Mismatch negativity in bipolar disorder: A neurophysiological biomarker of intermediate effect?

Abstract

The event-related potential, mismatch negativity (MMN), has been touted as a robust and specific neurophysiological biomarker of schizophrenia. Earlier studies often included bipolar disorder (BD) as a clinical comparator and reported that MMN was significantly impaired only in schizophrenia. However, with the increasing number of MMN studies of BD (with larger sample sizes), the literature is now providing somewhat consistent evidence of this biomarker also being perturbed in BD, albeit to a lesser degree than that observed in schizophrenia. Indeed, two meta-analyses have now shown that the effect sizes in BD samples suggest a moderate impairment in MMN, compared to the large effect sizes shown in schizophrenia. Pharmacologically, MMN is an extremely useful non-invasive probe of glutamatergic (more specifically, N-methyl-d-aspartate [NMDA] receptor) disturbances and this system has been implicated in the pathophysiology of both schizophrenia and BD. Therefore, it may be best to conceptualize/utilize MMN as an index of a psychopathology that is shared across psychotic and related disorders, rather than being a diagnosis-specific biomarker. More research is needed, particularly longitudinal designs including studies that assess MMN over an individual's life course and then examine NMDA receptor expression/binding post-mortem. At this point and despite a disproportionate amount of research, the current evidence suggests that with respect to BD, MMN is a neurophysiological biomarker of intermediate effect. With replication and validation of this effect, MMN may prove to be an important indicator of a common psychopathology shared by a significant proportion of individuals with schizophrenia and bipolar spectrum illnesses.

Keywords: Bipolar disorder; Glutamate; Mismatch negativity; NMDA receptor; Neurophysiological biomarker; Schizophrenia.