Skip to main content Accessibility help

Mismatch negativity: Alterations in adults from the general population who report subclinical psychotic symptoms

  • C Döring (a1) (a2), M Müller (a1) (a2), F Hagenmuller (a1) (a2), V Ajdacic-Gross (a1) (a2), H Haker (a1) (a3), W Kawohl (a1) (a2), W Rössler (a1) (a4) and K Heekeren (a1) (a2)...



Deficits of mismatch negativity (MMN) in schizophrenia and individuals at risk for psychosis have been replicated many times. Several studies have also demonstrated the occurrence of subclinical psychotic symptoms within the general population. However, none has yet investigated MMN in individuals from the general population who report subclinical psychotic symptoms.


The MMN to duration-, frequency-, and intensity deviants was recorded in 217 nonclinical individuals classified into a control group (n = 72) and three subclinical groups: paranoid (n = 44), psychotic (n = 51), and mixed paranoid-psychotic (n = 50). Amplitudes of MMN at frontocentral electrodes were referenced to average. Based on a three-source model of MMN generation, we conducted an MMN source analysis and compared the amplitudes of surface electrodes and sources among groups.


We found no significant differences in MMN amplitudes of surface electrodes. However, significant differences in MMN generation among the four groups were revealed at the frontal source for duration-deviant stimuli (P = 0.01). We also detected a trend-level difference (P = 0.05) in MMN activity among those groups for frequency deviants at the frontal source.


Individuals from the general population who report psychotic symptoms are a heterogeneous group. However, alterations exist in their frontal MMN activity. This increased activity might be an indicator of more sensitive perception regarding changes in the environment for individuals with subclinical psychotic symptoms.


Corresponding author

*Corresponding author. Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, PO Box 1930, 8021 Zurich, Switzerland. Tel.: +0041 44 296 7400. E-mail (K. Heekeren).


