February 21, 1997

VUMC team to track schizophrenia’s onset

VUMC team to track schizophrenia's onset

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Dr. Herbert Meltzer

A team of Vanderbilt University Medical Center physicians and psychologists is studying the evolution of schizophrenia in adolescents and how the brain changes during the initial onset of the severe mental disorder.

The group will focus on adolescents and young adults who may be pre-psychotic.

The team is led by Dr. Herbert Y. Meltzer, professor of Psychiatry and Pharmacology at VUMC and director of the division of Pharmacology at the Psychiatric Hospital at Vanderbilt.

Also studying the young people will be Drs. Thomas F. Catron, assistant professor of Psychiatry, Susan McGurk, assistant professor of Psychiatry, and Robert M. Kessler, professor of Radiology and Radiological Sciences.

Meltzer is one of the world's leading authorities on the treatment of schizophrenia, a lifelong illness which affects about 1 percent of the population. In the Metropolitan Nashville area alone, there are an estimated 10,000 people with schizophrenia, Meltzer said.

About 95 percent of schizophrenia cases begin between the ages of 17 and 25. For most of those with this illness, about one to two years before psychoses emerge, various other types of changes in behavior develop which may be clues to the impending emergence of psychotic symptoms such as paranoia, delusions and hallucinations.

These behavioral changes include: disorganized thinking and magical thinking; withdrawal and loss of interest in usual activities; lack of spontaneity and initiative; sleep disturbance; poor concentration and deterioration of school performance; and deterioration in grooming.

"These young people are not yet delusional or hallucinating but their parents and friends become aware of these symptoms and disturbed behavior," Meltzer said.

Focusing on this time period in the course of schizophrenia is the major new direction of Meltzer's work.

"Our goal in working with these young people is to evaluate their cognitive function are emerging during their pre-psychotic phase. Secondly, we're looking at whether the new medications given to them are able to prevent the emergence of psychosis."

Meltzer said that early prevention of the brain-damaging psychoses can mean the difference in a productive life for many schizophrenics.

"People who become schizophrenic are born with the vulnerability to develop this disorder. Whether or not they will develop it depends on their environment and stress. However, the genetic factor is by far the most powerful factor. We're hoping to prevent whatever is preventable in the area of cognitive dysfunction. Our goal is to prevent young adults from going over the barrier and having psychosis emerge.

"Some people are born with brittle bones," he said. "If they break a bone, it may never heal properly and they may be permanently handicapped. But if somehow, despite the brittleness, they're protected from the break, they can manage to get through life without great disability."

Without intervention, about half the individuals who are genetically predisposed will develop schizophrenia, Meltzer said. That number has been determined by studying identical twins with schizophrenia. In about half of identical twins with schizophrenia, when one is affected with schizophrenia, the other is not. "Something is either causing one of the twins to show the vulnerability, or causing the other twin to be protected," he said.

Schizophrenia is characterized by "positive symptoms" such as delusions and hallucinations, and "negative symptoms" such as withdrawal, lack of pleasure, lack of motivation and energy and flat affect. It is also characterized by a third group of symptoms called "disorganization" which includes incoherent disassociations, poverty of thought content, and inappropriate affect.

The fourth area of schizophrenia is "cognitive dysfunction" and is one of the main areas of Meltzer's interest.

"People with schizophrenia have significant abnormalities in memory, attention and executive function of judgment," Meltzer said.

"Cognitive dysfunction is what leads to most of the social disability of this illness. Our goal is to achieve much more than just the remission of positive and negative symptoms and disorganization. We carefully monitor quality of life and we're seeking to improve that substantially for patients with schizophrenia."

Schizophrenia can be treated with drugs such as clozapine, said Meltzer, one of the co-developers of the drug. It is most useful in patients who fail to respond adequately to other drugs, Meltzer said. About 30 percent of patients with schizophrenia are treatment-resistant. The drug, however, has some toxic side effects, especially on the bone marrow. Patients on the drug have to have blood drawn and analyzed weekly.

Young adults are currently being recruited for the study. Meltzer is working with pediatricians and adolescent psychiatrists who refer patients to VUMC, as well as the Alliance for Mentally Ill and the Mental Health Association. In addition, Meltzer hopes to work with the Metropolitan Nashville School Board and private high schools and colleges to survey students in this age range to help identify those who fit the profile of a someone who may be pre-psychotic.

"Many of the symptoms and behaviors in the profile are non-specific. For that reason, a family history of serious mental illness becomes extremely valuable in helping determine who may be most likely to become psychotic. The evaluations we provide may identify people who develop disorders other than schizophrenia, or none at all."