title: Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome.
abstract: Dysfunction of the γ-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive-compulsive disorder. The purpose of this study was to identify a possible dysfunction of the γ-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20 mCi of [(11)C]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABA(A) receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABA(A) receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABA(A) receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics.
authors.affiliation: Controlled Substance Staff, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993, USA. alicja.lerner@fda.hhs.gov
authors.forename: Alicja
authors.initials: A
authors.lastname: Lerner
authors.forename: Anto
authors.initials: A
authors.lastname: Bagic
authors.forename: Janine M
authors.initials: JM
authors.lastname: Simmons
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Mari
authors.forename: Omer
authors.initials: O
authors.lastname: Bonne
authors.forename: Ben
authors.initials: B
authors.lastname: Xu
authors.forename: Diane
authors.initials: D
authors.lastname: Kazuba
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Murphy
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002247:Carbon Isotopes; D016022:Case-Control Studies; D005260:Female; D005442:Flumazenil; D018757:GABA Modulators; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011963:Receptors, GABA-A / Q000378:metabolism; D005879:Tourette Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002247:Carbon Isotopes; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid