Project Summary: 22q11.2 deletion syndrome (22q11DS) is associated with an increased risk for psychiatric disorders, including psychosis with similar symptoms to individuals with idiopathic schizophrenia (SZ), and about 1-2% of cases of idiopathic SZ have 22q11.2 deletions. Thus, targeted approaches detailing specific brain dysfunction in 22q11DS may elucidate critical neural mechanisms in psychosis. Specifically, approaches that capture abnormalities common to individuals at-risk for psychosis and with a genetic risk to psychosis, such as 22q11DS, may help explain risk and resilience for psychosis. Minor physical anomalies (MPAs) are phenotypic abnormalities of aberrant development. MPAs include subtle abnormalities of morphological structures encompassing numerous body parts including eyes, ears, mouth and head. Abnormalities of the face and head likely represent a disruption of early embryologic development, including the olfactory system and facial morphology, making these promising entry points for understanding neurodevelopmental neuropathology associated with 22q11DS and psychosis In this study, we seek to compare 1) measures of olfactory function; 2) structural abnormalities of the olfactory system and 3) structural abnormalities of the face in a large cohort of patients with 22q11DS (n=100), including those with and without psychosis, to typically developing (TD) individual. Finally, we will employ machine learning algorithms to select features that best differentiate 22q11DS+ from 22q11DS- and use those features to classify individual with idiopathic risk for psychosis (PS). In addition, analyses will leverage recent advances in machine learning to predict salient features associated with dimensional measures of psychosis. We believe this innovative approach can significantly advance our understanding of the etiology of psychosis and provide advances to precision medicine in psychiatry. Through the proposed multi-level analysis, this innovative research will provide a substantial advance in our understanding of the neurodevelopmental substrates of psychosis.