Early life stress changes the way our genes function

Pervasive and enduring effects of early life stressPervasive and enduring effects of early life stress

• Obesity (ANNA)

• Neurodevelopmental delays

• HPA axis dysfunction (stress)

• Metabolic disorder

• Cardiovascular disease

• Immune system dysfunction

• Major depressive disorder

• Post Traumatic Stress Disorder

• Cancer

Child Abuse and NeglectACE study Vincent Fellitti

Scientific Gaps

“Nature” versus “Nurture”(Genetics versus environment)

Jean-Baptiste de LamarckJean-Baptiste de Lamarck

DNA building blocks

Can be chemically modified (the addition of a methyl group (-CH3))by our environment, e.g. stress!!!!

Epigenetics (environment determines activity of genes)

ACTIVE GENEACTIVE GENE

INACTIVE GENEe.g. a gene that reduces stress

INACTIVE GENEe.g. a gene that reduces stress

Filling in the scientific gaps

-Studies on animal behavior (maternal care)

-Studies of CAN victims (epigenome)

Moshe Szyf

Patrick McGowan

Michael Meaney

Epigenetic interference by maternal careEpigenetic interference by maternal care

•Behaviour of pup determined by care of mother. •This is reflected in the pup’s activity of genes.•Altering the epigenome (DNA-methylation) alters behaviour.

HPA stress responsFight or flight respons

Glucocorticoid receptor (GR) takes away the cortisol after the stress event. In stressed pups this receptor is less active due to methylation of this gene. Cortisol level remains high.

Glucocorticoid receptor (GR) takes away the cortisol after the stress event. In stressed pups this receptor is less active due to methylation of this gene. Cortisol level remains high.

GR

What about CAN victims?

• Chronic childhood stress alters the stress response by epigenetic changes (lifetime changes).

• Many other genes are altered in the same way especially genes involved in the immune system, brain development, heart disease, cancer, psychiatric and substance abuse disorders. A high risk for Tom, Rita and Anna.

• Epigenetic changes due to stress can be transmitted to the next generation.

Good news!

• Some children are resilient for the effect of CAN (genetic, epigenetic).

• Epigenetic changes are reversible in theory (Interference throught medication or cognitive therapy).

Writers, readers, erasers

Take home message

• Gene function is altered by childabuse and neglect.

• This causes frequent major health problems throughout life.