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EDITIONS
 Sunday, 26 January, 2003, 00:01 GMT
Missing gene link to aggression
Anxious man
Anxiety could be due to a missing gene
People who are over-aggressive or excessively anxious may be missing a gene, say scientists who conducted experiments on mice.

The gene, called PET-1, was removed from specially-bred mice by scientists at Case Western Reserve University in the US.

They found that the mice had heightened levels of both anxiety and aggression - when the mice were given a "territory", their response time to attack an intruder was significantly lower than a normal wild mouse, and they tended to launch an attack more often.

Although mice are already fairly nervous creatures, when the genetically-modified animals were placed in a test chamber with a choice between an "unprotected" open space and "safe" enclosed space, they tended to stay in the latter for longer periods than normal mice.

This is the first gene shown to impact adult emotional behaviour

Dr Evan Deneris, Case Western Reserve University
This, said the testers, was a clear sign that the mice were suffering more anxiety.

Brain cell

Dr Evan Deneris, who led the study, said: "The behaviour of the PET-1 knockout mice is strikingly reminiscent of some human psychiatric disorders that are characterised by heightened anxiety and violence."

The gene appears to be important in the development of a certain kind of brain cell in the foetus.

The cells produce a chemical called serotonin, which is known to be important in humans for the control of mood.

People who do not make enough serotonin can suffer from mood disorders such as depression and anxiety. Popular drugs such as Prozac work by increasing the amount of serotonin available to the brain.

Mice lacking PET-1 did not produce enough serotonin cells, and the ones they did make were defective.

Dr Deneris said: "We have now shown that PET-1 is required specifically for foetal development of serotonin neurons. This is the first gene shown to impact adult emotional behaviour through specific control of foetal serotonin neuron development."

While humans and mice share many genetic characteristics, and PET-1 is present in the human genome, it remains to be discovered whether the gene has a similar role.

Early diagnosis

However, Dr Deneris believes that, if this proves to be the case, tests could be developed to spot people who are at risk before their symptoms become severe.

Professor Peter McGuffin, from the Institute of Psychiatry in London said that it was hard to conceive that a gene test would be able to outperform the doctor's old fashioned skill in diagnosing psychiatric disorders.

However, he said that a gene test could predict who would respond to a particular drug and who would not.

He told BBC News Online: "Of course, what you observe in a mouse is quite different from what you observe in a clinic.

"What is unusual here is that anxiety and aggression don't normally go together in human patients - so the gene they have knocked out may just have thrown a spanner in the works rather than relate specifically to anxiety or aggression."

Another researcher, Dr Marianne van den Bree, a senior lecturer at the University of Wales in Cardiff, told BBC News Online: "We currently think that the balance between genes and environment in problems like aggression is about 50/50.

"There are likely to be many different genes involved which have an influence on this, so developing a test will be very difficult."

The latest study was published in the journal Neuron.

See also:

02 Aug 02 | Health
22 Jan 01 | Business
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