Electroencephalography and Event-Related Potential Biomarkers in Individuals at Clinical High Risk for Psychosis

Abstract Clinical outcomes vary among youth at clinical high-risk for psychosis (CHR-P), with approximately 20% progressing to full-blown psychosis over 2-3 years and 30% achieving remission. Recent research efforts have focused on identifying biomarkers that precede psychosis onset and enhance the accuracy of clinical outcome prediction in CHR-P individuals, with the ultimate goal of developing staged treatment approaches based on the individual’s level of risk. Identifying such biomarkers may also facilitate progress toward understanding pathogenic mechanisms underlying psychosis onset, which may support the development of mechanistically-informed early interventions for psychosis. In recent years, EEG-based event-related potential (ERP) measures with established sensitivity to schizophrenia have gained traction in the study of CHR-P and its clinical outcomes. In this review, we describe the evidence for ERP abnormalities in CHR-P and discuss how they inform our understanding of information processing deficits as vulnerability markers for emerging psychosis and as indicators of future outcomes. Among the measures studied, P300 and mismatch negativity are notable because deficits predict conversion to psychosis and/or CHR-P remission. However, the accuracy with which these and other measures predict outcomes in CHR-P has been obscured in the prior literature by the tendency to only report group-level differences, underscoring the need for inclusion of individual predictive accuracy metrics in future studies. Nevertheless, both P300 and mismatch negativity show promise as electrophysiological markers of risk for psychosis, as target engagement measures for clinical trials, and as potential translational bridges between human studies and animal models focused on novel drug development for early psychosis.