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Georg Winterer, MD; Michael F. Egan, MD; Thomas Raedler, MD; Carmen Sanchez, BS; Douglas W. Jones, PhD; Richard Coppola, DSc; Daniel R. Weinberger, MD

Arch Gen Psychiatry. 2003;60:1158-1167.

Background  We assessed the suitability of event-related potential frontal and temporoparietal P300 changes as intermediate phenotypes in genetic studies of schizophrenia. We applied a principal component analysis approach based on the notion that P300 abnormalities in siblings of schizophrenic patients may involve a widespread network of relatively weak cortical generators and because an earlier, smaller study that used a topographic analysis of covariance model did not show that localized P300 changes predict risk for schizophrenia.

Methods  P300 changes in 66 schizophrenic patients, 115 healthy siblings of schizophrenic patients, and 89 unrelated controls were studied during a standard auditory oddball paradigm. Principal components were calculated across electrodes, revealing frontal and temporoparietal components for latency and amplitude, respectively. For the frontal and temporoparietal P300 amplitude and latency components, the intraclass correlations (ICCs) between sib-pairs (pairs of unaffected siblings and schizophrenic index patients) and the relative risk ratios () were determined.

Results  Compared with controls, schizophrenic patients and their unaffected siblings showed significant reductions in the temporoparietal P300 amplitude component. Both groups were also characterized by a significantly higher frontal P300 amplitude component. Significant ICCs and increased relative risk ratios were found for the frontal (ICC_U = 0.18; P = .04; = 3.4) and temporoparietal (ICC_U = 0.24; P = .01; = 1.7) P300 amplitude components.

Conclusions  Temporoparietal P300 amplitude reduction and frontal P300 amplitude increase seem to be quantitative phenotypes associated with increased risk of schizophrenia. Both measures may be useful for increasing the statistical power of genetic studies of schizophrenia.

From the Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Md.

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