P300 and genetic risk for schizophrenia.

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 (lambda) 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; lambda = 3.4) and temporoparietal (ICCU = 0.24; P =.01; lambda = 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.

[1]  D. I. Boomsma,et al.  Genetics of the human electroencephalogram (EEG) and event-related brain potentials (ERPs): a review , 1994, Human Genetics.

[2]  Georg Juckel,et al.  Dipole Localization of P300 and Normal Aging , 2004, Brain Topography.

[3]  P. Schlattmann,et al.  P300 and LORETA: Comparison of Normal Subjects and Schizophrenic Patients , 2004, Brain Topography.

[4]  M. Egan,et al.  Prefrontal neurons and the genetics of schizophrenia , 2001, Biological Psychiatry.

[5]  R. Coppola,et al.  Event-related potentials and genetic risk for schizophrenia , 2001, Biological Psychiatry.

[6]  R. Coppola,et al.  An association between reduced interhemispheric EEG coherence in the temporal lobe and genetic risk for schizophrenia , 2001, Schizophrenia Research.

[7]  W. Herrmann,et al.  Association analysis of GABAA β2 and γ2 gene polymorphisms with event-related prefrontal activity in man , 2000, Human Genetics.

[8]  M. Egan,et al.  Relative risk of attention deficits in siblings of patients with schizophrenia. , 2000, The American journal of psychiatry.

[9]  Adolf Pfefferbaum,et al.  Trait and state aspects of p300 amplitude reduction in schizophrenia: a retrospective longitudinal study , 2000, Biological Psychiatry.

[10]  Tyrone D. Cannon,et al.  P300 subcomponent abnormalities in schizophrenia: III. Deficits in unaffected siblings of schizophrenic probands , 2000, Biological Psychiatry.

[11]  Margaret Niznikiewicz,et al.  The effect of family status and schizotypy on electrophysiologic measures of attention and semantic processing , 2000, Biological Psychiatry.

[12]  Adolf Pfefferbaum,et al.  P300 reduction and prolongation with illness duration in schizophrenia , 2000, Biological Psychiatry.

[13]  J. Daléry,et al.  Alteration of event related potentials in siblings discordant for schizophrenia , 2000, Schizophrenia Research.

[14]  M. Smithson.  Statistics with confidence , 2000 .

[15]  Heinrich Sauer,et al.  Genetic influence on auditory information processing in schizophrenia: P300 in monozygotic twins , 1999, Biological Psychiatry.

[16]  R. Coppola,et al.  Cortical activation, signal-to-noise ratio and stochastic resonance during information processing in man , 1999, Clinical Neurophysiology.

[17]  F L Bookstein,et al.  Identification of neural circuits underlying P300 abnormalities in schizophrenia. , 1999, Psychophysiology.

[18]  F. Bloom,et al.  P300, alcoholism heritability, and stimulus modality. , 1999, Alcohol.

[19]  J. Polich,et al.  P3a and P3b from typical auditory and visual stimuli , 1999, Clinical Neurophysiology.

[20]  H. Möller,et al.  P300 subcomponents reflect different aspects of psychopathology in schizophrenia , 1999, Biological Psychiatry.

[21]  Martha E Shenton,et al.  P300 topography differs in schizophrenia and manic psychosis , 1999, Biological Psychiatry.

[22]  A. Fallgatter,et al.  Distinct neurophysiological mechanisms for manic and cycloid psychoses: evidence from a P300 study on manic patients , 1998, Acta psychiatrica Scandinavica.

[23]  Alessandro Bertolino,et al.  Hippocampal N-acetyl aspartate in unaffected siblings of patients with schizophrenia: a possible intermediate neurobiological phenotype , 1998, Biological Psychiatry.

[24]  Martha E Shenton,et al.  High-density recording and topographic analysis of the auditory oddball event-related potential in patients with schizophrenia , 1998, Biological Psychiatry.

[25]  Y. Hirayasu,et al.  Abnormalities of auditory event-related potentials in schizophrenia prior to treatment , 1998, Biological Psychiatry.

[26]  M E Shenton,et al.  First-episode schizophrenic psychosis differs from first-episode affective psychosis and controls in P300 amplitude over left temporal lobe. , 1998, Archives of general psychiatry.

[27]  B. Turetsky,et al.  P300 Subcomponent Abnormalities in Schizophrenia: Longitudinal Stability and Relationship to Symptom Change , 1998, Biological Psychiatry.

[28]  J. Gorman,et al.  Effect of Antipanic Treatment on Response to Carbon Dioxide , 1997, Biological Psychiatry.

[29]  R. M. Murray,et al.  The Maudsley Family Study, II: Endogenous event-related potentials in familial schizophrenia , 1997, Schizophrenia Research.

[30]  S. Moldin.  Detection and replication of linkage to a complex human disease , 1997, Genetic epidemiology.

[31]  E. Lander,et al.  Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results , 1995, Nature Genetics.

[32]  J. Francis.  Statistica for Windows , 1995 .

[33]  E. Halgren,et al.  Intracerebral potentials to rare target and distractor auditory and visual stimuli. III. Frontal cortex. , 1995, Electroencephalography and clinical neurophysiology.

[34]  E. Halgren,et al.  Intracerebral potentials to rare target and distractor auditory and visual stimuli. II. Medial, lateral and posterior temporal lobe. , 1995, Electroencephalography and clinical neurophysiology.

[35]  Walter J. Muir,et al.  Auditory P300 event-related potentials and neuropsychological performance in schizophrenia and bipolar affective disorder , 1995, Biological Psychiatry.

[36]  E. Halgren,et al.  Intracerebral potentials to rare target and distractor auditory and visual stimuli. I. Superior temporal plane and parietal lobe. , 1995, Electroencephalography and clinical neurophysiology.

