It’s hard to believe that only a half century after Francis Crick and James Watson discovered what human genes consist of: DNA molecules residing on chromosomes inside each cell of our bodies, the chemical composition of some 80 percent of all 100,000 human genes has been identified, thanks to the Human Genome Project. These discoveries are surely among the most spectacular of modern medical science. If the human genome—all 100,000 human genes—was printed out, it would fill one million telephone book pages!

What do such findings mean for psychiatric medicine? A bundle, a recent symposium on "Brain Research and the Mapping of the Human Genome: Applications to Primary Care and Psychiatric Medicine" revealed. The program was held in Washington, D.C., and was jointly sponsored by the Washington Psychiatric Society, APA, and the Medical Society of the District of Columbia.

It’s long been known that inheritance can play a major role in mental illness. Take the case of autism. The likelihood of any individual in the entire population having it is only 0.05 percent, yet a person who has a sibling with autism has an increased risk 100- to 200-fold beyond that; a person who has an identical twin with autism has a 2,000-fold increased risk. These statistics, said Steven Hyman, M.D., director of the National Institute of Mental Health in Bethesda, Md., demonstrate that genes in autism "have an enormous amount to say."

Genes don’t play as hefty a role in depression as they do in autism, he added, yet nonetheless they do have an influence. The situation is similar for schizophrenia.

But only recently, through the Human Genome Project and other types of genetic research, have investigators actually been in a position to zero in on some of the genes involved in mental disorders. For instance, the gene that causes the devastating neuropsychiatric disease Huntington’s chorea has been pinpointed. It is on chromosome number 4. Mutations in genes on the X chromosome have been found for a fair number of cases of mental retardation. Some genes that cause Alzheimer’s disease have been located. Although the actual genes that cause schizophrenia, bipolar disorder, depression, and autism have not yet been identified, the general regions on chromosomes where such genes are located—sort of "hot spots"—have been fingered.

Godfrey Pearlson, M.D., a psychiatrist and a genetics researcher and professor at Johns Hopkins University School of Medicine in Baltimore, explains it: "Some people say that the best analogy for genes and hot spots is that the entire human genome is like a map of the United States. The chromosomes are cities, and the hot spots are like districts within cities. The actual gene is like a house address. So with Alzheimer’s disease, there are probably 15 or 20 separate addresses, of which we’ve already got a handful. In schizophrenia, depression, and autism, the best that we’ve got is part of a city." Still, part of a city is worth a lot more than what genetic researchers had for such diseases a few years ago.

It’s also becoming apparent that most mental disorders are not due to the inheritance of just one bad gene, but of at least several, and that various genes can play different roles in a mental disorder’s development. For instance, Pearlson reported, a gene on chromosome number 12 seems to contribute to late-onset Alzheimer’s, whereas a gene on chromosome number 19 seems to lower the age of onset of Alzheimer’s if the person is destined to develop it in the first place.

David Mrazek, M.D., chair of psychiatry and behavioral sciences at George Washington University School of Medicine in Washington, D.C., conjectures that a bipolar gene on chromosome number 4, near where the Huntington’s gene is located, is necessary for manic symptoms, but not sufficient for full-blown bipolar disorder, whereas a bipolar gene on chromosome number 12 provides the extra boost necessary to get the illness totally under way.

In contrast, it is likewise becoming evident that genes involved in the same mental disease may lead to similar pathology. For instance, Pearlson pointed out, all of the risk genes for Alzheimer’s that have been discovered have to do with either the production or metabolism of the beta amyloid precursor protein. This protein is made inside nerve cells of the brain, then is chopped up by enzymes and transported into spaces outside the nerve cells to become plaques. Plaques then kill nerve cells, and as nerve cells die, neurotransmitters are lost, leading to such symptoms of Alzheimer’s as depression and agitation.

Not surprisingly, the understanding of genes for mental illness have barely been scratched. Obviously more will be learned as more mental illness genes are discovered. What will help in such psychiatric genetics research will be not just the completion of the Human Genome Project, but the amassing of many variations (mutations) for each type of gene identified. Such variations are already being collected from patients with mental disorders as well as from their family members, Hyman reported. Thousands of gene samples, he predicted, will eventually become available and tell much more about the genetic risks involved in mental illnesses.

