Features of Duration Mismatch Negativity Around the Onset of Overt Psychotic Disorders: A Longitudinal Study

Abstract

Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2 years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.

Forecasting prognostic trajectories with mismatch negativity in early psychosis

“…In this longitudinal study, we aimed to confirm the usefulness of dMMN as a common prognostic biomarker across the early psychosis periods, from CHR to FEP. In line with many previous studies (Erickson et al, 2016; Higgins et al, 2021; Tateno et al, 2021), dMMN amplitudes at the FCz electrode site were impaired in both FEP and CHR patients; thus, these amplitudes were used for further analysis for prognosis prediction. From the baseline assessment, dMMN amplitude was smaller in FEP-TR patients than in FEP-nonTR patients and was predictive of later treatment resistance.…”

“…Because MMN generation is associated with neurotransmission at the N-methyl-D-aspartate (NMDA) receptor, MMN has been widely studied across the course of psychotic disorders to elucidate the pathophysiological mechanism of schizophrenia (Javitt & Freedman, 2015; Javitt, Steinschneider, Schroeder, & Arezzo, 1996; Uno & Coyle, 2019). Reduced duration deviant MMN (dMMN) amplitude has been consistently reported in schizophrenia and early psychosis patients, including FEP patients and CHR individuals, although the degree of dMMN impairment is less significant than in chronic schizophrenia patients (Erickson, Ruffle, & Gold, 2016; Haigh, Coffman, & Salisbury, 2017; Hamilton, Boos, & Mathalon, 2020; Kim, Cho, Yoon, Lee, & Kwon, 2017; Nagai et al, 2013; Tateno et al, 2021). Although little is known about dMMN as a prognostic predictor of FEP patients (Higgins, Lewandowski, Liukasemsarn, & Hall, 2021; Lho et al, 2020), previous studies, including our own, showed that dMMN was predictive of a transition to psychotic disorder, remission, and symptomatic and functional improvement in CHR individuals (Bodatsch et al, 2011; Fujioka et al, 2020; Kim et al, 2018; Perez et al, 2014).…”

Duration Mismatch Negativity Predicts Remission in First-Episode Schizophrenia Patients

“…While the present study found no change in fMMN over time, this could be partly explained by sampling issues as described below (i.e., small sample size and relatively long illness duration of FES cohort). While dMMN may be a more static biomarker of schizophrenia than fMMN, our earlier study in CHR cohort suggested that dMMN amplitude may also exhibit longitudinal decline during transition period into psychosis ( 29 ). The study by Lho et al also showed a decrease in dMMN of FES over time ( 23 ).…”

“…However, this finding needs replication in patients with fewer confounding factors (especially illness chronicity and medication) and longer clinical follow-up to clarify the potential utility of baseline MMNs as biomarkers to predict prognosis. Furthermore, it remains unknown whether an active decline in MMN amplitude demonstrated during the early course of schizophrenia ( 23 , 29 , 30 ) could be associated with a later clinical course.…”

N400 event‐related brain potential and functional outcome in persons at clinical high risk for psychosis: A longitudinal study

“…The neurophysiological technique of electroencephalographic event-related brain potentials (ERPs) may also be useful for predicting outcomes in CHR patients. The mismatch negativity (MMN) and P300 ERP waveforms, which reflect passive and attention-dependent processing of infrequent stimuli, respectively, and are reliably reduced in schizophrenia, 22 have shown promise in CHR patients for predicting conversion to psychosis, [23][24][25][26][27][28][29] symptomatic improvement, 19,30,31 and functional recovery. 19,32 Another ERP measure that may be useful in this regard, given that it has also been found to be abnormal in schizophrenia, is the N400 waveform reviewed in Mohammad and Delisi and Kiang and Gerritsen.…”