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Are Auditory-Evoked Frequency and Duration Mismatch Negativity Deficits Endophenotypic for Schizophrenia? High-Density Electrical Mapping in Clinically Unaffected First-Degree Relatives and First-Episode and Chronic Schizophrenia

  • Elena Magno
    Affiliations
    The Cognitive Neurophysiology Laboratory, St. Vincent's Hospital, Dublin, Ireland

    Trinity College Institute of Neuroscience, School of Psychology, Trinity College, Dublin, Ireland
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  • Sherlyn Yeap
    Affiliations
    The Cognitive Neurophysiology Laboratory, St. Vincent's Hospital, Dublin, Ireland

    The Cognitive Neurophysiology Laboratory, Nathan S. Kline Institute for Psychiatric Research, Program in Cognitive Neuroscience and Schizophrenia, Orangeburg, New York

    Trinity College Institute of Neuroscience, School of Psychology, Trinity College, Dublin, Ireland
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  • Jogin H. Thakore
    Affiliations
    The Cognitive Neurophysiology Laboratory, St. Vincent's Hospital, Dublin, Ireland

    Trinity College Institute of Neuroscience, School of Psychology, Trinity College, Dublin, Ireland
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  • Hugh Garavan
    Affiliations
    The Cognitive Neurophysiology Laboratory, St. Vincent's Hospital, Dublin, Ireland

    The Cognitive Neurophysiology Laboratory, Nathan S. Kline Institute for Psychiatric Research, Program in Cognitive Neuroscience and Schizophrenia, Orangeburg, New York

    Trinity College Institute of Neuroscience, School of Psychology, Trinity College, Dublin, Ireland
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  • Pierfilippo De Sanctis
    Affiliations
    The Cognitive Neurophysiology Laboratory, St. Vincent's Hospital, Dublin, Ireland

    The Cognitive Neurophysiology Laboratory, Nathan S. Kline Institute for Psychiatric Research, Program in Cognitive Neuroscience and Schizophrenia, Orangeburg, New York
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  • John J. Foxe
    Correspondence
    Address reprint requests to John J. Foxe, Ph.D., The Cognitive Neurophysiology Laboratory, Nathan S. Kline Institute for Psychiatric Research, Program in Cognitive Neuroscience and Schizophrenia, 140 Old Orangeburg Road, Orangeburg, New York 10962
    Affiliations
    The Cognitive Neurophysiology Laboratory, St. Vincent's Hospital, Dublin, Ireland

    The Cognitive Neurophysiology Laboratory, Nathan S. Kline Institute for Psychiatric Research, Program in Cognitive Neuroscience and Schizophrenia, Orangeburg, New York

    Trinity College Institute of Neuroscience, School of Psychology, Trinity College, Dublin, Ireland

    Program in Cognitive Neuroscience, Department of Psychology, The City College of the City University of New York, New York, New York.
    Search for articles by this author

      Background

      Mismatch negativity (MMN) is a negative-going event-related potential (ERP) component that occurs in response to intermittent changes in constant auditory backgrounds. A consistent finding across a large number of studies has been impaired MMN generation in schizophrenia, which has been interpreted as evidence for fundamental deficits in automatic auditory sensory processing. The aim of this study was to investigate the extent to which dysfunction in MMN generation might represent an endophenotypic marker for schizophrenia.

      Methods

      We measured MMN to deviants in duration (25 msec, 1000 Hz) and deviants in pitch (50 msec, 1200 Hz) relative to standard tones (50 msec, 1000 Hz) in 45 chronic schizophrenia patients, 25 of their first-degree unaffected biological relatives, 12 first-episode patients, and 27 healthy control subjects.

      Results

      In line with previous work, MMN amplitudes to duration deviants (but not to pitch deviants) were significantly reduced in patients with chronic schizophrenia compared with control subjects. However, both duration and pitch MMNs were completely unaffected in the first-degree biological relatives and this was also the case for the first-episode patients. Furthermore, length of illness did not predict the extent of MMN deficit.

      Conclusions

      These findings suggest that the MMN deficit seen in schizophrenia patients is most likely a consequence of the disease and that MMN, at least to basic auditory feature deviants, is at best only weakly endophenotypic for schizophrenia.

      Key Words

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