Often the efficacy and tolerability of standard psychopharmacological treatment for Tourette Syndrome (TS) and the commonly occurring co-morbid disorders, such as obsessive-compulsive disorder (OCD), are limited. Currently we see an increasing use of complementary and alternative treatments for TS in the community. However, there are no scientific studies of these agents showing that they are effective. The purpose of this study is to test the efficacy and safety of omega-3 fatty acids derived from fish oil in the treatment of children and adolescents with TS. We hypothesize that orally administered omega-3 fatty acids will reduce tics and obsessive compulsive symptoms in children and adolescents with TS through pro-serotonergic and anti-inflammatory effects. Fish oil has received attention as a therapeutic agent in autoimmune illnesses and in preliminary studies to be of benefit in mood disorders. Though anecdotal, some children with TS have been described as deriving benefit from fish oil. There is considerable evidence suggesting the involvement of serotonin dysfunction in both disorders, along with an autoimmune inflammatory process in a subgroup of children with TS and OCD. There are also scientific data suggesting that serotonin dysfunction is triggered by inflammatory mediators such as cytokines. Omega-3 fatty acid appears to act by down-regulation of pro-inflammatory cytokine production and through pro-serotonergic activity, thus addressing some of the pathways implicated in the basic causes of TS and OCD. This is a 20 week, double blind, placebo controlled, parallel group study using a flexible dose titration design. Forty patients, ages 6-18, will be randomly assigned to receive either omega-3 fatty acids or placebo. Omega-3 fatty acids will be initiated at a dose of 500 mg and flexibly titrated to a possible maximum dose of 6000 mg. Clinical ratings, completed at baseline and weeks 1, 2, 3, 4, 6, 8, 12, 16 and 20 after the initiation of the study, will include the Yale Global Tic Severity Scale, Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions Scale for Tics and OCD. This is the second year of TSA funding for this study. We hypothesize that Omega-3 fatty acids will be significantly more effective than placebo in reducing TS and OCD symptoms. If this hypothesis is confirmed, our results will provide support for future studies of complementary and alternative agents. Vilma Gabbay, M.D., Barbara J. Coffey, M.D., M.S., Carmen Alonso, M.D. New York University Child Study Center, New York, NY Award: $75,000 (Year 2 Award) Tourette Association of America Inc. – Research Grant Award 2004-2005