The cause of Gilles de la Tourette Syndrome (TS) is unknown. Earlier hypotheses of a psychiatric origin have now been replaced by the belief that TS is associated with damages in the level of specific chemicals in the brain known as neurotransmitters. Several chemicals have been implicated, but one in particular, a neurotransmitter called dopamine, has been the center of attention of research into this condition. In part this focus has been because the majority of medications currently used to treat tics work by reducing the concentration of dopamine or by blocking its effects in the brain. There is modest biochemical evidence supporting a dysfunction of the dopaminergic system. A single postmortem study in patients with TS that examined the binding of a drug which attaches to nerve terminals at a site where dopamine re-uptake occurs, has raised the possibility of an increased number of these dopaminergic re-uptake sites being present in the brains of patients with TS. Positron emission tomography (PET) is a scanning technique that allows us to study the function of brain pharmacology in life. This is done by giving subjects an injection of a small amount of chemicals labelled with radioactivity so that their uptake can be traced. These chemicals are called radiotracers. The scanner takes pictures of the brain that allow us to identify the nerve cells that “take up” the injected radiotracer. The amount of radioactivity that a patient receives with this technique is very small, equivalent to 1-2 years background radiation (radiation emitted by the earth and the sun) to which we are all exposed. The subject experiences no effects from the injected radiotracer, and the only discomfort associated with the procedure is from receiving the intravenous injection itself. We have previously used PET and a radiotracer called ‘8F-dopa to study the capacity of nerves to store dopamine in 10 patients with TS. Our results suggest that this brain function was normal whether patients were receiving treatment or were free of drugs. We now have a new radiotracer “C-RTI121 that allows us to study the dopamine re-uptake sites on dopaminergic terminals. In view of that post mortem report, we are planning to study a group of patients with untreated TS to see if their dopamine re-uptake is abnormal in life. Our hope is that this study will help to determine whether dopaminergic terminals function normally in TS, and thus throw light on the etiology or basic causes of this condition Prof. David J. Brooks, Dr. Nora Turjanski, MRC Cyclotron Unit Hammersmith Hospital, London, England Award $16,640 Tourette Association of America Inc. – Research Grant Award 1995