title: GABA and glutamate levels in occlusal splint-wearing males with possible bruxism.
abstract: OBJECTIVE
  The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the pathophysiology of anxiety behavioural disorders such as panic disorder and post-traumatic stress disorder and is also implicated in the manifestation of tooth-grinding and clenching behaviours generally known as bruxism. In order to test whether the stress-related behaviours of tooth-grinding and clenching share similar underlying mechanisms involving GABA and other metabolites as do anxiety-related behavioural disorders, we performed a Magnetic Resonance Spectroscopy (MRS) study for accurate, in vivo metabolite quantification in anxiety-related brain regions.
  
  
  METHODS
  MRS was performed in the right hippocampus and right thalamus involved in the hypothalamic-pituitary-adrenal axis system, together with a motor planning region (dorsal anterior cingulate cortex/pre-supplementary motor area) and right dorsolateral prefrontal cortex (DLPFC). Eight occlusal splint-wearing men (OCS) with possible tooth-grinding and clenching behaviours and nine male controls (CON) with no such behaviour were studied.
  
  
  RESULTS
  Repeated-measures ANOVA showed significant Group×Region interaction for GABA+ (p = 0.001) and glutamate (Glu) (p = 0.031). Between-group post hoc ANOVA showed significantly lower levels of GABA+ (p = 0.003) and higher levels of Glu (p = 0.002) in DLPFC of OCS subjects. These GABA+ and Glu group differences remained significant (GABA+, p = 0.049; Glu, p = 0.039) after the inclusion of anxiety as a covariate. Additionally, GABA and Glu levels in the DLPFC of all subjects were negatively related (Pearson's r = -0.75, p = 0.003).
  
  
  CONCLUSIONS
  These findings indicate that the oral behaviours of tooth-grinding and clenching, generally known as bruxism, may be associated with disturbances in brain GABAergic and glutamatergic systems.
authors.affiliation: Purdue University School of Health Sciences, 550 Stadium Mall Drive, West Lafayette, IN 47907, USA; Department of Radiology, Indiana University School of Medicine, 550 North University Boulevard Room 0663, Indianapolis, IN 46202, USA. Electronic address: shdharma@iupui.edu.
authors.forename: Shalmali
authors.initials: S
authors.lastname: Dharmadhikari
authors.affiliation: Department of Oral Biology, Indiana University School of Dentistry, 1121 West Michigan Street, Indianapolis, IN 46202, USA. Electronic address: lromitoc@iu.edu.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Romito
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Goodman Hall, Suite 4700, 355 West 16th Street, Indianapolis, IN 46202, USA; Department of Radiology, Indiana University School of Medicine, 550 North University Boulevard Room 0663, Indianapolis, IN 46202, USA. Electronic address: mdzemidz@iupui.edu.
authors.forename: Mario
authors.initials: M
authors.lastname: Dzemidzic
authors.affiliation: Purdue University School of Health Sciences, 550 Stadium Mall Drive, West Lafayette, IN 47907, USA; Department of Radiology, Indiana University School of Medicine, 550 North University Boulevard Room 0663, Indianapolis, IN 46202, USA. Electronic address: udydak@iupui.edu.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dydak
authors.affiliation: Department of Radiology, Indiana University School of Medicine, 550 North University Boulevard Room 0663, Indianapolis, IN 46202, USA. Electronic address: jx3@iupui.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Goodman Hall, Suite 4700, 355 West 16th Street, Indianapolis, IN 46202, USA; Indiana University Health Sleep Disorders Center, Indiana University School of Medicine, 714 N. Senate Avenue, Suite 120, Indianapolis, IN 46202, USA. Electronic address: cbodkin@iupui.edu.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Bodkin
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Goodman Hall, Suite 4700, 355 West 16th Street, Indianapolis, IN 46202, USA; Indiana University Health Sleep Disorders Center, Indiana University School of Medicine, 714 N. Senate Avenue, Suite 120, Indianapolis, IN 46202, USA. Electronic address: smanchan@iu.edu.
authors.forename: Shalini
authors.initials: S
authors.lastname: Manchanda
authors.affiliation: Department of Oral Biology, Indiana University School of Dentistry, 1121 West Michigan Street, Indianapolis, IN 46202, USA; Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS-5035, Indianapolis, IN 46202, USA. Electronic address: kbyrd@iupui.edu.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Byrd
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002012:Bruxism / Q000378:metabolism* / Q000517:prevention & control*; D016022:Case-Control Studies; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D017090:Occlusal Splints; D011795:Surveys and Questionnaires; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Anxiety; Bruxism; GABA; MRS; Metabolites; Pathophysiology