Epigenetic Impact of Adversity: Risk, Resilience, & Nature-
Nurture Interplay
Dr. Frances A. Champagne
Associate Professor, Department of Psychology
Columbia University
© 2011 Children’s Studies Center, Brooklyn College
Brain Physiology Behavior
Early Life Adversity
Our experiences or “nurture” can have long-term effects on our brain and behavior
How does this occur?
When the DNA is read it is said to be “expressed”
difficult to read
easier to read
Gene activity is dependent on an active process
of “unwrapping” DNA and making it accessible
The New Science of Genetics = EPIGENETICS
Epigenetics
the study of those factors that alter whether DNA will be “expressed” without altering the DNA sequence
Factors that will change the likelihood
that a book with be read.
DNA Methylation
DNA
M
M
M
M
M M
methyl
chemicals
M
M
M
DNA methylation makes DNA less accessible and
reduces gene activity
All the cells in our body are genetically identical…
… yet our body contains cells which are dramatically different – EPIGENETICALLY VARIABLE
Genetically Identical – Epigenetically Variable
Though twins are genetically identical and epigenetically similar when they are young, as they age they become more dissimilar in their epigenetic patterns
Variation emerges across the lifespan
Experiences occurring during fetal development can have long-term effects
Brain and body are developing rapidly providing a “window of opportunity” for variation – and for the effects of trauma/adversity/stress
Radtke et al Translational Psychiatry (2011) 1, e21
Intimate partner violence experienced during
pregnancy predicts DNA methylation in children
degre
e o
f D
NA
meth
yla
tion
partner
violence
NO partner
violence
effect persists
into adolescence
(10-19 years)
prenatal stress
NO stress
DNA region within the glucocorticoid receptor gene
degre
e o
f D
NA
meth
yla
tion
Prenatal stress predicts DNA methylation in mice
Mueller and Bale, Journal of Neuroscience (2008)
cccctctgctagtgtgacacacttcgc
gcaactccgcagttggcgggcgcgg
accacccctgcggctctgccggctgg
ctgtcaccctcgggggctctggctgc
cgacccacgggcgggctccgagcg
gttccaagcctcggagtgggcgggg
gcg ggaggg agcctggg agaa
cccctctgctagtgtgacacacttcgc
gcaactccgcagttggcgggcgcgg
accacccctgcggctctgccggctgg
ctgtcaccctcgggggctctggctgc
cgacccacgggcgggctccgagcg
gttccaagcctcggagtgggcgggg
gcg ggaggg agcctggg agaa
Offspring reared by Low
care female
Offspring reared by High
care female
Glucocortociod Receptor Methylation in Response to Maternal Care in Rodents
M
M M
M M
M
M
M
M
M M
Weaver et al. Nature Neuroscience (2004)
LOW LG HIGH LG
Maternal Licking/Grooming Increased GR methylation
Decreased GR methylation
Decreased GR expression
Increased GR expression
Increased stress response
Decreased stress response
Weaver et al. Nature Neuroscience (2004)
Cross-fostering studies
confirm the influence of
rearing environment on
this epigenetic process
infant experience
0
5
10
15
20
25
nurturing maltreatment
degre
e o
f D
NA
meth
yla
tion
***
Infant Abuse Associated with Increased DNA Methylation in the Rodent Brain
Roth et al. Biological Psychiatry (2009)
Childhood Abuse Associated with Increased DNA Methylation in the
Human Brain
degre
e o
f D
NA
meth
yla
tion
McGowan et al. Nature Neuroscience (2009)
Transmission of Maternal Behavior
Humans parental bonding attachment child abuse
Primates mother-infant contact maternal rejection infant abuse
Rodents Individual differences in contact and licking/grooming
cccctctgctagtgtgacacacttcgc
gcaactccgcagttggcgggcgcgg
accacccctgcggctctgccggctgg
ctgtcaccctcgggggctctggctgc
cgacccacgggcgggctccgagcg
gttccaagcctcggagtgggcgggg
gcg ggaggg agcctggg agaa
cccctctgctagtgtgacacacttcgc
gcaactccgcagttggcgggcgcgg
accacccctgcggctctgccggctgg
ctgtcaccctcgggggctctggctgc
cgacccacgggcgggctccgagcg
gttccaagcctcggagtgggcgggg
gcg ggaggg agcctggg agaa
Offspring reared by Low
LG Dam
Offspring reared by High
LG Dam
Estrogen Receptor DNA Methylation in Response to Maternal Care
M
M M
M M
M
M
M
M
M M
Champagne et al. Endocrinology (2006)
Epigenetic Variation
nutrition
drug use pesticides
hormones
smoking
What factors induce epigenetic changes?
abuse
neglect stress
nurturing