It may turn out, Hyman said, that different combinations of genes confer risk in different families. In fact, in a decade, Herbert , M.D., president of the New York Presbyterian Hospital and Healthcare System in New York City and a former APA president, predicted, psychiatric genetics will be so far advanced that APA’s Diagnostic and Statistical Manual of Mental Disorders (DSM) will list that gene X is related to this mental disorder and gene Y to that one.

As more and more genes become linked to various mental disorders, genetic screening for mental illnesses will become a distinct possibility. For instance, within five to 15 years, Alan Guttmacher, M.D., senior clinical advisor to the director of the National Human Genome Research Institute of the National Institutes of Health, anticipates that a person will be able to visit his or her physician, have a swab of DNA taken from inside his or her cheek and sent to a computer to be scanned for various genetic mutations, and get back a genetic profile saying that he or she has, say, a 20 percent risk for colon cancer and a 40 percent risk for bipolar disorder.

Mrazek offers a similar prediction. Let’s say that in 10 years you’ll have a 15-year-old patient, Charles, who used to be a good student, but who is now depressed, withdrawn from friends, reckless. His father has been treated for bipolar disorder. Is he coming down with it as well? To help find out, you’ll take a blood sample from him, feed it into a computer, and five minutes later you’ll have a genetic profile on him—in other words, his genetic risk for having bipolar disorder. What’s more, Pardes reported, wonderful computer techniques are being developed to screen large populations for certain genetic factors, which will undoubtedly influence psychiatrists’ practices.

But just because genetic screening for mental disorders will become possible does not necessarily mean that it should be done, pointed out Walter Bland, M.D., acting chair of psychiatry at Howard University College of Medicine in Washington, D.C. For example, what kind of an impact would such screening have on a person if he or she had a high chance of developing Alzheimer’s? Genetic screening is already available for Huntington’s chorea, and those persons who have found that they are going to get it often become terribly depressed or even commit suicide. And would the results of widespread genetic screening for mental disorders always be accurate?

Not necessarily, Hyman contended: Even if you had all 10 mutant genes needed to produce a particular disease, you still might not get the disease because genetic risk does not always equal fate.

And how about the effects of such test results on people’s health insurance? Would companies discriminate against people with heightened genetic risks for various mental conditions? This is a possibility. Guttmacher, in contrast, believes that it will eventually become apparent that each individual has genetic risks of one kind or another, that no one is altogether genetically normal, and such revelations will level the playing field as far as health insurance companies are concerned.

The prospect of genetic screening for mental disorders likewise prompts the question: Should psychiatrists start individuals found at genetic risk for certain psychiatric conditions on medications before they actually develop the conditions? This is what Guttmacher calls "medication to preserve health rather than treat disease." Mrazek predicted that such preventive tactics will become common during the next 10 years. Mrazek and his colleagues, in fact, are already attempting to see whether such intervention might be effective for bipolar disorder. The drug divalproex sodium has been known for some time to counter mania in persons with bipolar disorder. So Mrazek and his team are giving it to boys who have at least one parent with the condition and who exhibit periodic disruptive behavior to see whether it can keep them from becoming bipolar.

Yet regardless of the future of genetic screening for mental illnesses and of the future for such preventive measures, research in psychiatric genetics will undoubtedly lead to new therapies for mental conditions. Take the case of beta-secretase, one of the enzymes that breaks beta amyloid precursor protein down in the brains of Alzheimer’s patients. Scientists have identified what beta-secretase is, they have found the gene that produces it, and they suspect that the gene is one of the ones that leads to Alzheimer’s. They are now looking for drugs that can block beta-secretase’s activity. Such drugs are expected to slow the progression of Alzheimer’s, said Pearlson.

Eliot Sorel, M.D., president of the Washington Psychiatry Society and chair of the Washington symposium, summed up, "This is the new psychiatry! We live in extraordinary times of psychiatric medicine." As Guttmacher sees it, in the near future genetic medicine is going to play a large role in psychiatry, and psychiatrists should get ready now.