Medical College of Georgia research teasing out how the brain's off-switch mechanism contributes to schizophrenia could lead to new drugs, experts said.
MCG researcher Lin Mei was honored for his schizophrenia work this month with a $100,000 Distinguished Investigator Award from NARSAD, the leading charity funding research into mental illness. He was among 11 chosen from 150 prominent mental health researchers, said selection committee chairman Jack Barchas, the chairman of the Department of Psychiatry at Weill Medical College of Cornell University. The scientists who reviewed Dr. Mei's work universally praised it as "elegant," Dr. Barchas said.
"That in our business is extraordinarily high praise," he said. "That says that it is extremely well thought out. He has ways of cutting right to the gut issues."
The problem with schizophrenia is that, unlike other disorders such as Parkinson's or Alzheimer's diseases, the disease process is not as distinctive, Dr. Mei said.
"It doesn't have a clear-cut pathologic hallmark," he said, which has hampered the ability to study it.
Dr. Mei has focused on two genes that have been associated with the disease -- neuregulin-1 and ErbB4. Both are involved in the development of neurons early on, said Dr. Mei, who is the chief of the Program of Developmental Neurobiology at MCG.
But they are also involved in the regulation of two key neurotransmitter systems, the chemical signals that neurons in the brain use to communicate. One is glutamate, an excitatory transmitter that turns neurons on; the other is GABA, an inhibitory transmitter that turns them off.
Those neurotransmitters appear to be involved in activities such as memory or learning. Two of the clinical symptoms of schizophrenia, in addition to auditory or visual hallucinations, are social disconnect or isolation and impaired learning and memory, Dr. Mei said.
Neuregulin appears to promote the release of GABA, the inhibitor of neuron function, which could lead to decreased ability to learn and remember, he said.
Dr. Mei was recently awarded a three-year, $514,000 grant from the National Institutes of Health to create a genetically altered mouse that produces more neureglin-1. It would be difficult to ascertain if the mouse is experiencing hallucinations, he said.
"An easier question for us to ask is to see whether they have learning and memory defects, in particular working memory defect," Dr. Mei said.
And that is what is exciting about the work, Dr. Barchas said.
"It's actually important work just in terms of our knowing more about how the brain works," he said. And it could lead to compounds that target neuregulin.
"This is the type of thing that absolutely leads to new medications and to new approaches," Dr. Barchas said. "It's a wonderfully promising, wonderfully exciting piece of work."
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WHAT IS SCHIZOPHRENIA?
Schizophrenia affects 1.1 percent of the adults in the United States, according to the National Institute of Mental Health. The cost of treating the disease was $22.8 billion in 2002 alone, according to a study in the Journal of Clinical Psychiatry.