title: Hippocampal glutamatergic/NMDA receptor functioning in bipolar disorder: A study combining mismatch negativity and proton magnetic resonance spectroscopy.
abstract: Disturbances in the hippocampal glutamate (Glu)/N-methyl-d-aspartate (NMDA) system have been implicated in the pathophysiology of bipolar disorder (BD). Here we aim to provide a targeted integration of two measures of glutamatergic functioning in BD; the association between mismatch negativity (MMN) and in vivo hippocampal-Glu measured via proton magnetic resonance spectroscopy ((1)H MRS). Participants comprised of 33 patients with BD and 23 matched controls who underwent a two-tone passive, duration deviant MMN paradigm and (1)H MRS. Levels of Glu/creatine (Cr) in the hippocampus were determined. Pearson's correlations were used to determine associations between MMN and Glu/Cr. In controls, MMN amplitude was positively associated with Glu/Cr at the left temporal site. We did not find any significant associations with Glu/Cr and frontocentral MMN nor did we find any significant associations in BD patients. The results provide further insight into the neurophysiology of MMN, with evidence supporting the role of hippocampal-Glu signalling through the NMDA receptor in temporal MMN. Our data also demonstrate that Glu/Cr regulation of MMN is dampened in BD, which may indicate a lack of tightly regulated hippocampal NMDA functioning. These findings provide insight into the underlying basis of glutamatergic transmission disturbances implicated in the disorder.
authors.affiliation: Clinical Research Unit, Brain and Mind Research Institute, 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, University of Sydney, Sydney, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Lagopoulos
authors.affiliation: Clinical Research Unit, Brain and Mind Research Institute, 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, University of Sydney, Sydney, Australia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hermens
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000378:metabolism* / Q000503:physiopathology*; D003401:Creatine / Q000378:metabolism; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D003401:Creatine
keywords: Glutamate; Hippocampus; Mismatch negativity; Proton magnetic resonance spectroscopy