title: Restless legs syndrome and central nervous system gamma-aminobutyric acid: preliminary associations with periodic limb movements in sleep and restless leg syndrome symptom severity.
abstract: BACKGROUND
  Previous research has demonstrated abnormalities in glutamate and N-acetyl aspartate (NAA) in the thalamus in individuals with restless legs syndrome (RLS) compared with healthy matched controls. However, levels of these transmitters in other RLS-related brain areas and levels of the most common inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have not been assessed.
  
  
  METHODS
  This study examined GABA, glutamate, and NAA levels in the dorsal anterior cingulate cortex (ACC), thalamus and cerebellum with the use of proton magnetic resonance spectroscopy ((1)H-MRS) at 4 tesla (4 T) and Megapress difference-editing in 18 subjects with RLS and a matched control group without RLS. Actigraphy was performed on the nights before scans to assess periodic limb movements of sleep (PLMS).
  
  
  RESULTS
  Levels of GABA, glutamate, and NAA were no different between RLS and control subjects in any of the three voxels of interest. However, GABA levels were positively correlated with both PLM indices and RLS severity in the thalamus and negatively with both of these measures in the cerebellum in RLS subjects. In addition, NAA levels were higher in the ACC in RLS than in controls.
  
  
  CONCLUSIONS
  Our preliminary data suggest that known cerebellar-thalamic interactions may modulate the intensity of RLS sensory and motor symptoms. In addition, anterior cingulate cortex may be associated with the affective components of the painful symptoms in this disorder.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Departments of Psychiatry and Neurology, Sleep Disorders Clinical Research Program, Massachusetts General Hospital, Boston, MA, USA. Electronic address: jwwinkelman@partners.org.
authors.forename: John W
authors.initials: JW
authors.lastname: Winkelman
authors.affiliation: Departments of Psychiatry and Neurology, Sleep Disorders Clinical Research Program, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Schoerning
authors.affiliation: Departments of Psychiatry and Neurology, Sleep Disorders Clinical Research Program, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Platt
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Brain Imaging Center, McLean Hospital, Boston, MA, USA.
authors.forename: J Eric
authors.initials: JE
authors.lastname: Jensen
mesh_terms: D056044:Actigraphy; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D016022:Case-Control Studies; D002531:Cerebellum / Q000737:chemistry / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000032:analysis / Q000502:physiology; D006179:Gyrus Cinguli / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008297:Male; D017286:Polysomnography; D066244:Proton Magnetic Resonance Spectroscopy; D012148:Restless Legs Syndrome / Q000378:metabolism / Q000503:physiopathology*; D012720:Severity of Illness Index; D013788:Thalamus / Q000737:chemistry / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000032:analysis* / Q000502:physiology
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate
keywords: Anterior cingulate cortex; Cerebellum; Gamma-aminobutyric acid; Glutamate; Periodic limb movements of sleep; Restless legs syndrome; Thalamus