Investigating the role of glutathione in mismatch negativity: An insight into NMDA receptor disturbances in bipolar disorder

•Disturbances in the N-methyl-d-aspartate (NMDA) receptor in bipolar disorder were investigated via mismatch negativity (MMN) and proton magnetic resonance spectroscopy.•In controls, MMN amplitude was negatively associated with in vivo glutathione.•The association between glutathione and MMN was abnormal in bipolar disorder.

ObjectiveWe 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 (1H-MRS).MethodsTwenty-eight people with BD and 22 matched controls underwent a two-tone passive, duration deviant MMN paradigm as well as 1H-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.ResultsIn 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.ConclusionsThe 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.SignificanceThese results provide insight into the underlying basis of hippocampal NMDA disturbances implicated in BD.