This application represents an integrated plan of research and training which will allow the Candidate to acquire the necessary skills to become independent as a clinical investigator. The Candidate has demonstrated a commitment towards the pursuit of clinical excellence and original research in the area of Obsessive Compulsive Disorder (OCD) in children and adolescents over many years, manifested by a highly reputed clinical program, small grant support and original scientific publications. The Candidate is seeking the support of a Mentored Clinical Scientist Development Award in order to undertake a comprehensive program of didactic and mentored training and clinical research using the proposed research plan as a vehicle for scientific development. The Candidate is in an outstanding environment for this purpose and has assembled a highly qualified group of consultants who are leaders in their field and who are dedicated to the Candidate's research career success. The scientific development plan proposed includes training in Clinical Research Methods in Child Psychiatry-20 percent, Clinical Research Methods in Adults with Obsessive Compulsive and Related Disorders-10 percent, and courses at the Harvard School of Public Health in epidemiology and biostatistics which comprise the Formal Didactic Training-10 percent. The Candidate's background, scientific biography, research objectives and career goals reveal a clear and constant trajectory and a coherent plan for a career studying OCD in the pediatric population. The rationale for the Candidate's proposed Research Plan-35 percent, derives from the premise that OCD is very likely a heterogeneous disorder and further, that an understanding of this etiologic heterogeneity is important, not only for clinical purposes, but also as a fundamental step in future neurobiological research. The Candidate contends, using his own work and the reviewed literature, that age at onset of OCD represents the most compelling variable to study to examine etiologic heterogeneity because OCD which begins in childhood differs in important ways from the adult-onset disorder. To this end, the Candidate proposes to test several competing hypotheses to determine whether the childhood-onset form of OCD is the same or different from adult-onset OCD by studying the clinical correlates and familial aggregation of psychiatric disorders in 100 juvenile OCD probands, 50 adult OCD probands with juvenile-onset OCD and 50 adult OCD probands with adult-onset OCD and their first degree relatives. By providing data that are independent from findings in the proband, family-genetic data provide a powerful method to investigate whether juvenile-onset OCD is a clinically meaningful subtype of OCD. The clinical, scientific, and public health relevance of confirming or refuting these hypotheses is discussed.
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