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.
Conflict of interest statement
Auditory and Visual Oddball Stimulus Processing Deficits in Schizophrenia and the Psychosis Risk Syndrome: Forecasting Psychosis Risk With P300HK Hamilton et al. Schizophr Bull 45 (5), 1068-1080. PMID 30753731.Identification of neurophysiological abnormalities associated with schizophrenia that predate and predict psychosis onset may improve clinical prediction in the psychosis …
Clinical Significance of Auditory Target P300 Subcomponents in Psychosis: Differential Diagnosis, Symptom Profiles, and CourseG Perlman et al. Schizophr Res 165 (2-3), 145-51. PMID 25934167.Auditory target P300 amplitude yields both a schizophrenia-specific component (i.e., P3b) and a transdiagnostic psychosis component (i.e., P3a). The P3b component may als …
Trait and State Aspects of P300 Amplitude Reduction in Schizophrenia: A Retrospective Longitudinal StudyDH Mathalon et al. Biol Psychiatry 47 (5), 434-49. PMID 10704955.Auditory, and possibly visual, P300 amplitudes track fluctuations in clinical state, but only auditory P300 amplitude is a trait marker of schizophrenia.
The P300 Event-Related Potential in Bipolar Disorder: A Systematic Review and Meta-AnalysisM Wada et al. J Affect Disord 256, 234-249. PMID 31200163. - ReviewThis meta-analysis provides evidence for P300 abnormalities in patients with BD compared to HCs. Our results suggest that P300 may be trait markers rather than state mark …
Updating P300: An Integrative Theory of P3a and P3bJ Polich. Clin Neurophysiol 118 (10), 2128-48. PMID 17573239. - ReviewThe empirical and theoretical development of the P300 event-related brain potential (ERP) is reviewed by considering factors that contribute to its amplitude, latency, an …