7. Project Summary/Abstract: There is a worldwide movement in the early intervention for adolescents and young adults appearing to develop early signs of psychosis or described as at clinical high risk (CHR) for psychosis, led mainly by researchers in Australia, Europe, and North America. Within the Asian Network for Early Psychosis, Taiwan and Singapore have started to address the CHR population. To our knowledge, we are the first research group carrying out CHR studies in a low-middle income country in Asia. Since 2012, supported by NIMH/Fogarty 1R21MH093294-01A1 and an NIMH R01 MH101052-01, we have worked closely with the Shanghai Mental Health Center (SMHC), to develop a CHR research program in Shanghai, China. The completed R21 and on-going R01 projects aim at identification of the risk factors for CHR conversion over approximately one year. In our current proposal, in response to NIH FOA PAR-14-332, Global Brain and Nervous System Disorders Research across the Lifespan (R01), we will continue to enhance research capacity building at SMHC, and collaboratively carry out an extensive follow-up study of clinical outcomes such as conversion to psychosis and level of disability, and we will evaluate the evolution of biomarkers such as event related potentials, resting state functional magnetic resonance imaging (MRI), white matter as assessed by diffusion tensor imaging MRI, and neurocognition. We will follow-up 300 well characterized CHR and Healthy Control (HC) participants between the ages of 15-45 for two more follow-up assessments. The longitudinal nature of the project is novel in China and worldwide as this will be the first study to comprehensively examine biopsychosocial parameters predictive of psychosis conversion and illness progression for up to 6 years, including two new follow-ups of the biomarkers (4 assessments including baseline). Moreover, unlike many studies in the West, virtually 100% of the participants are psychotropically naïve when they enter the study, and the assessments are done at one site (SMHC), reducing confounds associated with medications and multiple sites. Our goal is to work collaboratively with researchers at the SMHC to establish a sustainable CHR longitudinal program of research in China and to lay a solid foundation for CHR early intervention.This project aims to: 1). Develop predictors for conversion to psychosis, 2). Investigate clinical and biomarker progression in CHR, 3). Demonstrate an association between clinical features, biological measures and disability in CHR, and 4). Explore the feasibility of early intervention with CHR subjects. Capacity building and research training will be conducted during and beyond the proposed project to facilitate sustainable research at SMHC.

8. Project Narrative: This application is a response to FOA PAR-14-332, “Global Brain and Nervous System Disorders Research across the Lifespan (R01)” and proposes to further develop the ongoing NIH supported collaboration between investigators from the Shanghai Mental Health Center (SMHC), P.R. China, a World Health Organization designated center for research and training in mental health, and a team of U.S. researchers working with the SMHC for 4 years. We will provide research capacity building and research training, and conduct a longitudinal follow-up study of SMHC subjects at clinical high risk for psychosis and healthy controls for up to 6 years after baseline assessment. This will be among the first studies world-wide to examine a range of biomarkers predictive of psychosis conversion and reflecting illness progression over a long duration.