A Meta-Analysis of Mismatch Negativity in Schizophrenia: From Clinical Risk to Disease Specificity and Progression

Abstract

Background The observation that mismatch negativity (MMN) is consistently impaired in schizophrenia has generated considerable interest in the use of this biomarker as an index of disease risk and progression. Despite such enthusiasm, a number of issues remain unresolved regarding the nature of MMN impairment. The present study expands upon an earlier meta-analysis of MMN impairment in schizophrenia by examining impairment across a range of clinical presentations, as well as across experimental parameters. Methods One hundred and one samples of schizophrenia patients were included in the present study, including first-episode (N=13), chronic (N=13), and mixed-stage (N=75) samples. Additionally, MMN was examined in three related conditions: bipolar disorder (N=9), unaffected first-degree relatives (N=8), and clinical high risk (N=16). Results We found that MMN impairment (1) likely reflects a vulnerability to disease progression in clinical high risk populations rather than a genetic risk for the condition; (2) is largely unrelated to duration of illness after the first few years of illness, indicating that impairment is not progressive throughout the lifespan; (3) is present in bipolar disorder, albeit to a lesser degree than in schizophrenia; and (4) is not modulated by experimental parameters such as magnitude of change between standard and deviant tones or frequency of deviant tones, but may be modulated by attentional demands. Conclusions Such findings lay the foundation for a better understanding of the nature of MMN impairment in schizophrenia, as well as its potential as a clinically useful biomarker.

Dissociable auditory mismatch response and connectivity patterns in adolescents with schizophrenia and adolescents with bipolar disorder with psychosis: A magnetoencephalography study

“…Indeed, there may be a greater impairment of MMN with time (Erickson et al, 2016;Kaur et al, 2013), and young patients with the most impaired MMN amplitudes at baseline are reported to show the most severe levels of disability at follow-up (Kaur et al, 2013). Hence, detection of differential abnormalities in these ERPs in the earliest stages of the disease process will be important to our understanding of the development of psychosis.…”

114. Electrophysiological, Cognitive and Clinical Profiles of At-Risk Mental State: The Longitudinal Minds in Transition (MinT) Study

“…MMN reduction is a robust finding in schizophrenia [13,17]; while MMN reduction has been postulated to be a general index of cognitive decline across multiple disorders [18], it has moderate specificity for schizophrenia [10,19] relative to disorders such as bipolar affective disorder, in which MMN is also reduced but with a smaller effect size [14]; the MMN process is largely "automatic" in nature; it does not require active attention and can be easily recorded in individuals while reading a book or watching a movie [20]. Moreover, the MMN abnormality can be linked to the underlying neurochemical (e.g.…”

“…Although MMN can be elicited by almost any perceptible change in auditory stimulus features, MMN reduction in schizophrenia has a larger effect size for duration, rather than frequency or intensity, deviant stimuli [14]. It has been suggested that MMN in response to duration deviants may be a more reliable bio-marker for psychosis during the early phase of the illness, whereas gradually increasing deficits in MMN to frequency deviants index progression of the illness during the chronic phase [29][30][31].…”

“…The incorporation of objective, quantifiable, physiological measures might improve their predictive power [8,9]. Currently, one of the most reliable markers of schizophrenia is the reduction of an electrophysiological signal recorded from the brain referred to as mismatch negativity (MMN) [10][11][12][13][14]. MMN is an early negative component of the event-related potential (ERP), which is elicited by any discriminable change in a repetitive background of auditory stimulation.…”

The Relationship between Mismatch Negativity and the <b><i>COMT</i></b>Val108/158Met Genotype in Schizophrenia

“…MMN offers an index of cognitive dysfunction in various disorders [6], but it remains one of the most robust and replicable findings in patients with schizophrenia, reflecting both cognitive and functional decline. MMN shows qualities of endophenotypes in schizophrenia and is thus likely useful as a biological biomarker [7]. …”