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This proposal is a five-year study of psychopathology and dysfunction in children at risk for attention deficit disorder and related disorders. The proposed study will extend our work evaluating family-genetic and psychosocial risk factors in DSM-III-R attention deficit hyperactivity disorder (ADHD). Our ongoing work has identified 141 child and adolescent probands with ADHD, their high risk biological siblings, and a contrast group of 119 healthy controls of similar age, sex, social class, and ethnic background, and their siblings. We have collected cognitive, social functioning, and psychiatric diagnostic data, as well as measures of environmental adversity, from these probands and 466 parents and siblings of ADHD probands and 370 parents and siblings of normal controls. We now propose a five-year high risk study of these probands and their siblings. This effort represents the second step of a long-term project aimed at prospectively testing hypotheses about risk factors in ADHD and related disorders from early childhood to adulthood. To achieve our goals for the next five years, we have two major aims: 1) to assess, at yearly intervals, children at risk for psychopathology and social dysfunction and 2) to identify risk and protective factors that predict and/or mediate outcome. Two high risk groups can be defined from our current sample: 1) ADHD probands and 2) their siblings. ADHD children are known to be at high risk for additional psychopathology (e.g. conduct disorder, major depression), poor adaptive functioning and impaired school performance. However, relatively little is known about the risk and protective factors that determine the emergence, persistence, and remission of these outcomes. The broad age range of ADD probands in our sample will allow us to examine these factors at different stages of development. Our current sample includes 42 siblings of ADHD probands who have not yet passed through the age of risk for ADHD. Since this group is at high risk for ADHD, we will be able to prospectively identify risk factors for the initial onset of ADHD. We will also be following 133 siblings of ADHD probands who have passed through the age risk without developing ADHD. Although no longer at risk for ADHD, these children are still at risk for disorders known to be associated with ADHD and may be at risk for impaired social and cognitive functioning. The study includes up to four years (six from the initial assessment) of longitudinal follow-up evaluation of these children. The rationale and main impetus for this study stem directly from our group's prior work, which supports the hypotheses to be tested, the estimation of sample size, and the overall feasibility of this project. The main hypothesis will examine critical components of risk. Studies of high-risk children have major public health relevance due to the fact that they can identify early precursors of psychopathology that may offer the opportunity for primary prevention or early intervention programs. The results of this research could lead to protocols for early detection of children who are at risk for later psychopathology and dysfunction.

Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.