Study of GABA-A Receptors in the Generation of Tics in Patients With Tourette's Syndrome
Condition: Tourette Syndrome
MeSH terms: Tourette Syndrome; Syndrome
Study type: Observational

Summary: 
      This study will investigate how the brain generates tics in patients with Tourette's syndrome
      and which areas of the brain are primarily affected. Tourette's syndrome is a
      neuropsychiatric disorder characterized by motor and vocal tics, and is associated with
      behavioral and emotional disturbances, including symptoms of attention deficit hyperactivity
      disorder and obsessive-compulsive disorder. This study will examine whether tic generation is
      related to changes in brain cell receptors for a chemical messenger called gamma-aminobutyric
      acid (GABA).

      Healthy normal volunteers and patients with Tourette's syndrome between 21 and 65 years of
      age may be eligible for this study. Candidates will be screened with a medical history and
      physical and neurological examinations.

      Participants will undergo positron emission tomography (PET) scanning to measure brain blood
      flow. For this procedure, the subject receives an injection of H215O, a radioactive substance
      similar to water. A special camera detects the radiation emitted by the H215O, allowing
      measurement of the blood flow. Subjects will receive up to five injections of H215O during
      the scanning. They will also be injected with another radioactive chemical, (11C) flumazenil,
      which binds to GABA receptors, to measure the density and distribution of these receptors.
      This will reveal which areas of the brain in patients with Tourette's syndrome have abnormal
      binding of flumazenil compared with the brains of healthy control subjects.

      During the PET procedure, the subject lies on a table in the PET scanner. A small catheter
      (plastic tube) is placed in an arm vein for injecting the radioactive tracers, and a mask is
      placed on the face to help keep the head still during scanning. The mask has large openings
      for eyes, nose and mouth, so that it does not interfere with talking or breathing. The entire
      test takes about 3 hours.

      On a separate day, participants will also undergo magnetic resonance imaging (MRI), a
      diagnostic test that uses a magnetic field and radio waves to produce images of the brain.
      For this procedure, the subject lies still on a stretcher that is moved into the scanner (a
      narrow cylinder containing the magnet). Earplugs are worn to muffle loud noises caused by
      electrical switching of radio frequency circuits used in the scanning process. The scan lasts
      about 45 to 60 minutes.

      ...
    

Detailed description: 
      The purpose of this study is to determine if symptoms of Tourette's syndrome are due to
      dysfunction of GABA-ergic neurons causing disinhibition originating in basal ganglia, and
      involving thalamus, frontal and prefrontal cortices and contributing to tic generation.

      The major inhibitory neurotransmitter in central nervous system is gamma-aminobutyric acid
      (GABA), which acts mainly through the GABA A receptors. Pathological processes involving
      GABA-ergic neurons cause alterations in the density of GABA A receptors of the targeted
      neurons. These changes can be visualized and measured with Positron Emission Tomography using
      as a radioactive ligand [11C] flumazenil. We will examine changes in the density and
      distribution of GABA A receptors in 17 adult patients with a DSM-IV-TR (American Psychiatric
      Association 2000) diagnosis of a tic disorder and 17 control subjects. This study should
      provide new information concerning localization and degree of dysfunction of GABA-ergic
      neurons in areas involved in Tourette's syndrome, which, in turn, might open new
      possibilities in pharmacological treatment of this disorder.
    

Keywords: Basal Ganglia; Neuroimaging; Inhibitory Neurons; Disinhibition; Tics; Tourette's Syndrome; Tourette Syndrome; Healthy Volunteer; HV; Normal Control