The P300 as a possible endophenotype for schizophrenia and bipolar disorder: Evidence from twin and patient studies

It has been proposed that psychophysiological abnormalities in schizophrenia, such as decreased amplitude of the evoked potential component P300, may be genetically influenced. Studies of heritability of the P300 have used different and typically more complex tasks than those used in clinical studies of schizophrenia. Here we present data on P300 parameters on the same set of auditory and visual tasks in samples of twins, and patients with schizophrenia or bipolar disorder to examine the P300 as a possible endophenotype. Evidence from the twin study indicated that the auditory, but not visual, P300 amplitude is genetically influenced at centro-parietal sites. Similarly, auditory and to a lesser extent visual P300 amplitude were decreased in schizophrenia and bipolar disorder. Results indicate that the auditory P300 may serve as an endophenotype for schizophrenia. However, given that schizophrenia and bipolar disorder patients could not be distinguished on these measures at midline sites, it appears that the P300 may be a marker for functional psychosis in general rather than being specific to schizophrenia.

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

[2]  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.

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

[4]  Ron Kikinis,et al.  Association between smaller left posterior superior temporal gyrus volume on magnetic resonance imaging and smaller left temporal P300 amplitude in first-episode schizophrenia. , 2002, Archives of general psychiatry.

[5]  E. Bramon,et al.  Auditory P300 in patients with bipolar disorder and their unaffected relatives. , 2008, Bipolar disorders.

[6]  E Donchin,et al.  A new method for off-line removal of ocular artifact. , 1983, Electroencephalography and clinical neurophysiology.

[7]  W. Iacono,et al.  Using the brain P300 response to identify novel phenotypes reflecting genetic vulnerability for adolescent substance misuse. , 2006, Addictive behaviors.

[8]  J. Ford Schizophrenia: the broken P300 and beyond. , 1999, Psychophysiology.

[9]  B. O’Donnell,et al.  Auditory event-related potential abnormalities in bipolar disorder and schizophrenia. , 2004, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[10]  Scott R. Sponheim,et al.  Neural Anomalies During Sustained Attention in First-Degree Biological Relatives of Schizophrenia Patients , 2006, Biological Psychiatry.

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

[12]  I. Gottesman,et al.  Psychiatric endophenotypes and the development of valid animal models , 2006, Genes, brain, and behavior.

[13]  W. Sommer,et al.  Postperceptual effects and P300 latency. , 1998, Psychophysiology.

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

[15]  Bernice Porjesz,et al.  P300: The Similarities and Differences in the Scalp Distribution of Visual and Auditory Modality , 2004, Brain Topography.

[16]  S. Morzorati,et al.  Heritable features of the auditory oddball event-related potential: peaks, latencies, morphology and topography. , 1994, Electroencephalography and clinical neurophysiology.

[17]  K. McGraw,et al.  Forming inferences about some intraclass correlation coefficients. , 1996 .

[18]  S. Hillyard,et al.  Similarities and differences among the P3 waves to detected signals in three modalities. , 1980, Psychophysiology.

[19]  D. Boomsma,et al.  Stability of Genetic and Environmental Influences on P300 Amplitude: A Longitudinal Study in Adolescent Twins , 2001, Behavior genetics.

[20]  E. Stip,et al.  Visual P300 in Treatment-Resistant Schizophrenic Patients , 1999, Brain and Cognition.

[21]  Yoshio Hirayasu,et al.  Disruption of neural systems of visual attention in schizophrenia. , 2002, Archives of general psychiatry.

[22]  J. Polich,et al.  P300 as a clinical assay: rationale, evaluation, and findings. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[23]  M. Marie-cardine,et al.  Auditory event-related potentials and clinical scores in unmedicated schizophrenic patients , 1999, Psychiatry Research.

[24]  J. Ford,et al.  N1 and P300 abnormalities in patients with schizophrenia, epilepsy, and epilepsy with schizophrenialike features , 2001, Biological Psychiatry.

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

[26]  D. Smit,et al.  Genetic Contribution to the P3 in Young and Middle-Aged Adults , 2007, Twin Research and Human Genetics.

