Yale Bulletin and Calendar

March 30, 2001

Volume 29, Number 24

Researchers discover that chronic
schizophrenia in men causes
progressive decline in brain volume

Men with chronic schizophrenia lose brain volume at a faster rate than the normal aging changes seen in men without the mental illness, a study by a Yale researcher shows.

"We found that there was evidence of progressive decline in brain volume in men with chronic schizophrenia, and it tended to occur in the frontal and temporal lobes," says Dr. Daniel Mathalon, assistant professor of psychiatry at the School of Medicine. "These are the two regions already implicated in the pathophysiology of schizophrenia."

The research, published in a recent issue of the Archives of General Psychiatry, was conducted while Mathalon was at Stanford University. Mathalon is first author of the study and Dr. Adolf Pfferbaum, currently at SRI International, is senior author and the study's principal investigator.

Mathalon says it has been known for some time that patients with schizophrenia have reduced brain volume, even at the onset of their illness, but it is not clear why this is so. While current theories emphasize an abnormality in brain development, his study looked at whether the decreased brain volume is progressive over time, consistent with a neurodegenerative aspect to the illness.

The study included 24 men who had been suffering from schizophrenia for an average of 15 years, and 25 men without the illness. The subjects were all men because the research was conducted at the Veterans Administration Palo Alto Health Care System hospital. Two magnetic resonance imaging scans were conducted on each of the men over an average interval of four years.

"The most intriguing finding is that patients who had more severe symptoms and who had been hospitalized for longer periods of time in the interval between scans lost brain tissue faster," Mathalon says. "This is consistent with the emerging, yet unproven, idea that having psychotic symptoms might actually be associated with some kind of toxicity to the brain."

He said the theory that schizophrenia involves a neurodegenerative process is also supported by observations of progressive changes in symptoms and decline in level of functioning during the course of the illness.

"While we don't know the mechanism producing this brain tissue loss, post-mortem studies indicate it is not the kind of classic neurodegeneration seen in Alzheimer's or Parkinson's disease," Mathalon says.

Although the study showed that some of the changes in brain volume were small, 14 of the 18 regions examined showed faster progression in the men with schizophrenia than in the healthy men. For example, men with schizophrenia showed an average of 3% decline per year in the volume of gray matter in the temporal lobes of the brain compared to a 0.9% decline in the healthy men.

The accelerated decline in gray matter volume was also seen in the right frontal lobe. In addition, the study found faster expansion of the cerebrospinal fluid volume in the sulci of the right frontal cortex and bilateral prefrontal and posterior temporal cortex, as well as in the left lateral ventricle.

The other researchers involved in the study were Edith Sullivan of Stanford University and Dr. Kelvin Lim, now at the Nathan Kline Institute.

The research was supported by grants from the National Institutes of Health, Bethesda, Maryland, and by the Department of Veterans Affairs, Washington, D.C.

-- By Jacqueline Weaver

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