Visual P300 and Risk for Psychosis Onset in Youth at Clinical High Risk

Current clinical criteria are not sufficiently predictive of psychosis onset to inform treatment decision-making among individuals who are at clinical high risk for psychosis (CHR). Identifying biomarkers may improve outcome prediction among CHR individuals and clarify the pathogenesis of psychosis. Using data from the 8-site North American Prodrome Longitudinal Study (NAPLS-2), we examined whether visual P300 event-related potential amplitude, which is reduced in schizophrenia, is affected in CHR individuals and associated with future outcomes.

Five hundred thirty-eight CHR individuals and 230 healthy comparison (HC) participants completed baseline electroencephalography recording during a 3-stimulus visual oddball task. The P3b elicited by infrequent target stimuli and P3a elicited by infrequent nontarget novel stimuli were measured. CHR participants who converted to psychosis (n = 71) were compared with nonconverters who were followed for 24 months (n = 218), whose risk symptoms either persisted (n = 132) or remitted (n = 86) during follow-up.

P300 amplitudes were modestly reduced across target (P3b) and novel (P3a) stimuli in CHR individuals compared with HCs (Cohen's d = 0.14), with greater deficits observed in future CHR-converters than in CHR-nonconverters (d = 0.28) and HCs (d = 0.39). CHR-converters had reduced target P3b compared with CHR-nonconverters (d = 0.32) and HCs (d = 0.41), whereas CHR-nonconverters and HCs did not differ (d = 0.07). Novelty P3a was reduced in CHR-converters compared with HCs (d = 0.37) but not CHR-nonconverters (d = 0.24). Adjusting for symptom severity, greater target P3b deficits predicted earlier psychosis conversion (odds ratio, 0.76 [95% CI, 0.59-0.97], p = .029).

Visual target P3b deficits are associated with future psychosis conversion and the imminence of conversion, showing promise as a biomarker of psychosis onset among at-risk individuals.