"Finding a gene for bipolar disorder is like finding a needle in a haystack, but by focusing our search on families with a distinctive form of the illness we were able to pinpoint a region of the genome where disease genes are likely to be found," said James Potash, M.D., lead author of the article.

The combination of a consistent worldwide prevalence of roughly 1 percent for serious psychiatric disorders (about 1 percent) and the persistent tendency to run in families has always suggested a strong genetic role, according to the authors. "But pinning down that role is complicated by the many variations in symptoms, even within the same family," said Potash. "There are probably many different genes and environmental factors that can cause any given mental illness."

Based on previous suggestions that certain broad regions of the human genome, especially on chromosomes 13 and 22, may contain genes that contribute to both bipolar disorder and schizophrenia, Potash and his American colleagues focused on families with the psychotic form of bipolar disorder.

The concept behind the current study is that of two slightly overlapping circles, explained Potash. One circle contains all of the genes that contribute to schizophrenia, and the other circle contains all of the genes that contribute to bipolar disorder. The area of overlap between the two circles represents the genes that are common to both diseases as well as for psychotic bipolar disorder.

The researchers carefully evaluated and took blood samples from 65 patients with psychotic bipolar disorder and from their extended families. They extracted DNA and scanned it with probes, looking for matching sequences that were more likely to appear in people with mental illness than in healthy relatives. As the researchers noted the chromosomal locations of the markers, they were able to narrow the sequence within which the genes were located.

The 10 families in which 3 or more members had psychotic bipolar disorder showed strong genetic linkage to specific regions of chromosomes 13 and 22. These results differed significantly from those for all 65 families, which collectively showed little or no linkage evidence in these two regions.

"These results confirmed our expectation that genes for the psychotic form of bipolar disorder are likely to be found in the same regions that show linkage to both bipolar disorder as a whole and to schizophrenia," said Potash.

One important implication of the study is that "overlap" genes may contribute to brain abnormalities that are present in both bipolar disorder and schizophrenia; this may explain why the same antipsychotic medications are effective for both diseases, noted Potash.