Abuse Leaves Its Mark on the Brain

Child abuse doesn't just cause emotional problems; it also causes long-lasting changes the brain. A new study shows that in men who were abused as children, a gene involved in stress control is affected even decades later, following a pattern also seen in stressed baby rats.

Rat studies have revealed that maternal neglect alters the workings of the hypothalamic-pituitary-adrenal (HPA) axis, a system that secretes particular hormones in response to stress (ScienceNOW, 2 August 2004). In the abused animals, the regulatory region of a gene for the glucocorticoid receptor, responsible for damping down the HPA response, doesn't do its job properly. As a result, the animals experience chronically higher stress levels.

Now, researchers have identified the same phenomenon in human brains. Neuroscientist Michael Meaney and colleagues at McGill University in Montreal, Canada, compared postmortem brains of 12 men who had been abused as children and had committed suicide with those of two age-matched groups: nonabused men who had also killed themselves, and nonabused men who had died suddenly from other causes.

The researchers extracted DNA from the hippocampus, a brain area where the gene is active. They found that the abused men showed the same changes as the abused rats: increases in methylation at a site in the promoter of the gene, which made it less capable of modifying the stress response. The change was not seen in the two other groups.

"This is a beautiful study," says neuroscientist Eric Nestler of Mount Sinai School of Medicine in New York City. It supports the idea that epigenetic changes--that is, events that affect gene expression but not the DNA sequences of the genes themselves--in specific nervous system genes "may be an important mechanism by which environmental exposures cause long-lasting behavior change."

Over the past decade, evidence has been accumulating that "abused individuals are less healthy in adulthood," Meaney says. They suffer not just from mental illness but also from obesity, heart disease, and autoimmune disorders. This research, he says, may be a first step in finding out why.