Advancing Epigenetics Towards Systems Biology

Abuse affects genes

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We're all well aware that a difficult childhood can have a great impact on the course of someone's life. Childhood abuse can even drive individuals to commit suicide. A study published in Nature Neuroscience this month elucidates the molecular basis of how stress can shape the way genes work, predisposing abuse victims to ill fates.

Brona McVittie reports :: February 2009

Building upon research published last May, which showed that child abuse can leave epigenetic marks on DNA, a team of McGill University and Douglas Institute scientists recently explored the links that such changes might have on the likelihood of abuse victims to commit suicide. They looked at epigenetic marks on genes that mediate our stress-response.

The team knew from previous studies in rats that parenting has a measurable physical impact on behavioural responses to stress. The way a mother treats her pups determines the extent to which certain proteins get made from DNA. In particular the team has studied expression of glucocorticoid receptors, low levels of which are associated with mood disorders.

Comparing brain tissue from three groups; 12 suicide victims who were abused, 12 suicide victims who weren't abused and 12 normal individuals, the team found different epigenetic marks on the gene that makes glucocorticoid receptors in the brains of the abused group to those in non-abuse victims or normal individuals.

Coupling this with previous research findings, the results suggest that childhood experiences can lower the expression of glucocorticoid receptors, which has a knock-on effect on the hypothalamic-pituitary-adrenal (HPA) function. The subsequent over-activation of the HPA axis affects our ability to cope with stress, leaving affected individuals at risk of suicide.

"We are starting to understand the biological implications of psychological abuse," confirms Moshe Szyf (McGill University, Quebec). Even though the genes we inherit from our parents remain with us throughout our lives, epigenetic changes such as DNA methylation can shape their effects on us. Epigenetic changes can be environmentally triggered and markedly affect development and behaviour.

"The function of our DNA is not as fixed as previously thought," adds Michael Meaney (Douglas Institute, Quebec). "The interaction between genes and the environment plays a crucial role in determining our resistance to stress and the risk for suicide. Epigenetic marks are the product of this interaction."

The McGill Group for Suicide Studies was set up to support research into suicide. Such research will be helpful for developing intervention and prevention programs to help people suffering from mental distress, who are at risk of committing suicide. After all, epigenetic marks are reversible.

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