Journal Mobile Options
Table of Contents
Vol. 44, No. 6, 2011
Issue release date: October 2011

Genetic Liability to Schizophrenia Measured by P300 in Concordant and Discordant Monozygotic Twins

Sharma A. · Sauer H. · Smit D.J.A. · Bender S. · Weisbrod M.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Differential effects of genes and environment can contribute to etiological heterogeneity in schizophrenia. Twins concordant and discordant for schizophrenia may differ in genetic predisposition to schizophrenia with concordant twins having a higher genetic liability and discordant twins having a lower genetic liability to schizophrenia. We aimed to investigate whether P300 amplitude (which has been postulated as a genetic marker for schizophrenia) reflected this heterogeneity. Sampling and Methods: We compared P300 amplitudes across 36 monozygotic twin pairs (6 concordant for schizophrenia/schizoaffective disorder, 11 discordant and 19 healthy control pairs) performing an auditory oddball task, using multiple regression (age, gender, birth order, premorbid IQ as covariates). We further looked at the correlation between the Brief Psychiatric Rating Scale (BPRS) and P300 amplitude in affected twins, and compared concordant and discordant affected twins on the Global Assessment Scale (GAS). Results: Multiple regression yielded a highly significant model (p = 0.004) though the explained variance was limited (21%). The main effect of the group on P300 amplitude was significant (p = 0.0001): affected concordant twins showed a significantly lower P300 amplitude as compared to affected discordant (p = 0.005, Cohen’s d = 1.08) and control twins (p = 0.000, d = 1.16). Discordant affected and unaffected twins did not differ significantly from each other or from control twins. P300 did not correlate significantly with the BPRS and the affected groups did not differ across the GAS. Conclusions: Our results provide evidence for etiological heterogeneity within schizophrenia pointing to different pathophysiological mechanisms that may underlie more and less genetically determined forms of schizophrenia. They also indicate that P300 correlates with a differing degree of genetic liability to schizophrenia independently of the psychopathological status and even in the presence of similar functional profiles.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Jablensky A: Subtyping schizophrenia: implications for genetic research. Mol Psychiatry 2006;11:815–836.
  2. Heinrichs RW: Meta-analysis and the science of schizophrenia: variant evidence or evidence of variants? Neurosci Biobehav Rev 2004;28:379–394.
  3. Tsuang M: Schizophrenia: genes and environment. Biol Psychiatry 2000;47:210–220.
  4. Murray RM, Lewis SW, Reveley AM: Towards an aetiological classification of schizophrenia. Lancet 1985;i:1023–1026.

    External Resources

  5. Goldin LR, DeLisi LE, Gershon ES: Unravelling the relationship between genetic and environmental risk factors in psychiatric disorders. Br J Psychiatry 1987;151:302–305.
  6. Wahl OF: Monozygotic twins discordant for schizophrenia: a review. Psychol Bull 1976;83:91–106.
  7. Cannon TD, et al: The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study. Arch Gen Psychiatry 1998;55:67–74.
  8. Cardno AG, et al: Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry 1999;56:162–168.
  9. Smit DJ, et al: Genetic contribution to the P3 in young and middle-aged adults. Twin Res Hum Genet 2007;10:335–347.
  10. Hall MH, et al: Heritability and reliability of P300, P50 and duration mismatch negativity. Behav Genet 2006;36:845–857.
  11. Katsanis J, et al: P300 event-related potential heritability in monozygotic and dizygotic twins. Psychophysiology 1997;34:47–58.
  12. Rogers TD, Deary I: The P300 component of the auditory event-related potential in monozygotic and dizygotic twins. Acta Psychiatr Scand 1991;83:412–416.
  13. Polich J, Burns T: P300 from identical twins. Neuropsychologia 1987;25:299–304.
  14. Bramon E, et al: Meta-analysis of the P300 and P50 waveforms in schizophrenia. Schizophr Res 2004;70:315–329.
  15. Jeon YW, Polich J: Meta-analysis of P300 and schizophrenia: patients, paradigms, and practical implications. Psychophysiology 2003;40:684–701.
  16. Blackwood D: P300, a state and a trait marker in schizophrenia. Lancet 2000;355:771–772.
  17. Weisbrod M, et al: Left lateralized P300 amplitude deficit in schizophrenic patients depends on pitch disparity. Biol Psychiatry 1997;41:541–549.
  18. Bramon E, et al: Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study. Neuroimage 2005;27:960–968.
  19. Sponheim SR, McGuire KA, Stanwyck JJ: Neural anomalies during sustained attention in first-degree biological relatives of schizophrenia patients. Biol Psychiatry 2006;60:242–252.
  20. Winterer G, et al: P300 and genetic risk for schizophrenia. Arch Gen Psychiatry 2003;60:1158–1167.
  21. Hall MH, et al: Substantial shared genetic influences on schizophrenia and event-related potentials. Am J Psychiatry 2007;164:804–812.
  22. Weisbrod M, et al: Genetic influence on auditory information processing in schizophrenia: P300 in monozygotic twins. Biol Psychiatry 1999;46:721–725.
  23. World Health Organization: Schedules for Clinical Assessment in Neuropsychiatry. SCAN. Geneva, World Health Organization, 1992.
  24. Overall JE, Gorham DR: The brief psychiatric rating scale. Psychol Rep 1962;19:799–812.

