Mismatch negativity in schizophrenia: a meta-analysis

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Abstract

Background

Mismatch negativity (MMN) is an auditory event-related potential that provides an index of automatic context-dependent information processing and auditory sensory memory. Many studies have reported abnormalities in the generation of MMN in schizophrenia. The objective of this study was to assess the magnitude of this deficit and associated factors.

Method

Studies of MMN in schizophrenia were identified and included in a meta-analysis to estimate the mean effect size. Effects of duration of illness, gender ratio, age of patients, type of MMN (duration versus frequency MMN) and characteristics of the test paradigms (deviant probability, magnitude of standard-deviant difference) on effect size were assessed.

Results

Of 62 identified studies 32 met our inclusion criteria. The mean effect size was 0.99 (95% confidence intervals: 0.79, 1.29). Overall, no specific factor was significantly associated with MMN deficits, although MMN to stimuli differing in duration appeared more impaired in schizophrenia than MMN to frequency deviants. In addition, effect sizes of frequency MMN were significantly correlated with duration of illness.

Conclusions

MMN deficits are a robust feature in chronic schizophrenia and indicate abnormalities in automatic context-dependent auditory information processing and auditory sensory memory in these patients. Reports of normal MMN in first-episode schizophrenia and the association of deficits in frequency MMN with illness duration suggest that MMN may index ongoing neuropathological changes in the auditory cortex in schizophrenia.

Section snippets

Literature search

A literature search was conducted in MEDLINE (years 1990–2003) using the following key words: schizophrenia, mismatch negativity, MMN. Also, the reference lists of published papers were searched in order to manually locate other relevant studies. The initial search identified 62 articles.

Inclusion and exclusion criteria

For inclusion in the meta-analysis a study had to meet following criteria: (1) MMN data were reported either as mean and standard deviation, or alternatively, as t-value of a t-test or as F-value representing

Study characteristics

Our initial search identified 62 publications. Thirty-two fulfilled the aforementioned criteria (Alain et al., 1998, Bramon et al., 2004, Baldeweg et al., 2002, Catts et al., 1995, Davalos et al., 2003, Grzella et al., 2001, Hirayasu et al., 1998, Javitt et al., 1993, Javitt et al., 1995, Javitt et al., 1998, Javitt et al., 2000a, Javitt et al., 2000b, Jessen et al., 2001, Kasai et al., 1999, Kasai et al., 2002a, Kathmann et al., 1995, Kirino and Inoue, 1999b, Lembreghts and Timsit-Berthier,

Discussion

The results of our meta-analysis indicate that MMN deficits are robust in patients with chronic schizophrenia. The estimate of the overall effect size was 0.99, which is considered large by accepted standards. Even after applying the so-called “trim and fill” method to correct for potentially unpublished data the ES remained robust. Given the evidence that MMN deficits have not been observed in other major psychiatric disorders such as major depression and bipolar disorder (Catts et al., 1995,

Acknowledgment

We would like to thank Sue Duvall and Stephan Leucht for their help with the statistical analyses.

References (118)

  • D.C. Javitt et al.

    Impairment of early cortical processing in schizophrenia: an event-related potential confirmation study

    Biol. Psychiatry

    (1993)
  • D.C. Javitt et al.

    Impaired mismatch negativity (MMN) generation in schizophrenia as a function of stimulus deviance, probability, and interstimulus/interdeviant interval

    Electroencephalogr. Clin. Neurophysiol.

    (1998)
  • D.C. Javitt et al.

    Associated deficits in mismatch negativity generation and tone matching in schizophrenia

    Clin. Neurophysiol.

    (2000)
  • F. Jessen et al.

    Amplitude reduction of the mismatch negativity in first-degree relatives of patients with schizophrenia

    Neurosci. Lett.

    (2001)
  • S. Kahkonen et al.

    Dopamine modulates involuntary attention shifting and reorienting: an electromagnetic study

    Clin. Neurophysiol.

    (2002)
  • K. Kasai et al.

    Mismatch negativity and N2b attenuation as an indicator for dysfunction of the preattentive and controlled processing for deviance detection in schizophrenia: a topographic event-related potential study

    Schizophr. Res.

    (1999)
  • K. Kasai et al.

    Do high or low doses of anxiolytics and hypnotics affect mismatch negativity in schizophrenic subjects? An EEG and MEG study

    Clin. Neurophysiol.

    (2002)
  • K. Kasai et al.

    Neuromagnetic correlates of impaired automatic categorical perception of speech sounds in schizophrenia

    Schizophr. Res.

    (2003)
  • N. Kathmann et al.

    Delayed peak latency of the mismatch negativity in schizophrenics and alcoholics

    Biol. Psychiatry

    (1995)
  • R.S.E. Keefe et al.

    Performance of patients with schizophrenia on a pen and paper visuospatial working memory task with short delay

    Schizophr. Res.

