An Almost-Smoking Gun

What causes the scrambling of mind that characterizes schizophrenia? At alecture given in the spring of 1993 at Harvard Medical School, Daniel Weinberger, M.D., chief of the National Institute of Mental Health's Brain Disorder Branch, spoke of the latest findings. "We don't have a smoking gun yet," he admitted, "but we have a gun that is threatening to smoke."

Many researchers have identified differences in the brains of schizophrenics compared to non-schizophrenics. A few years ago, Dr. Torrey was one of the first to use magnetic resonance imaging to show that the fluid-filled ventricles in the brains of schizophrenics are larger than those of their non-schizophrenic twins. More recently, researchers at the University of California at Irvine found, in a post-mortem study of seven schizophrenics, that most of the neural cells that should have migrated during the second trimester of pregnancy to higher brain regions, the hippocampus and neocortex, never made it out of lower brain areas such as the white matter of the temporal and frontal lobe.

Then, in August of 1992, The New England Journal of Medicine published a major study linking a specific symptom of schizophrenia with specific changes in the brain. Harvard University researchers found that the jumbled and disordered thinking of schizophrenia was associated with brain-size reductions of up to 19 percent in regions of the temporal lobe crucial to speech and language. The more disordered the thinking, the smaller the regions. "This is one of the first times that a relationship has been found between specific clinical symptoms of schizophrenia and brain reduction i a specific area," said Althea Wagma, Ph.D., chief of the NIMH Schizophrenia Research Branch's neuroimaging the electrophysiology research program. "This may have significant implications for how we ought to design future studies, to ask questions about the relationship between brain dysfunction and behavioral dysfunction."

Genes almost surely play a role in these changes: a recent study in the British journal Nature reported the presence of repeated segments of the gene that codes for the dopamine receptor protein on the surface of brain cells. And since excess amounts of the neurotransmitter dopamine have been shown to be associated with schizophrenia, researchers believe that the genetic mutation may be the cause, by preventing brain cells from properly absorbing dopamine.

Many other studies of inheritance patterns have also suggested a genetic link. Most recently, Josef Parnas, M.D., of Copenhagen University published a study showing that 16 percent of the children of schizophrenic mothers grow up to be schizophrenic themselves--compared to just 1.9 percent of the children of non-schizophrenic mothers.

Yet genes are clearly not the only cause.

Other studies have shown that higher rates of schizophrenia occur in offspring whose birth was marked by obstetric complications and in those born to mothers who caught the flu during the fifth month of pregnancy.

Other environmental causes have also been suggested: a 14-year-old study of 49,000 young Swedish men by Glyn Lewis, M.D., of London's Institute of Psychiatry found that those who had grown up in cities were 65 percent more likely to develop schizophrenia than those who had been raised in rural areas. In perfect dose-response fashion, those reared in large towns had a risk midway between that of city reared and country reared.

Although Lewis noted that viral illnesses and head injuries are both more common in cities, it could also be the stress of urban life that contributes to the risk of developing schizophrenia. Indeed, other studies have found that in the U.S., the states with the greatest proportion of people living in cities (particularly in the Northeast) have about twice the rate of schizophrenia as those with the fewest. Worldwide, the disease appears to be far more common in westernized countries than in Third World countries. Historically, too, some researchers believe that schizophrenia has become increasingly prevalent in the past 200 years, with the rise of urbanization.

ILLUSTRATION