Brain anatomy yields schizophrenia clues.

Brain anatomy yields schizophrenia clues

Subtle but significant changes in brain anatomy are common features of people with schizophrenia, researchers report in the March 22 NEW ENGLAND JOURNAL OF MEDICINE. They base their conclusion on brain scans of 15 sets of identical twins, each pair consisting of one twin with schizophrenia and one without.

The findings provide the best evidence yet that nongenetic abnormalities exert an important influence on the development of schizophrenia, says Daniel R. Weinberger of the National Institute of Mental Health (NIMH) in Bethesda, Md., who conducted the study with Richard L. Suddath and three other NIMH colleagues. One possibility is that brain cells for some reason do not migrate to their appropriate destinations during the fetal development of people who later develop schizophrenia, Weinberger says.

In 12 of the 15 twin pairs, the researchers could identify the one with schizophrenia just by looking at magnetic resonance imaging (MRI) scans of the brain. Magnetic resonance imaging is a technique for taking pictures of various structures in a living brain. Visual clues to schizophrenia consisted of cearly enlarged ventricles -- three fluid-filled spaces deep within the brain.

Mathematical analysis of the data showed that, compared with their healthy twins, 14 of the 15 schizophrenics had at least one enlarged ventricle and also displayed size reductions in the temporal lobes, the hippocampus and the volume of the left temporal lobe's gray matter. The widely dispersed brain abnormalities occur in areas considered crucial to regulating emotion and motivation.

A control group of seven healthy identical-twin pairs showed no size differences in the same brain structures.

Brain abnormalities were not more severe among the schizophrenics with a long history either of the disorder or of antipsychotic drug treatment, the scientists note. Thus, the changes appear linked directly to schizophrenia, they say.

Previous studies using MRI and computerized tomography have charted and enlargement of brain ventricles among a substantial portion of people with schizophrenia, but researchers disagree over the extent of the brain's shrinkage as well as the cause of the anatomical abnormalities.

Weinberger suggests that early in brain development, a misdirection of cells -- possibly caused by a viral infection, autoimmune disorder or birth injury--causes structural abnormalities that remain largely "silent" until the central nervous system undergoes maturational changes in late adolescence, when symptoms and schizophrenia typically emerge.

Although his findings and an earlier study of twins by other researchers provide "nearly definitive evidence" of structural brain abnormalities associated with schizophrenia, the significance of the observation remains unclear, writes M.-Marsel Mesulam of Beth Israel Hospital in Boston in an editorial accompanying the research report. Not all schizophrenic patients have large ventricles, Mesulam says, and large ventricles can also appear in people with manic depression or Alzheimer's disease.

Moreover, another research team studying schizophrenic brains has reported detecting clear ventricular enlargement only on the MRI scans of male patients -- a finding at odds with the NIMH study, which revealed abnormalities in most of the eight male and seven female twins with schizophrenia. Nancy C. Andreasen of the University of Iowa in Iowa City and her co-workers, who describe the contrasting results in the January ARCHIVES OF GENERAL PHYSCIATRY, maintain that schizophrenia is actually several different disorders and that studes using different proportions of each type may yield different findings.

They add that evidence of metabolic and chemical changes in the brain may reveal more about schizophrenia's perplexing nature than anatomical changes picked up by MRI.