Bipolar disorder discovery

Two Irish researchers have identified a gene mutation linked to bipolar disease - a crucial finding, writes Dick Ahlstrom

Two Irish researchers have formed a link between a common mental condition and a specific malfunctioning part of the genetic code. The discovery opens up the potential for greatly improved diagnosis and early warning of the condition and the possibility of new treatments.

Consultant clinical geneticist at Our Lady's Hospital for Sick Children, Dr Willie Reardon, and clinical director at St Ita's Hospital Portrane, Dr Richard Blennerhassett, collaborated on the study. It gives medical researchers a very clear genetic target for understanding bipolar affective disorder, more commonly known as manic depression.

"This is the holy grail of psychogenetic disease," states Reardon. "We have stumbled upon a massively important connection." Reardon's work is funded by the Children's Medical and Research Foundation at Our Lady's Hospital.

The two publish their findings this week in the American Journal of Medical Genetics. It focuses on a connection between bipolar disorder and an abnormality to chromosome 11q24.2.

The Journal has run an editorial on their findings, an indication of their significance. Dr Reardon is in London this morning to discuss his findings with the Clinical Genetics Society of the UK.

The connection between 11q24.2 and bipolar disorder came via a question asked by a patient being seen by Reardon. It was established she had an abnormality in that chromosome and coincidentally had after a 13 year struggle finally been diagnosed with bipolar disorder.

"She asked is my bipolar disease coincidental to the chromosome 11 problem you have identified. I realised there was potentially something very important in her question," says Reardon.

He found one or two other references to bipolar and 11q24.2. He asked Blennerhassett to reconfirm both the bipolar diagnosis and the chromosome 11q24.2 abnormality and to consider the possibility of a connection. "We then got quite excited about this."

There is a huge international effort that includes scientists in Ireland trying to discover any gene abnormalities that predispose a person to conditions such as schizophrenia, depression and bipolar disorder, says Reardon. Typified by severe mood swings that range from from high elation to deep depression, bipolar disorder affects about 2.6 per cent of the general population.

Reardon and Blennerhassett believe they have found at least one such connection and are now involved in follow-up work to confirm this. "We have to proceed slowly because there have been many false dawns," he says.

They are collaborating with Dr Simon Holden and Prof Richard Trembath of Guy's Hospital London, who are now studying 11q24.2 in an effort to identify the exact location of the abnormality.

"We are looking at comparable patients, comparing the break points on chromosome 11q24.2 and then looking at associative studies in family groups where bipolar disorder has been reliably diagnosed," explains Reardon.

Diagnosis is not a simple matter. The patient who prompted the study of 11q24.2 had endured 13 years of mental illness before being diagnosed and successfully treated with lithium for bipolar disorder.

Pinpointing a genetic precursor to bipolar disorder would be an important advance, Reardon says. "I find myself with a platform to work from," he says. "This gives us a wonderful launching pad."

It is not guaranteed that 11q24.2 will be definitively implicated in bipolar disorder, "but it gives us a very constructive way of looking for these connections", he adds.

If the connection is confirmed it may be possible to devise a genetic test for the 11q24.2 abnormality. It might also be possible to identify whether the genetic change causes an essential protein to go missing or malfunction. Such information could lead to new kinds of treatments targeting the genetic cause.

The study is "a triumph for the importance of listening to the patient", he believes. "You don't dismiss something a patient suggests. You must always, no matter how unlikely the initial assumption, discuss it as a possibility."