Scientists say they've identified a flawed gene that appears to promote manic-depression, or bipolar disorder, a finding that could eventually help guide scientists to new treatments.

A particular variant of the gene was associated with only about 3 percent of cases in a study, but researchers said other variants might be involved with more.

Follow-up research might help reveal the mysterious underlying biology that makes some people susceptible to the disorder, and so help scientists devise new treatments, said the study's senior author, Dr. John Kelsoe of the University of California, San Diego.

The work is reported in Monday's issue of the journal Molecular Psychiatry.

Previous studies have suggested that other genes are involved in manic-depression. But one expert, Dr. Melvin McInnis of Johns Hopkins University in Baltimore, said in an interview that he thinks Kelsoe's new work and another recent study provide the strongest evidence for involvement of particular genes in the disease.

Manic-depression, which affects about 2.3 million American adults, involves episodes of depression and mania, states of abnormally high mood or irritability.

While effective treatment is available, scientists would like to find better medications.

Genetics clearly play a role. Kelsoe's work focused on a gene called GRK3, which influences the brain's sensitivity to chemical messages brain cells send each other. Defects in the gene might promote manic-depression by making people oversensitive to these messages, which are carried by dopamine and other substances, he said.

Kelsoe and colleagues found statistical evidence tying a particular variant of the GRK3 gene to the disease. They tracked the inheritance of this variant from parent to child in families with a history of bipolar disorder. Overall, the variant was passed along more often than one would expect by chance to a child who later developed the disease.

That suggests the variant promotes susceptibility to bipolar disorder.

The association between the variant gene and the disorder appeared in one group of 153 families and a second group of 275 families. That association is only statistical, and Kelsoe said researchers now are looking for biological evidence that this variant of the gene acts abnormally.

In any case, Kelsoe said other investigators will need to confirm his study's finding in other families to build the case that GRK3 is truly related to manic-depression.

``It's likely only one of many genes involved in the disease,'' Kelsoe said. ``Who knows how many such genes there are? It's likely in the dozens.''

On the Net:

National Institute of Mental Health: www.nimh.nih.gov/publicat/bipolarmenu.cfm

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Last updated: 06/20/2003 - 08:17 AM