A study on schizophrenia has implicated machinery that maintains the flow of potassium in cells and revealed a potential molecular target for new treatments. Expression of a previously unknown form of a key such potassium channel was found to be 2.5 fold higher than normal in the brain memory hub of people with the chronic mental illness and linked to a hotspot of genetic variation.
An extensive series of experiments suggest that selectively inhibiting this suspect form could help correct disorganized brain activity in schizophrenia without risk of cardiac side effects associated with some existing antipsychotic medications. Scientists at the National Institutes of Health and European colleagues report on threads of converging evidence in the May, 2009 issue of the journal Nature Medicine.
"The end game in linking genes with complex disorders like schizophrenia requires that we not only demonstrate statistical association, but also show how a gene version acts biologically to confer risk," explained Daniel Weinberger, M.D., director of National Institute of Mental Health's (NIMH) Genes Cognition and Psychosis Program, who led the research. "We found schizophrenia-like effects in brain circuitry and mental processing in perfectly healthy people who carry the risk-associated version of this potassium channel gene, even though they don't show any psychotic behavior."
Evidence suggests that schizophrenia stems from complex interactions between multiple genes and environmental factors. Several candidate genes have recently been statistically linked to the illness in large genome-wide association studies.
"Our study goes further, spanning discovery of a new gene variant, confirmation of its association with the illness, and multi-level probes into how it works in human post mortem brain tissue, the living human brain, and neurons," added Weinberger.
By regulating the flow of potassium ions into the cell,
|Contact: Jules Asher|
NIH/National Institute of Mental Health