Researchers link genetic errors to schizophrenia

In individuals with schizophrenia, mutations were more likely to disrupt signaling genes that help organize brain development. Each mutation was different, and impacted different genes. However, several of the disrupted genes function in related neurobiological pathways.

The findings suggest that schizophrenia is caused by many different mutations in many different genes, with each mutation leading to a disruption in key pathways important to a developing brain. Once a disease-causing mutation is identified, other different disease-causing mutations may be found in the same gene in different people with the illness.

Thus, for most cases of schizophrenia, the genetic causes may be different. This observation has important implications for schizophrenia research. Currently, most genetic studies examine for mutations that are shared among different individuals with the illness. These approaches will not work if most patients have different mutations causing their condition.

Fortunately, there are now genomic technologies available that allow researchers to discover rare mutations within each individual with a disorder. As these technologies improve, it will be possible to detect other types of disease-causing mutations. Eventually, the identification of genes disrupted in individuals with schizophrenia will allow the development of new treatments more specifically targeted to disrupted pathways.

The research team included many other scientists at a variety of institutions, including Evan Eichler and his colleagues at the University of Washington, and investigators at the State University of New York at Stony Brook, Case Medical Center in Cleveland, the University of North Carolina, the University of California Los Angeles, the National Cancer Institute, and the National Institute on Aging.

This work was supported by many different grants from several foundations and agencies, including the Forrest C. and Frances H. Lattner Foundation, NARSAD, the Simons Foundation, the Stanley Medical Research Foundation, the Howard Hughes Medical Institute, the National Institute on Aging, the National Institute of Mental Health, and the Mental Health Division of the Washington State Department of Social and Health Services.