Child Abuse Changes the Child's D.N.A.

February 24th, 2009

Toronto, Feb 24 (IANS) Childhood traumas can alter your DNA and leave a lasting effect on the brain, a Canadian study has found.
According to researchers at Montreal’s McGill University and Douglas Institute, traumas in childhood - and maternal care - can shape the way your genes work and thus make you suicide-prone.

As part of their research, the scientists studied a sample of 36 brains which included 12 suicide victims who were abused, 12 suicide victims who were not abused and 12 others.

The researchers found that the brains of the abused group had different epigenetic markings.

These markings control the hypothalamic-pituitary-adrenal (HPA) function in the brain which regulates response to stress and increases the risk of suicide, a university statement said Monday.

The current research has built upon an earlier study to uncover how parental care affects the DNA in the brains of a group of male suicide victims who suffered abuse as children, the statement added.

“We know from clinical experience that a difficult childhood can have an impact on the course of a person’s life,” said Gustavo Turecki, associate professor of psychiatry in the university.

“Now we are starting to understand the biological implications of such psychological abuse,” he said.

“The function of our DNA is not as fixed as previously believed,” added co-researcher Michael Meaney.

“The interaction between the environment and the DNA plays a crucial role in determining our resistance to stress thus the risk for suicide. Epigenetic marks are the product of this interaction,” he said.

Though the DNA inherited from parents remains fixed throughout life, it is marked by a chemical coating during gestation and later in development.

These (epigenetic) marks punctuate the DNA and programme it for responses to different situations in later life, the statement said.

Citing their earlier study on rats that shows that maternal care also influences hypothalamic-pituitary-adrenal (HPA) function in the brain, the researchers said that in humans, child abuse alters HPA stress responses and increases the risk for suicide.

However, these effects can also be reversed in adult life through treatments that alter these epigenetic marks in the brain.

Further research on brain tissue can help develop intervention and prevention programmes to help people, the researchers said.

The study has been published in the Feb 22 issue of the journal Nature Neuroscience.

Published yesterday in the journal Nature Neuroscience, the McGill University and Douglas Institute study is the first of its kind in unravelling the epigenetics of suicide.

Epigenetics looks at the way the environment or lifestyle can alter DNA and shape the way genes function and control behaviour.

"This is not about how you are wired. This is not written in your genes but results from the way you interact with the environment," said Douglas Institute psychiatrist and neuroscientist Gustavo Turecki, who runs the Quebec Suicide Brain Bank.

Colleague Michael Meaney had demonstrated in previous studies the effect on certain genes in rat pups neglected by their mothers. They showed more stress later in life - and also "epigenetic" changes in their brains.

Researchers looked at a sample of 36 brains, all men: 12 suicide victims who were abused, 12 suicides that had no history of abuse, and 12 that died accidentally.

Specifically, researchers looked at the glucocorticoid gene receptor in the hippocampus in the brain.

"For the first time these findings - the effects we saw in rats - are translated into humans," Turecki said. "If you were abused you will have changes in the way your brain works that are going to determine how you deal with stress, and this could be one way where you are more at risk of suicide."

The study builds on a previous one published in May by the same group that focused on ribosomal RNA - molecules critical for learning and memory - in the brains of men who had killed themselves.

The current study's lead author, Patrick McGowan of McGill, said his team is trying to tease apart the effect of early childhood on suicide itself.

People with a childhood history of abuse are at greater risk of depression and mental illness later in life.

About 90 per cent of people who commit suicide also suffer from mental health issues. More men then women die from suicide, a four to one ration in Quebec.

"Many roads lead to Rome and many factors contribute to whether a person commits suicide. This may be one factor, acting through the stress pathway," McGowan said.

It raises the possibility of designing epigenetic therapies in mental health, McGill's pioneer epigeneticist Moshe Szyf added.

"The social environment like childhood abuse can cause such a profound chemical change in DNA that stays for so long," Szyf said. "Why couldn't an opposite social environment erase those marks? So the potential is there."

Szyf is now looking at differences in social economic status in childhood and the effect on adult DNA, using blood samples.

"The goal is to find markers ... an explanation in the genome markings for the early onset of adult disease," Szyf said. "We all know events early in life can have a profound impact later in life, but we don't know why. That can provide a mechanism."

Epigenetic expert Arturas Petronis of the University of Toronto, who did not participate in the study, called the research "solid," interesting and significant in showing a correlation between complex behaviour and molecular changes due to early environment.

cfidelman@thegazette.canwest.com
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Published on 22 February 2009, 10:28 Last Update: 2 day(s) ago by Insciences
Tags: Childhood trauma Genetics Medicine Hypothalamic-pituitary-adrenal
Study confirms effects of early environment in brains of suicide victims

McGill University and Douglas Institute scientists have discovered that childhood trauma can actually alter your DNA and shape the way your genes work. This confirms in humans earlier findings in rats, that maternal care plays a significant role in influencing the genes that control our stress response.

Using a sample of 36 brains; 12 suicide victims who were abused; 12 suicide victims who were not abused and 12 controls, the researchers discovered different epigenetic markings in the brains of the abused group. These markings influence the hypothalamic-pituitary-adrenal (HPA) function, a stress-response which increases the risk of suicide.

This research builds upon findings published last May that showed how child abuse can leave epigenetic marks on DNA.

