Science

Spreading waves of gray matter loss occur in early-onset schizophrenia

Last Updated: 2001-09-24 17:00:13 EDT (Reuters Health)

WESTPORT, CT (Reuters Health) - Patients with early-onset schizophrenia exhibit accelerated loss of gray matter that envelop increasing amounts of cortex throughout adolescence, according to the results of a prospective study based on high-resolution MRI.

Dr. Paul Thompson, of the University of California at Los Angeles School of Medicine, and associates scanned subjects at 2-year intervals at three time points. Included were 12 patients with onset of psychotic symptoms by 12 years of age, 12 healthy age- and gender-matched control subjects, and 10 age- and gender-matched subjects with transient psychosis who were receiving the same medication as the patients with schizophrenia.

The investigators computed the three-dimensional distribution of gray matter in the brain and compared scans using "a novel computational cortical pattern-matching strategy that aligns corresponding locations on the cortical surface, across time and across subjects," according to their report in the Proceedings of the National Academy of Sciences for September 25.

All subjects exhibited loss of gray matter over time. In normal subjects the loss averaged 0.9% to 1.4% per year, but in those with schizophrenia, it was accelerated to >5% per year. The earliest deficits in schizophrenics were evident in the parietal and motor cortex regions.

"Within 2 to 4 years, there was a tremendous 'wildfire' of tissue loss that spread forward across the rest of the brain surface, engulfing a lot of tissue that was previously unaffected," Dr. Thompson told Reuters Health.

Severe deficits in the lateral temporal and dorsolateral pre-frontal cortex, characteristic of adult and childhood schizophrenia, were not present in schizophrenics at the baseline scan at age 13--even though the mean duration of symptoms at that point was 3 years--but were apparent at the last scan about 5 years later. The deficits progressed into the temporal lobes and frontal eye fields, and the pattern of gray matter loss correlated with the severity of psychotic symptoms.

In the medication-matched subjects, gray matter loss was accelerated in the frontal cortices compared with healthy controls. The loss was less pervasive than among schizophrenics, and the non-schizophrenic individuals exhibited no temporal lobe deficits.

"Wouldn't be intriguing if schizophrenia was a disorder of teenage brain development?" Dr. Thompson mused. "One thought is that if normal brain remodeling goes wrong, the whole cascade of development becomes abnormal and leads to the disease."

According to Dr. Thompson, the most exciting aspect of his team's findings may be the implications for therapy. "Now that imaging can define the wildfire of change in the brain, it becomes much easier to tell if new drugs are opposing it," he noted.

While current antipsychotics have a beneficial effect on symptoms, they don't appear to oppose the spread of deficits in the brain, he continued. "So I think the emphasis will shift to drugs that save cells and their connections."

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