Previous theories have emphasized genetic effects "inside the skin" via endophenotypes within the broader developmental psychopathology theory. Expanding on the mechanisms of gene-environment correlation, we propose a new integrative framework emphasizing how genetic effects "outside the skin" (Reiss & Leve, 2007) accumulate due to individual variation in social information processing in negative environments and sociocultural contexts as part of developmental cascades to psychopathology. In this gene-environment cascade theoretical framework, genetic predisposition for psychopathology, as well as stable traits and behaviors, can lead to negative environments via gene-environment correlations that can be exacerbated or buffered by an individual's social information processing. Moreover, these "environments" range from dyadic social relationships to broader sociocultural contexts. Over time, these processes exacerbate one another as part of developmental cascades, resulting in accumulating risk for psychopathology. By focusing on gene-environment correlations and integrating disparate social-emotional, cognitive, and sociocultural research domains, this framework delineates key processes by which early genetic predisposition can contribute to developmentally distinct and accumulating risk for psychopathology over the life course. Implications for intervention and methodological advances that facilitate testing models are presented. This new framework moves the field further away from genetic determinism by informing targets of early psychosocial prevention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).