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Schizophrenia Tied to Multiple Genetic Errors
Date:3/27/2008

Finding could lead to specific treatments for individual patients, study says

THURSDAY, March 27 (HealthDay News) -- Scientists have found that deletions and duplications in DNA are more common in people with schizophrenia, and these errors are in genes related to brain development and neurological function.

Because these deletions and duplications differ from person to person, the study findings could eventually lead to new individualized treatments for those suffering from the disabling mental disorder, the researchers said.

"We found areas in people's DNA that are either deleted or duplicated -- we all have some of these, and some are rare," said lead researcher Dr. Jon M. McClellan, an associate professor of psychiatry at the University of Washington, in Seattle. "The assumption is that common ones are probably less likely to cause illnesses, but the rare ones might."

The researchers looked to see if people with schizophrenia had more rare mutations than healthy individuals did. "We found they had a lot more," McClellan said. "So there was about a threefold increased risk of having a rare deletion or duplication in someone with schizophrenia versus healthy people."

For those who developed schizophrenia early in life, there was a fourfold increased risk of rare deletions and duplications, McClellan added.

The findings were published in the March 27 edition of the journal Science.

For the study, McClellan's team analyzed DNA from 150 people with schizophrenia and 268 people without the disease. The researchers found deletions and duplications of genes in 15 percent of those with schizophrenia, compared to only 5 percent among people without the disorder.

Genetic deletions and duplications were even greater among people whose schizophrenia started when they were young -- before 12 years of age. Among these people, 20 percent had the rare gene mutations.

The results were confirmed by a second team of researchers led by Anjene Addington and Judith Rapoport at the U.S. National Institutes of Mental Health. In their study, Addington and Rapoport found that the rate of rare duplications and deletions of genes was even higher among people who developed schizophrenia before they were 12 years old.

Among people with schizophrenia, these mutations were likely to alter genes that help in brain development. While each mutation was unique and affected different genes, several mutations were related to parts of the brain that control neurobiological development, the researchers found.

McClellan noted that many different mutations in many genes can disrupt brain development resulting in schizophrenia. Therefore, in people with schizophrenia, the genetic causes may be different for different people, he said.

"If it's the case that most people have a different genetic cause for schizophrenia, the way that most research is done now isn't going to work," McClellan said. Current research is designed to find commonalities between people with schizophrenia, he said, adding, "That may not be the best way to go."

The encouraging news is that new technologies are available that can find these rare gene mutations in individual patients with schizophrenia. And, as these technologies improve, it may one day be possible to develop new treatments targeted for specific genes in affected individuals, McClellan said.

One mental-health expert thinks these findings could serve as a breakthrough in understanding schizophrenia.

"This is a groundbreaking study which presents a novel approach to identifying genetic factors predisposing to schizophrenia," said Dr. Daphne Holt, an instructor in medicine at Harvard Medical School, and associate director of the Massachusetts General Hospital First Episode and Early Psychosis Program.

"The idea that multiple rare mutations may account for a substantial portion of the incidence of schizophrenia is at variance with the current dogma of the field, which is that a number of mildly deleterious, common alleles [genes] combine with environmental factors to lead to the development of schizophrenia," Holt said.

"I believe that this study could lead to a change in the overall direction of the field, and I look forward to further replication and extension of these findings," Holt said.

According to the National Institute of Mental Health, schizophrenia affects about 1.1 percent of the adult American population in a given year. People with schizophrenia sometimes hear voices others don't hear, believe that others are broadcasting their thoughts to the world, or become convinced that others are trying to harm them. These experiences can make them fearful and withdrawn and make it difficult to have relationships with other people.

More information

For more on schizophrenia, visit the U.S. National Institute of Mental Health.



SOURCES: Jon M. McClellan, M.D., associate professor, psychiatry, University of Washington, Seattle; Daphne Holt, M.D., Ph.D., instructor, medicine, Harvard Medical School, and associate director, Massachusetts General Hospital First Episode and Early Psychosis Program, Boston; March 27, 2008, Science


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