An immunologic etiology has been hypothesized as the underlying pathophysiologic mechanism in some children with tic disorders. In these individuals, it is postulated that antibodies (possibly formed against infectious agents) cross-react with specific central nervous system neurons and cause tics. Several laboratory studies have reported elevated serum levels of anti-neuronal antibodies in a small number of children with tic disorders. However, the mere presence of anti-neuronal antibodies in the serum of patients with Tourette Syndrome does not imply causation. Thus, animal models have been developed to study whether sera can induce behaviors in rodents that are analogous to tics in humans. It is hypothesized that, if there are active antibodies against striata antibodies in the serum, infusion directly into rodent striatum should induce behavioral changes. To date, three research centers (Brown, Yale and Johns Hopkins) are independently performing microinfusion studies. Results, however, have been inconsistent, thus requiring further clarification. For example, several studies have reported that infusions induced increased stereotypies or vocalizations, whereas one study showed no significant change in rodent behavior. It should be noted that these investigations have used different infusion sites, measurements of anti-neuronal antibodies, concentrations of infused sera, lengths of behavioral observation, and behavior measurement scales. The goal of this proposal is to clarify existing concerns about this rodent model. Three investigators will simultaneously participate in a blinded protocol analyzing the same serum samples using similar methodologies. Key elements in this proposal include an investigator’s meeting to standardize the process of rating stereotypies, develop clearly defined methodologies, and each use the same implementation of a blinded protocol. It is anticipated that such a careful collaboration will shed light on the questions that persist concerning the relationship between the immune system and tic manifestation in some children. Harvey Singer, M.D., Director Child Neurology, Johns Hopkins Hospital, Baltimore, MD Joseph J. Hallett, M.D., Assist. Prof. of Pediatrics, Brown Univ. Sch. of Medicine, Pawtucket, RI Paul J. Lombroso, M.D., Assoc. Prof. Yale Univ. Sch. of Medicine, New Haven, CT Award: $75,000 This award has been funded by the Ochsman Family Foundation Tourette Association of America Inc. – Research Grant Award 2002-2003