Genomes and Genes
Pharmacogenetics in Tourette Syndrom
Principal Investigator: H S Singer
Abstract: When individuals with Tourette syndrome (TS) are treated with medications to suppress tics, some improve, others have little or no response, and several may develop significant side effects. In order to explain this variability, pharmacogenetic research has focused on two major areas, drug metabolism and drug site of action. In this study, genetic variations of metabolizing enzymes (CYP2D6), dopamine & serotonin transporters (DAT, 5-HTT) dopamine receptors (D2, D3, D4) and serotonin receptors (5HT2a and 5HT2c) will be determined with the goal of predicting a TS patients response to treatment and a diagnostic category (TS or control). Fifteen established polymorphisms will be investigated in individuals with the diagnosis of TS using DNA obtained by buccal swabs. The first major objectives is to determine whether the presence of specific patterns of neurotransmitter polymorphisms predict the tic-suppressing pharmacologic effect of the atypical neuroleptic, risperidone. Patient response to pharmacotherapy will be based on a prospective evaluation of tic reduction, as measured by the Total Tic score of the Yale Global Tic Severity Scale, in 200 individuals with TS. This approach is similar to one that has been successfully used in schizophrenia to predict, with nearly 80% success, the response to the atypical neuroleptic, clozapine. Our second goal is to determine whether there are associations between genetic variations in dopamine or serotonin receptors and the etiology of TS. This question will be addressed in a cohort of 500 individuals with TS & compared with an equal number of age and sex-matched controls. This application, defines a study (to my knowledge, the first of its kind in TS), which will use DNA obtained from buccal mucosa, to establish a predictive therapeutic index in TS patients. The identification of genetic polymorphisms that are associated with clinical disease or treatment success, has obvious benefits.
Funding Period: 2003-09-15 - 2006-08-31
more information: NIH RePORT
- Norepinephrine transporter polymorphisms in Tourette syndrome with and without attention deficit hyperactivity disorder: no evidence for significant associationChristopher A Rippel
Department of Neurology, Johns Hopkins University School of Medicine, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
Psychiatr Genet 16:179-80. 2006..Further research with additional NET polymorphisms and larger sample sizes are indicated in the pursuit of biomarkers for therapeutic responders...
- Tic disorders: neural circuits, neurochemistry, and neuroimmunologyKendra Harris
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
J Child Neurol 21:678-89. 2006..We review the neural circuits and neurochemistry of Tourette syndrome and evaluate the evidence for and against a role for autoimmunity in the expression of tics...