circuitry
Experience/Behavior(early development in context)
Sensitive Periods in Early Brain Development
Vision
0 1 2 3 7654
High
Low
Years
Habitual ways of respondingEmotional
control
Symbol
Peer social skillsNumbers
Hearing
Graph developed by Council for Early Child Development (ref: Nash, 1997; Early Years Study, 1999; Shonkoff, 2000.)
Pre-school years School years
Language
The Early Development Instrument
What Does the EDI Measure?
All ChildrenIncluded in Age 5 School Entry Year
‘Shallow’ Archeology
Gene Function
Cell/Synapse
Neural Circuitry
Experience/Behavior
Shallow Archeology
• HPA axis --- cortisol• ANS system --- epinephrine/ne• Prefrontal cortex• Social affiliation --- amygdala/locus cereleus• Immune function -- the ‘peripheral brain’
SES Differences in Prefrontal Cortex Activity by School Age
Deep Archeology
‘Social Epigenesis’ and other processes that can influence
gene expression
mRNAmRNA
TranslationTranslation
proteinprotein
Coding sequence StopStart
Promoter
RNAplmrsRNA
plmrs
TranscriptionTranscription
Molecular level
CH3CH3
It does not only occur during basic fetal development, when cells are specializing……it can continue after birth and be influenced by the broader environment!
What’s new about this?
Biological Embedding: Epigenetic Marks of Early Life
Early Life 15-40 yrs
1958 British Birth Cohort Study
(Int J Epid, March 2012)
• 40 adult males selected from SES extremes in both childhood and adulthood
• Genome-wide methylation analysis from blood DNA at 45 years of age
• 20,000 gene promoter regions
Methylation levels for 1,252 promoters associated with childhood SEP
Methylation levels for 1,141 promoters associated with childhood abuse
But only approx. 80 promoters associated with maternal smoking during pregnancy!
Wisconsin Study of Families and Work
Essex, Boyce, Hertzman & Kobor, 2011
N = 570
Stress:•depression symptoms•expressed anger•parenting stress•role overload•financial stress
PreschoolInfancy
N = 109
Epigenetic profiling:•Buccal epithelial cells•Illumina microarray•~28,000 CpG sites in ~14,000 gene promoters
• Differential methylation of multiple CpG sites by parental stress in infancy and preschool
• Mothers’ stressors in infancy more related to differences in methylation for both girls and boys
• Fathers’ stressors in preschool associated with methylation differences primarily for girls
• A pattern commensurate with prior knowledge of maternal v paternal and gender-specific influences on development
Epigenetic vestiges of early developmental adversity
Since 2010, 34 life course studies have included measurements of DNA
methylation
Ng et al. Genome Biology 2012,
(Ng et al, Genoome Biology 2012; 13:246)
Journal Articles Referring to Biological Embedding*
* Databases searched by M. Wiens -- Ebsco, Google Scholar, PubMed, Scirus, and Web of Knowledge -- August 2012**2012 includes Jan-July only (part-year)
Milestones in Biological Embedding 1
• 2004: Meaney/Szyf paradigm first cited as animal evidence of biological embedding
• 2006: first human GxE interaction (childhood maltreatment by MAOA) to be cited as evidence of biological embedding
• 2006: biological embedding first used to account for development origins of adult disease
• 2006: biological embedding linked to racial health disparities in North America
Milestones in Biological Embedding 2
• 2008: biological embedding first used to account for why parents’ social standing is associated with neural development in brains of children
• 2008: biological embedding first used to account for the childhood SES/CHD risk relationship
• 2008: biological embedding first used to justify investment in the early years as human capital investment
• 2010: biological embedding first used to ‘explain’ life course influences of ACE’s
Milestones in Biological Embedding 3• 2010: biological embedding first used as central
organizing concept in ‘stress’ study (of inflammation)
• 2011: biological embedding first demonstrated in human epigenetics
• 2011: biological embedding used to account for SES differences in telomere length
• 2012: biological embedding first used to account for validity of allostatic load
2011: Biological Embedding becomes Conventional Wisdom
“A scientific consensus is emerging that the origins of adult disease are often found among developmental and biological disruptions occurring during the early years of life. These early experiences can affect adult health in two ways – either by cumulative damage over time or by the biological embedding of adversities during sensitive developmental periods……..”
(Leckman JF, March JS. Editorial: Developmental neuroscience comes of age. J Child Psychol Psychiatr. 2011;52(4):333-8.)
www.earlylearning.ubc.ca
Merci!