Hippocampal glutamatergic/NMDA receptor functioning in bipolar disorder: a combined MMN and 1H-MRS study

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.