    External Resources

  25. Endicott J, et al: The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 1976;33:766–771.
  26. Lehrl S: Mehrfach-Wortschatz-Intelligenztest MWT-B. Erlangen, Straube, 1977.
  27. Oldfield RC: The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971;9:97–113.
  28. Erdmann J, et al: The use of microsatellites in zygosity diagnosis of twins. Acta Genet Med Gemellol (Roma) 1993;42:45–51.
  29. Semlitsch HV, et al: A solution for reliable and valid reduction of ocular artifacts, applied to the P300 ERP. Psychophysiology 1986;23:695–703.
  30. Ettinger U, et al: Prefrontal and striatal volumes in monozygotic twins concordant and discordant for schizophrenia. Schizophr Bull, 2010, E-pub ahead of print.
  31. Williams RL: A note on robust variance estimation for cluster-correlated data. Biometrics 2000;56:645–646.
  32. Cohen J: Statistical Power Analysis for the Behavioral Sciences, ed 2. New York, Academic Press, 1988.
  33. Perneger TV: What’s wrong with Bonferroni adjustments. BMJ 1998;316:1236–1238.
  34. de Wilde OM, et al: P300 deficits are present in young first-episode patients with schizophrenia and not in their healthy young siblings. Clin Neurophysiol 2008;119:2721–2726.
  35. Leonhard K: The Classification of Endogeneous Psychoses, ed 5. New York, Irvington Publishers, 1979.
  36. Franzek E, Beckmann H: Different genetic background of schizophrenia spectrum psychoses: a twin study. Am J Psychiatry 1998;155:76–83.
  37. Strik WK, et al: Specific P300 features in patients with cycloid psychosis. Acta Psychiatr Scand 1997;95:67–72.
  38. Gonul AS, et al: Effects of olanzapine on auditory P300 in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:173–177.
  39. Coburn KL, et al: P300 delay and attenuation in schizophrenia: reversal by neuroleptic medication. Biol Psychiatry 1998;44:466–474.
  40. Klein C, et al: Topography of the auditory P300 in schizotypal personality. Biol Psychiatry 1999;45:1612–1621.
  41. Turetsky B, Colbath EA, Gur RE: P300 subcomponent abnormalities in schizophrenia. 2. Longitudinal stability and relationship to symptom change. Biol Psychiatry 1998;43:31–39.
  42. Ford JM, et al: P300 amplitude is related to clinical state in severely and moderately ill patients with schizophrenia. Biol Psychiatry 1999;46:94–101.
  43. Higashima M, et al: P300 and the thought disorder factor extracted by factor-analytic procedures in schizophrenia. Biol Psychiatry 1998;44:115–120.
  44. Datta A, et al: The p300 as a marker of waning attention and error propensity. Comput Intell Neurosci 2007:93968.
  45. Polich J: P300 clinical utility and control of variability. J Clin Neurophysiol 1998;15:14–33.
  46. Sautter FJ, et al: Patterns of neuropsychological deficit in cases of schizophrenia spectrum disorder with and without a family history of psychosis. Psychiatry Res 1994;54:37–49.
  47. Wolitzky R, et al: Etiological heterogeneity and intelligence test scores in patients with schizophrenia. J Clin Exp Neuropsychol 2006;28:167–177.
  48. Owen MJ, Craddock N, Jablensky A: The genetic deconstruction of psychosis. Schizophr Bull 2007;33:905–911.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50