DESCRIPTION (provided by applicant): This cooperative agreement (U01) application responds to NIH RFA-DA-15-015, Adolescent Brain Cognitive Development (ABCD) study. The University of Hawaii (UH) is #2 of 9 Research Sites of the Prospective Research in Studies of Maturation (PRISM) Consortium. The Consortium's objective is to establish a national, multisite, longitudinal cohort to prospectively examine the neurodevelopmental and behavioral effects of substance use (SU) from early adolescence through the period of risk for SU and SU disorders. This 10-year longitudinal study of 11,000 children will measure brain development, SU, cognition, emotion, executive function, mental health, physical health, environment, and collect biospecimens for future genetic and epigenetic studies. The Consortium has an optimized research protocol and 4 specific aims: 1) Using advanced multi-modal neuroimaging to evaluate premorbid factors and the impact associated with diverse patterns of SU on structure and function of the developing brain. 2) Disentangle the predictors and consequences of diverse patterns of SU on physical health, psychosocial and cognitive development, academic achievement, motivation and emotional regulation. 3) Examine how the quantity and combination of substances used affect the expression of psychopathology and, conversely, how the emergence of psychopathology influences SU. 4) Assess how each substance used contributes to the use of other substances (gateway interactions). To further evaluate neurochemical and neurophysiological changes in these youth, we will additionally perform 1H MR spectroscopy (MRS), perfusion MRI (using arterial spin labeling or ASL), and quantitative susceptibility mapping (QSM), in approximately half of our volunteers, in collaboration with PRISM sites at Penn, UCLA, Utah, Hawaii, JHU, and Baylor. We are proposing a multi-PI leadership approach for our site. The PIs have complementary and inter- disciplinary expertise that encompasses all areas required to manage this comprehensive project. We have expertise in SUD research, clinical assessments, subject sampling and recruitment, and MR methodology. Additional unique qualifications of our site are: 1) we have access to a racially diverse population (including Native Hawaiians and Pacific Islanders) that is disproportionately affected by SUD, 2) we have a strong track record of MR research in SUD and at risk populations, such as adolescents, and 3) we have participated in and led several multi-center research studies that involve complex multi-modal MR outcome measures and subject assessments. Therefore, we have all the necessary resources, experience and expertise to conduct the proposed research, and our effort will complement that of other outstanding research sites to collectively achieve the overall goals of the PRISM Consortium.

PUBLIC HEALTH RELEVANCE: The developing brain in adolescence is characterized by accelerated brain remodeling, guided by genetic vulnerabilities and influences from various environmental factors, including substance use (SU). The University of Hawaii is one of nine research sites of the ABCD-PRISM Consortium formed to conduct a longitudinal cohort study that will use advanced imaging, clinical and neurocognitive evaluations to prospectively examine the impact and potential risk factors associated with SU on brain development, behavioral and mental health outcomes, in 11,000 youth ages 9-10 years followed through their adolescence. This research will lead to better understanding of the predictors for adolescent SU and its consequences on brain development, and ultimately to more effective interventions for SU and other mental disorders.