title: Trait and state aspects of P300 amplitude reduction in schizophrenia: a retrospective longitudinal study.
abstract: BACKGROUND
  The P300 component of the auditory event-related brain potential (ERP) is consistently reduced in schizophrenia. Longitudinal data are examined to determine whether P300 amplitude is a trait marker of schizophrenia or a state marker tracking clinical fluctuations over time.
  
  
  METHODS
  Schizophrenic men (DSM-III-R) (n = 36) received ERP and the Brief Psychiatric Rating Scale (BPRS) assessments on multiple occasions, at varying intervals, under varying medication states. Automatically elicited auditory P3a and effortfully elicited auditory and visual P3b amplitudes were assessed. Brief Psychiatric Rating Scale scores were regressed on P300 amplitude within patients using both multiple regression models and nonparametric analyses of individual patient slopes. Event related brain potentials in patients were compared to ERPs from 34 age-matched control men, and stability of P300 over time was estimated with intraclass correlations.
  
  
  RESULTS
  P300 amplitude, regardless of elicitation method or sensory modality, tracked BPRS Total and positive symptom scores over time, decreasing with symptom exacerbations and increasing with improvements. In addition, effortful auditory and visual P3b amplitudes tracked negative symptoms, and automatic auditory P3a tracked depression-anxiety symptoms. When analyses were limited to unmedicated occasions, auditory P3a and P3b persisted in tracking BPRS Total scores, with additional tracking of positive symptoms by P3b and mood symptoms by P3a. Mean auditory and visual P3bs, averaged over all measurement occasions for each individual, were inversely related to mean negative symptoms. Auditory P3a and P3b, but not visual P3b, amplitudes were smaller in patients than control subjects, even when patients were least symptomatic. P300 amplitudes showed high test-retest reliability in control subjects and patients and moderate stability over time in patients.
  
  
  CONCLUSIONS
  Auditory, and possibly visual, P300 amplitudes track fluctuations in clinical state, but only auditory P300 amplitude is a trait marker of schizophrenia.
authors.affiliation: Department of Psychiatry, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Mathalon
authors.forename: J M
authors.initials: JM
authors.lastname: Ford
authors.forename: A
authors.initials: A
authors.lastname: Pfefferbaum
mesh_terms: D000328:Adult; D000339:Affect; D015415:Biomarkers; D016022:Case-Control Studies; D018913:Event-Related Potentials, P300 / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012559:Schizophrenia / Q000175:diagnosis* / Q000503:physiopathology*; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers