Progressive Impairment of Mismatch Negativity Is Reflective of Underlying Pathophysiological Changes in Patients With First-Episode Psychosis

Abstract

Background: Although mismatch negativity (MMN) is associated with the pathophysiology of schizophrenia, whether MMN progressively worsens during the initial years of psychotic disorder has not yet been sufficiently studied. We aimed to investigate whether longitudinal reduction of MMN occurs in patients with first-episode psychosis (FEP) and whether it is reflective of change in cognitive functioning or clinical status. Methods: MMN and the clinical status of 25 patients with FEP were measured and the Trail Making Test (TMT) was administered at baseline and reassessed after 1 year of usual treatment. The MMN of 25 matched healthy controls (HCs) was measured at baseline. Repeated-measures analysis of variance was used to compare MMNs at baseline among the groups, and paired t-test was utilized to compare the baseline and 1-year MMN amplitudes of FEP patients. To identify the association between changes in MMN and changes in cognitive, symptomatic, or functional status over 1 year, multiple regression analysis was used to control for other possible confounders. Results: MMN amplitudes at baseline were significantly attenuated in FEP patients compared to those in HC. The 1-year follow-up MMN amplitude decreased significantly at the Fz electrode site in the FEP group. Additionally, the decreased MMN amplitude significantly correlated with worsened TMT part B (TMT-B) performance over 1 year but did not correlate with symptomatic or functional improvement. Conclusions: FEP patients with an MMN amplitude reduction showed worsening of cognitive functioning, which might reflect pathophysiological progression during the early years of a psychotic episode.

EEG-Based Measures in At-Risk Mental State and Early Stages of Schizophrenia: A Systematic Review

“…Most of the studies did not find significant differences between HCs, FEP ( 188 , 189 ), FES ( 193 , 194 , 198 , 201 , 206 ), and HR subjects ( 180 , 194 , 201 , 204 , 206 , 207 ) in dMMN latency, with the exception of one study that found delayed latency in dMMN peak in FEP subjects ( 196 ), as compared to HCs.…”

“…Discrepant findings have been reported with the regard to the dMMN amplitude. In particular, some studies found a reduction of dMMN amplitude in FEP (66,151,(188)(189)(190)(191) and FES subjects (65,95,181,182,190,(192)(193)(194)(195)(196) as compared to HCs, while other studies did not find any abnormality in dMMN amplitude in FEP and FES subjects (183,(197)(198)(199)(200). Furthermore, a study, involving ML to distinguish FES from HCs with dMMN measures in addition to other neuroimaging and clinical evaluations, highlighted that this EEG-index did not contribute significantly to the discriminant ML-model (158).…”

Duration Mismatch Negativity Predicts Remission in First-Episode Schizophrenia Patients

“…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 ). Thus, future longitudinal studies in a larger cohort at various stages of psychosis would be required to clarify the specific role of MMN in the disease pathophysiology ideally using a multimodal approach (e.g., neuroimaging and biochemical investigations).…”

“…However, previous studies have suggested the role of MMN as a "breakthrough biomarker" for schizophrenia (19); it has reduced amplitude with larger effect size than other psychiatric disorders such as bipolar disorder (20), remains stable over time, and is independent of staterelated changes (21). In particular, reduced amplitude of dMMN exists in various stages of psychosis, including CHR status before onset and both first-episode and chronic stages of schizophrenia (22)(23)(24), as a rather stable vulnerability marker and also reflects cognitive and social functions in various clinical conditions (25,26). It has been demonstrated that high baseline amplitude of dMMN in CHR individuals is associated with functional and symptomatic improvement regardless of psychosis onset (27,28), potentially implicating its role as a predictor of remission in patients with psychotic disorders.…”

“…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.…”