epigenetic impact of adversity: risk, resilience, & nature- nurture

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

Nature vs. Nurture

DNA

Brain Physiology Behavior

Early Life Adversity

Our experiences or “nurture” can have long-term effects on our brain and behavior

How does this occur?

DNA is like books in a library. Limitless potential to inform and inspire…but they need to be read.

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)

Postnatal Maternal

Care

Variation in Brain &

Behavior

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















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)

Champagne et al. Frontiers in Neuroendocrinology (2008)

Epigenetic Variation

nutrition

drug use pesticides

hormones

smoking

What factors induce epigenetic changes?

abuse

neglect stress

nurturing

Childhood adversity can have long-term

epigenetic consequences which may be

inherited by subsequent generations

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M

M

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epigenetic impact of adversity: risk, resilience, & nature- nurture

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