Lead author, Dr Ian Blair, says: "We are the first group in the world to take a multi-faceted approach to identify a bipolar risk gene - we used a number of families, unrelated patients, and therapeutic drug mouse models. Each of these three lines of investigation led us to a gene called FAT."
Contributing author Professor Phil Mitchell, Head of Psychiatry at UNSW, says: "Over the last twenty years we have collected blood samples from 67 families right across Australia. This amounts to hundreds of family members (904), some of whom are spread across four generations. This was a strong starting point in our hunt for a Bipolar gene."
"We know that the FAT gene codes for a protein that is involved in connecting brain cells together, what we need to do now is find out exactly how it contributes to the increased risk of bipolar disorder," explains Dr Blair.
While other scientists have found genes associated with Bipolar, most of them haven't stood up to scrutiny. The Sydney discovery has been verified in four independent study groups: two in the UK, one in Australia, and one in Bulgaria.
Bipolar disorder is a major psychiatric illness affecting around two people in every 100. Tragically, around one in six people suffering from the condition will commit suicide.
Mood-stabilising medications are typically prescribed to help control bipolar disorder. Lithium was the first mood-stabilising medication approved by the U.S. Food and Drug Administration (FDA) for treatment of mania. For decades it has been widely prescribed for the treatment bipolar disorder, yet no one knows for sure why it works.
"Lithium has a number of severe side effects that include tremor and weight gain. Kidney dysfunction may develop in a small proportion of patients when it is administered for long periods of time," says Professor Mitchell.
This new research has raised the possibility that lithium exerts its therapeutic affect by altering FAT gene expression, as well as the expression of genes encoding FAT's protein partners.
"Once we understand exactly what the FAT gene does, we will be able to develop better diagnostic tests for bipolar disorder. In the future, we hope our research will lead to new, targeted medicines specifically for bipolar disorder that don't have the unpleasant side effects that lithium has," says Dr Blair.
The bipolar project team has been a collaborative endeavour over the last decade involving Sydney-based scientists and clinicians from the Garvan Institute of Medical Research, the University of New South Wales and Macquarie University. Additional collaborations provided critical supporting data.
This research was E-published ahead of print on 10 January 2006 in Molecular Psychiatry
Positional cloning, association analysis, and expression studies provide convergent evidence that the cadherin gene FAT contains a bipolar disorder susceptibility allele. IP Blair, AF Chetcuti, RF Badenhop, A Scimone, MJ Moses, LJ Adams, N Craddock, E Green, G Kirov, MJ Owen, JBJ Kwok, JA Donald, PB Mitchell, PR Schofield
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