Pleased with the response to an earlier Post survey, researchers are seeking more people willing to help uncover genetic clues to the sometimes devastating illness.

Post readers who responded to the health survey "Mood Disorder Family Tree," published in the March/April '96 issue, are aiding researchers in their painstaking search for the genetic roots of manic-depression, a potentially lethal disorder also known as bipolar illness. Left untreated, one out of five manic-depressives will commit suicide.

Dr. John Nurnberger, Jr., M.D., Ph.D., director of the Institute of Psychiatric Research at Indiana University, recently told us he was very impressed with the response to the first survey, and he designed a second questionnaire to help identify additional families who might wish to participate in this genetic study of bipolar illness.

If four or more members in your family have had mood problems, you could help Dr. Nurnberger and his colleagues study the genetic causes of the disease by filling out the questionnaire on the opposite page. {Note: An electronic version of this form is available on this web site. Click here to access it.}

Dr. Nurnberger is also studying the genetics of alcoholism. In 1941, The Saturday Evening Post published "Alcoholics Anonymous," a story written by Jack Alexander that was influential in the early and rapid development of the AA organization. Reprints of that article are still being distributed by AA. Dr. Numberger's scientific findings may prove helpful in the ongoing battle against alcoholism and teenage drinking in our country. We asked Dr. Numberger what he has gleaned from his research thus far.

Q. Could you tell us about the research you've done on the familial and hereditary aspects of bipolar illness?

A. We have been identifying families with multiple cases of bipolar disorder for the last eight years or so here at the Indiana University Medical Center. We are studying these families carefully and taking blood samples for analysis of DNA. We've looked at the DNA in the laboratory in conjunction with other centers at Washington University in St. Louis, Johns Hopkins, and the National Institute of Mental Health intramural program. We are currently preparing our results for publication from the first series that we have done with that collaboration, It does show that a number of genes are possibly linked to bipolar illness, not just one. We are pursuing the possible areas with additional studies now.

Q. Is it too soon to start thinking about genetic testing for bipolar illness?

A. Yes. The work needs to be replicated. We need to understand if a gene is there, exactly what the gene is, and exactly where it is. We should understand that we are dealing with vulnerability genes. It is not the same situation as it is with Huntington's disease, for instance, where you have a single gene that will determine whether somebody gets the illness. Here you have a situation where the presence of a particular gene probably increases the risk, but it is not an absolute positive or negative.

Q. And more than one chromosome might be involved?

A. That's the way it looks. Looking at the studies that exist thus far, I would say the best evidence exists for a gene on chromosome 18, but there is also evidence for a gene on chromosome 21. There may be one on 11, one on the X chromosome, and possibly one on the other end of chromosome 18. We have been looking at the long arm of that chromosome, but there may be one on the short arm as well.

Q. How many families have you studied in your research at Indiana University?

A. We have screened out 1,500 patients with bipolar I disorder. Of those, we have identified about 50 that meet our criteria for having multiple cases closely related to each other and a family size that is large enough to study with persons within the family available for study. We are pursuing a number of the families you have helped us identify with the first survey you published and are interested in seeing something like it appear again.

Q. Do early identification and treatment make a big difference in the course of the illness?

A. We suspect that they really do make a big difference, because people can devastate their lives in so many ways with untreated mania and depression that might be prevented. There is also increasing evidence that early treatment may actually alter the course later.

Q. Do you have useful information that might help our readers identify some of the symptoms in their teenagers or young people as they begin to occur in manic-depression?

A. If you or a member of your family have severe or persistent depression or an elevated mood, it's something that should be evaluated by a professional. We advise, particularly people who come from families in which there are multiple cases of depression or manic-depressive illness, that they are wise to be aware of the symptoms and signs that may indicate it's appropriate to seek professional help. The National Institute of Mental Health has publications that are helpful for people in identifying the signs and symptoms. Most university medical centers can help provide information as well. We can help provide information to people in this area about appropriate treatment possibilities. If you are looking at a change in somebody's mood that goes on for several weeks and seems to be interfering in their functioning, then it's reasonable to get a professional evaluation.

Q. In the third or fourth generation of a family affected with bipolar disease, does it -become less intense or is it ore likely, to get worse?

