Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study

INTRODUCTION We assessed the usefulness of the P300 wave as endophenotype for schizophrenia by means of a meta-analysis of the literature as well as our own family study. METHOD Meta-analysis: We conducted a systematic search for articles published between 1983 and 2003 that reported P300 measures in non-psychotic relatives of schizophrenic patients and in healthy controls. Meta-regression analyses were performed using a random effects procedure. The pooled standardized effect size (PSES) was calculated as the difference between the means of the two groups divided by the common standard deviation. Local study: We examined the P300 wave with a standard two-tone oddball paradigm in 30 patients with schizophrenia, 40 non-psychotic relatives, and 40 controls using linear mixed models. RESULTS Meta-analysis: We pooled 472 relatives and 513 controls. The P300 amplitude was significantly reduced in relatives (PSES = 0.61; 95% CI: 0.30 to 0.91; P < 0.001). The P300 latency was significantly delayed in relatives (PSES of -0.50; 95% CI: -0.88 to -0.13; P = 0.009]. Local study: The patients showed a trend for amplitude reductions (P = 0.06) and significant latency delays (P < 0.01). The relatives displayed normal amplitude but had significant latency delays (P = 0.01). The P300 amplitude and especially the P300 latency are promising alternative phenotypes for genetic research into schizophrenia.

[1]  H. Semlitsch,et al.  A solution for reliable and valid reduction of ocular artifacts, applied to the P300 ERP. , 1986, Psychophysiology.

[2]  D J Porteous,et al.  Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. , 2001, American journal of human genetics.

[3]  M K McGue,et al.  P300 event-related potential heritability in monozygotic and dizygotic twins. , 1997, Psychophysiology.

[4]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[5]  C. Begg,et al.  Operating characteristics of a rank correlation test for publication bias. , 1994, Biometrics.

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

[7]  H. Jasper,et al.  The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[8]  I. Gottesman,et al.  The endophenotype concept in psychiatry: etymology and strategic intentions. , 2003, The American journal of psychiatry.

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

[10]  K. Coburn,et al.  P300 delay and attenuation in schizophrenia: reversal by neuroleptic medication , 1998, Biological Psychiatry.

[11]  David Friedman,et al.  Auditory event-related potentials in children at risk for schizophrenia: The complete initial sample , 1988, Psychiatry Research.

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

[13]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[14]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

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

[16]  John Polich,et al.  P300 asymmetry in schizophrenia: a meta-analysis , 2001, Psychiatry Research.

[17]  Douglas W. Jones,et al.  P300 and genetic risk for schizophrenia. , 2003, Archives of general psychiatry.

[18]  G. Geffen,et al.  Genetic sources of covariation among P3(00) and online performance variables in a delayed-response working memory task , 2002, Biological Psychology.

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

[20]  J. Born,et al.  Event-related potential correlates of impaired selective attention in children at high risk for schizophrenia , 1992, Biological Psychiatry.

[21]  J. Polich,et al.  Meta-analysis of P300 and schizophrenia: patients, paradigms, and practical implications. , 2003, Psychophysiology.

[22]  P. Schlattmann,et al.  Association of the G1947A COMT (Val108/158Met) gene polymorphism with prefrontal P300 during information processing , 2003, Biological Psychiatry.

[23]  R. Straub,et al.  Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Surveys.,et al.  Standard occupational classification , 1990 .

[25]  J. Endicott,et al.  A diagnostic interview: the schedule for affective disorders and schizophrenia. , 1978, Archives of general psychiatry.

[26]  J. Beckmann,et al.  A highly significant association between a COMT haplotype and schizophrenia. , 2002, American journal of human genetics.

[27]  Kari Stefansson,et al.  Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. , 2003, American journal of human genetics.

[28]  H. Jasper Report of the committee on methods of clinical examination in electroencephalography , 1958 .

[29]  Margot Albus,et al.  Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families. , 2003, American journal of human genetics.

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

[31]  J. Polich,et al.  Meta-analysis of P300 normative aging studies. , 1996, Psychophysiology.

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

[33]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[34]  Daniel N. Allen,et al.  252 WAIS-R factor structure in schizophrenia , 1997, Schizophrenia Research.

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

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

[37]  David Friedman,et al.  Event-related potentials in children at risk for schizophrenia during two versions of the continuous performance test , 1986, Psychiatry Research.

[38]  N. E. Morton,et al.  Segregation analysis of complex phenotypes: An application to schizophrenia and auditory P300 latency , 1993, Schizophrenia Research.

[39]  Joseph Zubin,et al.  Electrophysiological and behavioral signs of attentional disturbance in schizophrenics and their siblings , 1989, Schizophrenia Research.

[40]  Denis C. Shields,et al.  Segregation analysis of complex phenotypes: an application to schizophrenia and auditory P300 latency. , 1994 .

[41]  Elvira Bramon,et al.  Mismatch negativity in schizophrenia: a family study , 2004, Schizophrenia Research.

[42]  Vicente Molina,et al.  Long-Term Olanzapine Treatment and P300 Parameters in Schizophrenia , 2004, Neuropsychobiology.

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

[44]  D. Kammen,et al.  Utility of WAIS-R short forms in schizophrenia , 1997, Schizophrenia Research.

[45]  Robin M. Murray,et al.  Can biological markers identify endophenotypes predisposing to schizophrenia , 1997 .

[46]  E. Bramon,et al.  Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. , 2004, Archives of general psychiatry.

[47]  R. Murray,et al.  Normal cerebral asymmetry in familial and non-familial schizophrenic probands and their unaffected relatives , 2004, Schizophrenia Research.

[48]  Georg Juckel,et al.  P300 and symptom improvement in schizophrenia , 2001, Psychopharmacology.

[49]  Shih-Jen Tsai,et al.  Association study of a functional catechol-O-methyltransferase-gene polymorphism and cognitive function in healthy females , 2003, Neuroscience Letters.

[50]  J. Nurnberger,et al.  Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. , 1994, Archives of general psychiatry.

[51]  E. Bramon,et al.  Meta-analysis of the P300 and P50 waveforms in schizophrenia , 2004, Schizophrenia Research.

[52]  Anders M. Dale,et al.  Cortical volume and speed-of-processing are complementary in prediction of performance intelligence , 2005, Neuropsychologia.

[53]  G. Baal,et al.  Twin and family studies of the human electroencephalogram: a review and a meta-analysis , 2002, Biological Psychology.

[54]  D. Weinberger,et al.  Cortical signal-to-noise ratio: insight into the pathophysiology and genetics of schizophrenia , 2003, Clinical Neuroscience Research.

[55]  Kristine B Walhovd,et al.  The relationship between P3 and neuropsychological function in an adult life span sample , 2003, Biological Psychology.