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Updated: Jun 6, 2025

Standardized Data Acquisition for Neuromelanin-Sensitive Magnetic Resonance Imaging of the Substantia Nigra
Published on: September 8, 2021
Different abnormalities of mismatch negativity in schizophrenia and depression as assessed with
Ileana Andriola1, Christian Valt2, Verdiana Marsella2
1Department of Translational Biomedicine and Neuroscience - University of Bari Aldo Moro, Bari, Italy; University Hospital Polyclinic of Bari: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy.
Abstract:
Mismatch negativity (MMN) is widely considered a candidate diagnostic biomarker for schizophrenia (SCZ). Although blunted MMN responses have been reliably observed in psychosis, the evidence for MMN deficits in other disorders, such as major depressive disorder (MDD), is mixed. This study explores whether MMN alterations in amplitude or latency are unique to SCZ or extend to non-psychotic MDD patients. Seventeen patients diagnosed with a first MDD episode, 18 with recurrent MDD, 17 with first episode of SCZ spectrum disorder, and 18 with chronic SCZ, along with two groups of age- and sex-matched neurotypical controls (NC, 17 and 18), participated in a passive auditory MMN task during magnetoencephalography (MEG) recording. We examined the magnetic MMN (mMMN) amplitude and latency, exploring potential links between observed MMN alterations and psychotropic medication treatments. The mMMN amplitudes were significantly attenuated in SCZ compared to NC. Although, on average, mMMN amplitudes also appeared to be small in MDD, there was no significant difference between MDD and SCZ or NC. Notably, MDD patients had longer mMMN latencies compared to SCZ and NC, especially those with recurrent MDD. These results remained consistent after controlling for mood stabilizers, antidepressants, or benzodiazepines. These findings show that mMMN amplitude reductions may be more pronounced in psychotic disorders than in depressive disorders, whereas abnormal mMMN latencies may be more specific to MDD, suggesting differential mMMN alterations in SCZ and MDD. Caution is advised regarding mMMN amplitude as a diagnostic biomarker for SCZ, as small reductions also occur in MDD.
Insights
Mismatch negativity (MMN) amplitude reductions are more pronounced in schizophrenia (SCZ) than major depressive disorder (MDD). However, longer MMN latencies may specifically indicate MDD, suggesting distinct neurophysiological markers for these conditions.
Area of Science:
- Neuroscience
- Psychiatry
- Biomarker Research
Background:
- Mismatch negativity (MMN) is a potential biomarker for schizophrenia (SCZ).
- Evidence for MMN deficits in major depressive disorder (MDD) is inconsistent.
- This study differentiates MMN alterations in SCZ versus non-psychotic MDD.
Purpose of the Study:
- To investigate if MMN amplitude or latency changes are unique to SCZ or also present in MDD.
- To explore the diagnostic specificity of MMN as a biomarker for SCZ.
- To examine the relationship between MMN alterations and psychotropic medication.
Main Methods:
- Magnetoencephalography (MEG) was used to record magnetic MMN (mMMN) in patients with first-episode MDD, recurrent MDD, first-episode SCZ spectrum disorder, chronic SCZ, and neurotypical controls (NC).
- Passive auditory MMN task was administered.
- mMMN amplitude and latency were analyzed, controlling for psychotropic medications.
Main Results:
- Significantly attenuated mMMN amplitudes were observed in SCZ compared to NC.
- While mMMN amplitudes were smaller in MDD, no significant difference was found compared to SCZ or NC.
- MDD patients exhibited longer mMMN latencies than SCZ and NC, particularly those with recurrent MDD.
- Results remained consistent after controlling for psychotropic medications.
Conclusions:
- mMMN amplitude reductions appear more characteristic of psychotic disorders like SCZ than depressive disorders like MDD.
- Abnormal mMMN latencies may be a more specific indicator for MDD.
- mMMN amplitude is not a definitive diagnostic biomarker for SCZ due to potential overlap with MDD.
- Differential alterations in mMMN suggest distinct neurophysiological underpinnings for SCZ and MDD.