A. There is some evidence that it may get worse in some families. In a study done at Johns Hopkins, they found that the illness was actually getting worse as it came down through the generations and that the younger members of family were getting ill earlier and having more episodes,

Q. What if a grandfather had bipolar disease and out of his four children, one child was affected. Would only that child bear children who would be affected?

A. It doesn't necessarily work that way in the families that we have studied. Sometimes it skips a generation.

Q. Several year's ago you were working on something that had to do with manic-depressives and the thickness of their eyelids or the way they responded to light. Is that still something you're interested in?

A. It is still something I'm interested in, but not something we are actively doing at this point. Those tests are pretty difficult and time-consuming. I would say the evidence at this point is not clinically useful. We are still looking at it a research test that may tell us something about how the brain works in people with bipolar disorder.

Q. Is there anything on, an EEG that, will help distinguish between a manic-depressive person and someone who is not?

A. I think the problem that we have with all of the testing that has been studied is the variability of the bipolar syndrome. We are finding multiple genes and think there are multiple causes for the disorder. There are different ways that people can get ill, and so when you look at any biologic marker, it may just identify a subgroup of people with a disorder, and it becomes hard to use as a diagnostic test.

Q. What other areas of research are you studying?

A. We are involved in a similar multicenter study in alcoholism where we are finding multiple cases of illness within single families. We have identified many families with generations of alcoholism. This is part of a six-center study, funded by the National Institute of Alcohol Abuse and Alcoholism. The interesting thing is that there is so much overlap between alcoholism and depression and manic-depressive illness. When we look at our families with manic-depressive illness or bipolar affective disorder, almost half of the affected persons have alcoholism as well. When we look at our alcoholic families, a large number of the people with alcoholism have depression.

Q. Is there something in the genes?

A. There may be. Actually some of the best evidence for single gene effects is in alcoholism. It is a fact that Oriental populations metabolize alcohol differently. Many people from Oriental backgrounds have a flushing reaction to alcohol that actually protects against alcoholism in population studies.

Q. Because it's uncomfortable?

A. Yes, presumably that is what is operating here. People who have those particular enzyme varieties are less likely to become alcoholic. Further study may provide evidence for a larger effect that is not just in Oriental populations but in other populations as well. It may not be identified as a flushing reaction, but it may still operate to predispose some people to drink more than others.

Q. Are Native Americans more vulnerable to alcoholism?

A. Statistically, there is a greater likelihood that someone who is Native American will have problems in controlling his or her drinking, and we don't know why. There is suspicion that at least some of that has to do with genetic effects. Studies are going on supported by the National Institute of Alcohol Abuse and Alcoholism in Native American populations to try to identify vulnerability genes.

Q. We want to help people understand how important it is to enforce the laws about keeping kids from drinking while they are teenagers. Aren't some kids more vulnerable than others?

A. It is actually possible to think about individual vulnerability to alcoholism. We haven't developed a diagnostic blood test yet, but we know that alcoholism runs in families. If people come from a family in which there are alcoholic drinking problems, they are wise to be particularly careful about their own drinking. They want not to be drinking early and to limit their alcohol when they do start, if they start at all.

Q. There are support groups for families of alcoholics. If these people could be taught about their genetic vulnerability, that might make a big difference.

A. The National Institute of Alcohol Abuse and Alcoholism has been very forthcoming in this regard. I think that they make an effort to include discussion of genetic vulnerability factors in a lot of their publications.

Q. Alcoholism and teenage drinking are big problems in this country.

A. Yes, they certainly are. But we do have pharmacologically specific treatments for alcoholism that we can use now—new medications to decrease the craving for alcohol and can enable people to stay sober longer.

Q. Are diabetics more likely to become alcoholics because of the way they metabolize sugar?

A. That is an interesting question. I don't really know, but one of the things that we've been looking at recently is sweet preference. Alcoholics do seem to have preference for sweet solutions, sweet drinks. There is also literature in animal studies suggesting that sweet preference goes along with alcohol preference.

We thank Dr. Nurnberger for this helpful information. We look forward to learning the results of his ongoing studies. If you would like to be a part of Dr. Nurnberger's bipolar study, please fill out the questionnaire.

Reprinted with permission from The Saturday Evening Post Society, a division of Benjamin Franklin Literary and Medical Society, Inc. © 1997.