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Intercepting Schizophrenia

A new approach to treating schizophrenia.

WebMD Feature

March 6, 2000 (Petaluma, Calif.) -- It seems to come out of nowhere, often striking young people in their teenage years. A seemingly healthy kid suddenly becomes withdrawn and depressed, then confused and even paranoid. As hallucinations and delusions take hold, victims become trapped in the demon-haunted world of schizophrenia.

One of the most severe forms of mental illness, schizophrenia afflicts an estimated 2.5 million Americans. One in 10 schizophrenics eventually commits suicide, according to Nancy Andreasen, M.D., Ph.D., a psychiatrist at the University of Iowa.

New antipsychotic drugs effectively control some of the worst symptoms, such as hallucinations and delusions. Yet only one out of five schizophrenics gets total relief. So researchers are trying a bold and controversial new approach: treating people at risk for the disease even before they are diagnosed.

Before the Demons Emerge

"The earlier treatment starts, the better the prognosis," says psychiatrist Barbara Cornblatt, M.D., Director of High-risk studies at Hillside Hospital in New York. That's because the symptoms of full-blown schizophrenia -- hallucinations and delusions, for instance -- are themselves toxic to the brain, damaging its circuitry in ways that can't be reversed.

In a pioneering study, Yale University psychiatrist Thomas McGlashan, M.D., is putting at-risk patients as young as 12 years of age on antipsychotic medications before they show clear symptoms. McGlashan hopes his experiment will show that drugs can head off the worst symptoms or even prevent the disease.

There's good reason to think it will. In 1996, psychiatrist Patrick McGorry, M.D., a researcher at the University of Melbourne in Australia, began treating young patients considered at risk for schizophrenia. Of 31 volunteers treated with low doses of an antipsychotic drug called Risperdal, only four developed psychotic symptoms in the six months after they were taken off the drug. In contrast, of 28 patients who received only psychotherapy, 10 developed schizophrenia during the same six-month period.

Who's at Risk?

Such early treatment remains controversial because psychiatrists can't yet always tell who is most at risk. "The dilemma is knowing what kinds of warning signs warrant early treatment, especially when you're talking about putting a young teenager on medication," says Rex Cowdry, MD, medical director of the National Alliance for the Mentally Ill.

Genes and behavior both provide some clues. Although only 1% of the general population develops the disease, the danger for a child with one schizophrenic parent jumps to between 10 and 15%, according to a February 25, 1999 study in the New England Journal of Medicine.

If both parents suffer from the disease, that child's odds of getting the disease soar to 50%. The sibling of a schizophrenic runs a 10 to 15% risk, and an identical twin's risk is 50%.

In addition to inherited risk, researchers have identified emotional warning signs, some showing up as early as age 9. In Cornblatt?s studies, for instance, patients who have gone on to develop schizophrenia have been found to have problems in childhood with short-term memory, as measured by psychological tests. Extreme problems with focusing attention in distracting settings has also been found to be a danger sign.

But tests for these problems aren't reliable enough to be used to screen all children. Instead, psychiatrists such as Cornblatt and McGlashan find patients at risk for schizophrenia by using educated guesswork: They cull at-risk patients from larger groups of young people who are referred for symptoms such as sudden depression and extreme withdrawal -- for example, an honor student who abruptly refuses to attend school or see friends. Preliminary studies suggest that about a quarter to a half of the teenagers identified this way will go on to develop schizophrenia. This means that as many as three-quarters could receive unnecessary treatment.

Hope Mixed with Caution

No one knows the long-term dangers of putting such patients on antipsychotic drugs, Cowdry says. The latest generation of drugs is safer and more effective than older ones, but the drugs still have troublesome side effects, such as weight gain and drowsiness. And once patients start taking these medications, no one knows when, if ever, they will be able to stop.

That problem may fade if research into biochemical signs of schizophrenia leads to a reliable laboratory test. Some scientists already think they're zeroing in on genes associated with schizophrenia. And at Johns Hopkins University in Baltimore, Md., scientists reported abnormally high levels of an enzyme called reverse transcriptase in the spinal fluid of recently diagnosed schizophrenic patients.

"There's a tremendous sense of hope and excitement in the field," says Cornblatt. After six months in her early-treatment program at Hillside Hospital -- a program that includes psychotherapy and sometimes antipsychotic medications -- 80% of at-risk kids have stabilized or improved. "For the first time," she says, "there's reason to think we may eventually be able to prevent this horrible, disabling disease."

Peter Jaret is a contributing editor for WebMd and Health and National Wildlife magazines. His work has appeared in Newsweek, National Geographic, Men's Journal, Vogue, Glamour, and many other magazines. He lives in Petaluma, Calif.

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