UC San Diego

Abstract Background: Reductions in the auditory P300 event-related potential (ERP) component are well established in schizophrenia and reflect early attention-mediated auditory processing deficits. Two subcomponents of P300 are evident depending on oddball task conditions; P3b is elicited by infrequent target stimuli and reflects top-down attention allocation, whereas P3a is elicited by infrequent non-target novel distractor stimuli and reflects bottom-up orienting of attention. The present study examined whether auditory P300 abnormalities precede illness onset and are associated with future clinical status by assessing both target P3b and novel P3a in individuals at clinical high risk for psychosis (CHR) and healthy controls (HC) collected as part of the North American Prodrome Longitudinal Study. Methods: CHR (n = 552) and HC (n = 235) participants completed baseline EEG recording during an auditory oddball task. CHR participants were further categorized by clinical status after 24 months of study participation (n = 298) and included a subgroup who transitioned to psychosis (CHR-Transition; n = 73), a subgroup who did not transition but remained symptomatic (CHR-Symptomatic; n = 135), and a subgroup who did not transition and was in symptom remission (CHR-Remission; n = 90). Results: CHR participants had reduced target P3b and novel P3a amplitudes relative to HC (Ps < .001). There was also an effect of 24-month clinical status group on both P3b and P3a amplitudes (P < .001 and P = .006, respectively). Planned contrasts revealed that compared to HC, CHR participants had smaller target P3b amplitudes at baseline (P < .001). In addition, CHR-Transition participants had attenuated P3b amplitudes at baseline relative to all CHR participants who did not transition to psychosis (P = .037). Furthermore, both CHR-Transition and CHR-Symptomatic had smaller P3b amplitudes than both HC (Ps < .001) and CHR-Remission (P = .003 and P = .005, respectively), while P3b of CHR-Remission did not differ from HC at baseline (P > .05). In contrast, although CHR participants also had smaller novel P3a amplitudes than HC at baseline (P < .001), P3a did not differentiate CHR-Transition participants from CHR participants who did not transition within 24 months (P > .05). Despite CHR-Transition and CHR-Symptomatic having smaller P3a amplitudes than HC (P = .028 and P = .002, respectively), they did not differ from CHR-Remission (Ps > .05) at baseline. Moreover, target P3b predicted the time to psychosis onset in CHR participants over and above novel P3a amplitude (P = .024). Conclusion: Both target P3b and novel P3a are reduced in individuals identified to be at risk for developing a psychotic disorder, and P3b in particular appears sensitive to future transition to psychosis. Given this association with clinical outcomes, results implicate target P3b as a neurophysiological vulnerability marker for psychosis.