This application is for a Scientist Development Award for Clinicians (SDAC) to further the principal investigator's research training in human genetics and its application to the study of severe, chronic psychopathology in children and adolescents. Funding is requested to free time to pursue didactic instruction and collaborative research in this area. The preceptor will be Michael Boehnke, Ph.D., Associate Professor of Biostatistics at the University of Michigan. The scientific focus for SDAC activities will be obsessive-compulsive disorder (0CD). 0CD is a common psychiatric syndrome that often begins in childhood, persists into adulthood, and aggregates in families. It is relatively consistent in its clinical presentation across the lifespan. Recent family studies indicate that a form of 0CD is related genetically to Gilles de la Tourette syndrome. Family studies using current diagnostic procedures and analytic methods are necessary for investigating the possible modes of expression and transmission of 0CD in families. The general aim of the family case-control study described in this application is to systematically assess and compare the clinical characteristics and family psychiatric history of child, adolescent, and adult probands with 0CD. It is hypothesized that (1) early-onset 0CD is more frequent in males than in females, (2) the prevalence of 0CD is higher in the relatives of probands with early-onset 0CD than in the relatives of probands with late-onset 0CD, (3) the inheritance of 0CD is influenced by a single major locus, (4) chronic tic disorders are more frequent in male 0CD probands, and (5) the prevalence of chronic tic disorders is higher in the relatives of female 0CD probands than in the relatives of male 0CD probands. The data will be inspected for other findings, including comparisons with matched normal controls and their relatives. In summary, this study will advance our knowledge of the etiology of 0CD, and will provide a medium for the scientific development of the principal investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Unknown (K20)
Project #
5K20MH001065-05
Application #
2460269
Study Section
Epidemiology and Genetics Review Committee (EPI)
Project Start
1993-08-01
Project End
1999-02-28
Budget Start
1997-08-01
Budget End
1999-02-28
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Psychiatry
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
McGrath, Lauren M; Yu, Dongmei; Marshall, Christian et al. (2014) Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study. J Am Acad Child Adolesc Psychiatry 53:910-9
Davis, Lea K; Yu, Dongmei; Keenan, Clare L et al. (2013) Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet 9:e1003864
Stewart, S E; Mayerfeld, C; Arnold, P D et al. (2013) Meta-analysis of association between obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene SLC1A1. Am J Med Genet B Neuropsychiatr Genet 162B:367-79
Veenstra-VanderWeele, Jeremy; Xu, Tim; Ruggiero, Alicia M et al. (2012) Functional studies and rare variant screening of SLC1A1/EAAC1 in males with obsessive-compulsive disorder. Psychiatr Genet 22:256-60
Mathews, Carol A; Badner, Judith A; Andresen, J Michael et al. (2012) Genome-wide linkage analysis of obsessive-compulsive disorder implicates chromosome 1p36. Biol Psychiatry 72:629-36
Hanna, Gregory L; Himle, Joseph A; Hanna, Barbara S et al. (2011) Major depressive disorder in a family study of obsessive-compulsive disorder with pediatric probands. Depress Anxiety 28:501-8
Cross, Sarah; Kim, Soo-Jeong; Weiss, Lauren A et al. (2008) Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism. Neuropsychopharmacology 33:353-60
Hanna, Gregory L; Veenstra-Vanderweele, Jeremy; Cox, Nancy J et al. (2007) Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive-compulsive disorder. Biol Psychiatry 62:856-62
Dickel, Diane E; Veenstra-VanderWeele, Jeremy; Bivens, Nancy Chiu et al. (2007) Association studies of serotonin system candidate genes in early-onset obsessive-compulsive disorder. Biol Psychiatry 61:322-9
Dickel, Diane E; Veenstra-VanderWeele, Jeremy; Cox, Nancy J et al. (2006) Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry 63:778-85

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