Neurodevelopmental Mechanisms Underlying Stress Vulnerability during Adolescence

About This Grant

PROJECT SUMMARY The onset of youth psychopathology is often preceded by exposure to stressful life events (SLEs). Despite substantial research on the neurodevelopmental consequences of severe forms of adversity, like maltreatment, the mechanisms that explain the powerful link between less severe but common SLEs and adolescent psychopathology remain understudied. This project is focused on uncovering these mechanisms using an innovative research design that leverages intensive longitudinal within-subject assessments to characterize how SLEs are related to dynamic changes in in emotion, cognition, behavior, and neural function over time in ways that may contribute to the emergence of psychopathology. The study capitalizes on a unique dataset acquired during the first project period designed to study these processes at a sufficiently fine-grained level of temporal specificity to identify mechanisms underlying the link between SLEs and adolescent psychopathology as they unfold in real time. The dataset acquired in the initial project-the Studying Adolescence in Rea/­ Time (STAR) study-is truly unique, including more than 1,500 monthly neuroimaging sessions, 1,800 monthly assessments of clinical and behavioral data, 1,400 months of usable continuous passive data from smartphones and wearable devices, 1,300 months of neuroendocrine samples, and 45,000 completed ecological momentary assessment (EMA) surveys. The intensive longitudinal design of the STAR study allows mechanisms linking SLEs to psychopathology to be identified in real time and in the real world along multiple data streams that cut across numerous RDoC domains and levels of analysis (neuroimaging, clinical, and behavioral measures; digital phenotyping; neurobiology; and EMA), generating true translational targets for intervention. The renewal focuses first on how monthly fluctuations in exposure to SLEs within individuals are associated with the pace of biological aging across multiple bodily systems-including pubertal development, cellular aging, and BrainAGE-and the role these metrics of aging play as mechanisms linking SLEs with psychopathology. Second, we evaluate metrics of brain function that serve as mechanisms in the relationship between SLEs and psychopathology by leveraging cutting edge methods from precision neuroscience to identify cortical networks separately within each individual in our study. This approach to characterizing brain mechanisms underlying risk for psychopathology has been proposed as a crucial path forward that addresses recently discovered problems in the stability of brain-behavior associations. Integrative analyses will isolate those mechanisms-across numerous levels of analysis-that explain the most unique variance in individual­ level prediction of psychopathology risk in this dataset. Study findings will provide critical information regarding the specific domains of emotion, cognition, social behavior, biology, and neural function that are influenced by exposure to SLEs and increase vulnerability to psychopathology. These mechanisms represent modifiable targets for interventions to prevent the onset of stress-related psychopathology in children and adolescents.