Cortical signal-to-noise ratio: insight into the pathophysiology and genetics of schizophrenia

During the past two decades, it has been convincingly demonstrated that schizophrenic patients and subjects genetically at risk for schizophrenia show abnormalities of cortical and particularly prefrontal function. Depending on clinical state and task conditions, hypo- and hyperfrontality have been frequently described with functional neuroimaging and electrophysiological techniques; however, the underlying neurophysiological deficits remained largely obscure. There is now growing empirical evidence that cortical signal-to-noise ratio (SNR) during information processing is fundamentally disturbed and may be key to a further understanding of schizophrenic pathophysiology. The evidence comes from animal and human electrophysiological and neuroimaging investigations as well as neuropsychological and computational simulation studies. This research has also shown that dopamine signaling in prefrontal cortex is a critical factor in modulation of cortical SNR and in neurocognitive performance. Moreover, it was recently demonstrated that genetically determined variations in dopamine signaling, mediated by a functional polymorphism in the gene for the enzyme catechol-o-methyltransferase, has a significant impact on the cortical SNR, prefrontal information processing, and as a result, is a susceptibility gene for schizophrenia. This review summarizes the current state of research on the pathophysiology of schizophrenia with emphasis on cortical-SNR and the involvement of potentially relevant, molecular and genetic determinants of the cortical dopaminergic signaling. (C) 2003 Elsevier Science B.V. All rights reserved.