Regulatory Protein Reduced in Schizophrenia Patients

Researchers have found that DARPP-32 (an acronym for dopamine and cyclic AMP regulated phosphoprotein of 32, 000 molecular weight), a key regulatory protein involved in controlling receptors, ion channels, and other physiological factors in the brain, is significantly reduced in people with schizophrenia. This finding was reported in the August 2002 issue of Archives of General Psychiatry.

"DARPP-32 is activated and de-activated ultimately by neurotransmitters that are implicated in the development of schizophrenia,” explained Dr. Paul Greengard of the Laboratory of Molecular and Cellular Neuroscience of the Rockefeller University (New York, NY, USA). "A reduction of DARPP-32, required for functions in the brain, could contribute to the cognitive dysfunction seen in the disease.”

The investigators studied the brains from 14 patients who had suffered from schizophrenia before their deaths. They found that DARPP-32 levels were reduced significantly in the dorsolateral prefrontal cortex, which has consistently been associated with the symptoms of schizophrenia. Low levels of DARPP-32 also were found in patients who had had schizophrenia, but normal levels were seen in people who did not have the disease.

"This is the first study to show reduced levels of this important regulatory molecule in schizophrenia,” said Dr. William Bunney, professor of psychiatry at the University of California, Irvine (USA). "If DARPP-32 plays such a key role in controlling physiological activity in this part of the brain, perhaps there could be methods we could use to eventually maintain normal levels of the molecule.”

"This study showed us that DARPP-32 is reduced in an area of the brain most often linked to schizophrenia,” explained Dr. Hugh Hemmings, professor of anesthesiology at Weill Cornell Medical College (New York, NY, USA). "But it does not tell us that DARPP-32 causes this disease. We need to study whether it is a cause or another adaptation of the existing disease, and gain a more detailed understanding of its regulatory effects in the brains of schizophrenic patients and of people without the disease.”




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Rockefeller University
University of California, Irvine
Weill Cornell Medical College