A FAT chance of becoming manic-depressive

A collaboration, led by Sydney scientists at the Garvan Institute of Medical Research and University of New South Wales, has discovered the first risk gene specifically for bipolar disorder, also known as manic-depressive illness. This means that people who have a particular form of this gene are twice as likely to develop the disease.

Dr Ian Blair, lead author of the research paper published in Molecular Psychiatry, 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.”

“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 the it contributes to the increased risk of bipolar disorder,” explains Dr Blair.

Bipolar disorder is a major psychiatric illness affecting around one person in every 50. 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.

Dr Blair’s 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.

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.

“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.