Progress in Bipolar Genetics Slow, but Promising. (Multiple Genes Involved)

By Sherman, Carl | Clinical Psychiatry News, December 2001 | Go to article overview

Progress in Bipolar Genetics Slow, but Promising. (Multiple Genes Involved)


Sherman, Carl, Clinical Psychiatry News


ATLANTA -- There is little question of an inherited predisposition to bipolar disorder, but the details have proven difficult to unravel, with strong candidate genes emerging on four different chromosomes, Dr. J. Raymond DePaulo said at the annual meeting of the American Academy of Clinical Psychiatrists.

Although the elucidation of genetics is predictably knotty where multiple genes are involved, potential clinical rewards more than justify the effort, given the ambiguities of bipolar diagnosis and the benefits of earlier and more precise treatment.

"I think we'll be able to do this in 10 years," said Dr. DePaulo of Johns Hopkins University Baltimore.

Evidence from family series and twin studies suggests the heritability of bipolar disorder is high: 50%-80%. But genome-wide studies have yet to locate any specific dominant or recessive gene responsible. "Single gene forms of the disorder, if they exist, must be very uncommon," he said.

If multiple genes are involved, these probably will be hard to find: In such cases, each typically has a "smallish" effect on the phenotype, and many people may carry one or two mutations without symptoms. The task is complicated given that bipolar disorder takes a number of forms--each perhaps representing a genetic subtype--that may be difficult to distinguish clinically.

The regions with the strongest probability of linkage to bipolar disorder are on chromosomes 4, 12, 18, and 21. He described research into one of these regions, paternally transmitted 18q, which has been linked to the disorder in pedigree series.

In two separate studies, the families of 58 patients with bipolar disorder I and at least two first-degree relatives with a recurrent affective disorder were investigated: The most common disorder in family members was bipolar disorder II, in 80. Bipolar I was seen in 47, recurrent unipolar depression in 62, and schizoaffective disorder in 4. …

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