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Schizophrenia Cause: Neural Circuits, Not Mom

Newly Arising Gene Mutations Converge, Cause Schizophrenia
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WebMD Health News
Reviewed by Laura J. Martin, MD

Aug. 8, 2011 - An unlucky collection of tiny changes in the genetic code causes most cases of schizophrenia, a game-changing new study finds.

These "de novo" mutations aren't passed on from parents to their children, helping to explain why so many cases of schizophrenia occur in people with no family history of mental illness.

The finding, by Columbia University psychiatrist Maria Karayiorgou, MD, and colleagues, comes from a "deep gene sequencing" study of 53 people with schizophrenia and 22 people without the condition, and their parents.

"I think it is a huge relief for many of the families affected by schizophrenia to know that there is a clear cause for their disease -- which has been doubted many times -- and that the parents did not pass it on to their child," Karayiorgou tells WebMD.

The "fascinating study" is the tipping point toward a new understanding of schizophrenia, says Michael L. Cuccaro, PhD, associate professor at the University of Miami's Hussman Institute for Human Genomics. Cuccaro was not involved in the Karayiorgou study.

"This is evidence that points us in a different direction," Cuccaro tells WebMD. "There has been a real shift from thinking of schizophrenia as having a distinct genetic cause to seeing it as an accumulation of rare genetic events."

Different Genetic Changes Converge in Schizophrenia

In 27 of their 53 schizophrenia patients, Karayiorgou's team found 40 small changes (single nucleotide variants or SNVs) in 40 genes. The patients had more of these mutations than did the people without schizophrenia. But most importantly, virtually all the mutations in the patients affected the function of a gene.

"I am not sure why these point mutations occur. But the fact we find them in the numbers we do in schizophrenia -- and in autism -- suggest they are an important disease-causing mechanism," Karayiorgou says.

None of the schizophrenia patients in the study had the same mutations in the same genes. Yet somehow these very different combinations of genetic changes result in a single disease.

"It shows there are very complicated interrelationships between these genes that give rise to these consequences," Cuccaro says.

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