Project Summary/Abstract The proposed research and training plan are designed to promote my development as an independent investigator in the field of neighborhood characteristics as they relate to conversion to psychosis through neurobiological and psychosocial mediators among youth at clinical high risk for psychosis (CHR-P). Urban upbringing (growing up in cities as compared to rural areas) is one of the strongest environmental risk factors for schizophrenia. More recent studies have suggested that social stress might explain this association. In particular, neighborhood residential instability (NRI) has been used to measure social fragmentation and has also been associated with increased schizophrenia rates and prevalence. In addition, my published work found that NRI predicts an earlier age at onset of psychosis among individuals with first-episode psychosis even after controlling for known risk factors. Furthermore, my preliminary data indicate that county-level residential instability (a rough proxy for NRI) during childhood 1) predicts conversion to psychosis and 2) predicts smaller corticolimbic gray matter volume (GMV) among a subset of youth at CHR-P who never moved. Dr. Walker (one of my mentors) has shown that psychosocial deprivation as measured by reduced childhood peer relationships, parental absence, and emotional neglect is associated with smaller corticolimbic GMV, whereas threat (defined as exposures that involve harm; e.g., childhood sexual and physical abuse) is not. Based on these findings, I hypothesize that NRI leads to psychosocial deprivation, which in turn contributes to smaller corticolimbic GMV, which ultimately increases risk for psychosis. To test this hypothesis, I propose the following Specific Aims: (1) Test the association between NRI and conversion to psychosis and corticolimbic GMV, including the cortical, perigenual anterior cingulate cortex, and hippocampal GMV and control regions including insula and thalamus. (2) Test the association between NRI and psychosocial deprivation and threat. (3) Explore the experiences and circumstances of youth at CHR-P living in residential areas that differ in NRI, from very unstable to highly stable. The proposed studies will provide a novel integration of multiple levels of investigation including public health, developmental studies in humans, and the impact of environmental factors on the brain and behavior to discover novel targets for intervention both at the individual and neighborhood levels to prevent or mitigate psychosis conversion in high-risk individuals. Future research will further elucidate the relationship of neighborhood characteristics with the psychosocial and neurobiological factors associated with risk for psychosis, such as investigating whether NRI exposure at specific developmental periods and regional brain changes would have a differential impact on psychosis. If NRI leads to psychosocial deprivation and neurobiological changes, for example, target...