This Mentored Research Scientist Development Award will support the candidate in establishing an independent research career using longitudinal developmental neuroimaging to investigate genetic risk for substance use disorders (SUDs). Career development training areas include: 1) Functional magnetic resonance imaging (fMRI) methods and statistical analyses with a particular focus on pediatric neuroimaging;2) The genetic basis of complex behaviors, and gene-brain-behavior relationships;3) Theoretical constructs regarding risk of psychopathology;and 4) Longitudinal research methods and statistical analyses. The proposed research plan is to examine the contribution of specific genetic polymorphisms and early-life stress on the neural correlates of SUD risk in children using fMRI. Both behavioral and emotional dysregulation at an early age are strong predictors of SUDs later in life. A complex neuronal circuit, including the striatum, amygdala and prefrontal cortex, regulates these processes. The proposed research plan will investigate these neural systems cross-sectionally in a sample of 7 to 11 year old boys and girls (n=60) from the ongoing UM/MSU Longitudinal Study (R37 AA07065), and longitudinally in this sample at 2-year intervals. The cross-sectional study will investigate effects of, and interactions between, early stress and genetic variants (COMT, SLC6A4, MAO-A, TPH, BDNF) on brain responses to tasks designed to probe behavioral risk for SUDs. The longitudinal study will investigate the effects of early stress and genetic variants on the maturation of brain functional responses to these same tasks. It will also begin to address the influence of drug use on brain development, as well as the predictive value of early brain functional responses in identifying risk for later substance abuse problems. The proposed training and research activities will provide a solid foundation for the candidate to become an independent investigator specializing in longitudinal developmental neuroimaging studies of risk for SUDs.
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