Comprehensive review of multidimensional biomarkers in the ShangHai At Risk for Psychosis (SHARP) program for early psychosis identification

Psychosis is recognized as one of the largest contributors to nonfatal health loss, and early identification can largely improve routine clinical activity by predicting the psychotic course and guiding treatment. Clinicians have used the clinical high-risk for psychosis (CHR) paradigm to better understand the risk factors that contribute to the onset of psychotic disorders. Clinical factors have been widely applied to calculate the individualized risks for conversion to psychosis 1-2 years later. However, there is still a dearth of valid biomarkers to predict psychosis. Biomarkers, in the context of this paper, refer to measurable biological indicators that can provide valuable information about the early identification of individuals at risk for psychosis. The aim of this paper is to critically review studies assessing CHR and suggest possible biomarkers for application of prediction. We summarized the studies on biomarkers derived from the findings of the ShangHai at Risk for Psychosis (SHARP) program, including those that are considered to have the most potential. This comprehensive review was conducted based on expert opinions within the SHARP research team, and the selection of studies and results presented in this paper reflects the collective expertise of the team in the field of early psychosis identification. The three dimensions with potential candidates include neuroimaging dimension of brain structure and function, electrophysiological dimension of event-related potentials (ERPs), and immune dimension of inflammatory cytokines and complement proteins, which proved to be useful in supporting the prediction of psychosis from the CHR state. We suggest that these three dimensions could be useful as risk biomarkers for treatment optimization. In the future, when available for the integration of multiple dimensions, clinicians may be able to obtain a comprehensive report with detailed information of psychosis risk and specific indications about preferred prevention.