title: Investigating the role of glutathione in mismatch negativity: An insight into NMDA receptor disturbances in bipolar disorder.
abstract: OBJECTIVE
  We aim to provide a targeted integration to investigate neuronal mechanisms underlying mismatch negativity (MMN) in bipolar disorder (BD), by looking at the association between temporal MMN and in vivo hippocampal glutathione (GSH) measured via proton magnetic resonance spectroscopy ((1)H-MRS).
  
  
  METHODS
  Twenty-eight people with BD and 22 matched controls underwent a two-tone passive, duration deviant MMN paradigm as well as (1)H-MRS. GSH concentration in the left hippocampus was determined and Pearson's correlations were used to identify associations between MMN amplitude and in vivo GSH concentration.
  
  
  RESULTS
  In controls MMN amplitude was negatively associated with GSH at the left temporal site (r=-0.542, 95% C.I.: -0.810, -0.060), and a similar trend at the right (r=-0.374, 95% C.I.: -0.678, 0.007). There were no significant associations in BD.
  
  
  CONCLUSIONS
  The results provide insight into the relationship between MMN and in vivo GSH, and demonstrate that the metabolite system regulating MMN is abnormal in BD, compared to controls. This may indicate a lack of tightly regulated hippocampal NMDA functioning, or that NMDA receptor regulation in BD is mediated by other factors.
  
  
  CONCLUSIONS
  These results provide insight into the underlying basis of hippocampal NMDA disturbances implicated in BD.
authors.affiliation: Clinical Research Unit, Brain and Mind Research Institute, The University of Sydney, Sydney, Australia. Electronic address: kate.chitty@sydney.edu.au.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Chitty
authors.affiliation: Clinical Research Unit, Brain and Mind Research Institute, The University of Sydney, Sydney, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Lagopoulos
authors.affiliation: Clinical Research Unit, Brain and Mind Research Institute, The University of Sydney, Sydney, Australia.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
authors.affiliation: Clinical Research Unit, Brain and Mind Research Institute, The University of Sydney, Sydney, Australia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hermens
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000378:metabolism*; D004569:Electroencephalography / Q000379:methods; D005260:Female; D005978:Glutathione / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D011340:Problem Solving / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D005978:Glutathione
keywords: Bipolar disorder; Glutathione; Hippocampus; Mismatch negativity; N-methyl-d-aspartate (NMDA) receptor; Proton magnetic resonance spectroscopy