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New light on brain mechanisms in Bipolar Disorder

18 August 2008

Depressed boy

Bipolar Disorder may be linked to the control of the activity of brain cells, according to a new genetic study led by scientists at Cardiff, the Broad Institute of Massachusetts Institute of Technology and Harvard University.

Bipolar Disorder is characterised by severe disturbances in mood ranging from depression to elation and can cause deep suffering in at least 1 per cent of the population.

In the largest analysis of its kind to date for Bipolar Disorder, genes from more than 10,000 people were studied by the team, led jointly by Professor Nick Craddock of the School of Medicine and Drs Pamela Sklar and Shaun Purcell of Massachusetts General Hospital, and the Stanley Center for Psychiatric Research at the Broad Institute in the US. The study involved collaborating groups in the UK, Europe and US, including the Wellcome Trust Case Control Consortium (WTCCC).

The researchers examined about 1.8 million genetic variations in 10,596 people – including 4,387 with Bipolar Disorder.

The scientists found an association between Bipolar Disorder and two genes which help make proteins that control the activity of nerve cells by managing the flow of sodium and calcium ions into and out of the cells.

A gene called Ankyrin 3 (ANK3) showed the strongest association with bipolar disorder. The ANK3 protein is part of the cellular machinery which controls the activity of cells. The second strongest association was found in a gene responsible for channels controlling calcium flow in the brain.

The results point to the possibility that Bipolar Disorder might stem, at least in part, from malfunction of these brain mechanisms.

Professor Craddock, of the School’s Department of Psychological Medicine, said: "The activity of nerve cells depends upon a delicate chemical balance. We do not know yet if the newly-discovered genetic variations affect the balance, and if so, how. However, finding these genetic associations is very significant and we hope will, in time, pave the way towards new kinds of treatment."

One of the problems with bipolar disorder research is that it is thought to involve many different gene variants, each exerting relatively small effects. Researchers therefore need large samples to detect relatively weak signals of illness association and are keen for more people with bipolar disorder to help with the research.

Professor Craddock and a large group of international collaborators have reported their findings online in Nature Genetics.