BEHAVIOR
November 30, 2004

A Case of Nerves: Genetics and Schizophrenia

A possible genetic clue to the sensory confusion of schizophrenia.
The psychiatric disorder schizophrenia remains devastatingly common, affecting around one percent of the world's population. Yet we know little about what causes it and how it works. Now, new research on animals has uncovered an important clue about how a defective gene might help cause the disease.

"Our research in mice suggests that defects in a gene may interfere with communication between nerve cells in the brain," said Ashok Hegde, Ph.D., of Wake Forest University Baptist Medical Center. "We believe this may cause a common symptom of schizophrenia — being unable to filter out unimportant sensory information."

Schizophrenia tends to run in families and has long been thought to have a genetic component. Hegde and his research team studied RGS4, a gene that is believed to control the release of neurotransmitters, molecules that help nerve cells communicate. People with schizophrenia have smaller amounts of a protein that is produced by the RGS4 gene.

In normal people, these neurotransmitters act as gatekeepers, allowing communication only if the information from outside is necessary and relevant. Scientists believe that in those with schizophrenia, the gatekeeper neurotransmitters are not doing their job. The result is that schizophrenics are overwhelmed with too much information, causing mental confusion and stress.

"Our next step will be to see if defects in RGS4 can actually cause schizophrenia-like symptoms," Hegde indicated at the October 2004 meeting of the Society for Neuroscience. To do this, Hegde and his team plan to study the startle response. Normal people are startled when they hear a loud noise. However, if they hear a not-so-loud noise followed by a loud noise, they are not as startled as they are by the loud noise alone. People with schizophrenia are equally startled in both scenarios. Because mice and rats have startle responses that are similar to those of people, the researchers will study mice to see if a shortage of RGS4 causes an abnormal startle response and other schizophrenia-like symptoms.

Asked for his take on these findings, TheDoctor's Dr. Bruce McEwen, Alfred E. Mirsky Professor and head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at Rockefeller University in New York City, said, "The information that this gene affects certain kind of neurotransmission is a good lead. Inhibitory neurons do function as gatekeepers. The really telling work, however, remains to be done. Showing that this gene affects the acoustic startle response is one step, but it is a long way from explaining schizophrenia itself, which has not been modeled in any animal so far and may be impossible to model."
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