Pivotal brain processor decreased in schizophrenia

August 14, 2002

Irvine, Calif. -- Levels of a pivotal signal processor in the brain are reduced significantly in people with schizophrenia, a study by scientists at UC Irvine, Weill Cornell Medical College and Rockefeller University has found.

The findings suggest that the processor, which helps regulate key neurotransmitters in an area of the brain linked to schizophrenia, could eventually play a key role in reversing the brain dysfunctions associated with the disease. The study appears in the August issue of Archives of General Psychiatry.

Dr. William Bunney, the Della Martin professor of psychiatry at UCI; Dr. Paul Greengard, professor of neuroscience at Rockefeller University; and Dr. Hugh Hemmings, professor of anesthesiology at Weill Cornell, and their colleagues found the processor, a chemical called DARPP-32, was reduced in the brains of deceased victims of schizophrenia.

DARPP-32 is the subject of increasing scientific scrutiny. The neurotransmitters dopamine, glutamate and serotonin; the antidepressant Prozac; and even drugs of abuse like cocaine, opiates and nicotine all have been found to work on the brain through the actions of DARPP-32. The molecule is suspected of integrating information throughout the brain and providing a blueprint for physiological activity. Greengard won the Nobel Prize for Medicine in 2000 for his work on DARPP-32.

"DARPP-32 is a key regulatory protein, involved in controlling receptors, ion channels and other physiological factors and is activated and de-activated ultimately by neurotransmitters that are implicated in the development of schizophrenia," Greengard said. "A reduction of DARPP-32 required for functions in the brain could contribute to the cognitive dysfunction seen in the disease."

The researchers studied the brains of 14 deceased people who had schizophrenia. DARPP-32 was found to be reduced significantly in an area of the brain called the dorsolateral prefrontal cortex, which has consistently been associated with the symptoms of schizophrenia. The researchers found low levels of DARPP-32 in people who had schizophrenia, but normal levels in people who did not have the disease. DARPP-32 was not found to be reduced in another area of the brain also associated with schizophrenia.

"This is the first study to show reduced levels of this important regulatory molecule in schizophrenia," said Bunney. "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."

The DARPP-32 molecule is known to control the actions of two neurotransmitters linked to schizophrenia -- dopamine and glutamate. Schizophrenia affects about two million people in the United States; its cause is unknown. The dysfunctions in schizophrenia often result in severe social problems, delusions, hallucinations, reduced emotional responses and grossly disorganized behavior, according to the National Association for Research on Schizophrenia and Depression.

"This study showed us the DARPP-32 is reduced in an area of the brain most often linked to schizophrenia," Hemmings said. "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."
The researchers' work was supported by a number of gifts and grants, including those from the National Association for Research on Schizophrenia and Depression and the National Institutes of Health.

The researchers' colleagues in the study included Katherine Albert and Anna Adamo of Cornell and Steven Potkin, Schahram Akbarian, Curt Sandman and Carl Cotman of UCI.


Joe Bonner, Rockefeller University
(212) 327-8998

Jonathan Weil, Weill Cornell Medical College
(212) 821-0566


A complete archive of press releases is available on the World Wide Web at www.today.uci.edu.

University of California - Irvine

Related Schizophrenia Articles from Brightsurf:

Schizophrenia: When the thalamus misleads the ear
Scientists at the University of Geneva (UNIGE) and the Synapsy National Centre of Competence in Research (NCCR) have succeeded in linking the onset of auditory hallucinations - one of the most common symptoms of schizophrenia - with the abnormal development of certain substructures of a region deep in the brain called the thalamus.

Unlocking schizophrenia
New research, led by Prof. LIU Bing and Prof. JIANG Tianzi from the Institute of Automation of the Chinese Academy of Sciences and their collaborators have recently developed a novel imaging marker that may help in the personalized medicine of psychiatric disorders.

Researchers discover second type of schizophrenia
In a study of more than 300 patients from three continents, over one third had brains that looked similar to healthy people.

New clues into the genetic origins of schizophrenia
The first genetic analysis of schizophrenia in an ancestral African population, the South African Xhosa, appears in the Jan.

Dietary supplement may help with schizophrenia
A dietary supplement, sarcosine, may help with schizophrenia as part of a holistic approach complementing antipsychotic medication, according to a UCL researcher.

Schizophrenia: Adolescence is the game-changer
Schizophrenia may be related to the deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms.

Study suggests overdiagnosis of schizophrenia
In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), Johns Hopkins Medicine researchers report that about half the people referred to the clinic with a schizophrenia diagnosis didn't actually have schizophrenia.

The ways of wisdom in schizophrenia
Researchers at UC San Diego School of Medicine report that persons with schizophrenia scored lower on a wisdom assessment than non-psychiatric comparison participants, but that there was considerable variability in levels of wisdom, and those with higher scores displayed fewer psychotic symptoms.

Recognizing the uniqueness of different individuals with schizophrenia
Individuals diagnosed with schizophrenia differ greatly from one another. Researchers from Radboud university medical center, along with colleagues from England and Norway, have demonstrated that very few identical brain differences are shared amongst different patients.

Resynchronizing neurons to erase schizophrenia
Today, a decisive step in understanding schizophrenia has been taken.

Read More: Schizophrenia News and Schizophrenia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.