This has been the enduring mystery: How do events in the outside world get inside your head? That is, how do things that affect whether a child grows up to be contented and well-adjusted or a neurotic mess—things like abuse and neglect—change the gray matter to produce the brain activity and circuitry that corresponds to these psychological states? By turning some genes on and other genes off, according to a study posted this evening in the May 6 edition of the online PLoS ONE.
One of my favorite studies ever done showed how this happens in rats. In the 1990s Michael Meaney of McGill University saw that when a Mother Rat rarely licks and grooms her pups, the pups grow up to be fearful, stressed-out, jumpy and neurotic. If a Mother Rat is attentive and grooms her pups a lot, they grow up to be less neurotic, less fearful, more curious, mellower. The reason isn’t genetic, at least not in the usual sense. That is, it isn’t that mellow moms have mellow pups and neglectful moms have neurotic pups because the pups inherited mom’s mellow or neurotic DNA. (Pups born to attentive moms but reared by neglectful ones grow up to be stressed out, while pups born to neglectful moms but reared by attentive ones grow up to be less fearful, less neurotic. That is, they resemble their adoptive mom, not their biological one.)
Instead, licking and grooming removes the silencer on a gene that makes stress-hormone receptors in the rats’ brains. The more such receptors the brain has in the hippocampus, the fewer stress hormones are released and the mellower the rat is. But in rats reared by neglectful mothers, the silencer stays firmly attached, the brain therefore has a small supply of stress-hormone receptors, and glands pump out a flood of the hormones, producing a rat that is constantly jumpy and on hair-trigger alert. There you have it: Maternal behavior alters whether a gene is on or off.
Now the same core team of scientists has found that something like this happens in people, too. They compared the brains of troubled individuals who committed suicide, and who had been abused or severely neglected when they were children, to a comparison group of people who had no history of childhood abuse and who died suddenly of other causes. What the scientists did not find was any significant differences in the two groups’ gene sequences—that is, the strings of As, Ts, Cs and Gs that make up the double helix were basically the same.
But there were stark differences in the on-off setting of genes that work in the brain’s hippocampus. In the suicides, the genes were turned off like lights during a blackout, the McGill scientists report. In particular, “ribosomal RNA genes,” which humans have about 400 copies of and which make a big chunk of the cellular machinery that produces proteins, were studded with “off” switches. (This was not so in the cerebellum, but only the hippocampus. The former is mostly involved in movement, while the hippocampus encodes memories—and is often shrunk in people who have experienced trauma.)
As you would expect, the suicides—because of the “off” genes—made fewer rRNAs in the hippocampus. That likely means they also made fewer proteins—the workhorses of cells, since they include enzymes.
The next question is what effect the turned-off genes have in the brain, and how that may explain the suicides. But for now, chalk up another advance in understanding how the experiences we have can reach into our very DNA.