Faulty circuit may trigger schizophrenia.

Scientists increasingly suspect that schizophrenia, a severe and often debilitating mental disorder that usually emerges in young adulthood, reflects disruptions of brain development that originate before or shortly after birth.

The exact nature of this neural damage remains poorly understood, but new evidence suggests that it may impair interconnected structures located at several sites in the brain.

Damage to the various parts of this far-flung circuit, which extends from the cerebellum at the back of the brain to the prefrontal cortex near the eyes, could account for the shifting spectrum of social, emotional, and thinking difficulties observed in people suffering from schizophrenia, reports a research team in the Sept. 3 Proceedings of the National Academy of Sciences.

"We theorize that defects in this single, complex brain circuit can explain any and all symptoms of schizophrenia," asserts psychiatrist Nancy C.

Andreasen of the University of Iowa College of Medicine in Iowa City, who directed the recent investigation.

In particular, Andreasen holds, a breakdown in this cerebral network causes cardinal signs of schizophrenia, most prominently a difficulty in integrating information rapidly from the outside world, formulating reactions swiftly, and expressing verbal or emotional responses.

Andreasen's group studied 13 neurologically healthy volunteers and 14 people diagnosed with schizophrenia who had not taken antipsychotic medication for at least 3 weeks. Positron emission tomography (PET) scans measured cerebral blood flow as participants recounted a story just after hearing it or retold a story they had heard a week earlier and then thought about in two practice sessions.

These tasks tap into learning and memory skills typically undermined by schizophrenia, Andreasen notes.

Schizophrenic participants remembered much less than the other volunteers on the immediate recall test, although the two groups performed equally well on the other task. During both tests, however, volunteers with schizophrenia displayed a consistent pattern of blood flow declines- signaling drops in neural activity-in certain brain areas. This implies that schizophrenia involves a fundamental breakdown in the circuit of brain structures used for these tasks, the researchers maintain.

Crucial components of this circuit include the cerebellum, which may pace thinking efforts; the thalamus, which filters incoming information (SN: 10/29/94, p. 284); and the prefrontal cortex, a center of complex thinking and judgment.

"This is an interesting study, but it will be a while before its implications are well understood," asserts Daniel R. Weinberger of the National Institute of Mental Health's Neuroscience Center in Washington, D.C. In particular, the cerebellum's impact on schizophrenia remains murky, he contends.

In addition, PET data cannot distinguish between brain areas that operate in parallel and those on a common circuit, Weinberger adds. - B. Bower