Department News
UIC Discoveries May Help Unlock Causes, Cures for Schizophrenia

The Department of Psychiatry's Psychiatric Institute is world renowned for its research into the causes of schizophrenia and treatments to help alleviate and perhaps one day cure this devastating disorder.

In the realm of basic science research, UIC investigators have developed specially bred mice that may soon help unlock the causes of schizophrenia and bipolar disorders, and may lead to new diagnostic methods and new drugs to treat these illnesses, perhaps even before psychotic symptoms arise. Our investigators' findings have been reported in recent issues of the world's most highly esteemed academic journals, including the Proceedings of the National Academy of Science, and Archives of General Psychiatry.

Schizophrenia, a psychotic disorder, is characterized by hallucinations, delusions, and marked withdrawal from social contact. Throughout a lifetime, males and females have about a one percent chance of developing the disorder. Bipolar disorders, marked by extreme mood swings, may effect another one percent of the population.
Until now, research in these diseases has been hampered by the lack of an animal model and the fact that human brains can be studied only after death. But now scientists in the Department of Psychiatry have successfully bred laboratory mice that can model certain aspects of schizophrenia and bipolar disorders.

The mouse model is an outgrowth of research begun at UIC in 1997. At that time Erminio Costa, MD, scientific director of the Psychiatric Institute within the Psychiatry Department, and his colleagues, found that a protein called reelin plays a key role in neural development. Scientists at UIC discovered that reelin functions throughout life, not just before birth, as was previously thought.

Since then, scientists at UIC and other universities have shown that reelin plays two key roles. During fetal growth, reelin helps direct brain cells to their proper places. Through the life span in adults, it controls the action of nerve cells.

Dr. Costa, one of two UIC faculty who are members of the National Academy of Science, and his co-investigators conducted a double-blind postmortem study of 60 brains and found that reelin levels are about fifty percent lower in schizophrenic and bipolar brains than in normal brains. During fetal growth, that shortage may impede the normal migration or final positioning of brain cells. In the adult, reelin shortage diminishes the brain's physical ability to adapt, thus disrupting a person's ability to process information, learn and remember.

A normal nerve cell is tree-shaped; its action center is at the branch-like dendrites. Here, nerve impulses leap from one cell to the next by way of a chemical signal. Normal dendrites grow microscopic thorns called spines. These spines are thought to be responsible for the biochemical exchanges that result in creative, innovative thinking. During learning and memorization, spines grow in size and number. This increase appears to enhance further learning and memory.

UIC researchers have found that in schizophrenic brains, reduced reelin levels diminish the size and number of spines. "Having less reelin and fewer spines doesn't necessarily mean a person will have schizophrenia, but these shortages clearly create an increased vulnerability to the disease," said Dr. Costa.

He and his colleagues will use the mouse model to explore how antipsychotic drugs work. "We've used antipsychotic drugs for decades," said Dr. Costa. "But every antipsychotic drug now in use was discovered by serendipity. No one really knows why they work," he said. "If we can use the model to learn how these drugs counteract the effect of low reelin and fewer spines, it will be an important step toward understanding the underlying causes of mental illness, and may lead to better treatments in the future," he said.

Additional Research

Other investigators in the Psychiatric Institute are exploring the course and manifestations of schizophrenia through the life span of afflicted patients. In fact, Martin Harrow, Ph.D, is director of the world's the longest running longitudinal study of the disorder. Patients in this study, which began in 1975, were assessed in the acute phase and are periodically reassessed. This program is viewed by the field as ranking among the world's leading research groups in advancing knowledge of disordered thinking, psychosis and course and outcome in schizophrenia. The study contributes to current theories on psychosis, thought disorders, negative symptoms and suicidal behavior, and it advances knowledge of the long-term course of schizophrenia.
The Psychiatric Clinical Research Center (PCRC), which is affiliated with the UIC Medical College's General Clinical Research Center, also contributes to current research on drugs to treat schizophrenia symptoms and related disorders. The clinic assesses safety and efficacy of new and developing psychopharmaceuticals, and provides thorough evaluation, diagnosis and treatment to severely mentally ill patients, many of whom are uninsured and have no other access to mental health services.
PCRC investigations have advanced the diagnosis and treatment of schizophrenia and mood disorders. Our researchers have helped develop agents such as risperidone, olanzapine and clozapine, and continue to test new therapeutic interventions.