Gene Is Linked to Depression

By Jamie Talan

July 18, 2003

Scientists for the first time have strong evidence that a specific gene plays a role in determining whether a
person will respond to stressful life events by sinking into severe depression.

The study of 847 young adults in New Zealand has found that the gene can double the risk of developing such depression in the
aftermath of a string of stressful life events.

"It's a beautiful study," said Dr. Daniel Weinberger, chief of the clinical brain disorders branch at the National Institute of Mental
Health in Bethesda, Md., which funded the study. "It offers strong proof for how genes influence how our environment affects

The study's participants had been part of an ongoing study of development and health since birth. The researchers, led by Terrie
Moffitt, a professor of psychology at the University of Wisconsin and at Kings College of London, focused on the serotonin
transporter gene, known as 5-HTT, because of its known association with conditions such as depression. The gene manufactures
a protein that shuttles serotonin, a chemical involved in transmission of impulses between nerve cells, around the brain.

The gene comes in long and short versions. An individual has two copies, one inherited from each parent.

The scientists found that 43 percent of those with two copies of the short version developed clinical depression after experiencing
at least four stressful events during a five-year period. By comparison, depression was evident in 33 percent of those with one
short version and only 17 percent of those with two copies of the long version.

Such life events include job loss, breakup with a spouse or other live-in partner, severe financial problems, a family death, or a
medical illness that led to a work leave.

Moffitt said researchers were surprised to find that the long version of the gene appeared to provide a protective effect. People
with two long copies "were no more likely to become depressed than those who had no stressors in their lives during this study
period," she said. "We did not expect to find this."

Seventeen percent of the study's participants had two copies of the short version; 31 percent had two copies of the long one; and
52 percent had one copy of each. The study appears in today's issue of the journal Science.

So far, the findings have no immediate application. Moffitt said the results need to be replicated in another study before testing of
individuals for presence of the long or short versions of the gene will be pursued. Nevertheless, she and her husband were tested;
they learned that she has two shortened versions and he has the longer ones. She said she has not experienced significant stress.

Last year, Weinberger and his colleagues published a brain scan study showing that people with the short version of the gene had
more activity in the brain region known as the amygdala, which regulates fear and emotion, than did those with the long version. It
was the first time scientists showed how a genetic mechanism can predispose how the brain perceives emotional stimuli.

Serotonin has become something of a household word as millions of people take a class of medicines called selective serotonin
reuptake inhibitors, such as Prozac, which regulate how the brain uses the chemical.

"This confirms what we've known clinically," said Dr. Robert Hirschfeld, chairman of psychiatry at the University of Texas
Medical Branch at Galveston. "Certain people respond more negatively to life events than others. And this seems to be built in."

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