A systematic review and meta-analysis of proton magnetic resonance spectroscopy and mismatch negativity in bipolar disorder

Aberrant glutamate neurotransmission has been implicated in the pathophysiology of bipolar disorder with accumulating evidence from imaging, post-mortem and pathology studies. Studies investigating in vivo changes to the glutamatergic system have not been as consistent and warrant clarification. Studies utilizing proton-magnetic resonance spectroscopy (1H-MRS) have reported increased levels of combined glutamate and glutamine (“Glx”), which have been linked to impairments in N-methyl-d-aspartate (NMDA) receptor function. Similarly, neurophysiological studies utilising mismatch negativity (MMN) as an index of NMDA receptor function, have reported impairments in bipolar disorder. Here, we provide a systematic review of the literature in regards to the concentration of Glx and the magnitude of MMN in bipolar disorder. Separate meta-analyses revealed that bipolar disorder was associated with increased Glx concentration and decreased MMN-both measured frontally. The current findings corroborate previous evidence indicating that bipolar disorder is characterized by a perturbed frontal glutamate system. These observed changes in bipolar disorder might manifest as impairments in neuronal-glial interactions that lead to disrupted neuronal output and ultimately result in the characteristic neurocognitive sequelae associated with this disorder.