Project Summary Understanding the effects of environmental risk exposure on neural and behavioral development is essential for targeting intervention and prevention efforts in public health policy. This is especially the case for psychotic disorders, which have a 1% incidence in the population, and are highly debilitating and treatment resistant (1). However, current understanding of environmental influences in the clinical high-risk (CHR) period immediately leading up to psychotic disorder onset is limited (2). Specifically, neural mechanisms underlying the effects of cumulative environmental risk factor exposure are poorly understood. Importantly, (a) allostatic load and aggregate dysregulation models of stress exposure suggest there are strong benefits in studying cumulative risk, as different types of risk exposure may have similar developmental consequences (3, 4) and (b) cumulative models have been shown to be more powerful in addition to offering an increased prospective prediction advantage (3-5). Nonetheless, in regards to environmental risk exposure, the literature has often focused on a single predictor. Measuring the effects of multiple types of environmental risk exposure on neural and behavioral outcomes is essential for targeting intervention and prevention efforts, as well as for informing future allocation of treatment and prevention resources in this population. The current proposal will measure cumulative risk exposure in 50 CHR and 50 healthy volunteers at an individual and structural level, in addition to predicting candidate neural mechanisms, symptoms, and social/occupational functioning longitudinally. First, this study aims to determine whether CHR individuals experience greater exposure to cumulative environmental risk (Aim 1). Cumulative environmental risk will be measured at an individual and structural level with structured interviews, multiple rater systematic social observation (SSO) software (6-9) and geocoding of Census data. Then, the proposal will seek to determine whether cumulative environmental risk exposure differentially affects neural connectivity in regions implicated in stress and affect regulation in CHR and typically developing individuals, using structural and functional imaging technology (Aim 2). Finally, the proposed project will examine whether cumulative environmental risk models are associated with symptoms and functioning, and whether they predict the course of these features longitudinally in CHR individuals (Aim 3). Notably, exploratory analyses will be conducted to analyze whether exposure during different developmental periods differentially predicts neural connectivity in areas of interest. Exploratory analyses will also examine exposure to individual versus structural environmental risk factors separately with regards to group differences and neural connectivity.