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Immune dysfunction role in schizophrenia?
SACRAMENTO, Calif.—A $10-million grant by the National Institutes of Mental Health (NIMH) will allow the University of California, Davis (UC Davis) to establish the newest of 15 prestigious Silvio O. Conte Centers for Basic or Translational Mental-Health Research in the United States. The center at UC Davis will advance schizophrenia research by investigating the novel hypothesis that an origin of the disease may be dysregulation of immune molecules that play a key role in the normal development and function of connections in the brain. The center will provide $2 million per year for five years to fund four interdisciplinary projects that will each be conducted distinctly but will all be related to a central research question.
The hypothesis at the heart of the UC Davis Conte Center is that schizophrenia is a neurodevelopmental disorder whose origins may lie in alterations to the brain’s structure caused by the activation of a family of immune molecules during fetal development. Under this hypothesis, the functional changes in connectivity that result from these alterations would lead to the appearance of psychosis early in life, which is consistent with schizophrenia’s typical emergence in teenagers and young adults.
Upon announcing in late March the receipt of the grant to establish the Conte Center, the university noted that its researchers plan to investigate how and when maternal immune activation alters immune signaling in the brain and whether this leads to changes in synaptic connectivity, gene expression, functional connectivity, dopamine dysregulation and neural inflammation, thus perhaps causing schizophrenia.
Previously, a team of five research groups with appointments in the UC Davis School of Medicine, the College of Biological Sciences, the College of Letters and Sciences and the School of Engineering collaborated on interdisciplinary research led by Kimberley McAllister, associate director of the Center for Neuroscience. The team found that maternal immune activation leads to long-term changes in the expression of immune molecules in their offspring’s brains, and they found this pattern to be consistent across multiple species. The implication of a central immune-signaling pathway in the brain that causes changes in neural circuitry and function could illuminate new targets for diagnostic tools and a new class of therapeutics for diagnosis and treatment of schizophrenia and other disorders that may be based on neural-immune conditions.
The Office of Research at UC Davis supported McAllister’s multidisciplinary endeavor with a grant through its Research Investments in the Sciences and Engineering (RISE) Program.
“This historic success by UC Davis demonstrates how modest campus investments in focused, interdisciplinary faculty teams can result in breakthrough discoveries that, in turn, can lead to major federal funding for research that addresses grand-challenge problems in medicine,” said vice chancellor for research evolution and ecology Harris Lewin in a news release announcing the Conte Center grant. “As a result, UC Davis now will join just a handful of institutions that will conduct coordinated translational research aimed at improved diagnosis and treatment of schizophrenia.”
“[The grant] places UC Davis in the upper echelon of mental health research institutions in the world, and is testimony to the strength and depth of our basic and translational science enterprise,” Cameron Carter, professor of psychiatry and behavioral sciences and principal investigator for the Conte Center grant, said in the news release.
Schizophrenia affects roughly 1 percent of the world’s population, with an estimated 3 million cases in the United States alone. According to a July 2014 article by Veronica Meade-Kelly, Broad Institute Communications, in the Harvard Gazette, schizophrenia is characterized by “hallucinations, paranoia, and a breakdown of thought processes,” and often shows itself in teenagers and young adults entering their 20s. Although medications are available to treat psychosis, one of the disorder’s symptoms, there have been no new medications with fundamentally new mechanisms of action developed since the 1950s. Since the advent of genomics research, scientists have discovered approximately two dozen genomic regions that are associated with the disorder.
According to estimates reported in a May 2014 Salk Institute for Biological Studies article about stem cell research related to the disease, nearly one in 10 patients with schizophrenia are driven to suicide by the burden of the disease. In addition, Americans spend an estimated $63 billion on treating schizophrenia and managing related disability.
NIMH’s Centers for Neuroscience of Mental Disorders and Centers for Neuroscience Research began funding scientists in 1988 for cutting-edge projects that approached unifying, well-defined scientific questions from many angles and at multiple levels. These centers were renamed in 1993 in memory of Pennsylvania’s U.S. Rep. Silvio O. Conte, a longtime champion of neuroscience and advocate for care and research benefiting the severely mentally ill.