The “clinical high risk” (CHR) for psychosis syndrome is an antecedent period characterized by attenuated psychotic symptoms that are marked by subtle deviations from normal development in thinking, motivation, affect, behavior, and a decline in functioning. Early intervention in this CHR population is critical to prevent psychosis onset as well as other adverse outcomes. However, the presentation of symptoms and subsequent course is highly variable, and there is a paucity of biomarkers to guide treatment development. Thus, to improve predictive models that are clinically relevant, several issues need to be addressed: 1) focusing on outcomes beyond psychosis; 2) taking into account heterogeneity in samples and outcomes; and 3) integrating data sets with a broad array of variables using innovative algorithms to overcome variability across studies. To address these challenges, the proposed “Psychosis Risk Evaluation Data Integration and Computational Technologies: Data Processing, Analysis, and Coordination Center” (PREDICT-DPACC) brings together a multidisciplinary team of highly experienced researchers with proven capabilities in all aspects of large-scale studies, CHR studies, as well as computational expertise. The ultimate goal is to identify new CHR biomarkers, and CHR subtypes that will enhance future clinical trials. To do so, the PREDICT-DPACC will 1) aggregate extant CHR- related data sets from legacy datasets; 2) provide collaborative management, direction, data processing and coordination for new U01 multisite network(s); and 3) develop and apply advanced algorithms to identify biomarkers that predict outcomes, and to stratify CHR into subtypes based on outcome trajectories, first from the extant data and then refined and applied to the new data. The PREDICT-DPACC team has the broad, comprehensive, and robust infrastructure that is sufficiently flexible to accommodate the inclusion of multiple data types and to optimally address the needs of the CHR U01 network(s). Carefully selected extant data will be rapidly obtained, processed, and uploaded to the NIMH Data Archive (NDA). Proposed analysis methods are powerful and robust, leveraging the expertise and experience of computer scientist developers, and experienced clinical researchers. The U01 network(s) will be coordinated by a team that is experienced in managing large studies, familiar with the needs of such studies, flexible, and is knowledgeable in all aspects of CHR studies, including measures, outcomes, biomarkers, and cohorts. Upon meeting the goals of this U24, and the supported U01 network(s), the expected outcomes of the PREDICT-DPACC will be new predictive biomarkers for CHR outcomes, new definitions of CHR subtypes that are clinically useful, and new curated and comprehensive CHR datasets (extant and new) as well as processing tools and prediction algorithms that are shared with the research community through the NIMH Data Archive.

NARRATIVE The “Clinical High Risk” (CHR) for psychosis syndrome in young people represents an opportune window for early intervention to prevent the onset of psychosis and other disorders, and to forestall disability; however, clinical heterogeneity and the paucity of biomarkers have hampered the development of effective intervention. To address these challenges, working with NIMH and key stakeholders, we will harmonize and aggregate existing “legacy” CHR data, and guide and coordinate the collection of new data across a network of sites, to develop biomarker algorithms that can predict individual trajectories for diverse outcomes. This proposal leverages a multidisciplinary team with broad and CHR-specific experience in large-scale multisite and multimodal studies (including clinical trials), along with expertise in data type-specific processing, coordination, analysis, and computational analyses (e.g., machine and deep learning tools from artificial intelligence, and advanced statistical approaches), ethics, community outreach, and data dissemination, all of which will ensure the success of this project.