Expression of a previously unknown, primate-specific, and brain-specific isoform (3.1) of a key potassium channel protein (KCNH2) that modulates neuronal firing was found to be 2.5-fold higher than normal in the hippocampus (brain memory hub) of people with schizophrenia, especially in those with schizophrenia risk-associated variations in the KCNH2 gene, according to a recent report. KCNH2-3.1 isoform levels were also found to be higher than normal in healthy individuals who carried the risk-associated KCNH2 gene variations, and these individuals were shown to exhibit some schizophrenia-like effects in brain circuitry and mental processing, even though they do not show psychotic behavior. "Our study goes further [than gene association studies], 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," said Dr. Daniel Weinberger, director of the National Institute of Mental Health's Genes Cognition and Psychosis Program. An extensive series of experiments suggest that selectively inhibiting the KCNH2-3.1 isoform could help correct disorganized brain activity in schizophrenia, without risk of the cardiac side effects associated with some existing antipsychotic medications. This work was reported in the May issue of Nature Medicine. [NIH release] [Nature Medicine abstract]Login Or Register To Read Full Story