Scientists have long thought the faulty neural wiring that predisposes individuals to behavioral disorders like autism and psychiatric diseases like schizophrenia must occur during development. But no one has ever shown that a risk gene for the disease actually disrupts brain development.
Now, UNC scientists have found that the 22q11 gene deletion on chromosome 22 – a mutation that confers the highest known genetic risk for schizophrenia – is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.
In a genetic animal model, the researchers discovered that the gene deletion alters the number of a critical subset of neurons that end up in the brain’s cerebral cortex – the region critical to reasoning and memory. The defect also causes another type of nerve cell – called GABAergic neurons – to be misplaced within the brain’s cortical layers, resulting in a subtle miswiring of the organ.
“For practically ever other disease, we know what cells take a hit,” said senior study author Anthony LaMantia, Ph.D., professor of cell and molecular physiology and co-director of the Silvio M. Conte Center for Research in Mental Disorders at the UNC School of Medicine.
“For multiple sclerosis the myelinating oligodendrocytes in the brain falter, for Lou Gehrig’s disease the motor neurons in the brain stem degenerate. But we really had no idea what was happening in schizophrenia, or in any of the psychiatric diseases for that matter – until now.”
The study was presented October 17, 2009 at the Society for Neuroscience meeting in Chicago, by Daniel Meechan, Ph.D., post-doctoral fellow in the LaMantia laboratory and the first author of the recent paper in Proceedings of the National Academy of Sciences that details the findings.