[37]  W Gaebel,et al.  Schizophrenics with small P300: a subgroup with a neurodevelopmental disturbance and a high risk for tardive dyskinesia? , 1995, Acta psychiatrica Scandinavica.

[38]  T. Beaty,et al.  Fundamentals of Genetic Epidemiology , 1994 .

[39]  E. Merrin,et al.  P300 responses to novel auditory stimuli in hospitalized schizophrenic patients , 1994, Biological Psychiatry.

[40]  Thomas Dierks,et al.  P300 asymmetries in schizophrenia revisited with reference-independent methods , 1994, Psychiatry Research: Neuroimaging.

[41]  J. Ford,et al.  ERPs in schizophrenia: Effects of antipsychotic medication , 1994, Biological Psychiatry.

[42]  C. C. Duncan,et al.  Event-related potential abnormalities correlate with structural brain alterations and clinical features in patients with chronic schizophrenia , 1994, Schizophrenia Research.

[43]  D. Blackwood,et al.  Methodological considerations in measurement of the P300 component of the auditory oddball ERP in schizophrenia. , 1994, Electroencephalography and clinical neurophysiology.

[44]  J. Ford,et al.  Schizophrenics have fewer and smaller P300s: A single-trial analysis , 1994, Biological Psychiatry.

[45]  S. Faraone,et al.  Neuropsychological risk indicators for schizophrenia: a review of family studies. , 1994, Schizophrenia bulletin.

[46]  S. Segalowitz,et al.  The reliability of ERP components in the auditory oddball paradigm. , 1993, Psychophysiology.

[47]  M. Tsuang.  Genotypes, Phenotypes, and the Brain , 1993, British Journal of Psychiatry.

[48]  D. Blackwood,et al.  Neuropsychological and P300 abnormalities in schizophrenics and their relatives , 1993, Psychological Medicine.

[49]  R Kikinis,et al.  Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia. , 1993, Archives of general psychiatry.

[50]  M E Shenton,et al.  P300 topographic asymmetries are present in unmedicated schizophrenics. , 1993, Electroencephalography and clinical neurophysiology.

[51]  Klaus P. Ebmeier,et al.  The effect of different high-pass filter settings on peak latencies in the event-related potentials of schizophrenics, patients with Parkinson's disease and controls. , 1992, Electroencephalography and clinical neurophysiology.

[52]  S. Steinhauer,et al.  Dissociation of neurocognitive deficits in a monozygotic twin pair concordant for schizophrenia. , 1992, The Journal of neuropsychiatry and clinical neurosciences.

[53]  Toshiaki Sakai,et al.  P300 in first degree relatives of schizophrenics , 1991, Schizophrenia Research.

[54]  J C Duffy,et al.  Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees. , 1991, Archives of general psychiatry.

[55]  J. Born,et al.  Endogenous event-related brain potentials and psychometric performance in children at risk for schizophrenia , 1991, Biological Psychiatry.

[56]  I Russell,et al.  Statistics--with confidence? , 1991, The British journal of general practice : the journal of the Royal College of General Practitioners.

[57]  J. Ford,et al.  Is There P300 Asymmetry in Schizophrenia?-Reply , 1991 .

[58]  R. McCarley,et al.  Is there P300 asymmetry in schizophrenia? , 1991, Archives of general psychiatry.

[59]  C. Ogura,et al.  Abnormalities in Event‐Related Potentials, N100, P200, P300 and Slow Wave in Schizophrenia , 1991, The Japanese journal of psychiatry and neurology.

[60]  E. Courchesne,et al.  Effects of task relevance and attention on P3 in schizophrenic patients , 1991, Schizophrenia Research.

[61]  Beth Dawson,et al.  Basic & Clinical Biostatistics , 1990 .

[62]  D L Braff,et al.  Increased distractibility in schizophrenic patients. Electrophysiologic and behavioral evidence. , 1990, Archives of general psychiatry.

[63]  J. Ford,et al.  P3 in schizophrenia is affected by stimulus modality, response requirements, medication status, and negative symptoms. , 1989, Archives of general psychiatry.

[64]  F H Duffy,et al.  CT abnormalities in schizophrenia. A preliminary study of their correlations with P300/P200 electrophysiological features and positive/negative symptoms. , 1989, Archives of general psychiatry.

[65]  E. Donchin,et al.  Is the P300 component a manifestation of context updating? , 1988, Behavioral and Brain Sciences.

[66]  J E Christie,et al.  Changes in Auditory P3 Event-related Potential in Schizophrenia and Depression , 1987, British Journal of Psychiatry.

[67]  Emanuel Donchin,et al.  Definition, Identification, and Reliability of Measurement of the P300 Component of the Event-Related Brain Potential , 1987 .

[68]  W. Pritchard,et al.  Cognitive event-related potential correlates of schizophrenia. , 1986, Psychological bulletin.

[69]  O. Saitoh,et al.  Abnormalities in late positive components of event-related potentials may reflect a genetic predisposition to schizophrenia. , 1984, Biological psychiatry.

[70]  F. Duffy,et al.  Altered P300 topography in schizophrenia. , 1983, Archives of general psychiatry.

[71]  W. Pritchard.  Psychophysiology of P300. , 1981, Psychological bulletin.

[72]  E. Donchin,et al.  P300 and tracking difficulty: evidence for multiple resources in dual-task performance. , 1980, Psychophysiology.

[73]  J J Bartko,et al.  ON THE METHODS AND THEORY OF RELIABILITY , 1976, The Journal of nervous and mental disease.

[74]  W. Roth,et al.  Some features of the auditory evoked response in schizophrenics. , 1972, Archives of general psychiatry.

[75]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[76]  E. John,et al.  Evoked-Potential Correlates of Stimulus Uncertainty , 1965, Science.