David L. Pauls, Ph.D. M.I.N.D. Institute Distinguished Lecturer Series – October 11, 2006 Biographical Information David L. Pauls, Ph.D., is Professor of Psychiatry (Genetics) at the Harvard Medical School and Director of the Psychiatric and Neurodevelopmental Genetics Unit in the Center for Human Genetic Research at Massachusetts General Hospital. He received his Bachelor of Arts degree from Fresno Pacific University, in Fresno, California, graduating summa cum laude with majors in mathematics, biology and chemistry, and his Ph.D. from the University of Minnesota in Genetics and Cell Biology. Dr. Pauls has been interested in the genetics of behavior throughout his academic career and his research has focused on elucidating the genetic and environmental factors important for the expression of child and adult psychiatric conditions. In 1980, he began his studies on Gilles de la Tourette syndrome (GTS) under the mentorship of Drs. Donald Cohen and Kenneth Kidd at the Child Study Center and Department of Genetics at the Yale University School of Medicine. In 1980 he and Dr. Kidd received one of the first research grants on GTS from the National Institute of Neurological Disease and Stroke - an award now in its 26th year. Dr. Pauls is also principal investigator of a genetic linkage study being conducted by the Tourette Syndrome Association International Consortium on Genetics. This group recently completed a genome-wide scan on a sample of over 300 affected sib-pair families and 18 large multigenerational families. In addition, he is an active collaborator on several other projects focused in the genetics of OCD and is chair of the Obsessive Compulsive Foundation Genetics Collaborative. He is also a member of the Obsessive Compulsive Disorder Genetics Consortium which just recently completed a genome-wide scan on approximately 300 families ascertained through an individual with OCD. In addition to his research on GTS and OCD, Dr. Pauls is actively investigating the genetics of autism, Asperger’s syndrome, specific reading disability and attention deficit disorder. Dr. Pauls is a member of Scientific Advisory Boards for the Obsessive Compulsive Foundation and the Trichotillomania Learning Center and the Board of Directors of the Asperger’s Association of New England. He also serves as the Chair on two separate consortia: the Obsessive Compulsive Foundation Genetics Collaborative and the Tourette Syndrome Association International Consortium for Genetics. Presentation Abstracts The Genetics of Gilles de la Tourette Syndrome (4 pm) Tourette Disorder (TD) is a neuropsychiatric disorder with a complex mode of inheritance characterized by waxing and waning multiple motor and phonic tics. This talk will report results of the largest genetic linkage study yet undertaken for TD. The sample analyzed includes 238 nuclear families yielding 304 “independent” sib-pairs and 18 separate multigenerational families; a total of 2,040 individuals. A whole genome screen using 390 microsatellite markers was completed. Analyses were completed using two diagnostic classifications: 1) only individuals with TD were included as affected; and 2) individuals with TD or chronic tics (CT) were included as affected. Significant evidence for linkage was observed for a region on chromosome 2p [-log(p) = 4.42, p = 3.8 x 10-5] in the analyses which included individuals with TD or CT as affected. Results in several other regions also provide suggestive evidence for additional susceptibility loci for TD. Gilles de la Tourette Syndrome and Obsessive Compulsive Disorder: What is the Relationship? (6 pm) Tourette Disorder (TD) and Obsessive Compulsive Disorder (OCD) are complex neuropsychiatric disorders TD is characterized by waxing and waning multiple motor (seemingly purposeless movements) and phonic tics (seemingly purposeless sounds and utterances) while OCD is characterized by recurrent intrusive thoughts (obsessions) and complex repetitive, seemingly purposeful movements (compulsions). Individuals with TD have symptoms of OCD much more frequently than expected by chance. Similarly, individuals with OCD that had its onset in childhood have a history of tics much more frequently than would be expected. Family data suggest that the two disorders may be alternative expressions of some shared familial etiology. This talk will summarize those studies and discuss how such seemingly disparate conditions could be genetically related.