The strongest known recurrent genetic cause of schizophrenia impairs communications between the brain's decision-making and memory hubs, resulting in working memory deficits, according to a study in mice.
"For the first time, we have a powerful animal model that shows us how genetics affects brain circuitry, at the level of single neurons, to produce a learning and memory deficit linked to schizophrenia," explained Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), part of the National Institutes of Health. "This new research tool holds promise for ultimately unraveling the underlying anatomical connections and specific genes involved."
NIMH grantees Joshua Gordon, M.D., Ph.D., Joseph Gogos, M.D., Ph.D., Maria Karayiorgou, M.D., and Columbia University colleagues, report on their discovery in genetically engineered mice in the April 1, 2010 issue of the journal Nature.
"Our findings pinpoint a specific circuit and mechanism by which a mutation produces a core feature of the disorder," said Gordon, who led the research.
Researchers have suspected such a brain connectivity disturbance in schizophrenia for more than a century, and the NIH has launched a new initiative on the brain's functional circuitry, or connectome. Although the disorder is thought to be 70 percent heritable, its genetics are dauntingly complex, except in certain rare cases, such as those traced to the mutation in question.
Prior to this study, neuroimaging studies in schizophrenia patients had found abnormal connections between the brain's prefrontal cortex, the executive hub, and the hippocampus, the memory hub, linked to impaired working memory. It was also known that a mutation in the suspect site on chromosome 22, called 22q11.2, boosts schizophrenia risk 30-fold and also causes other abnormalities). Although accounting for only a small portion of cases, this tiny missing section of genetic ma
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NIH/National Institute of Mental Health