PHILADELPHIA - Recent studies have identified many genes that may put people with schizophrenia at risk for the disease. But, what links genetic differences to changes in altered brain activity in schizophrenia is not clear. Now, three labs at the Perelman School of Medicine at the University of Pennsylvania have come together using electrophysiological, anatomical, and immunohistochemical approaches - along with a unique high-speed imaging technique - to understand how schizophrenia works at the cellular level, especially in identifying how changes in the interaction between different types of nerve cells leads to symptoms of the disease. The findings are reported this week in the Proceedings of the National Academy of Sciences.

"Our work provides a model linking genetic risk factors for schizophrenia to a functional disruption in how the brain responds to sound, by identifying reduced activity in special nerve cells that are designed to make other cells in the brain work together at a very fast pace" explains lead author Gregory Carlson, PhD, assistant professor of Neuroscience in Psychiatry. "We know that in schizophrenia this ability is reduced, and now, knowing more about why this happens may help explain how loss of a protein called dysbindin leads to some symptoms of schizophrenia."

Previous genetic studies had found that some forms of the gene for dysbindin were found in people with schizophrenia. Most importantly, a prior finding at Penn showed that the dysbindin protein is reduced in a majority of schizophrenia patients, suggesting it is involved in a common cause of the disease.

For the current PNAS study, Carlson, Steven J. Siegel, MD, PhD, associate professor of Psychiatry, director of the Translational Neuroscience Program; and Steven E. Arnold, MD, director of the Penn Memory Center, used a mouse with a mutated dysbindin gene to understand  how reduced dysbindin protein may cause symptoms of schizophrenia.

Click here to view the full release.