Mismatch negativity in schizophrenia spectrum and bipolar disorders: Group and sex differences and associations with symptom severity

Atle Bråthen Pentz; Clara Maria Fides Timpe; Elizabeth Marie Normann; Nora Berz Slapø; Ingrid Melle; Trine Vik Lagerberg; Nils Eiel Steen; Lars T Westlye; Erik G Jönsson; Unn K Haukvik; Torgeir Moberget; Ole A Andreassen; Torbjørn Elvsåshagen

doi:10.1016/j.schres.2023.09.012

Mismatch negativity in schizophrenia spectrum and bipolar disorders: Group and sex differences and associations with symptom severity

Schizophr Res. 2023 Nov:261:80-93. doi: 10.1016/j.schres.2023.09.012. Epub 2023 Sep 15.

Affiliations

¹ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway. Electronic address: atle.pentz@medisin.uio.no.
² NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
³ University of Copenhagen, Copenhagen, Denmark.
⁴ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway.
⁵ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁶ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway; Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Sciences, Stockholm Region, Stockholm, Sweden.
⁷ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway; Department of Adult Psychiatry, Institute of Clinical Medicine, University of Oslo, Norway; Department of Forensic Psychiatry Research, Oslo University Hospital, Norway.
⁸ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway. Electronic address: torbjorn.elvsashagen@medisin.uio.no.

PMID: 37716205
DOI: 10.1016/j.schres.2023.09.012

Abstract

Objective: Research increasingly implicates glutamatergic dysfunction in the pathophysiologies of psychotic disorders. Auditory mismatch negativity (MMN) is an electroencephalography (EEG) waveform linked to glutamatergic neurotransmission and is consistently attenuated in schizophrenia (SCZ). MMN consists of two subcomponents, the repetition positivity (RP) and deviant negativity (DN) possibly reflecting different neural mechanisms. However, whether MMN reduction is present across different psychotic disorders, linked to distinct symptom clusters, or related to sex remain to be clarified.

Methods: Four hundred participants including healthy controls (HCs; n = 296) and individuals with SCZ (n = 39), bipolar disorder (BD) BD typeI (n = 35), or BD type II (n = 30) underwent a roving MMN paradigm and clinical evaluation. MMN, RP and DN as well their memory traces were recorded at the FCZ electrode. Analyses of variance and linear regression models were used both transdiagnostically and within clinical groups.

Results: MMN was reduced in SCZ compared to BD (p = 0.006, d = 0.55) and to HCs (p < 0.001, d = 0.63). There was a significant group × sex interaction (p < 0.003) and the MMN impairment was only detected in males with SCZ. MMN amplitude correlated positively with Positive and Negative Syndrome Scale total score and negatively with Global Assessment of Functioning Scale score. The deviant negativity was impaired in males with SCZ. No group differences in memory trace indices of the MMN, DN, or RP.

Conclusion: MMN was attenuated in SCZ and correlated with greater severity of psychotic symptoms and lower level of functioning. Our results may indicate sex-dependent differences of glutamatergic function in SCZ.

Keywords: Bipolar disorder type I; Bipolar disorder type II; Mismatch negativity; Schizophrenia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bipolar Disorder*
Electroencephalography
Evoked Potentials, Auditory / physiology
Female
Humans
Male
Schizophrenia*
Sex Characteristics