Families with severe form of bipolar disorder help scientists narrow the search for disease genes
- Public release date: 1-Apr-2003
Contact: Trent Stockton tstockt1@... 410-955-8665
Johns Hopkins Medical Institutions
Families with severe form of bipolar disorder help scientists narrow the search
for disease genes
After years of frustrating searches for genes that contribute to mental
illness, researchers at Johns Hopkins studying families with a severe form of
manic depressive illness, called psychotic bipolar disorder, may be one step
closer to finding the genetic underpinnings of both bipolar disorder and
"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., assistant professor of psychiatry at
Johns Hopkins and lead author of a report on the study in the April issue of
the American Journal of Psychiatry.
Although genes are unlikely to tell the whole story of major psychiatric
diseases, the persistent frequency of mental illness in about 1 percent of the
global human population, regardless of cultural or ethnic differences, and its
tendency to run in families have always pointed to a strong genetic role. "But
pinning down that role is complicated by the many variations in symptoms, even
within the same family," says Potash. "There are probably many different genes
and environmental factors that can cause any given mental illness."
Motivated by previous suggestions that certain broad regions of the DNA
sequence, especially on human chromosomes 13 and 22, may contain genes that
contribute to both bipolar disorder and schizophrenia, Potash and colleagues
focused on those families with the psychotic form of bipolar disorder. Like
bipolar disorder, psychotic bipolar disorder is characterized by see-sawing
episodes of depression and mania, but it is distinctive because these mood
changes often are accompanied by such psychotic symptoms as hallucinations and
The concept for the new study is that of two slightly overlapping circles,
explains Potash. In one circle are all of the genes that contribute to
schizophrenia. The other circle has all of the genes that contribute to bipolar
disorder, while the intersection of the two circles contains 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 bipolar disorder and from their extended families. They extracted blood
cell DNA and scanned it with DNA probes, looking for matching sequences that
are more likely to appear in those with mental illness than in those without
it. By noting where these markers lay on chromosomes, the researchers were able
to narrow in on where the genes were located.
Out of 65 bipolar disorder families studied, the 10 families in which 3 or more
members had psychotic bipolar disorder showed strong genetic "linkage" to
specific regions on chromosomes 13 and 22. These results differed significantly
from those for all 65 families, which 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," says Potash.
One important implication of the study is that these "overlap genes" may
contribute to brain abnormalities that are shared by bipolar disorder and
schizophrenia, and could help explain why the same anti-psychotic medications
are effective treatments for both diseases, says Potash.
Authors on the report are Potash, Dean MacKinnon, Sylvia Simpson, Francis
McMahon, J. Raymond DePaulo, Melvin McInnis, Peter Zandi, Virginia Willour,
Tsuo-H. Lan, Yuqing Huo, Dimitrios Avramopoulos, Yin Shugart.
The study was funded by the National Institute of Mental Health, the National
Alliance for Research on Schizophrenia and Depression, the Stanley Medical
Research Institute, the Dana Foundation, the Alexander Wilson Schweizer Fund,
the Affective Disorders Fund and the George Browne Laboratory Fund.
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