Schizophrenia Genetics Linked to Disruption in Brain's Processing of Sound

Scientists have been able to identify a number of genes that increase a person's risk of developing schizophrenia, but the link between these genetic differences and the altered brain activity that happens in schizophrenic people is unclear. To investigate how schizophrenia works at the cellular level, three labs at the Perelman School of Medicine at the University of Pennsylvania have united several different approaches--electrophysiological, anatomical, and immunohistochemical--along with a unique high-speed imaging technique.

"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," said 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."

An earlier study conducted at Penn found that most schizophrenia patients have a reduced dysbindin protein, which suggests that the protein may cause some symptoms of schizophrenia. The researchers in this current study used a mouse with a mutated dysbindin gene to investigate the connection further. They discovered that the brains of mice with the mutated gene had a number of sound-processing deficits. When dysbindin protein levels are reduced, special nerve cells that control fast brain activity lose their effectiveness, interfering with the brain's ability to process the large amount of information it receives.

This fast brain activity has also been shown to be important to short-term memory in humans, and it is reduced in people with schizophrenia. This symptom of schizophrenia is resistant to currently available treatments, and insights from this new study could potentially point to more effective avenues of treatment. The findings are reported this week in the Proceedings of the National Academy of Sciences.

Source: University of Pennsylvania School of Medicine

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