(Great Neck, NY - May 07, 2007) — Researchers have demonstrated for the first time that malfunction of a gene called DISC1 that in previous research had been associated with schizophrenia and depression does indeed cause symptoms of those disorders in genetically engineered mice.
The research team, headed by NARSAD 2006 Distinguished Investigator John C. Roder, Ph.D., has published a paper in which they suggest their findings offer a possible animal model for developing treatments for schizophrenia and depression. They also indicate that their findings support the theory that the two disorders share common genetic mechanisms.
Dr. Roder, Steven Clapcote, David Porteous and colleagues reported their findings in the May 3 issue of the journal Neuron. In their experiments, the researchers sought to explore the consequences of intentionally mutating a gene called "Disrupted in schizophrenia 1" (DISC1), which prior research has found to be associated, in one family, with schizophrenia, bipolar disorder, and major depression.
The researchers performed their experiments with the hypothesis that different mutant variations of DISC1 might have different pathological effects. To test this theory, they screened a large population of mouse mutants to isolate two with different mutations in DISC1.
They found that, indeed, 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 study showed.
Similarly, the other mutant mouse strain showed behaviors that reflected depressive symptoms. These symptoms, too, could be alleviated by an antidepressant, the researchers found.
Significantly, both types of DISC1 mutant mice exhibited the same kind of reduced brain volume seen in people with schizophrenia and depression. Both types also showed biochemical abnormalities in the function of a protein produced by the DISC1 gene.
The researchers concluded that the different effects of antipsychotic and antidepressant drugs on the two mutant DISC1 strains “might provide clues to effective medications for these patient groups. Indeed, these mice could represent a model system to explore novel treatment and preventative strategies for certain symptoms of major mental illness,” they wrote.
The findings, they said, “lend further credence to the growing recognition that schizophrenia and bipolar disorder share, at least in part, common genetic etiologies and thus underlying molecular mechanisms.”
The study was supported by grants from NARSAD: The Mental Health Research Association, the Canadian Institutes of Health Research, the Japanese Ministry of Education, Culture, Sports, Science and Technology, and the Medical Research Council of the United Kingdom. This article is adapted in part with permission from Cell Press.
