(July 20, 1999) Forty years ago, scientists found the first modern drug to treat schizophrenia. Now they may be getting close to the next big step: preventing it. New studies hint at ways to pick out people on their way to developing the disorder, and scientists are testing whether they can be helped. It's all very preliminary; but the federal government announced in April that it will pay for more studies, a big boost to the young field. And researchers are planning conferences to examine this bold notion of preventing schizophrenia.

"Its time has come," says psychiatrist Jeffrey Lieberman of the University of North Carolina at Chapel Hill.

Schizophrenia strikes one of every 100 people, typically in their late teens or in their 20s. It can mess up their education, work and social life. People lose touch with reality. At times they hear or see things that aren't there or adopt bizarre beliefs and behaviors. Their speech is confused and their emotions dulled. They withdraw from others. Nobody knows what causes schizophrenia, so scientists interested in prevention have had no idea whom to treat, let alone how.

Though genetics seem to be a risk factor, the children and siblings of schizophrenia patients run only a 10 percent chance of getting the disease someday. If you treated them all, you'd include nine people needlessly for every one who truly needed attention. And most cases of schizophrenia appear in people who aren't closely related to patients. Scientists long have known that most people who develop schizophrenia show behavioral changes months or years beforehand. But those changes - such as withdrawing from friends, having trouble concentrating, failing in school - aren't specific to schizophrenia. Lots things can cause them. They could simply be a bad case of adolescence. So early behavioral changes haven't been useful in predicting who will get schizophrenia.

Even if you could identify those at risk, how would you treat them? One choice might be the anti-psychotic drugs that bring many schizophrenia patients back to reality. But these drugs have side effects, which are an issue when some people you treat would never have gotten schizophrenia anyway. Older drugs carry the risk of movement problems like rigidity, tremors, grimacing, lip-smacking and tongue movements. Newer medications, though less hazardous, can produce sedation and weight gain.

Still, the improved medications are among the recent developments making some scientists more hopeful about prevention. Another is recent studies showing that the earlier treatment for schizophrenia starts, the better off the person will be in the long run. So maybe the disease itself causes some kind of brain changes that would be worth preventing. Meanwhile, research in identifying whom to treat is finding answers. A big boost is the recent findings of Patrick McGorry of the University of Melbourne in Australia. He and colleagues are studying how to identify people at very high risk of developing serious psychosis, the loss of touch with reality that's the hallmark of schizophrenia and related disorders. The researchers found that 41 percent of young people who showed certain behavioral signs developed psychosis within a year. Those at high risk fell into three categories:

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Siblings or children of people with schizophrenia or a related condition, who themselves show anxiety, depression or a recent decline in day-to-day functioning like withdrawing from friends or failing at school

People with schizophrenia-like symptoms that aren't serious enough for diagnosis, such as suspiciousness, hearing imaginary noises, seeing visual distortions such as flashes, or holding odd beliefs such as the notion that a television program is broadcasting a special message to them. But these notions are fleeting, and the people are in touch enough with reality to entertain some doubts. People with hallucinations that last only a few hours, or delusions or bizarre thoughts that pass on their own in less than a week. McGorry stressed that his results came from people who sought mental health help and might not apply to people who don't. Barbara Cornblatt, a psychologist at the Albert Einstein College of Medicine's Hillside Hospital in Glen Oaks, N.Y., hopes combining behavioral signs like McGorry's with certain laboratory tests will point the way to predicting schizophrenia. To study that, she has given a battery of tests to 50 teens so far. The tests include such things as watching a red laser dot pass back and forth on a wall, and studying four-digit numbers that flash one by one on a computer screen. The laser-dot exam reveals how well the eyes track a moving object. Many people with schizophrenia have trouble doing that, and often their close relatives do, too. In the number test, participants signal when they see two identical numbers in a row. That measures how well they can pay attention, even when researchers try to distract them with sounds or other sights on the computer screen. Cornblatt recently found that when children of schizophrenia patients do poorly on this test, they run a heightened chance of developing the disease or a related one years later. Now the question is whether the same thing happens in adolescents whose behavior suggests a risk. Once you can reliably identify people at high risk of getting schizophrenia, how would you treat them to prevent it? McGorry said he's gotten preliminary but encouraging results with an approach similar to what psychiatrists use to prevent relapse in schizophrenia. It includes low doses of an anti-psychotic drug and psychotherapy to deal with each person's symptoms, improve self-esteem and help manage stress. Others have picked up on that idea. Yale University researchers recently started testing a different medication, in a study that will include four other medical centers. There are also some hints that psychotherapy might help. It's not yet clear how long a person would have to be treated to benefit. But even if scientists can only delay schizophrenia, that might be worth it. For one thing, McGorry said, a delay could save thousands of dollars in health care costs per person per year. And the later in a person's life schizophrenia appears, the better off he or she will be long-term. So keeping the brain intact long enough to learn social and work skills, and get through college, appears worthwhile. The new research may only be catching up with what's happening in psychiatrists' offices across the country. At a recent meeting of the American Psychiatric Association, a speaker asked who was already giving anti-psychotic drugs to people who appeared headed for schizophrenia. Plenty of audience members raised their hands. The new research might reveal how much good they are doing.