This is a resubmission of a five-year study proposed to analyze the non-genetic contributions of family background to risk to childhood and adolescent depression and conduct disturbance. The unique power of the design lays in the use of 2320 adult MZ and DZ twins with their spouses and children ascertained from approximately 100,000 adults twins that will be ascertained through the Mid-Atlantic Twin Registry. The study of the children of twins allows for the true environmental impact of specific parental variables on children's behavioral and emotional problems to be disentangled from the secondary consequences of underlying genetic liability shared by parents and their children. Because the design can sort out which putative family environmental risk factors do actually have a significant environmental impact on the child and which ones only appear to do so because they are associated with genetic mediation, intervention efforts can focus on variables that actually do carry an environmentally mediated risk. Unlike many other genetic studies, the study of the children of twins will allow the impact of specified putative environmental risk factors to be identified and estimated, including parental psychopathology, marital conflict, and impaired parenting. As currently proposed, the design can simultaneously resolve the direction of transmission from both parents to child and child to parent (evocative genotype-environment correlation.) A sample of approximately 12,000 children of 6000 twin pairs between the ages of 9 and 18 will initially be screened for depression/anxiety and conduct disturbance through mailed questionnaire and telephone follow-up. Twin pair families with at least one child in the top 5 percent of each symptom category within the age ranges of 9-13 and 14-18 will be followed up with an extensive psychiatric home interview. The assessment of parent and child psychopathology, specific aspects of the home environment, and life events will be gathered by face-to-face semi-structured interviews with children, both twins, and respective spouses. Other data will be collected from parents, children, and teachers using supervised self-report questionnaires. Pubertal morphological status will be assessed using self-report based on a standard Tanner staging system. The data from this study will enable us to address the contributions of 1) genes and environment to parent-offspring resemblance, 2) passive and evocative genotype-environment correlation and genotype x environment interaction, and 3) the long-term adult consequences of genetic effects expressed in childhood and adolescence.
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