    (1997)
  • E. Kirino et al.

    The relationship of mismatch negativity to quantitative EEG and morphological findings in schizophrenia

    J. Psychiatr. Res.

    (1999)
  • I. Kreitschmann-Andermahr et al.

    Impaired sensory processing in male patients with schizophrenia: a magnetoencephalographic study of auditory mismatch detection

    Schizophr. Res.

    (1999)
  • I. Kreitschmann-Andermahr et al.

    Effect of ketamine on the neuromagnetic mismatch field in healthy humans

    Brain Res. Cogn. Brain Res.

    (2001)
  • E. Mervaala et al.

    Electrophysiological and neuropsychological effects of a central alpha 2-antagonist atipamezole in healthy volunteers

    Behav. Brain Res.

    (1993)
  • P.T. Michie

    What has MMN revealed about the auditory system in schizophrenia?

    Int. J. Psychophysiol.

    (2001)
  • P.T. Michie et al.

    Duration and frequency mismatch negativity in schizophrenia

    Clin. Neurophysiol.

    (2000)
  • P.T. Michie et al.

    Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders

    Biol. Psychiatry

    (2002)
  • T. Murakami et al.

    The effects of benzodiazepines on event-related potential indices of automatic and controlled processing in schizophrenia: a preliminary report

    Prog. Neuro-psychopharmacol. Biol. Psychiatry

    (2002)
  • R. Näätänen et al.

    “Primitive intelligence” in the auditory cortex

    Trends Neurosci.

    (2001)
  • R. Näätänen et al.

    The mismatch negativity (MMN): towards the optimal paradigm

    Clin. Neurophysiol.

    (2004)
  • R.D. Oades et al.

    Auditory event-related potential (ERP) and difference-wave topography in schizophrenic patients with/without active hallucinations and delusions: a comparison with young obsessive-compulsive disorder (OCD) and healthy subjects

    Int. J. Psychophysiol.

    (1996)
  • R.D. Oades et al.

    Impaired attention-dependent augmentation of MMN in nonparanoid vs. paranoid schizophrenic patients: a comparison with obsessive-compulsive disorder and healthy subjects

    Biol. Psychiatry

    (1997)
  • B. O'Donnell et al.

    Auditory ERPs to non-target stimuli in schizophrenia: relationship to probability, task-demands, and target ERPs

    Int. J. Psychophysiol.

    (1994)
  • B. Oranje et al.

    The effects of a sub-anaesthetic dose of ketamine on human selective attention

    Neuropsychopharmacology

    (2000)
  • E. Pekkonen et al.

    Auditory sensory memory and the cholinergic system: implications for Alzheimer's disease

    NeuroImage

    (2001)
  • D.F. Salisbury et al.

    Mismatch negativity amplitudes and Heschl's gyrus volume in first-episode schizophrenia

    Schizophr. Res.

    (2003)
  • Y. Sato et al.

    Impairment in activation of a frontal attention-switch mechanism in schizophrenic patients

    Biol. Psychol.

    (2003)
  • H. Schreiber et al.

    Event-related potential correlates of impaired selective attention in children at high risk for schizophrenia

    Biol. Psychiatry

    (1992)
  • E. Schröger et al.

    Preattentive periodicity detection in auditory patterns as governed by time and intensity information

    Brain Res. Cogn. Brain Res.

    (1996)
  • A.M. Shelley et al.

    Mismatch negativity: an index of a preattentive processing deficit in schizophrenia

    Biol. Psychiatry

    (1991)
  • A.M. Shelley et al.

    Diminished responsiveness of ERPs in schizophrenic subjects to changes in auditory stimulation parameters: implication for the theories of cortical dysfunction

    Schizophr. Res.

    (1999)
  • N. Shinozaki et al.

    The difference in mismatch negativity between the acute and post-acute phase of schizophrenia

    Biol. Psychol.

    (2002)
  • E. Sussman et al.

    Dynamic sensory updating in the auditory system

    Brain Res. Cogn. Brain Res.

    (2001)
  • E. Sussman et al.

    Attention affects the organization of auditory input associated with the mismatch negativity system

    Brain Res.

    (1998)
  • C. Alain et al.

    Separate memory-related processing for auditory frequency and patterns

    Psychophysiology

    (1999)
  • C. Alain et al.

    Deficits in automatically detecting changes in conjunction of auditory features in patients with schizophrenia

    Psychophysiology

    (2002)
  • K. Alho

    Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes

    Ear Hear.

    (1995)
  • D.L. Braff et al.

    Sensorimotor gating and schizophrenia

    Arch. Gen. Psychiatry

    (1990)
  • S.V. Catts et al.

    Brain potential evidence for an auditory sensory memory deficit in schizophrenia

    Am. J. Psychiatry

    (1995)
  • J. Cohen

    (1988) Statistical power analysis for the behavioral sciences

    (1988)
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