White Matter Defects May Lead to Schizophrenia

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"What we wanted to determine was whether altering white matter can affect aspects of the disease," he continued.

Corfas and his team blocked NRG1-erbB signaling in oligodendrocytes in mice. Oligodendrocytes are the cells that form the myelin, or fatty encasing, of nerve fibers. The brain's white matter is made up of myelinated nerve fibers.

When the signaling was blocked, the mice had more oligodendrocytes than normal mice, but the cells had fewer branches and formed a thinner sheath around the nerve fibers. This resulted in slower conduction of electric impulses.

The mice also had alterations in the nerve cells that make and use dopamine, a brain chemical that is known to be altered in people with schizophrenia.

The behavior of the mice was also altered.

"Alterations in signals cause defects, very specific and relatively subtle in white matter structure and function, and these cause dramatic effects on behavior that are in some ways similar to what you would expect to see in neuropsychiatric patients," Corfas said. "They also involve alterations in neurochemicals that are known to be altered in schizophrenia."

The findings are expected to be published online by the Proceedings of the National Academy of Sciences during the week of April 23.

Keith A. Young is associate professor of psychiatry and behavioral science at Texas A&M Health Science Center College of Medicine and co-director of the Central Texas Veterans Health Care System Neuropsychiatry Research Program, who recently presented a paper on this topic at the International Congress on Schizophrenia Research. He said: "What they (the study authors) did in this study was only manipulate this gene or this gene product in white matter, so it's pretty clear that the genetic defects that we've seen in schizophrenia may be being expressed through the white matter and not other cell types. They were so specific in genetic manipulation that it really tightly links this receptor with myelin deterioration."

But Young also cautioned that animal models of schizophrenia are far from perfect.