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Fighting fear

At last there's hope for those whose lives are ruled by terror

THE genetic basis for most panic attacks and other devastating anxiety
disorders has been discovered. The breakthrough could make it possible to
develop drugs that help people conquer their fears.

“It looks like they have found an entirely new mechanism of disease,” says
Raymond Crowe, a psychiatrist at the University of Iowa who studies the genetics
of panic disorder. “It’s a very important finding.” According to some estimates,
more than 10 per cent of people suffer from some form of anxiety disorder.

Xavier Estivill’s team at the Centre for Medical and Molecular Biology in
Barcelona was studying families with a history of problems such as panic
disorders, agoraphobia (fear of public places) and social phobia. The
researchers discovered that a small region on chromosome 15 was duplicated in 90
per cent of the affected family members.

To make sure this genetic anomaly was not just specific to these families,
the researchers analysed 70 unrelated sufferers. Remarkably, 97 per cent had the
duplication, which Estivill calls DUP25, compared with only 7 per cent of other
individuals.

“The duplicated region contains more than 60 genes,” says Monica Gratacos, a
member of the team. Only 23 have been identified so far, she says, but these
include genes for proteins that control communication and interaction between
neurons. Too much of one or more of these proteins might make the brain
oversensitive to stressful situations, the researchers think.

But while having DUP25 greatly increases the risk of anxiety disorders, it
doesn’t necessarily condemn you to a life of fear. “The environment is also very
important,” says Gratacos. “Even if you have the duplication you may not have
any kind of fear [disorder].” In the affected families, for instance, 20 per
cent of people with DUP25 had no anxiety illness at all.

The team is now trying to identify exactly which genes on DUP25 lead to
anxiety disorders. If they can do this, it might be possible to find drugs that
suppress either the genes or their protein products. “It’s not so easy,” says
Gratacos. “It will take at least five or ten years.”

But perhaps the most bizarre feature of DUP25 is that its behaviour defies
the usual rules of heredity. With each generation, it can appear, disappear or
switch from one form to another. It even varies within individuals—not all
cells from some patients had the duplication. “It’s very surprising and
exciting, so it needs to be confirmed in other patient populations,” says David
Ledbetter, a geneticist at the University of Chicago.

  • More at: Cell (vol 106, p 367)

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