UNIT OF PSYCHIATRIC AND NEURODEVELOPMENTAL GENETICS
Department of Psychiatry, Massachusetts general Hospital
David Pauls, PhD
The primary focus of the newly created Psychiatric and Neurodevelopmental Genetics Unit at MGH is to understand the genetic and environmental mechanisms involved in the development of mental and Neurodevelopmental disorders. The Unit will consist of geneticists, psychologists, psychiatrists and statisticians. The research examines components of the clinical phenomenology of these conditions and their transmission within families and employs clinical, quantitative and molecular genetic approaches encompassing family/genetic studies, segregation studies, genetic linkage studies, functional genomic studies and prospective longitudinal studies designed to exploit the linkage and functional genomics findings to examine the interactions of identified genes and environmental factors. At the present time the research has focused on four developmental neuropsychiatric disorders: the Gilles de la Tourette syndrome (GTS), obsessive compulsive disorder (OCD), high functioning autism/Asperger's syndrome and specific reading disability. It is expected that in the near future, research programs on other disorders (e.g., panic disorder, bipolar affective disorder and schizophrenia among others) will be initiated.
The genome has been sequenced. The speed with which new genes have been characterized has increased dramatically over the last several years. Determining the function of genes that are important for the manifestation of behavior will require new strategies designed to examine the effect of specific environments on the expression of specific allelic variants. It is highly likely that the most effective research strategies necessary to achieve these goals have yet to be developed. These new strategies will need to include creative ways of understanding behavioral phenotypes since the current nosological systems appear to be inadequate in the search for genes. Furthermore, it will be necessary to develop new methods for measuring aspects of the environment. Accurate measurement of the inherited phenotype and the relevant environments will be critical for the elucidation of gene-environment interactions that may be important in the manifestation of these complex phenotypes. While new paradigms will need to be developed, the research questions will still focus on what components of the phenotype in question are inherited and what environmental factors are important in modifying and interacting with the products of those genes.
Grant Support. NINDS-NS 16648: A Genetic Study of GTS and OCD; NICHD-HD 21887: Genotypic and Phenotypic Heterogeneity in Dyslexia; NICHD-HD 03008: Mental Retardation and Developmental Psychopathology; NICHD-HD 35482: Neurobiology and Genetics of Autism and Related Conditions; NINDS-NS 40024: A Genetic Linkage Study of GTS.
Project Sites. Department of Psychiatry, MGH-East, CNY 149, 2nd, 5th, and 10th Floors, McLean Hospital
Project Director and Contact Person. David L. Pauls, PhD, Department of Psychiatry, Massachusetts General Hospital-East, 149 13th Street, 10th Floor, Charlestown, MA 02129. Tel.: (617) 726-0826; Fax: (617) 726-0830; e-mail: dpauls@partners.org
Training Opportunities. Pre and post-doc positions in both genetic epidemiology and molecular genetics. Please contact Dr. Pauls for more information.
Representative Publications.
Pauls, D.L. and Leckman, J.F. (1986). The inheritance of Gilles de la Tourette's syndrome and associated behaviors: Evidence for autosomal dominant transmission. New England Journal of Medicine, 315:993-997.
Pauls, D.L., Leckman, J.F., and Cohen, D.J. (1993). The familial relationship between Gilles de la Tourette's Syndrome, attention deficit disorder, learning disabilities, speech disorders and stuttering. Journal of the American Academy of Child and Adolescent Psychiatry, 32:1044-1050.
Leckman, J.F., Grice, D.E., Boardman, J., Zhang, H., Vitale, A., Bondi, C., Alsobrook, J., Peterson, B.S., Cohen, D.J., Rasmussen, S.A., Goodman, W.K., McDougle, C.J., and Pauls, D.L. (1997). Symptoms of obsessive compulsive disorder. American Journal of Psychiatry, 154:911-917.
Alsobrook II, J.P. and Pauls, D.L. (1998). Molecular approaches to child psychopathology. Human Biology, 70:413-432.