A
Genetic Link to Depression
by Paul Recer,
Associated Press, July 17, 2003
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Traumatic life
events, like the death of a loved one or the loss of a job, send
some people into a deep depression, while others cope with the
same problem and move on. The difference may be a gene that
control chemical messengers in the brain, a study shows.
The study focused on two forms of a gene called 5-HTT, which
helps regulate a brain chemical called serotonin. It found that
adults who carried a short form of this gene were more prone to
slip into depression after experiencing serious life events than
were adults who carried a long form of 5-HTT.
Experts said the study, appearing Friday in the journal Science,
for the first time shows a proven direct genetic link between
emotionally distressing events and the onset of clinical
depression.
"It is a very important discovery and a real advance for the
field," said Dr. Thomas R. Insel, director of the National
Institute of Mental Health. "The effects of stress on depression
only get played out in certain individuals and those are
individuals…with a particular variation of this single gene."
Insel said the finding has no immediate clinical application,
but it gives a fundamental new understanding of the linkage
between genes and depression.
The World Health Organization has identified depression as the
fourth leading cause of disease burden, which is defined as
years patients must live with a disability. It's estimated that
about 121 million people worldwide suffer from depression. Since
the disorder is now being diagnosed more frequently, the WHO
estimates that depression will become the first cause of disease
burden worldwide by the year 2020.
Clinical depression can cause a constant, persistent sadness and
lethargy, a sense of personal worthlessness, a loss of interest
in normal activities, changes in diet and sleep, and frequent
thoughts of death. Untreated, depression can often lead to
suicide. The condition also has been linked to a higher
incidence of heart disease and death, particularly in men.
Although drugs successfully treat depression in millions of
people, the precise causes and controls for the disorder remain
elusive. Often patients must go through a trial-and-error period
before the best treatment for them personally is identified.
In the Science study, researchers from the University of
Wisconsin, Madison; King's College in London, England, and the
University of Outage in New Zealand analyzed the type of 5-HTT
gene carried by 847 adults in New Zealand who were part of a
long-term health study.
There are two forms of the 5-HTT gene, the long and the short.
An individual can inherit two copies of the long form, two of
the short, or one of each.
The researchers focused on subjects in the study who had had
traumatic life events over a five-year period. These events
could include such things as a death in the family, a marriage
breakup or the loss of a job.
Patients with at least one copy of the short form of 5-HTT were
more at risk of depression, the study found, suggesting that
this form of the gene caused a heightened sensitivity to stress.
Patients with only the long 5-HTT gene were more resistant to
depression following serious emotional events and tolerated
stress better.
Depression was diagnosed in about 33 percent of the study
subjects who had at least one short 5-HTT gene copy and who had
experienced four traumatic events over a five-year period. Among
those with two copies of the long form of 5-HTT, only 17 percent
were diagnosed with depression after four traumatic events.
Researchers said tests showed that those with even one copy of
the short 5-HTT gene were almost three times more likely to
think about or attempt suicide than those with only the long
5-HTT.
Insel said the difference in the forms of the 5-HTT gene is not
in the proteins they produce, but in the regulation of
serotonin, a neurotransmitter that carries signals between nerve
cells. The short version of 5-HTT is not as effective in
controlling the serotonin flow as is the long version, he said.
Lead authors of the study are Dr. Avshalom Caspi of King's
College London, and Dr. Terrie Moffitt of the University of
Wisconsin.
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