Auditory and Visual Oddball Stimulus Processing Deficits in Schizophrenia and the Psychosis Risk Syndrome: Forecasting Psychosis Risk With P300

Abstract

Identification of neurophysiological abnormalities associated with schizophrenia that predate and predict psychosis onset may improve clinical prediction in the psychosis risk syndrome (PRS) and help elucidate the pathogenesis of schizophrenia. Amplitude reduction of the P300 event-related potential component reflects attention-mediated processing deficits and is among the most replicated biological findings in schizophrenia, making it a candidate biomarker of psychosis risk. The relative extent to which deficits in P300 amplitudes elicited by auditory and visual oddball stimuli precede psychosis onset during the PRS and predict transition to psychosis, however, remains unclear. Forty-three individuals meeting PRS criteria, 19 schizophrenia patients, and 43 healthy control (HC) participants completed baseline electroencephalography recording during separate auditory and visual oddball tasks. Two subcomponents of P300 were measured: P3b, elicited by infrequent target stimuli, and P3a, elicited by infrequent nontarget novel stimuli. Auditory and visual target P3b and novel P3a amplitudes were reduced in PRS and schizophrenia participants relative to HC participants. In addition, baseline auditory and visual target P3b, but not novel P3a, amplitudes were reduced in 15 PRS participants who later converted to psychosis, relative to 18 PRS non-converters who were followed for at least 22 months. Furthermore, target P3b amplitudes predicted time to psychosis onset among PRS participants. These results suggest that P300 amplitude deficits across auditory and visual modalities emerge early in the schizophrenia illness course and precede onset of full psychosis. Moreover, target P3b may represent an important neurophysiological vulnerability marker of the imminence of risk for psychosis.

Keywords: auditory deviance processing; clinical high risk; electroencephalography; event-related potential; longitudinal.

Fig. 1.

Left: Scalp topography maps, depicting mean P300 amplitudes around the peak latency ±10 ms (indicated by gray bars in waveforms), are shown for novel and target stimuli presented in auditory and visual modalities. Middle: Waveforms for novels (P3a at Cz) and targets (P3b at Pz) are shown for healthy control, psychosis risk syndrome, and schizophrenia. Right: Column graphs show group means and standard errors for P300 amplitudes (top) and age-corrected z-scores (bottom).

Fig. 2.

Left: Scalp topography maps, depicting mean P300 amplitudes around the peak latency ± 10 ms (indicated by gray bars in waveforms), are shown for novel and target stimuli presented in auditory and visual modalities. Middle: Waveforms for novels (P3a at Cz) and targets (P3b at Pz) are shown for PRS-C and PRS-NC. Right: Column graphs show conversion outcome group means and standard errors for P300 amplitudes (top), age-corrected z-scores (middle), and adjusted mean z-scores (bottom), reflecting the ANCOVA adjusting for pathological aging effects. PRS, psychosis risk syndrome.

Fig. 3.

Greater target P3b deficits and older age in participants meeting psychosis risk syndrome criteria are associated with an earlier transition to psychosis. Estimated cumulative survival functions are plotted for the 25th and 75th percentiles of target P3b age-corrected z-scores and age.