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Schizophrenia, bipolar link found. (Disorders may Share Gene Complex).

Bipolar disorder may be associated with a gene complex that previously was associated with schizophrenia, results of a new genetic study show.

The discovery marks the first time that bipolar disorder and schizophrenia have been associated consistently with a gene complex, according to Dr. Elliot Gershon, a psychiatrist and the study's senior investigator. "This supports what many of us have speculated in print for awhile, which is that there are some shared vulnerability genes for both forms of major mental illness--even though they're not inherited generally in the same families."

Dr. Gershon, professor and chairman of psychiatry at the University of Chicago, and his colleagues found that small differences in DNA called single nucleotide polymorphisms occurred in areas of chromosome 13q more frequently in families that had at least two members with bipolar disorder than in members of control families without the disorder. The area in question contains a complex of two overlapping genes-G72 and G30-that are not near other genes on the chromosome.

The study included 371 people from 22 extended families in pedigrees from the clinical neurogenetics branch of the National Institute of Mental Health and 474 people from 152 families in pedigrees from the NIMI-I Mental Health Genetics Initiative. Both pedigree series were made up primarily of people of European descent (Am. J. Hum. Genet. 72[5]:1131-40, 2003).

Specific and global differences in the gene complex were associated significandy with bipolar disorder in the clinical neurogenetics sample. In the NIMH sample, however, specific differences in the gene complex were not associated significantly with bipolar disorder. Only the global difference in the DNA sequence of the gene complex was significantly associated with bipolar disorder in the NIMH sample.

In an interview, Dr. Gershon estimated that people who have the single nucleotide polymorphisms in the gene complex have a 25%-200% increase in the risk of developing bipolar disorder. The increased risk only adds a little to the complex inheritance pattern that exists for bipolar disorder, he said.

Last year, Ilya Chumakov, Ph.D., of Genset Corp., Evry, France, and his associates discovered the same two genes by comparing control subjects with a sample of 213 French-Canadian patients and 183 Russian patients with schizophrenia. In this study, a set of single nucleotide polymorphisms in the G72 gene of schizophrenic patients occurred at a frequency different from control subjects, suggesting that the gene increased susceptibility to schizophrenia (Proc. Nati. Acad. Sci. 99[21]:13675-80, 2002).

Dr. Chumakov and colleagues showed that the protein product of 072 indirectly affects the activation of N-methyl-D-aspartate (NMDA) receptors. Decreased activity of NMDA receptors is proposed as the molecular mechanism that increases the susceptibility to schizophrenia.

The researchers were unable to determine the role of G30.

"This is probably the most plausible evidence to date for a specific gene that is in a linkage candidate region that could play a role in both disorders," said Dr. Douglas F. Levinson of the University of Pennsylvania in Philadelphia.

Dr. Levinson told CLINICAL PSYCHIATRY NEWS that the bipolar and schizophrenia studies together do not prove that 072 plays a role in both disorders, or even in each alone. However, he added that "these are the kinds of exciting studies where even if only 20%30% of the findings turn out to be correct, we'll know enormously more about schizophrenia and bipolar disorder and their relationship in 3-5 years than we have ever known."
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Author:Evans, Jeff
Publication:Clinical Psychiatry News
Geographic Code:1USA
Date:Jun 1, 2003
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