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Old 01-12-06, 10:27 AM
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New gene linked to bipolar disorder

* 14:08 12 January 2006
* NewScientist.com news service
* Emma Young

A gene involved in causing bipolar disorder in as many as 10% of patients with the condition has been identified by researchers in Australia. Other teams have previously claimed to have found bipolar susceptibility genes, but this is the first time that the evidence has been close to conclusive, the researchers claim.

The work might also explain how lithium, which has been prescribed for bipolar sufferers for more than 30 years, can help patients. But while lithium works for some, one-third to one-half of patients do not benefit from existing treatments – none of which were created specifically for the disorder, which is characterised by extreme mood states.

“The long term goal is to get new drug targets that are specific for bipolar disorder,” says team member Ian Blair of the Garvan Institute of Medical Research in Sydney.

The new study of about 1200 patients from Australia, the UK and Bulgaria implicates a gene called Fat on chromosome four. This gene plays a role in cell adhesion in the brain. People with the newly identified polymorphism, or form of this gene, appear to be at twice the risk of developing bipolar disorder, though it is not yet clear exactly why, says Blair.
Altered expression

Over the years, a number of groups have identified genes which might be involved with bipolar disorder. These studies have involved looking for genetic mutations that are statistically more common in bipolar patients. But when such studies are replicated, the apparent gene associations often vanish, Blair says.

The Australian team also hunted out bipolar-related genes in this way, but they went further. They identified one gene that seemed to be implicated – the Fat gene – in four different groups of patients, one from Australia, two from the UK and one from Bulgaria.

They also gave the bipolar drugs lithium and valproate to mice, and investigated the effects on their brains. Fat was significantly down-regulated as a result of treatment. “This gene significantly altered in expression in response to these therapeutic drugs,” says Blair.

Existing drugs do have serious side effects. Lithium, for example can cause tremors and kidney dysfunction. Ultimately, the team hopes to develop new targeted drugs that avoid unpleasant side effects.

More work is also needed to reveal exactly which other genes might be involved. “This is a complex genetic disorder caused by the interaction of a number of genes and the environment,” Blair stresses.

Journal reference: Molecular Psychiatry (DOI: 10.1038/sj.mp4001784)
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Weblinks

* Garvan Institute of Medical Research
* http://www.garvan.org.au/
* Molecular Psychiatry
* http://www.nature.com/mp/index.html



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