But, in this, the first study of its kind, Moshe Szyf, a professor in the Department of Pharmacology and Therapeutics; Gustavo Turecki, associate professor in the Department of Psychiatry who practices at the Douglas Mental Health University Institute; Michael Meaney, a professor in the Departments of Psychiatry and Neurology and Neurosurgery, who is also at the Douglas; and McGill postdoctoral research fellow Patrick McGowan have built on their world-renowned epigenetics work to uncover how parental care affects the DNA in the brains of a group of Quebec male suicide victims who suffered abuse as children. The all-McGill study is set to be published in the February 22, issue of the journal Nature Neuroscience.

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

“Now we are starting to understand the biological implications of such psychological abuse,” added Dr. Szyf.

“The function of our DNA is not as fixed as previously believed, said Dr. Meaney. “The interaction between the environment and the DNA plays a crucial role in determining our resistance to stress thus the risk for suicide. Epigenetic marks are the product of this interaction.”

Epigenetics is the study of changes in the function of genes that don’t involve changes in the sequences of DNA. The DNA is inherited from our parents; it remains fixed throughout life and is identical in every part of the body. During gestation and even later in development, however, the genes in our DNA are marked by a chemical coating called DNA methylation. These marks are somewhat sensitive to one’s environment, especially early in life. The epigenetic marks punctuate the DNA and program it to express the right genes at the appropriate time and place.

The researchers discovered that maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of certain receptors in the brain. In humans, child abuse alters HPA stress responses and increases the risk for suicide.

In previous studies in laboratory rats, the group proved that simple maternal behaviour such as mothers who licked their pups during early childhood has a profound effect on the epigenetic marks on specific genes and effects on behaviour in ways that are sustained throughout life. However, these effects on gene expression and stress responses can also be reversed in adult life through treatments known to affect the epigenetic mark known as DNA methylation.

The brain samples in the latest study came from the Quebec Suicide Brain Bank, administered by Dr. Turecki of the Douglas Mental Health University Institute. With the support of the Bureau du Coroner du Québec (Office of the Chief Medical Examiner), the McGill Group for Suicide Studies (MGSS) founded the Quebec Suicide Brain Bank (QSBB) at the Douglas Mental Health University Institute, to promote studies on the phenomenon of suicide. Research carried out on brain tissue can help develop intervention and prevention programs to help people suffering mental distress and who are at risk of committing suicide.

The research was funded by the Canadian Institutes for Health Research and the National Institute of Child Health and Development (USA)

By: Sheryl Ubelacker, THE CANADIAN PRESS

22/02/2009 6:37 PM

TORONTO - Childhood trauma can alter the way genes in the brain work, potentially putting an individual at increased risk for suicide later in life, Canadian researchers have discovered.

A team of scientists from McGill University analyzed brain tissue from 12 suicide victims who had been abused as children and compared them to the tissue of 12 suicide victims who had not been traumatized and 12 people who died from other causes.

They found that the brain tissue from the abused group showed "epigenetic" changes that affect a person's response to stress, which is known to increase the risk of suicide.

Genes are inherited from a person's parents and remain unchanged throughout life. But exposure to environmental influences, be it social trauma or chemical substances, can alter how those genes function.

These changes, in which the DNA is marked by proteins, are known as epigenetic alterations and can occur even during gestation.

In the brain cells of suicide victims who had suffered severe sexual or physical abuse or neglect, the Montreal researchers found epigenetic markings in a gene that affects how a person reacts to stress.

"And what we found was that those individuals that had been abused and neglected during childhood were more likely to have increased epigenetic regulation of this gene," co-author Dr. Gustavo Turecki, a psychiatrist and neuroscientist, said from Montreal.

"What that means is that these people would be less well-prepared to deal with stress and to react to stress."

The samples of tissue used in the study came from the Quebec Suicide Brain Bank, which houses the brains - donated by families for the purposes of research - of about 200 people who died from suicide or other causes.

The McGill scientists, whose paper is published in this week's issue of the journal Nature Neuroscience, say that identifying epigenetic changes in abuse victims could one day pave the way for drugs that would reverse the damage.

To do that, said co-author Moshe Szyf, researchers would have to find similar epigenetic makings in the DNA of a person's blood, since brain tissue can only be analyzed after death.

"The implications at this stage are you want to identify these people and then probably offer them some sort of intervention," said Szyf, an epigeneticist in McGill's department of pharmacology and therapeutics. The goal, he said, would be to find drugs that could reverse the epigenetic changes.

"We don't know how to do it yet. We might know in the future, but we don't know how to do it now."

Dr. John Strauss, a child psychiatrist at the Centre for Addiction and Mental Health in Toronto, said the McGill study is important because it brings to "psychiatric disorders a way of explaining potential gene-environment interactions."

The difficulty is translating the method into subjects that are living, he said.

"Obviously, if there were some kind of marker that you could check in individuals to see if they are more at risk (for suicide), it might aid identification. It might also be used as a potential marker to follow people."

Strauss said such a test would allow doctors to see if epigenetic changes that occurred as a result of early trauma had "switched back," at which point drugs or other therapy could be reduced in frequency or intensity.

"But you need really accessible samples."

Szyf said the optimistic message from the study is that changes in the function of genes transformed by environmental factors are potentially reversible.

"I think what's nice about the study is we can see marks of early life in the genes of older people," he said. "And that illustrates the power of epigenetics because it serves as a memory of environmental exposure."

For instance, it's known that toxic chemicals like lead, mercury and PCBs can alter the function of a person's genes and result in disease, including some cancers.

"But it seems that social exposures are as toxic and can cause exactly the same kind of changes," Szyf said. "And we should be aware of the impact a bad social environment can have on our health."