TY - JOUR
T1 - P300 and Genetic Risk for Schizophrenia
AU - Winterer, Georg
AU - Egan, Michael F.
AU - Raedler, Thomas
AU - Sanchez, Carmen
AU - Jones, Douglas W.
AU - Coppola, Richard
AU - Weinberger, Daniel R.
PY - 2003/11
Y1 - 2003/11
N2 - 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 (λ) 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 (ICCU=0.18; P=.04; λ = 3.4) and temporoparietal (ICC U=0.24; P=.01; λ = 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.
AB - 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 (λ) 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 (ICCU=0.18; P=.04; λ = 3.4) and temporoparietal (ICC U=0.24; P=.01; λ = 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.
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U2 - 10.1001/archpsyc.60.11.1158
DO - 10.1001/archpsyc.60.11.1158
M3 - Article
C2 - 14609891
AN - SCOPUS:0242509953
SN - 0003-990X
VL - 60
SP - 1158
EP - 1167
JO - Archives of general psychiatry
JF - Archives of general psychiatry
IS - 11
ER -