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.