This Mentored Research Scientist Development Award (K01) will support the candidate in establishing an independent research career focused on the adult neurobehavioral outcomes of adolescent substance use disorders (SUDs). Career development activities will include: 1) Longitudinal research methodology and specific data analytic techniques; 2) Conceptualization of and construct development focusing on cognitive, behavioral, and affective aspects of dysregulation; and 3) Design and methodology of brain structure studies using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies. The central framework underlying the research plan is that adolescent SUDs exacerbate the propensity toward neurobehavioral dysregulation. Neurobehavioral dysregulation is reflected in a multiplicity of adulthood manifestations in affective, behavioral and cognitive domains, with hypothesized substrates in the prefrontal cortex, limbic system, and connections between these structures. The subjects (N=75) will be selectively recruited based upon SUD trajectories from 400 participants in an ongoing research program on adolescent SUDs (R01-DA-14635). Subjects will be divided into groups on the basis of SUD latent trajectories as follows: 1) Chronic, severe adolescent-onset SUD (n=25); 2) Mild adolescent-onset SUD (n=25); and 3) Matched community control, with no SUD history (n=25). The proposed research plan will characterize the following adult neurobehavioral outcomes: 1) Cognitive, behavioral, and affective aspects of neurobehavioral dysregulation, including executive cognitive functioning and selected personality disorder symptoms and diagnosis. 2) Prefrontal cortex and limbic system structure and white matter integrity and connectivity via MRI and DTI. It is anticipated that insights about risk profiles and SUD trajectories leading to adult neurobehavioral manifestations of dysregulation will allow for identification of relevant risk factors and neuroanatomical structures to be followed through critical developmental periods in future studies. The proposed career development and research activities will provide a solid foundation for the candidate to become an independent investigator specializing in neurobehavioral outcomes of adolescent SUDs.
