Research by a prominent neuroscientist at UIC is providing new clues to the molecular origins of schizophrenia, a devastating mental illness that afflicts nearly 2.5 million Americans.

Erminio Costa, a member of the National Academy of Sciences and scientific director of UIC's Psychiatric Institute, is studying a chemical found in the brain called reelin. Reelin plays a role in correctly positioning and aligning neurons in the developing brain. It is also present in certain areas of the adult brain, including the cerebral cortex, the region responsible for higher mental functions like language and problem solving.

In a postmortem study of the brains of schizophrenics, obtained from brain banks, Costa and his colleagues found that the level of reelin was half that in normal human brains.

To confirm that finding, the UIC scientists conducted a blind study of 60 brains taken postmortem from individuals diagnosed with schizophrenia, unipolar depression or bipolar disorder with psychosis, and individuals with no psychiatric abnormalities. They correctly identified those that came from psychotic patients by testing for levels of reelin. Controls in the experiment ruled out the possibility that the decrease in reelin was due to drugs the individuals had taken to treat their psychoses or to other possible effects.

Costa is now investigating the mechanism by which reelin acts, in collaboration with UIC neuroscientists Hector Caruncho, Dennis Grayson, Alessandro Guidotti, George Pappas, Christine Pesold, Neil Smalheiser and Doncho Uzunov. In a paper to be published in the Proceedings of the National Academy of Science, Costa and his colleagues report finding reelin associated with the dendritic spines of neurons in the cortex. These dendritic spines - branching fingerlike extensions of the neurons that receive inputs from a complex of other neurons - are thought to be involved in learning. The UIC scientists suggest that reelin may act by interfering with biochemical mechanisms important for memory and learning. In the schizophrenic brain, the density of dendritic spines in the cortex is far lower than in the normal brain. Costa speculates that the decreased levels of reelin may be indirectly related to this phenomenon.

Costa has also advanced a "two hit" model of schizophrenia. First, a defect in the gene for reelin causes the misplacement of cortical neurons. This misplacement alone is not sufficient to precipitate mental illness, according to Costa. Rather, it creates a "genetic vulnerability," or a predisposition for psychosis. This first hit is then followed by a second hit later in puberty or in early adulthood when the final pruning of neuronal connections occurs. While this pruning is a normal part of brain maturation, Costa speculates that in schizophrenics it somehow unveils the defects laid down during fetal development. Schizophrenia typically becomes evident when individuals are in their late teens or early twenties.

"If future scientific studies confirm that a defect in the expression of the reelin gene causes a predisposition for psychosis, there are important implications for treatment," Costa said. "We may one day be able to alter the gene's mechanisms that regulate the production of reelin. Moreover, early identification of the genetic defect through laboratory analysis, which is currently under study at UIC by Dr. Smalheiser, might help us take remedial steps before psychotic symptoms arise."

The Psychiatric Institute is part of UIC's College of Medicine, which is the nation's largest medical school. One out of six Illinois doctors is a graduate of the college, as are 70 percent of the minority physicians practicing in Chicago. The college produces more medical school faculty than all but five schools in the country.

The research was funded by the National Institute of Mental Health.

With 25,000 students, the University of Illinois at Chicago is the largest and most diverse university in the Chicago area and is one of only 88 national Research I universities. Located just west of Chicago's Loop, UIC is a vital part of the educational, technological, and cultural fabric of the entire metropolitan region.

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