Cortical signal-to-noise ratio: Prefrontal pathophysiology and genetics of schizophrenia – A two-center study in Bethesda (USA) and Berlin (Germany)

It has been convincingly demonstrated that subjects at risk for schizophrenia show abnormalities of prefrontal function (hypo- or hyperfrontality). However, the underlying neurophysiolgical deficits have remained largely obscure. Several indirect lines of evidence from animal studies have suggested that cortical signal-to-noise ratio (SNR) is fundamentally disturbed in schizophrenia. Recent own electrophysiological and neuroimaging studies of schizophrenia families have now provided for the first time empirical support for this notion. Accordingly, impaired SNR appears to be highly predictive for genetic risk for schizophrenia illness and was found to be a quantitative trait, which is associated with diminished working memory perfomance. Moreover, it was possible to detect the first associations between impaired SNR and schizophrenia susceptibility genes as obtained from positional cloning such as the COMT-gene (catechol-O-methyltransferase), which encodes an enzyme involved in dopamine catabolism, and the dysbindin gene DTNBP1 on chromosome 6p22.3, which appears to be critical for synaptic receptor clustering.

Winterer, G., Egan, M.F., Goldberg, T.E., Coppola, R., Weinberger, D.R. P300 and genetic risk for schizophrenia. Arch. Gen. Psychiatry, in press

Winterer, G., Coppola, R., Goldberg, T.E., Egan, M.F., Jones, D.W., Sanchez, C.E., Weinberger, D.R. Prefrontal broadband noise, working memory & genetic risk for schizophrenia. Am. J. Psychiat., accepted

Winterer, G., Egan, M.F., Goldberg, T.E., Coppola, R., Weinberger, D.R. Functional and effective frontotemporal connectivity & genetic risk for schizophrenia. Biol. Psychiat, in press