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 Research & Giving News Article  of Schizophrenia It is a major advance for scientists studying the devastating mental illness, which afflicts some 2 million Americans. Animal models of schizophrenia have been hard to design, in part because many factors are believed to contribute to symptoms clinically associated with the human form of the disease. Some are genetic, while others are environmental. How these two fundamentally different kinds of causation interact remains a matter of speculation and intense scientific investigation. Hence, the importance of an animal model that mimics both clinical and genetic aspects of schizophrenia in humans. This past May, NARSAD Distinguished Investigator John C. Roder, Ph.D., and colleagues, demonstrated that malfunction of a gene called DISC1 caused symptoms of both schizophrenia and depression in genetically engineered mice. (Click here for the full story.) Dr. Roder screened a large population of mouse mutants to isolate two strains with different mutations in DISC1. His team found that one of the mutant mouse strains exhibited behavioral abnormalities and memory deficiencies resembling the symptoms of schizophrenia in humans. These symptoms could be alleviated in the mice by antipsychotic drugs. The other mutant mouse strain showed behaviors that reflected depressive symptoms, which, similarly, the researchers found, could be alleviated by an antidepressant. These experiments support the theory that the two disorders share common genetic mechanisms. The newly reported work by Dr. Sawa, an associate professor of psychiatry and neuroscience and director of the program in molecular psychiatry at Johns Hopkins, has also focused on DISC1 (DISC stands for “disrupted in schizophrenia”). A mutant version of DISC1 has been statistically associated with the occurrence of schizophrenia in human patients. Healthy DISC1 genes direct cells to manufacture proteins that help nerve cells assume their proper positions in the brain. As reported online this week in Proceedings of the National Academy of Sciences, Dr. Sawa and colleagues generated mice that make an incomplete, shortened form of the DISC1 protein in addition to the regular type. The short form of the protein attaches to the full-length one, disrupting its normal duties. As these mice matured, they became more agitated when placed in an open field, had trouble finding hidden food, and did not swim as long as regular mice. These behaviors parallel the hyperactivity, olfactory defects and apathy observed in people with schizophrenia. Magnetic resonance imaging (MRI) of these mutant mice revealed defects in brain structure also characteristic of schizophrenia, including enlarged lateral ventricles, a region that circulates the spinal fluid and helps protect against physical trauma. Dr. Sawa notes that the observed defects in the mutant mice were not as severe as those typically seen in people with schizophrenia, perhaps, he speculates, because more than one gene is required to trigger the clinical disease. “However, this mouse model will help us fill many gaps in schizophrenia research,” he says. “We can use them to explore how external factors like stress or viruses may worsen symptoms. The animals can also be bred with other strains of genetically engineered mice to try to pinpoint additional schizophrenia genes.” In addition to his NARSAD Young Investigator award, Dr. Sawa was honored in 2007 with the Staglin Family Music Festival Award for Schizophrenia Research, annually earmarked for a single early-career scientist whose research is uncovering the causes of schizophrenia and leading to improved treatments. The $250,000 grant, over three years, is donated to NARSAD by The Staglin Family Music Festival for Mental Health, hosted by Shari and Garen Staglin at their Napa Valley vineyard to raise funds for mental health research. This article was adapted in part with permission of Johns Hopkins University. |
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