Mismatch negativity in patients with bipolar affective disorder: a systematic review and meta-analysis

Mismatch negativity (MMN) is a neural response to unexpected deviations from a regular sequence of stimuli. A diminished MMN is highly replicated in schizophrenia; however, whether this is observed in bipolar disorder (BD) is less clear.

To conduct a meta-analysis of MMN alterations in people with BD compared to healthy controls.

Electronic databases were searched until 20/10/2025, for between-subjects studies examining MMN amplitudes and or latencies in BD patients compared with controls. 15 studies consisting of 437 BD patients and 815 controls were included in this analysis.

The primary outcome was the difference in MMN amplitude between the BD and control groups, from studies using standard MMN paradigms. Meta-analysis revealed diminished MMN amplitudes (n = 14) in BD versus controls (standardised mean difference = 0.47, 95% confidence interval [0.28, 0.66], p < 0.0001). Exploratory secondary meta-regressions revealed no significant relationship between MMN amplitude and age, sex, symptoms, or illness duration. Subgroup analyses revealed MMN amplitude group difference for paradigms using duration versus frequency deviants.

MMN amplitude deficits are observed in bipolar disorder. As MMN deficits are consistently observed in schizophrenia, whether the MMN deficits observed in BD relate to psychotic symptoms or specific BD subtypes remains unclear. Limitations of this meta-analysis include low study numbers for some of the meta-regressions. Most included studies did not separate bipolar subtypes; therefore, it was not possible to determine whether the observed effects relate to affective or psychotic symptoms. Future research should distinguish putative BD subtypes and include measures of symptoms to clarify the potential of MMN as a clinical marker to guide treatment decisions.