[27]  Arthur Falek,et al.  Schizophrenia and genetics: A twin study vantage point. , 1976 .

[28]  Margaret J. Wright,et al.  Genetic Influence on the Variance in P3 Amplitude and Latency , 2001, Behavior genetics.

[29]  D. Linden The P300: Where in the Brain Is It Produced and What Does It Tell Us? , 2005, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[30]  Paul J. Harrison,et al.  Neuregulin 1 and Schizophrenia: Genetics, Gene Expression, and Neurobiology , 2006, Biological Psychiatry.

[31]  Robin M. Murray,et al.  Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study , 2005, NeuroImage.

[32]  B. Turetsky,et al.  Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures. , 2006, Schizophrenia bulletin.

[33]  E. Halgren,et al.  Generators of the late cognitive potentials in auditory and visual oddball tasks. , 1998, Electroencephalography and clinical neurophysiology.

[34]  J. Rohrbaugh,et al.  Heritability of event-related brain potentials in families with a history of alcoholism. , 1999, American journal of medical genetics.

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

[36]  W. Roth,et al.  Auditory event-related potentials and electrodermal activity in medicated and unmedicated schizophrenics , 1991, Biological Psychiatry.

[37]  W. Iacono,et al.  Heritability of P300 amplitude development from adolescence to adulthood. , 2006, Psychophysiology.

[38]  H. Möller,et al.  Superior temporal gyrus and P300 in schizophrenia: a combined ERP/structural magnetic resonance imaging investigation. , 2004, Journal of psychiatric research.

[39]  D. Blackwood,et al.  Long-latency auditory event-related potentials in schizophrenia and in bipolar and unipolar affective disorder , 1991, Psychological Medicine.

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

[41]  G. Potts,et al.  Disruption of auditory and visual attention in schizophrenia , 2007, Psychiatry Research: Neuroimaging.

[42]  G. Geffen,et al.  Genetic Covariation between Event-Related Potential (ERP) and Behavioral Non-ERP Measures of Working-Memory, Processing Speed, and IQ , 2005, Behavior genetics.

[43]  E. Gordon,et al.  Target and non-target ERP disturbances in first episode vs. chronic schizophrenia , 2002, Clinical Neurophysiology.

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

[45]  E. Bramon,et al.  Substantial shared genetic influences on schizophrenia and event-related potentials. , 2007, The American journal of psychiatry.

[46]  D. Boomsma,et al.  Individual differences in P300 amplitude: a genetic study in adolescent twins , 1998, Biological Psychology.

[47]  Robin M. Murray,et al.  Heritability and Reliability of P300, P50 and Duration Mismatch Negativity , 2006, Behavior genetics.

[48]  Geraldine McNeill,et al.  Blood pressure in relation to birth weight in twins and singleton controls matched for gestational age. , 2003, American journal of epidemiology.

[49]  J. Jolles,et al.  A controlled study of temporal lobe structure volumes and P300 responses in schizophrenic patients with persistent auditory hallucinations , 1999, Schizophrenia Research.

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

[51]  E. Bramon,et al.  Genetic overlap between bipolar illness and event-related potentials , 2007, Psychological Medicine.

[52]  H G Vaughan,et al.  The scalp topography of potentials in auditory and visual Go/NoGo tasks. , 1977, Electroencephalography and clinical neurophysiology.

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

[54]  S Sutton,et al.  Evoked potential correlates of information processing in psychiatric patients , 1973, Psychological Medicine.

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

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

[57]  J. Polich Clinical application of the P300 event-related brain potential. , 2004, Physical medicine and rehabilitation clinics of North America.

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

[59]  R. Johnson,et al.  Auditory and visual P300s in temporal lobectomy patients: evidence for modality-dependent generators. , 1989, Psychophysiology.

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

[61]  A. B. Prasad,et al.  British National Formulary , 1994 .

[62]  J. Lieberman,et al.  Auditory P300 in high-risk, recent-onset and chronic schizophrenia , 2005, Schizophrenia Research.