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The institution's principal publication for alumni, friends and physicians.
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  F E A T U R E S  
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Summer 2002 Issue
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FEATURES
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THE BRAIN GONE AWRY

Schizophrenia and depression are among the most common and debilitating mental disorders in the United States. To better understand how brain chemistry affects behavior, a consortium of neuroscientists and psychiatrists at UC Davis and three other leading academic medical centers are launching a massive basic-science research effort to study the underlying biology and the genetic basis of these disorders.

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It was a warm day in October when Sally DiVecchia first realized that something was wrong with her son Matthew. That's when the handsome and outgoing 19-year-old, who lived with his father in Pleasanton, Calif., began driving more than two hours to her home in Roseville for 10-minute visits. Despite coaxing him to stay, he would become agitated and leave almost as soon as he arrived.

"His thoughts were disorganized, and it was difficult for me to understand what exactly was going on," said DiVecchia, a board member of the National Alliance for the Mentally Ill. "At about the same time, he had a complete mental breakdown, hearing voices and thinking that people on television and radio were talking directly to him. In response, he telephoned a radio station and was directed to a local physician who admitted him to a mental health treatment center for observation."

The experience would be one of several hospitalizations for Matthew as doctors treated his psychotic symptoms, and family members watched the progressive decline of a formerly confident and capable young man.

"Physicians who saw Matthew were reluctant to initially diagnose him with schizophrenia because he was so young and talented," she said. "He had just graduated from high school and had started a television-antenna service business. But over time, it became clear that schizophrenia was indeed robbing my son of all of his wonderful abilities."

Schizophrenia is a complex mental illness that interferes with an individual's ability to think clearly, manage emotions, make decisions and relate to others, according to Donald Hilty, assistant professor of psychiatry at UC Davis and medical director of the Sacramento County Mental Health Treatment Center.

"Nearly 50 percent of individuals with schizophrenia are diagnosed before age 25, at a time when young adults are just discovering who they are and what they will be in life," he said.

According to the National Institute of Mental Health, one in 100 people suffers from schizophrenia, and at least one in 10 from depression. While many patients find relief from their symptoms through drug therapy,

when untreated these diseases impose a terrible burden on patients, their families and society. In the United States alone, the cost of treatment and management of schizophrenia is estimated at $60 billion a year; for depression, $44 billion a year.

UC Davis Center for Neuroscience, UC Irvine, Stanford University and the University of Michigan have joined forces in a massive research effort to better understand how the brain goes awry in schizophrenia and depression. Funded with a $38 million grant from the Pritzker Neuropsychiatric Disorders Research Fund, more than 50 senior neuroscientists, molecular biologists, geneticists and behavioral scientists, using microarray technology, are working to identify the genes that cause vulnerability to schizophrenia and major depression or that contribute to symptoms and behavioral patterns. Their findings will become new targets for drug development.

"We know that these disorders have their basis in disordered brain function," said Edward Jones, director of the UC Davis Center for Neuroscience and one of the principal investigators of the consortium. "We believe the cause is related to many genes and their protein products acting together. For example, people with schizophrenia who have difficulty switching from one focus of attention to another may have altered expression in genes that control the conduction of impulses between large numbers of nerve cells.

"It is also thought that environmental stress during fetal development may make the adult brain vulnerable to these disorders when a person is faced with stressful life events later in life."

PHOTO — Computerized mannequins with palpable pulses, audible heart tones, breath
sounds and voice are being used to train clinicians and students. The “patient” responds to over 40 medications and a variety of treatment procedures,
including direct intubation.  ""

Edward Jones is one of 50 senior scientists, molecular biologists, geneticists and behavioral scientists using the latest technology to better understand depression and schizophrenia.
 
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The consortium is investigating brain tissue of normal, schizophrenic and depressed individuals. The tissue samples are stored in an extensive "brain bank" established through a partnership between UC Davis and UC Irvine and housed at UC Davis at the Center for Neuroscience. Considered the best of its kind in the world, the bank processes many pairs of brains from patients with schizophrenia and unaffected adults that have been matched according to age, gender and other characteristics, and similarly matched samples from depressed patients and control subjects.

Using state-of-the-art microarray technology, scientists are evaluating the difference in the expression of genes. Microarrays, or "gene chips," allow scientists to measure the activity of thousands of genes at one time and to compare their expression in the brains of affected individuals and controls.

The process uses silicon wafers spotted with thousands of DNA sequences that code for genes representing essential nerve-cell functions. After adding RNA from a brain tissue sample to the chip and using fluorescent tags to track activity, a computer analyzes the results. Comparing gene expression in brain tissue from schizophrenic, depressed and normal subjects will enable researchers to find abnormally expressed genes. These candidate genes will then be studied in living patients and in families with a history of mental illness to determine how differences in expression are related to a vulnerability to the disorders. Scientists also will conduct experiments with genetically modified animals and cell cultures to understand how a gene's abnormal expression affects neural pathways and, ultimately, behavior. The information will lead the way to new treatments.

"The work is enormous in scope," said Jones. "The ability to generate vast amounts of data with microarray technology is what makes it possible even to consider the task of assessing the genetic landscape of 40 brain regions and multiple nerve-cell types. The efforts of single scientists studying a few genes at a time would be unlikely to make major inroads. The Pritzker Foundation has shown great foresight in taking the initiative to finance this consortium," he said.

DiVecchia, for one, looks forward to the day when her son can have access to better medications. "I hope that by the time he's my age, there will be something available so individuals with schizophrenia can return to society," said DiVecchia, who operates a Web site for Sacramentans looking for information on mental illness. "It is worth our time, money and effort to help these people be functional and productive."

For more information on mental illness visit http://namisacramento.org.

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  "It is thought that environmental stress during fetal development may make the adult brain vulnerable to disorders when a person is faced with stressful life events later in life." — Edward Jones.  
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