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

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 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 life span; 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.