May 24

Yale Screening High School youth for Schizophrenia_BostonGlobe>
Boston Globe
High school testing eyed for schizophrenia signs
By Ellen Barry, Globe Staff, May 25, 2002 page A1

PHILADELPHIA – Hoping to head off the most debilitating of mental illnesses before it strikes, Yale University researchers are laying plans to search for a secret hidden in the brains of ninth-graders: In every group of 100 students, one will go on to develop schizophrenia.

For generations, schizophrenia has been diagnosed in late adolescence, after lives and relationships are already damaged by its painful early stages. In a scattering of research centers, including Yale's, excitement is building around the possibility that doctors can spot ''pre-psychotic'' symptoms and intervene in ways that could delay or weaken the onset of schizophrenia.
Yale psychiatrists have been in talks with Connecticut schools to introduce a screen for high school freshmen. But the idea of such early screening is contentious. Critics warn that it may be too early to identify people in the general population as being at risk for psychosis – both because prediction is still inexact and because there is no consensus on how to treat people who have not yet developed full-blown symptoms.
Once a person is identified as at risk for schizophrenia, the most promising interventions – low-dose antipsychotic drugs – carry their own set of risks.
''We have to be cautious,'' said Jim McNulty, president of the National Alliance for the Mentally Ill. ''We don't know the long-term effects of medications on the human brain. It's a trade-off.''

A Yale research center called Prevention through Risk Identification, Management and Education , or PRIME, is developing a possible student screen now, although Dr. Thomas McGlashan, PRIME's chief investigator, said general screening was still some time in the future. ''We're talking about a year from now'' at the soonest, he said.

Schizophrenia, which afflicts 2.2 million Americans, tends to strike men in their late teens and early 20s and women slightly later, and rarely appears in older people.
At the heart of the Yale plan is a tantalizing possibility: that early treatment with antipsychotics during that ''window of vulnerability'' could protect them until the age when vulnerabililty lessens.

On Thursday, McGlashan presented hopeful new results at the American Psychiatric Association's annual meeting in Philadelphia. ''There is evidence to suggest that intervention in this stage can have a preventive effect,'' McGlashan said. McGlashan is a year from the end of a clinical drug trial in which 60 patients thought to be at risk for schizophrenia are administered either sugar pills or the antipsychotic drug Zyprexa as a prophylactic measure. After eight weeks of treatment, the Zyprexa group had only half the level of psychotic symptoms as the placebo group, said researcher Scott Woods. Those in the Zyprexa group also gained an average of 10 pounds in the eight-week period, contrasting to an average one-pound weight gain in the placebo group.

McGlashan has been under scrutiny for his research on pre-onset schizophrenia in the past, in large part because of the risks in giving powerful antipsychotic drugs to young people who are not diagnosed with any mental illness. Two years ago, he was cited by federal regulators for various ethical violations, including failing to fully inform participants of risks.

In the frustrating world of mental health care, early intervention has become a watchword, and Connecticut school officials have said they are eager to break ground by adding mental health to their roster of preventive health programs. ''We looked at it much like we look at eye screens and that sort of thing,'' said Nancy Pugliese, who coordinates substance abuse prevention programs for the Connecticut public schools. As part of that effort, Larry Davidson, a psychologist from the PRIME center, plans to begin an outreach program in the fall, teaching ninth-graders the early signs of psychosis, bipolar disorder, and other mental disorders. Both schools and parents must agree for students to be enrolled in the course, he said. When PRIME develops an accurate screen for pre-onset schizophrenia, it will be administered as part of the course, said Tandy Miller, the PRIME psychiatrist developing the screen.

Catching serious mental illness early is a wonderful opportunity, said Paul Appelbaum, chairman of the department of psychiatry at the University of Massachusetts and president-elect of the American Psychiatric Association. ''If we can actually intervene and try to prevent psychosis in half the people we're treating, isn't that a terrific accomplishment?'' Appelbaum said. The trouble, he said, is that even specialists are only right about half the time when they predict who is going to develop schizophrenia.

Patrick McGorry, who heads the Early Psychosis Prevention and Intervention Centre in Victoria, Australia, found that 40 percent of adolescents he identified as ''pre-psychotic'' experienced the onset of schizophrenia within a year. McGlashan's early results – published in the May issue of the American Journal of Psychiatry – show that 54 percent of 13 patients identified as pre-psychotic had developed schizophrenia within a year.

Therein lies the problem for potential screening. For the subjects who are incorrectly identified as pre-psychotic, the identification itself could be life-changing, Appelbaum said. ''Does it impact on your ability to get health insurance?'' he said. ''What about the self-stigma? You may begin to think of yourself as somebody who is going to be schizophrenic. Davidson said that stigma will be reduced through the educational efforts PRIME plans to start in September, funded by a $99,000 grant from the National Alliance for Research of Schizophrenia and Depression.

A similar educational effort in the classrooms and movie theaters of Norway had significant effects: the average delay from the first episode of psychosis to treatment went from 21/2 years to 2 months. The average delay before treatment in the United States is two years, largely because of a lack of awareness of the symptoms of mental illness, he said. If Connecticut high school students were identified as at risk for psychosis, teenagers and their families would be carefully monitored, possibly at the PRIME clinic or a planned affiliate clinic in Hartford, McGlashan said.

But doctors can not confidently advise any preventive treatment at the moment. Although there are numerous experimental treatments being explored for pre-onset psychosis – such as antidepressants or cognitive behavioral therapy – no method has been broadly tested as a preventive measure. ''You don't recommend any treatment unless you've got a thorough evaluation,'' Davidson said.

''The state of knowledge right now is that you would not make'' the recommendation to prescribe antipsychotics. One observer said it is crucial that a broad screening tool not be used to nudge subjects toward an experimental treatment. ''The assumption always is that screening does no harm,'' said Steven Hyman, who stepped down as the director of the National Institute of Mental Health to become Harvard's provost.

But screening for depression, a common disease for which treatment is reasonably safe and effective, is different from screening for a disease that is difficult to identify and treat. ''We don't have proven ways of knowing who is schizophrenic, and the risk-benefit ratio of treating them prior to onset of serious symptoms is not established,'' Hyman said.

Ellen Barry can be reached at <>   © Copyright 2002 Globe Newspaper Company.
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