This application is a request for a Mentored Research Scientist Developmental Award to develop necessary skills to conduct genetic epidemiological studies of depression in childhood and adolescence. Although recent advances in genetic research hold promise for the identification of genetic markers of potential relevance to the effective disorders, the successful application of such techniques will depend on clear and valid definitions of the phenotype which reflects genetic vulnerability. This proposal is designed to provide the applicant with necessary skills to conduct informative genetic epidemiological studies of depression geared toward the identification of homogeneous subtypes. The guiding hypothesis is that a critical indicator of a potentially homogeneous subtype is depression with an initial onset prior to adulthood, as suggested by recent family-genetic studies. This hypothesis will be tested through a refinement of the family study/high risk design by focusing on siblings of depressed youth as an informative family member matched for age and cohort. Within this framework, a pilot study has been designed to address two aims: (1) to determine the feasibility of longitudinal high-risk sibling studies; and (2) to sharpen diagnostic boundaries of phenotypic indicators of familial vulnerability for depression. In conjunction with the research goals, two primary training goals will be pursued: (1) training in the evaluation of depression, and related psychopathology, in children and adolescents; (2) training in the application of novel biostatistical techniques used to help sharpen diagnostic boundaries for genetic studies. The overall purpose of research and training is to acquire requisite skills to examine transactions between genetic and environmental risk factors specific to depression, and their interplay during sensitive developmental periods, as such a focus may eventually carry implications for future preventative efforts.
