Leaving a mark

Child abuse can leave lasting scars on its victims, both physical and psychological. It may also leave chemical marks in the brains of its victims who will later kill themselves.

In the brains of suicide victims, early abuse marks genes that encode ribosomal RNA, key gears in the cellular machinery that makes proteins, researchers from McGillUniversity in Montreal, Canada, report. The marks are methyl groups, chemical units that tattoo the DNA in a region that controls whether ribosomal RNA is turned on or off. Methyl tattoos help turn the genes off in a part of the brain associated with depression.

Published online in the May 7 PLoS ONE, the study is the first to implicate faulty protein production with child abuse and suicide.

“It’s certainly a novel concept,” says Schahram Akbarian of the University of Massachusetts Medical School in Worcester. Akbarian was not involved in the research.

Most neuroscientists ignore ribosomal RNAs, thinking of them as boring housekeepers, he says. The new research has generated an interesting hypothesis that ribosomal RNAs and protein production play a big part in keeping the brain mentally healthy.

The ribosomal RNAs, or rRNAs for short, were chosen for the study precisely because they are so mundane, says Michael Meaney, one of the principal researchers. The team compared levels of methylation of several genes in the brains of people who died from suicide and were also abused as children with levels in the brains of people who died in traffic accidents who were not abused. The researchers had preliminary data that suggested other genes were regulated differently in people who committed suicide and wanted to make sure that gene activity wasn’t just topsy-turvy in people who take their own lives. So the scientists decided to measure methylation in rRNA genes because, the researchers felt, those genes would surely not be affected by childhood experiences. “Wrong,” Meaney says of that belief.

Levels of methylation were substantially higher in the hippocampuses of people who took their own lives compared with people who died in traffic accidents, the researchers found. There was no significant difference in methylation in the cerebellums between the two groups. The hippocampus is a brain structure involved in learning and memory formation. It is often shrunken in chronically depressed people and antidepressants have been shown to stimulate the growth of new neurons in the structure. Childhood abuse is also linked to reduced volume of the hippocampus and to learning deficits.

Although the rRNA result was unexpected, it may help explain the link between neuron growth and depression, Meaney says. “Neurogenesis is going to depend on protein production,” he says. So child abuse could shut off rRNA genes by scarring them with methylation. That leads to depletion of rRNAs, which then dials down protein production, leading to reduced neuron growth and thus depression and suicide.

Meaney suspects that the results could be even more dramatic than indicated. The healthy population the researchers compared suicide victims with died in car accidents, but “there’s always the suspicion that highway accidents are not so accidental,” he says. Had some of the drivers committed suicide, the gap between the two groups would have possibly appeared narrower. About 10 percent of highway fatalities are suspected suicides. Some of the accident victims also had histories of drug and alcohol abuse that might mark the brain in ways similar to child abuse.