Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome

Alicja Lerner, Anto Bagic, Janine M. Simmons, Zoltan Mari, Omer Bonne, Ben Xu, Diane Kazuba, Peter Herscovitch, Richard E. Carson, Dennis L. Murphy, Wayne C. Drevets, Mark Hallett

Research output: Contribution to journalArticle

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 20mCi of [11C]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 GABAA receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABAA 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 GABAA receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics.

Original languageEnglish (US)
Pages (from-to)1926-1936
Number of pages11
JournalBrain
Volume135
Issue number6
DOIs
StatePublished - 2012

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Keywords

  • flumazenil
  • PET
  • tics
  • Tourette syndrome

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Lerner, A., Bagic, A., Simmons, J. M., Mari, Z., Bonne, O., Xu, B., Kazuba, D., Herscovitch, P., Carson, R. E., Murphy, D. L., Drevets, W. C., & Hallett, M. (2012). Widespread abnormality of the γ-aminobutyric acid-ergic system in Tourette syndrome. Brain, 135(6), 1926-1936. https://doi.org/10.1093/brain/aws104