Schizophrenia is umbrella disease of eight gene disorders, study finds

Schizophrenia is not a single disease caused by one gene but a group of eight distinct genetic disorders — each with its own set of symptoms, according to a study released Monday.

The new findings, published in The American Journal of Psychiatry, could help doctors diagnose and treat the often debilitating symptoms associated with the mental illness. While schizophrenia affects people in different ways, some of the most common manifestations include hallucinations or delusions, disorganized speech and behavior and a disassociation of thoughts and emotions.

Previous research led scientists to believe that about 80 percent of the risk of schizophrenia was genetic, but until now they could not determine where it originated. The study’s findings suggest that distinct clusters of gene variations, not a single gene, causes the disease.

“Genes don’t operate by themselves,” C. Robert Cloninger, one of the study’s senior researchers, explained. “They function in concert much like an orchestra, and to understand how they’re working, you have to know not just who the members of the orchestra are but how they interact.”

Researchers based their conclusions on a gene study of more than 4,000 people with schizophrenia and 3,800 people without the condition.

Individual genes have inconsistent connections to schizophrenia, but groups of interacting genes were found to contribute to an extremely high risk of the disease, making it nearly impossible for individuals with those genetic variations to avoid the illness, the report said.

They found that those specific genetic variations worked together to produce different severities of the mental illness. People who had distinct gene clusters — 42 of which were identified in the study — were 70 to 100 percent likely to develop schizophrenia, according to the report.

Of those clusters, researchers were able to identify eight qualitatively unique disorders — each with its own symptoms and level of severity — within what they now see as the umbrella disease of schizophrenia.

“What we’ve done here, after a decade of frustration in the field of psychiatric genetics, is identify the way genes interact with each other, how the ‘orchestra’ is either harmonious and leads to health or disorganized in ways that lead to distinct classes of schizophrenia,” Cloninger said.

The study marks a breakthrough for scientists hoping to treat patients suffering from the illness. Now that the genetic variations responsible for the symptoms have been identified, it may be possible to target specific pathways that lead to schizophrenia.

“In the past, scientists had been looking for associations between individual genes and schizophrenia,” said Dragan Svrakic, a co-researcher and professor of psychiatry at Washington University. “When one study would identify an association, no one else could replicate it. What was missing was the idea that these genes don’t act independently. They work in concert to disrupt the brain’s structure and function, and that results in the illness.”