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Original Investigation
August 7, 2019

Association Between P300 Responses to Auditory Oddball Stimuli and Clinical Outcomes in the Psychosis Risk Syndrome

Author Affiliations
  • 1Department of Psychiatry, University of California, San Francisco
  • 2San Francisco Veterans Affairs Health Care System, San Francisco, California
  • 3Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 4Department of Psychiatry, University of North Carolina at Chapel Hill
  • 5Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York
  • 6Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York
  • 7Department of Psychiatry, Hofstra Northwell School of Medicine, Hempstead, New York
  • 8Atlanta Veterans Affairs Medical Center, Decatur, Georgia
  • 9Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
  • 10Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut
  • 11Veterans Affairs Connecticut Health Care System, West Haven, Connecticut
  • 12Department of Psychiatry, University of California, San Diego, La Jolla
  • 13Veterans Affairs San Diego Healthcare System, La Jolla, California
  • 14Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Boston, Massachusetts
  • 15Veterans Affairs Boston Healthcare System, Brockton, Massachusetts
  • 16Hotchkiss Brain Institute Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
  • 17Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles
  • 18Department of Psychology, University of California, Los Angeles
  • 19Department of Molecular Medicine, Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, New York
  • 20Department of Psychology, Emory University, Atlanta, Georgia
  • 21Department of Psychology, School of Medicine, Yale University, New Haven, Connecticut
JAMA Psychiatry. Published online August 7, 2019. doi:10.1001/jamapsychiatry.2019.2135
Key Points

Question  Is auditory P300 event-related potential amplitude associated with future clinical outcomes among youths with the psychosis risk syndrome?

Findings  In this 8-site case-control study of 552 individuals meeting psychosis risk syndrome criteria, greater deficits in baseline P300 amplitude to target, but not novel oddball stimuli were associated with transition to psychosis and the imminence of this transition. Individuals with the psychosis risk syndrome that did not convert to psychosis after 2 years and instead achieved remission from the risk syndrome had normal target P300 amplitudes at baseline.

Meaning  The results suggest that P300 is a putative prognostic biomarker of clinical outcomes in the psychosis risk syndrome, including conversion to psychosis and remission from the risk state.


Importance  In most patients, a prodromal period precedes the onset of schizophrenia. Although clinical criteria for identifying the psychosis risk syndrome (PRS) show promising predictive validity, assessment of neurophysiologic abnormalities in at-risk individuals may improve clinical prediction and clarify the pathogenesis of schizophrenia.

Objective  To determine whether P300 event-related potential amplitude, which is deficient in schizophrenia, is reduced in the PRS and associated with clinical outcomes.

Design, Setting, and Participants  Auditory P300 data were collected as part of the multisite, case-control North American Prodrome Longitudinal Study (NAPLS-2) at 8 university-based outpatient programs. Participants included 552 individuals meeting PRS criteria and 236 healthy controls with P300 data. Auditory P300 data of participants at risk who converted to psychosis (n = 73) were compared with those of nonconverters who were followed up for 24 months and continued to be symptomatic (n = 135) or remitted from the PRS (n = 90). Data were collected from May 27, 2009, to September 17, 2014, and were analyzed from December 3, 2015, to May 1, 2019.

Main Outcomes and Measures  Baseline electroencephalography was recorded during an auditory oddball task. Two P300 subcomponents were measured: P3b, elicited by infrequent target stimuli, and P3a, elicited by infrequent nontarget novel stimuli.

Results  This study included 788 participants. The PRS group (n = 552) included 236 females (42.8%) (mean [SD] age, 19.21 [4.38] years), and the healthy control group (n = 236) included 111 females (47.0%) (mean [SD] age, 20.44 [4.73] years). Target P3b and novelty P3a amplitudes were reduced in at-risk individuals vs healthy controls (d = 0.37). Target P3b, but not novelty P3a, was significantly reduced in psychosis converters vs nonconverters (d = 0.26), and smaller target P3b amplitude was associated with a shorter time to psychosis onset in at-risk individuals (hazard ratio, 1.45; 95% CI, 1.04-2.00; P = .03). Participants with the PRS who remitted had baseline target P3b amplitudes that were similar to those of healthy controls and greater than those of converters (d = 0.51) and at-risk individuals who remained symptomatic (d = 0.41).

Conclusions and Relevance  In this study, deficits in P300 amplitude appeared to precede psychosis onset. Target P3b amplitudes, in particular, may be sensitive to clinical outcomes in the PRS, including both conversion to psychosis and clinical remission. Auditory target P3b amplitude shows promise as a putative prognostic biomarker of clinical outcome in the PRS.

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