Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: Characterization of demographic, clinical, cognitive, and functional correlates in COGS-2

Gregory A. Light, Neal R. Swerdlow, Michael L. Thomas, Monica E. Calkins, Michael F. Green, Tiffany A. Greenwood, Raquel E. Gur, Ruben C. Gur, Laura C. Lazzeroni, Keith H. Nuechterlein, Marlena Pela, Allen D. Radant, Larry J. Seidman, Richard F. Sharp, Larry J. Siever, Jeremy M. Silverman, Joyce Sprock, William S. Stone, Catherine A. Sugar, Debby W. TsuangMing T. Tsuang, David L. Braff, Bruce I. Turetsky

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Mismatch negativity (MMN) and P3a are auditory event-related potential (ERP) components that show robust deficits in schizophrenia (SZ) patients and exhibit qualities of endophenotypes, including substantial heritability, test-retest reliability, and trait-like stability. These measures also fulfill criteria for use as cognition and function-linked biomarkers in outcome studies, but have not yet been validated for use in large-scale multi-site clinical studies. This study tested the feasibility of adding MMN and P3a to the ongoing Consortium on the Genetics of Schizophrenia (COGS) study. The extent to which demographic, clinical, cognitive, and functional characteristics contribute to variability in MMN and P3a amplitudes was also examined. Participants (HCS n. =. 824, SZ n. =. 966) underwent testing at 5 geographically distributed COGS laboratories. Valid ERP recordings were obtained from 91% of HCS and 91% of SZ patients. Highly significant MMN (d. =. 0.96) and P3a (d. =. 0.93) amplitude reductions were observed in SZ patients, comparable in magnitude to those observed in single-lab studies with no appreciable differences across laboratories. Demographic characteristics accounted for 26% and 18% of the variance in MMN and P3a amplitudes, respectively. Significant relationships were observed among demographically-adjusted MMN and P3a measures and medication status as well as several clinical, cognitive, and functional characteristics of the SZ patients. This study demonstrates that MMN and P3a ERP biomarkers can be feasibly used in multi-site clinical studies. As with many clinical tests of brain function, demographic factors contribute to MMN and P3a amplitudes and should be carefully considered in future biomarker-informed clinical studies.

Original languageEnglish
Pages (from-to)63-72
Number of pages10
JournalSchizophrenia Research
Issue number1-3
StatePublished - 1 Apr 2015
Externally publishedYes

Bibliographical note

Funding Information:
Dr. Light reports having been a consultant to EnVivo/Forum and Astellas and serves on an advisory board for Neuroverse. Dr. Green has been a consultant to AbbVie, Biogen, DSP, EnVivo/Forum and Roche, and he is on the scientific advisory board of Mnemosyne. He has received research funds from Amgen. Dr. Lazzeroni is an inventor on a patent application filed by Stanford University on genetic polymorphisms associated with depression. Dr. Nuechterlein has received unrelated research support from Janssen Scientific Affairs, Genentech, and Brain Plasticity, Inc., and has consulted to Genentech, Otsuka, Janssen, and Brain Plasticity, Inc. Dr. Swerdlow has been a consultant for Genco Sciences, Ltd. All other authors declare that they have no conflict of interest.

Publisher Copyright:
© 2013.


  • Cognition
  • EEG
  • Function
  • Mismatch negativity
  • P300
  • P3a
  • Schizophrenia


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