DNA changes linked to health effects of childhood abuse

NEW YORK Thu Jul 31, 2014 2:14pm EDT

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NEW YORK (Reuters Health) - Trauma has lasting effects on mental and physical health that may stem from changes to DNA which undermine a person’s ability to rebound from stress, according to new research.

The small study of abused children adds to a growing body of evidence suggesting that experiences can alter gene activity, explaining how mental anguish can translate to lingering physical effects, and possibly opening new avenues for treatment, study authors say.

“This could explain why children with stressful childhood experiences have a different range of problems like not doing well in school, having academic problems, or problems with judgment and decision making,” said senior study author Seth Pollak, a psychologist and child development researcher at the University of Wisconsin-Madison.

For example, one of the affected DNA sites Pollak’s team focused on is involved in responding to a nerve-cell growth factor that “is what allows the brain to grow and heal during childhood and to develop,” he told Reuters Health.

The findings, Pollak said, support research showing that “genes aren’t fixed and stable” as was once thought. Scientists have long known that a person’s genes interact with their environment, but this kind of finding helps to illustrate how that actually works, he notes.

The study looked at the blood cells of children who had been abused to examine changes in methylation - a chemical code along the DNA strand that helps control when genes are activated. More or less methylation can silence a gene or boost its activity.

Past research in people and rodents has shown that traumatic experiences – including psychological stress - can alter DNA methylation, Pollak and his colleagues write in the journal Child Development.

Research in rats, for instance, focused on a gene that makes a receptor for the stress hormone cortisol. The receptor is critical to shutting down the stress response so the body can return to normal. Without it, stress reactions affecting the brain and immune system remain in high gear, with negative consequences to health.

Pollak and his team examined a stretch of DNA that controls the equivalent gene, known as the GR gene, in people.

They recruited 18 children between the ages of 11 and 14 whose experience of abuse was documented by state child protective services records. They also recruited 38 children from similar neighborhoods and family backgrounds without a record of abuse to act as a comparison group.

The researchers drew blood from each child and analyzed the methylation along a stretch of DNA that controls GR gene activity, the same stretch where changes had been seen in rats.

After adjusting for differences associated with socioeconomic status, the researchers found that children who had been abused had extra methylation at three sites along the DNA and had less than the other kids at a fourth site. The changes suggest the GR gene might be silenced when it should normally be active and might be over-active in certain other circumstances.

“We not only found the same effect in the children as had been found in the rodent, but we found it on the exact same part of the gene,” Pollak noted.

“If this gene isn’t turned on and you are not able to actually use (cortisol), then you experience emotions like any other individual - you get upset, you get angry, you get aroused but you can’t shut down,” Pollak said.

“It would lead to high levels of stress, arousal, anger, irritation but kind of an inability to regulate and come back to a calmer state,” he said.

“These are the kind of behavioral problems that have been associated with child abuse for a very long time. The whole idea that the very nature of the kind of parenting that we experience could change and turn on and off genes related to social behavior is so cool, it’s a game changer,” he added.

On the other hand, Pollak pointed out, humans are not rats. Finding the same changes at the same sites in the human and rat cells strongly suggests they result from the experience of stress, the team writes in their report, and “opens a window into the molecular mechanisms linking early stress exposure to the emergence of psychopathology.”

But, the researchers caution, they did not examine whether the affected gene was more or less active in the children’s bodies. The study also looked at blood cells, so they cannot be certain that the same changes are present in the kids’ brain cells.

“It’s very consistent with other evidence that’s coming out,” said Meghan Gunnar, a professor at the University of Minnesota who was not involved in the study.

Changes in the way genes are being regulated is certainly one very important potential mechanism that shapes how a child’s body is functioning, but it’s not the only way that experience can ‘get under the skin’ and have long term effects but it is certainly one way,” said Gunnar, who leads The Early Experience, Stress Neurobiology, and Prevention Science Network.

“Increasingly it’s looking like child abuse is not just a social or welfare problem. It’s now looking like a biomedical problem and we might want to view it the way we view disease,” Pollak said.

SOURCE: 1.usa.gov/1pG0N2K Child Development, online July 24, 2014.

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