UC Team Traces 'Circuit' Problems of Schizophrenics

TIMES STAFF WRITER

University of California scientists have created maps of an area deep in the brains of schizophrenics showing that the "circuitry" connecting key internal structures is haywire. The findings may reshape the study of the disorder, the researchers said Tuesday.

"The previous thinking has been, 'Where is the hole in the brain' " that causes schizophrenia, said UC Irvine professor of psychiatry Monte S. Buchsbaum, who led the 12-member research team from UC institutions.

The new thinking, based on the team's data, is that there is no single "black hole" or abnormality in a schizophrenic's brain, Buchsbaum said in an interview.

Rather, the circuitry among key brain structures--the thalamus, cortex and basal ganglia--and among sensory organs transmitting taste, touch, hearing or vision may be "connected improperly" and fail to communicate correctly, he said.

Buchsbaum and several collaborators plan to present their research formally on Sept. 13 to 4,000 neuroscientists at the 17th Congress Collegium Internationale Neuro-psychopharmacologicum in Japan. They offered a preview Tuesday to reporters and to financial backers of UCI's 6-year-old Brain Imaging Center, where the research was conducted. The results amplify studies reported in June in The Times.

The researchers found that:

* The brain circuitry of a schizophrenic is markedly different from that of a normal adult, but each can be quantified and described with detailed charts, much like a road maps.

* Brain metabolism in the schizophrenic's basal ganglia--a structure at the center of the brain that affects motor function as well as visual and emotional response--is significantly less active than in a normal adult.

* Both schizophrenics and adults with depressive illness have low metabolism rates in the basal ganglia and temporal lobes. But in other areas of the brain, these mentally ill adults show contrasting results. For instance, in the hippocampus, which is thought to control memory, depressives show a high rate of brain activity, but schizophrenics show a low rate of activity.

Buchsbaum suggested that as a schizophrenic's impaired circuitry is studied in more detail, eventually the right drug or combination of drugs may be used to repair the abnormal links in the brain.

Dr. Lewis L. Judd, director of the National Institute of Mental Health, which spent nearly $1 million on this project, said the team's brain circuitry finding is "a new observation that will now require confirmation by other laboratories."

Judd called Buchsbaum's project "a very important study" that confirms research in some areas and breaks new ground in others.

Schizophrenia, a devastating and incurable mental illness, affects 2% of Americans--5 million people across the country, about 46,000 in Orange County. Considered an incapacitating and lifelong disease, schizophrenia usually begins in adolescence and is characterized by disordered thinking, apathy and, frequently, hallucinations.

For decades, researchers have looked for its cause. Doctors, who once blamed upbringing and social conditions, have since the 1960s focused on brain abnormalities.

With new imaging technology in the 1980s called PETscan (Positron Emission Tomography), which measures brain metabolism after an injection of radioactive glucose, scientists can study what part of the brain might cause schizophrenia, as well as what chemicals might treat it.

But the question for the 1990s is not just what abnormal brain structure or chemical causes schizophrenia but, Buchsbaum said: "What is the circuit and how is the circuitry abnormal? . . . The circuitry story will be presented for the first time in Japan."

Buchsbaum, who used to work at the National Institute of Mental Health, was one of the world's pioneers in the use of PETscans. With this study of 18 schizophrenics, he claims another first: offering results from the largest PETscan study ever of "never-medicated" schizophrenics.

(The issue of no medication is important because some researchers have suggested that medication used to treat schizophrenics may alter brain structures.)

The study contrasted PETscan studies showing brain metabolism from 18 schizophrenics with those from 22 normal adults, as well as 39 depressed adults.

As Buchsbaum's team mapped the brain activity of normal adults and that of schizophrenics, they noticed, for instance, that in normal adults, activity between inner brain structures called the putamen and caudate are connected.

But in schizophrenics, their data showed, those gray masses--deep in the brain and thought to control motor coordination and possibly also emotion--were not connected.

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