title: A systematic review and meta-analysis of proton magnetic resonance spectroscopy and mismatch negativity in bipolar disorder.
abstract: 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 ((1)H-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.
authors: Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia. Electronic address: kate.chitty@sydney.edu.au.
authors: Kate M
authors: KM
authors: Chitty
authors: Jim
authors: J
authors: Lagopoulos
authors: Rico S C
authors: RS
authors: Lee
authors: Ian B
authors: IB
authors: Hickie
authors: Daniel F
authors: DF
authors: Hermens
mesh_terms: D001714:Bipolar Disorder / Q000378:metabolism* / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology; D005625:Frontal Lobe / Q000378:metabolism / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011522:Protons
chemical_list: D011522:Protons; D005973:Glutamine; D018698:Glutamic Acid
keywords: Anterior cingulate cortex; Bipolar disorder; Frontal lobe; Glutamate; Magnetic resonance spectroscopy; Meta-analysis; Mismatch negativity