Discovery that common mood disorders are inherited
together may reveal genetic underpinnings

The genetic underpinnings of panic disorder and manic depressive (bipolar) illness have long eluded scientists. Now, researchers at Johns
Hopkins studying the inheritance patterns of these conditions have concluded that they probably are not separate diseases at all, but different forms of a shared and complex biological condition.

"We've shown that panic attacks and panic disorder are related genetically to bipolar disorder and therefore likely share a common cause," says Dean F. MacKinnon, M.D., assistant professor of psychiatry at Hopkins and lead author of a report on the study in
the current issue of the American Journal of Psychiatry. "We still can't say what specific gene or genes cause what, but this is a major step toward solving these problems," says MacKinnon.

The scientists' case for a common foundation emerged from examining the disease pedigrees of 203 families in which at least one family
member had bipolar disorder. Interviews with family members led to the
identification of symptoms characteristic of major mood disorders and other psychiatric conditions in relatives.

"We found that if one family member has both panic disorder and bipolar disorder, then the risk of panic disorder in other relatives is greatly increased," says MacKinnon. "These links reflect the genetic complexity of thesedisorders."

While genes may not tell the whole story of major psychiatric diseases, the persistent frequency in about 1 percent of the global human
population, regardless of cultural or ethnic differences, and their 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. Some, for example, have intense
episodes of mania, others have mild mania, some with panic, some without.

"Gene expression is complex, and in these disorders, environmental factors and nature-nurture interactions are all certainly involved," says MacKinnon.

Further studies of families with both panic and bipolar disorder and with bipolar disorder alone should lead to other insights into both
conditions, says MacKinnon. For instance, panic and bipolar disorder may be the same underlying condition marked by different degrees of intensity of such symptoms as anxiety and fear, heart palpitations,
shortness of breath and dizziness. =93There might be a panic flavor of bipolar disorder so that if you have bipolar disorder, you also have
panic," says MacKinnon.

Alternatively, panic vulnerability may be a fairly common trait that shows itself preferentially under certain extreme forms of provocation, one of which is bipolar disorder.

"The exciting thing is that we can now begin to link up specific clinical features of these various disorders to a genetic model of complex
inheritance. We see that certain family members have different varieties of
disease, and now we create a model to account for this variation, and improve diagnosis and treatment,"says MacKinnon.

Other authors of the study are Peter P. Zandi, M.P.H.,
Jennifer Cooper, M.D., James B. Potash, M.D., M.P.H., Sylvia G. Simpson, M.D., M.P.H., Elliot Gershon, M.D., John Nurnberger, M.D., Ph.D., Theodore Reich, M.D., and J. Raymond DePaulo, M.D.

The research is supported by the National Institutes of Mental Health and the NIMH Bipolar Disorder Genetics Initiative, the Charles A.
Dana Foundation Consortium on the Genetic Basis of Manic Depressive Illness, the National Alliance for Research on Schizophrenia and Depression, and the Ted and Vada Stanley Foundation.

Related Web sites:

The Johns Hopkins Department of Psychiatry and Behavioral Sciences:
http://www.med.jhu.edu/jhhpsychiatry/master1.htm
Depression and Related Affective Disorders Association (DRADA):
http://www.hopkinsmedicine.org/drada/

Johns Hopkins Medical Institutions' news releases are available on an EMBARGOED basis on EurekAlert at http://www.eurekalert.org
Newswise at http://www.newswise.com and from the Office of
Communications and Public Affairs'direct e-mail news release service. To e nroll, call 410-955-4288 or send e-mail to bsimpkins@jhmi.edu.

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