This revised application for a Mentored Research Scientist Development Award (RFA-PA-95-049 K01) describes a career development and research plan with a long-term goal of understanding the neural bases of affect dysregulation (and affective disorders) in adolescence. The approach build's upon the applicant's previous neuroimaging studies of genetic influences on the functional dynamics of the amygdala and prefrontal cortex in adults. This application seeks to extend that line of investigation into a specific developmental and clinical framework to address key questions about affect regulation and pubertal brain maturation relevant for adolescent affective disorders. The training plan emphasizes a cognitive and affective neuroscience approach to understanding the development of affect regulation; it also includes specific activities aimed at increasing the applicant's knowledge of developmental, clinical, statistical and ethical issues relevant to this line of investigation. The research plan builds upon a well-established program project investigating neurobehavioral changes in pediatric affective disorders (P01-MH41712). Component one of the research plan involves the addition of genotyping and a neuroimaging study to an existing protocol that includes samples of depressed, anxiety disordered, and normal control children and adolescents. Component two involves the recruitment of a new sample of female controls to address a specific question about the impact of the pubertal rise in estrogen on amygdala-prefrontal functional interactions in normal development. Together, these studies and training program will enable the applicant to advance understanding of genetic and maturational influences on the development of affect regulation during adolescence within an affective neuroscience framework in ways that will help inform the etiology and diathesis (and eventually, more effective treatment) of early onset affective disorders.
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