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Wash U Study: Genetics Shows Schizophrenia Is Really Multiple Disorders

Jonathan Bailey | NIH

New research from Washington University suggests that schizophrenia is actually a group of eight distinct disorders, each with a different genetic basis.

The findings could eventually open the door to earlier diagnosis and treatment of this debilitating mental disorder, which affects more than 3 million people in the United States.

Washington University psychiatric geneticist Robert Cloninger, who helped lead the study, said it was already known that schizophrenia was at least somewhat heritable.

But previous research had found only weak or inconsistent links between schizophrenia and individual genes.

“People would find genes that were associated with schizophrenia, but when they would go to replicate that ― try to repeat it in another group of people ― it often wouldn’t replicate,” Cloninger said.

That suggested that schizophrenia might be caused not by single genes acting alone, but by groups of genes acting together in a complex way.

To try to figure that out, Cloninger and his colleagues compared genetic variations at specific sites in the genomes of about 4,200 people with schizophrenia, and about 3,800 people without the disease.

They then developed a new way to use statistics to identify groups of interacting gene clusters, and match them up with groups of symptoms ― and risk of disease in patients.

“If they had a particular cluster of genes, they had a 70 percent probability or greater of developing one of the forms of schizophrenia,” Cloninger said.

In all, the researchers identified eight different forms of schizophrenia, each with its own genetic underpinnings and symptoms. Those can range from a severe lack of motivation to paranoia and hallucinations.

Cloninger said he sees this study, which was published online in The American Journal of Psychiatry, as a significant step forward in the diagnosis and treatment of schizophrenia.

“Rather than saying that people are destined to become schizophrenic,” Cloninger said, “what we can actually say is that by understanding their risk at an early age, before they develop problems, we’re in a position to prevent the disorder, or to intervene in ways that will allow them to function in a more healthy fashion.”

Cloninger said this same approach could be used to explore the genetic basis for other complex disorders, like heart disease or diabetes.

“We don’t just have to look at the effects of individual genes one at a time,” Cloninger said. “But we actually can look at the way they work as members of an orchestra, and lead to either health or disease.”

Follow Véronique LaCapra on Twitter: @KWMUScience