Hippocampal glutamatergic/NMDA receptor functioning in bipolar disorder: A study combining mismatch negativity and proton magnetic resonance spectroscopy

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 (1H MRS). Participants comprised of 33 patients with BD and 23 matched controls who underwent a two-tone passive, duration deviant MMN paradigm and 1H 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 MIV1N. Our data also demonstrate that Glu/Cr regulation of MMN is dampened in BD, which may indicate a lack of tightly regulated hippocampal NIVIDA functioning. These findings provide insight into the underlying basis of glutamatergic transmission disturbances implicated in the disorder. (C) 2015 Elsevier Ireland Ltcl. All rights reserved