New research directions suggest that decreased ?-aminobutyric acid (GABA, major inhibitory neurotransmitter) activity and increased oxidative stress may play a role in the development of Tourette’s Disorder (TD). To date, no study has examined these systems directly in patients with TD. The use of proton magnetic resonance spectroscopy (1H MRS) has the major advantage of affording an in vivo non-invasive assessment of brain chemicals, including GABA and glutathione (GSH), the major antioxidant in the body. Using innovative 1H MRS techniques, we will quantify in vivo GABA in the anterior cingulate cortex (ACC) and striatum of 25 psychotropic medication-free adolescents with TD and 25 group-matched control subjects, and will assess striatal glutathione (GSH) in 15 adolescents with TD and 15 controls. Total Choline (tCho), total Creatine (tCr), and N-Acetylaspartate (NAA), biomarkers for neurocellular health and metabolism, will be quantified in the striatum and ACC as well. Medically healthy adolescents with TD, ages 12-17 years, with severity scores ?10 on the Yale Global Tic Severity Scale-Total Tic Subscale, and comparison subjects will be enrolled. The diagnosis of TD will be established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children – Present and Lifetime Version. Symptom severities for obsessive-compulsive disorder, attention deficit hyperactivity disorder, anxiety, and depression will be assessed via clinical- and self-administered measures. Participants will be scanned with 1H MRS, acquired at 3 Tesla and high spatial resolution, focusing on the striatum and the ACC. We hypothesize that adolescents with TD will have significantly decreased striatal and ACC GABA, GSH, tCho, tCr, and NAA concentrations compared to the group-matched healthy adolescents. Vilma Gabbay, M.D., M.S., Barbara J. Coffey, M.D., M.S., Dikoma C. Shungu, Ph.D. New York University School of Medicine, New York, NY Award: $75,000 (2nd Year) Commentary: This is an exploratory study that aims to identify alterations of specific brain chemicals in adolescents with Tourette’s Disorder (TD) as compared to adolescents without TD. This study requires a one-time, non-invasive brain scan, using a special imaging technique called proton magnetic resonance spectroscopy that enables the detection and measurement of brain chemicals. The investigators will assess the levels of chemicals thought to be implicated in TS in specific brain regions in 25 adolescents with TD and 25 comparison subjects, ages 12-17. Enhanced understanding of the neurochemistry of TD may help with the development of more effective therapeutic strategies. Tourette Association of America Inc. – Research Grant Award 2011-2012