Reprinted with premission from THE SATURDAY EVENING POST, May/June 2000, pp. 52-55
Surveying the Genetics of Bipolar Disorder
Editor's Note: "It has been extremely successful," says John Nurnberger, M.D., of the collaboration between researches into
the genetics of bipolar disorder at the Indiana University Institute of Psychiatric Research and Saturday
Evening Post families who are participating in the study. Dr. Nurnberger updated us on the current status
of his research and addressed the national efforts to prevent the escalating public-health threat of suicide--
an all-too-common tragedy among teenagers with bipolar and other psychiatric disorders.
Q: Are Post readers continuing to help your research into the genetics of manic-depression?
A: The Post readership has been extremely helpful. We have identified a number of families around the
country that are qualified for the study. We have been in touch with some families by letter and then by phone. In
other cases, we have traveled to meet with families. Sometimes we have done telephone interviews and sent
blood kits for blood samples to their local doctors. We have had tremendous cooperation from the families who have
responded. It has been extremely successful.
Q: Are you looking for additional families?
A: We certainly would like to identify more families with multiple cases of manic-depressive illness, or bipolar
affective disorder. We are particularly looking for families with a sibling pair-- that is, a brother-brother,
brother-sister, or sister-sister pair-- both of whom have bipolar disorder. These families are hard to find.
It is very helpful to us to have the nationwide communication that the Post survey provides.
Q: Recently, U.S. Surgeon General David Satcher proposed a national strategy for suicide prevention. He
citeded statistics of 31,000 people who end their lives each year and another 775,000 who attempt suicide.
Is there an indication that suicide is on the rise in our country?
A: Suicide is difficult to track. There have been some indications to that effect. We certainly know that
it is a significant public-health problem and is associated with depression and manic-depressive illness.
Q: In Dr. Kay Redfield Jamison's latest book, Night Falls Fast, she states that 90 to 95 percent of suicides are
associated with one of several major psychiatric illnesses--depression, bipolar illness, schizophrenia, drug
and alcohol abuse, and personality disorders. Are people with bipolar disorder more voulnerable to suicide?
A: There is no doubt about that. There is a substantial increse in risk in people with manic-depressive illness.
Figures in the literature suggest up to one out of every six people with manic-depressive illness may end
their lifes by suicide, which is much, much higher than the risk in the general population.
Q: Dr. Jamison's book does shed some light on the complex subject of suicide. Would it be helpful to people
interested in understanding mrore about the subject?
A: She is an excellent writer. Upon reviewing the areas that she touches on, it seems to me that the book
would be a very good one to recommend.
Q: Writer Danielle Steel addressed a Senate subcommittee in February on suicide prevention, urging
them to raise more funds for research and awareness of the national campaign. Our Jan./Feb. '99 issue,
suffered from manic-depression. How can parents recognize the signs of mental illness, including bipolar
disorder, in their children?
A: There are several different types of major mental illness. The signs of bipolar illness are usually evident
in mood changes. If a parent were to notice a mood change in an adolescent--either depress, irritability,
or elation-- that was unusual and went on for days or weeks at a time, then that might be a sign that some
kind of further evaluation was indicated. Usually there are other changes that accompany the mood change, including changes in sleep patterns, eating
habits, or in activities or interests. Commonly, when a person is depressed, they will lose interest in many things
they may have previously enjoyed. When a person has a manic episode, they may develop many new interests
all of a sudden or change their interests very drastically and abruptly. These would be major signs that a parent
would want to be aware of in terms of mood disorder. Sometimes, the initial signs of mood disorder are masked by use of drugs or alcohol. Sometimes problems
at school or problems with the law may be first noted. We should also think abou problems that may indicate schizophrenia, another major mental disorder. In this case,
changes in thinking are usually evident first. It might be that a child would not be making sense in the way
they were talking, or would be isolating him or herself from friends and family and be unable to progress
in school. If those signs were to present themselves, a further evaluation may be required.
Q: Are young people frequently misdiagnosed and prescribed medications that might not help them?
A: This is a complicated area. There are some instances in which kids wil be taking medications that
are not beneficial to them. It is certainly possible that antidepressants or stimulants may worsen
symptoms of medications on their children. If the condition is serious, they should get an evaluation
a qualified psychiatrist.
Q: Does it happen often that adults with manic-depression are prescribed the wrong medications?
