(Philadelphia, PA) The cause of schizophrenia remains a mystery, despite the millions of dollars spent trying to discover which genes play a role in its etiology. In at least 10 populations around the world, a significant association between schizophrenia and the gene for dysbindin has been noted making dysbindin the most highly replicated schizophrenia-associated gene described to date. In at least 10 populations around the world, a significant association between schizophrenia and the gene for dysbindin has been noted making dysbindin the most highly replicated schizophrenia-associated gene described to date. Now, researchers at the University of Pennsylvania School of Medicine are starting to place where dysbindin fits in the pathway that leads from a gene to a psychiatric disorder. Schizophrenia affects between 1 to 2 percent of people worldwide during their lifetime and about 2.2 million American adults have schizophrenia in a given year.

Using quantitative immunohistochemistry in postmortem brain tissue, the Penn investigators found that the expression of dysbindin protein was reduced in more than 80 percent of the patients with schizophrenia by an average of 40 percent relative to matched healthy controls. (For a color image illustrating this comparison, go to: (http://www.uphs.upenn.edu/news/news_photos/2004/may/arnoldDysbindinColor.html) "This is among the most significant findings I've seen yet in schizophrenia postmortem research, and it represents a critical lead for understanding schizophrenia," says senior author Steven Arnold, MD, Associate Professor of Psychiatry and Neurology. The research appears in the May issue of the Journal of Clinical Investigation.

The scientists also found that, in the same brain regions in which there was a decrease in dysbindin, there was also an increase in the amounts of presynaptic glutamate packets, or vesi
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
3-May-2004

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