This competitive renewal seeks support for 5 years of extensive data analysis of a unique data set, collected during the project's first four years, which includes the detailed assessment of both environmental risk factors and quantitative and diagnostic outcome measures of the most common psychopathologic conditions in women (major depressive disorder, generalized anxiety disorder, panic disorder, phobias and eating disorders) in 1,032 pairs of females same-sex twins from the population based Virginia Twin Registry and their parents. The twins have had 3 waves of evaluation at yearly intervals (questionnaire, face to face interview plus questionnaire and phone interview) and the parents have been seen once (face to face interview plus questionnaire). The proposed analyses, which will use state-of-the-art statistical and genetic methods, will produce advances in the understanding of the etiology of these conditions that have previously been beyond our grasp. Three groups of analyses are proposed. Traditional sociometric analyses will focus on the impact of traditional """"""""environmental variables"""""""" (e.g. early life experiences, chronic strains and life events) on quantitative and diagnostic outcomes and their buffering by social support and other putative personal characteristics (e.g. coping strategies, locus of control). Traditional genetic analyses (in which the environment is treated as a latent variable) will i) examine the role of genes and environment in the etiology of these disorders, ii) clarify the mechanisms whereby liability to these disorders is transmitted from parents to their offspring, and iii) using multivariate methods to clarify the role of genes and environment in the etiologic relationship between these major disorders. Integrated socio-genetic analyses will include i) the genetic analyses of traditional """"""""environmental variables"""""""" (e.g. social support), and ii) the detailed assessment of the role of genotype-environment interaction and correlation in the etiology of the major psychiatric disorders. Newly developed techniques will be used to explore direction of effects (low social support causing depression vs. depression causing low social support), examine the relationship between liability to illness and potential indices of liability (e.g. age at onset, number of episodes, length of episodes) and clarify the impact of rearing environment on risk for psychiatric illness.
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