A: It happens too often. It mat be that the history is not taken adequately to see that they don't just have a
history of depresssion, but they also have a history of mania. Or it may be that the person has been put
on a mood stabilizer but they are not taking the mood stabilizer.
Q: And this can lead to serious consequencees?
A: Yes, it can. It can lead to the development of a manic episode, which can be very disruptive, as we know
manic episodes can be. A person can damage relationships, jobs, and financial security very quickly.
Q: In a recent court ruling in Connecticut, a man with biploar diorder who robbed a bank was acquitted on
the grounds that the antidepressant Prozak and the tranquilizer Xanax, prescribed to treat a manic condition,
impaired his judgement. Does this ruling underscore the danger of putting a person with biploar disorder on the
A: In that case, this is a person with a diagnosis of bipolar disorder. In other words, this person has had a
manic episode in the past. In that situation, we would not put a person like this on Prozac unless they were
on a mood stabilizer like lithium or valproate. If a person with a history of mania is started on an antidepressant
like Prozac without a mood stabilizer, it make provoke an episode of mania or hypomania.
Q: Has there been further progress into locating the genes linked to bipolar disorder?
A: It will help us tremendoulsy. The information provieds a framework against which to test the results of our families.
It will show where the genes are located for many different functions in man. Genes that may cause
manic-depressive illness will be identified in the particular areas that we have evidence for linkage. We can
then specifically go to the genes in those areas and test them.
Q: Once the pharmaceutical companies have this information, will they be able to develop new drugs to better
address bipolar disorder?
A: No question about it.
Q: Have any new drugs come out to help people deal with manic-depression?
A: Lithium is the traditional standard. We are, however, using more and more valproate in the treatment
of bipolar illness. Recently, there has been interest in gabapentin. The evidence for gabapentin is not
as strong yet, as is the evidence for lithium and valproate. We also still use a fair amount of carbamazepine.
There are new agents, incuding lamotrigene [another anti-epileptic drug], that are being used as well.
In addition, there is interest in a number of experimental treatments for manic-depressive illness that have
possibilities for advancing the field significantly, both in the area of antidepressants and mood stabilizers. I
don't know that any of those are ready for widespread clinical use.
Q: In your clinical experience, what is one of the biggest myths about suicide?
A: One myth is that one should not talk about suicide to people wo are depressed, for fear that might put ideas
into their head. If there is a concern that someone is very depressed, then it needs to be evaluated. We
do have to ask questions about what people are thinking. Are they thinking of harming themselves?
There is nothing wrong with asking those questions. We need to ask those questions of people who are
significantly depressed. There is also this myth that people who make suicide gestures or attempts are giving
us a real warning that, in fact, they may carry out suicidal plans in the future. Whenever we see gestures
or attempts, we need to take them seriously.
Q: Prevention is the key message that Drs. Satcher and Jamison promote in their public-health messages.
Could most suicides be prevented with proper treatment?
A: There is no doubt that treatment of an acute episode will decrease the likelihood of suicidal thoughts
and acts. During an acute episode of depression, medical attention will make a difference and help to
prevent suicide. Long-term prevention is a more difficult issue. We are still working on the best strategies for that.
We have good evidence that lithium makes a real difference in the long time in people with bipolar illness.
We are trying to gather that evidence for other mood stabilizers, also.
Q: Is there anything you would like to add about your research at the Indiana Uinversity Institute of Psychiatric
A: We think this work is going to make a tremendous difference in how people regard these illnesses, in lessening
the stigma that may be attached, and in finding new treatments and ways of preventing these conditions. We
think these changes will come about over the next several decades. It will not be overnight. There are very
important strides being made along the way. We need people's help in doing this work. The only way that
we can make advances in understanding the genetics of these disorders is with help from the families of people
who have the disorders. We are very grateful to the families that have agreed to participate, and we hope
that more families will join them.
Q: Are other institutions that do similar research keenly watching the results of your study?
A: Yes. We are also collaborating with a number of institutions. We are now part of a nine-site study with
Johns Hopkins, Washington University in St. Louis, University of California in Irvine, University of California in
San Diego, University of Pennsylvania, University of Iowa, University of Chicago, and Rush-Presbyterian Medical
Center in Chicago.
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Reprinted with permission from The Saturday Evening Post Society, a
division of Benjamin Franklin Literary and Medical Society, Inc. © 1998.