Family history of psychosis moderates early auditory cortical response abnormalities in non-psychotic bipolar disorder

Authors

  • Jordan P Hamm,

    1. Department of Psychology, BioImaging Research Center, University of Georgia, Athens, GA, USA
    2. Department of Neuroscience, BioImaging Research Center, University of Georgia, Athens, GA, USA
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  • Lauren E Ethridge,

    1. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
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  • John R Shapiro,

    1. Department of Psychology, BioImaging Research Center, University of Georgia, Athens, GA, USA
    2. Department of Neuroscience, BioImaging Research Center, University of Georgia, Athens, GA, USA
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  • Godfrey D Pearlson,

    1. Olin Neuropsychiatry Research Center, Institute of Living, Hartford, USA
    2. Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, CT, USA
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  • Carol A Tamminga,

    1. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
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  • John A Sweeney,

    1. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
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  • Matcheri S Keshavan,

    1. Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
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  • Gunvant K Thaker,

    1. Department of Psychiatry, MPRC, University of Maryland, Baltimore, MD, USA
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  • Brett A Clementz

    Corresponding author
    1. Department of Psychology, BioImaging Research Center, University of Georgia, Athens, GA, USA
    2. Department of Neuroscience, BioImaging Research Center, University of Georgia, Athens, GA, USA
    • Corresponding author:

      Brett A. Clementz, Ph.D.

      Psychology Department

      University of Georgia

      Psychology Building

      Baldwin Street

      Athens, GA 30602

      USA

      Fax: 706-542-3275

      E-mail: clementz@uga.edu

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Abstract

Objectives

Bipolar I disorder is a disabling illness affecting 1% of people worldwide. Family and twin studies suggest that psychotic bipolar disorder (BDP) represents a homogeneous subgroup with an etiology distinct from non-psychotic bipolar disorder (BDNP) and partially shared with schizophrenia. Studies of auditory electrophysiology [e.g., paired-stimulus and oddball measured with electroencephalography (EEG)] consistently report deviations in psychotic groups (schizophrenia, BDP), yet such studies comparing BDP and BDNP are sparse and, in some cases, conflicting. Auditory EEG responses are significantly reduced in unaffected relatives of psychosis patients, suggesting that they may relate to both psychosis liability and expression.

Methods

While 64-sensor EEGs were recorded, age- and gender-matched samples of 70 BDP, 35 BDNP {20 with a family history of psychosis [BDNP(+)]}, and 70 psychiatrically healthy subjects were presented with typical auditory paired-stimuli and auditory oddball paradigms.

Results

Oddball P3b reductions were present and indistinguishable across all patient groups. P2s to paired stimuli were abnormal only in BDP and BDNP(+). Conversely, N1 reductions to stimuli in both paradigms and P3a reductions were present in both BDP and BDNP(−) groups but were absent in BDNP(+).

Conclusions

Although nearly all auditory neural response components studied were abnormal in BDP, BDNP abnormalities at early- and mid-latencies were moderated by family psychosis history. The relationship between psychosis expression, heritable psychosis risk, and neurophysiology within bipolar disorder, therefore, may be complex. Consideration of such clinical disease heterogeneity may be important for future investigations of the pathophysiology of major psychiatric disturbance.

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