A study led by researchers in Canada who analysed post mortem brain samples of suicide victims with a history of being abused in childhood found changes in DNA expression that were not present in suicide victims with no childhood abuse history or in people who died of other causes. The affected DNA was in a gene that regulates the way the brain controls the stress response.

The research was the work of scientists from the Douglas Mental Health University Institute and McGill University in Montreal, Quebec, and the Singapore Institute for Clinical Sciences and was published online on 22 February in Nature Neuroscience.

Previous studies have shown that child abuse or neglect changes the hormonal stress response and increases the risk of suicide in the victim. Animal studies show that maternal care can influence the expression of genes that control the stress response.

In this study the researchers looked at samples of the hippocampus from human suicide victims with a history of childhood abuse. The hippocampus is a region of the brain that plays a key role in regulating the stress response.

They found changes in expression of the NC3R1 gene that were not present in suicide victims with no history of being abused in childhood. The changes weren’t present in people who had died of other causes either.

For the study the researchers used samples from 36 brains: 12 came from suicide victims who had been abused as children, 12 came from suicide victims who had no such history, and 12 came from people who had died of other causes (the controls).

The researchers found that the child abuse victims had different “epigenetic” markings in a part of the brain that influences the hypothalamic-pituitary-adrenal (HPA) function, a stress-response that increases suicide risk.

This finding builds on an earlier study published in May last year that showed how child abuse can leave “epigenetic” marks on DNA.

Epigenetics studies the way that DNA is expressed: that is when the code behaves in a way that is not exactly what the DNA program says. DNA itself, the fundamental code, is inherited from the person’s biological parents and remains fixed through a person’s lifetime.

But the genes in the DNA are coated with a layer of chemicals called DNA methylation. These chemicals influence how the DNA is interpreted and they can be affected by changes in the environment, especially in early life such as when the new embryo is made, in the womb, and then later in childhood.

Co-author Dr Gustavo Turecki, associate professor in the Department of Psychiatry at McGill University and who practices at the Douglas Mental Health University Institute, said:

“We know from clinical experience that a difficult childhood can have an impact on the course of a person’s life.”

“Now we are starting to understand the biological implications of such psychological abuse”, added fellow co-investigator Moshe Szyf, a professor in the Department of Pharmacology and Therapeutics at McGill.

The interaction between environment and DNA plays a key role in our ability to resist and deal with stress and this affects the risk of suicide, said the researchers. Epigenetic marks are the product of DNA and environment.

The researchers found that different types of care from the mothers changed the hypothalamic-pituitary-adrenal (HPA) function in rats by altering the receptors in the brain. In earlier studies they showed that simple behaviours such as when mothers licked their baby rats in early life had a significant effect on epigentic markings on specific genes that affected behaviour throughout the offsprings’ lives.

But they also found that these epigenetic marks can be changed in adulthood with treatments that change the DNA coating: the treatment is called DNA methylation and it reverses the change to the stress response.

The brain samples in this latest study came from the Quebec Suicide Brain Bank and the Canadian Institutes for Health Research and the National Institute of Child Health and Development in the US paid for the research.

“Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.”
Patrick O McGowan, Aya Sasaki, Ana C D’Alessio, Sergiy Dymov, Benoit Labonté, Moshe Szyf, Gustavo Turecki & Michael J Meaney.
Nature Neuroscience Published online: 22 February 2009.

Click here for Abstract.

Sources: Journal abstract, McGill University.

Written by: Catharine Paddock, PhD