TY - JOUR
T1 - Mismatch negativity in patients with bipolar affective disorder
T2 - a systematic review and meta-analysis
AU - Caulfield, Alice
AU - Moura, Rita
AU - Brugger, Stefan
AU - Young, Allan H.
AU - Mehta, Mitul A.
AU - Adams, Rick A.
AU - Beck, Katherine
N1 - Publisher Copyright:
© The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
PY - 2026/3/12
Y1 - 2026/3/12
N2 - Introduction: 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. Aim: To conduct a meta-analysis of MMN alterations in people with BD compared to healthy controls. Methods: 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. Results: 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. Conclusion: 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.
AB - Introduction: 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. Aim: To conduct a meta-analysis of MMN alterations in people with BD compared to healthy controls. Methods: 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. Results: 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. Conclusion: 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.
KW - bipolar disorder
KW - electroencephalography
KW - meta-analysis
KW - mismatch negativity
UR - https://www.scopus.com/pages/publications/105036244079
U2 - 10.1177/02698811261436604
DO - 10.1177/02698811261436604
M3 - Review article
C2 - 41988789
AN - SCOPUS:105036244079
SN - 0269-8811
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
ER -