Project Summary Research has yet to understand why some with psychotic-like experiences (PLEs; early markers of psychosis risk) transition to psychosis spectrum disorders whereas others report only transient PLEs. This information will be critical for understanding the etiology of psychosis spectrum symptoms and for prevention and intervention efforts for this major public health concern (~90% of individuals with significant PLEs report mental health diagnoses in adulthood). According to the expanded proneness-persistence-impairment (PPI) model, potential distinguishing factors between transient PLEs and those transitioning to psychotic disorders is whether they are sustained and distressing (i.e., sustained dPLEs). Consistent with NIMH Strategic Objective 2, this K23 application will fill critical missing gaps in the literature by characterizing the key risk factors and clinical significance of early sustained dPLEs. The application will focus on ~11,800 children from the Adolescent Brain and Cognitive Development study initially aged 9-11-years-old followed annually over the course of the award. The analyses will test PPI model hypotheses, including investigating the most important factors distinguishing sustained from transient dPLEs, examining neurobiological correlates (e.g., resting state functional connectivity, cortical thickness, cognitive functioning), family history of psychosis, motor and speech developmental delays, and environmental predictors (adverse childhood experiences, cannabis use; Aim 1). Models will also test whether longitudinal changes in cognitive, neural predictors, and environmental risk factors distinguish sustained versus transient dPLEs (Aim 2). Lastly, the application will also fill a critical research gap by examining the clinical significance of sustained dPLEs, examining the social and educational functional impairments, treatment seeking behavior, and conducting additional data collection when the youth are ages 16 to 18 to assess the base rates of attenuated psychosis syndrome (APS) among youth endorsing sustained dPLEs (Aim 3). To assess rates of APS, the applicant and a masters-level clinician will interview a subset of ABCD participants (n=500) and their parents/caregivers using the Structured Interview of Prodromal Syndromes. Overall, the applicant will implement rigorous practices, including running all analyses for the aims and hypotheses outlined below on two-thirds of data and then replicating the exact same models on an untouched one-third of data. Under the mentorship of a diverse team of experts of developmental psychosis spectrum psychopathology, longitudinal analyses, machine learning, and neuroimaging analyses, this scientifically rigorous proposal will test hypotheses regarding cross- sectional and longitudinal predictors of sustained versus transient dPLEs for the future application of early identification and preventative interventions. The application addresses several gaps in the applicant’s training that are critical for success as an independent clinical investigator, including the need for further training in advanced statistical techniques (e.g., machine learning, longitudinal analyses, neuroimaging analyses) and increased exposure in the area of developmental psychosis spectrum psychopathology.

PROJECT NARRATIVE The current application will make important advances in understanding the nature of early markers of risk for psychotic disorders such as schizophrenia, otherwise known as psychotic-like experiences. Specifically, we do not yet understand why some individuals go on to develop more severe forms of psychotic-like experiences (i.e., sustained distressing psychotic-like experiences) and why for some individuals these experiences are transient. The current application will make significant strides in understanding the most important factors (such as family history and cognition) distinguishing sustained from transient distressing psychotic-like experiences, as well as understanding the clinical importance of these symptoms (including how many individuals with sustained distressing psychotic-like experiences seek treatment or have problems in school or at homes as a result of these symptoms).