Hide All
[1]Linscott, RJvan Os, JAn updated and conservative systematic review and meta-analysis of epidemiological evidence on psychotic experiences in children and adults: on the pathway from proneness to persistence to dimensional expression across mental disorders. Psychol Med 2013;43(6):11331149.
[2]Rössler, WVetter, SMüller, MGallo, WTHaker, HKawohl, Wet al.Risk factors at the low end of the psychosis continuum: much the same as at the upper end?. Psychiatry Res 2011;189(1):7781.
[3]Rössler, WAjdacic-Gross, VHaker, HRodgers, SMüller, MHengartner, MPSubclinical psychosis syndromes in the general population: results from a large-scale epidemiological survey among residents of the canton of Zurich, Switzerland. Epidemiol Psychiatr Sci 2015;24(1):6977.
[4]Rössler, WRiecher-Rössler, AAngst, JMurray, RGamma, AEich, Det al.Psychotic experiences in the general population: a twenty-year prospective community study. Schizophr Res 2007;92(1–3):114.
[5]Rössler, WSalize, HJvan Os, JRiecher-Rössler, ASize of burden of schizophrenia and psychotic disorders. Eur Neuropsychopharmacol 2005;15(4):399409.
[6]Scott, JChant, DAndrews, GMcGrath, JPsychotic-like experiences in the general community: the correlates of CIDI psychosis screen items in an Australian sample. Psychol Med 2006;36: 231238.
[7]Fusar-Poli, PBonoldi, IYung, ARet al.Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry 2012;69(3):220229.
[8]Schmidt, SJSchultze-Lutter, FSchimmelmann, BGet al.EPA guidance on the early intervention in clinical high risk states of psychoses. Eur Psychiatry 2015;30(3):388404.
[9]Brett, CMPeters, ERMcGuire, PKWhich psychotic experiences are associated with a need for clinical care?. Eur Psychiatry 2015;30(5):648654.
[10]van Os, JHanssen, MBijl, RVRavelli, AStrauss (1969) revisited: a psychosis continuum in the general population?. Schizophr Res 2000;45(1–2):1120.
[11]Kaymaz, NDrukker, MLieb, RWittchen, HUWerbeloff, NWeiser, Met al.Do subthreshold psychotic experiences predict clinical outcomes in unselected non-help-seeking population-based samples? A systematic review and meta-analysis, enriched with new results. Psychol Med 2012;42(11):22392253.
[12]Bodatsch, MKlosterkötter, JDaumann, JContributions of experimental psychiatry to research on the psychosis prodrome. Front Psychiatry 4 2013 170
[13]Onitsuka, TOribe, NNakamura, IKanba, SReview of neurophysiological findings in patients with schizophrenia. Psychiatry Clin Neurosci 2013;67(7):461470.
[14]Todd, JWhitson, LSmith, EMichie, PTSchall, UWard, PBWhat’s intact and what’s not within the mismatch negativity system in schizophrenia. Psychophysiology 2014;51: 337347.
[15]Umbricht, DKrljes, SMismatch negativity in schizophrenia: a meta-analysis. Schizophr Res 2005;76(1):123.
[16]Bodatsch, MBrockhaus-Dumke, AKlosterkötter, JRuhrmann, SForecasting psychosis by event-related potentials-systematic review and specific meta-analysis. Biol Psychiatry 2015;77(11):951958.
[17]Näätänen, RTodd, JSchall, UMismatch negativity (MMN) as biomarker predicting psychosis in clinically at-risk individuals. Biol Psychol 2015. [Epub ahead of print]
[18]Näätänen, RGaillard, AWMäntysalo, SEarly selective-attention effect on evoked potential reinterpreted. Acta Psychol 1978;42(4):313329.
[19]Winkler, ICzigler, IEvidence from auditory and visual event-related potential (ERP) studies of deviance detection (MMN and vMMN) linking predictive coding theories and perceptual object representations. Int J Psychophysiol 2012;83(2):132143.
[20]Rentzsch, JShen, CJockers-Scherübl, MCGallinat, JNeuhaus, AHAuditory mismatch negativity and repetition suppression deficits in schizophrenia explained by irregular computation of prediction error. PLoS One 2015;10(5):e0126775
[21]Friston, KA theory of cortical responses. Philos Trans R Soc Lond B Biol Sci 2005;360(1456):815836.
[22]Lin, YTLiu, CMChiu, MJet al.Differentiation of schizophrenia patients from healthy subjects by mismatch negativity and neuropsychological tests. PLoS One 2012;7(4):e34454
[23]Umbricht, DKoller, RSchmid, LSkrabo, AGrübel, CHuber, Tet al.How specific are deficits in mismatch negativity generation to schizophrenia?. Biol Psychiatry 2003;53(12):11201131.
[24]Bodatsch, MRuhrmann, SWagner, Met al.Prediction of psychosis by mismatch negativity. Biol Psychiatry May 2011;69(10):959966.
[25]Todd, JMichie, PTSchall, UKarayanidis, FYabe, HNäätänen, RDeviant matters: duration, frequency, and intensity deviants reveal different patterns of mismatch negativity reduction in early and late schizophrenia. Biol Psychiatry 2008;63(1):5864.
[26]Duncan, CCBarry, RJConnolly, JFet al.Event-related potentials in clinical research: guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400. Clin Neurophysiol 2009;120(11):18831908.
[27]Hay, RARoach, BJSrihari, VHWoods, SWFord, JMMathalon, DHEquivalent mismatch negativity deficits across deviant types in early illness schizophrenia-spectrum patients. Biol Psychol 2015;105: 130137.
[28]Light, GABraff, DLMismatch negativity deficits are associated with poor functioning in schizophrenia patients. Arch Gen Psychiatry 2005;62(2):127136.
[29]Michie, PTInnes-Brown, HTodd, JJablensky, AVDuration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders. Biol Psychiatry 2002;52(7):749758.
[30]Jessen, FFries, TKucharski, CNishimura, THoenig, KMaier, Wet al.Amplitude reduction of the mismatch negativity in first-degree relatives of patients with schizophrenia. Neurosci Lett 2001;309(3):185188.
[31]Bramon, ECroft, RJMcDonald, Cet al.Mismatch negativity in schizophrenia: a family study. Schizophr Res 2004;67(1):110.
[32]Magno, EYeap, SThakore, JHGaravan, HDe Sanctis, PFoxe, JJAre auditory-evoked frequency and duration mismatch negativity deficits endophenotypic for schizophrenia?. High-density electrical mapping in clinically unaffected first-degree relatives and first-episode and chronic schizophrenia. Biol Psychiatry 2008;64(5):385391.
[33]Kim, MKim, SNLee, SByun, MSShin, KSPark, HYet al.Impaired mismatch negativity is associated with current functional status rather than genetic vulnerability to schizophrenia. Psychiatry Resr 2014;222(1–2):100106.
[34]Todd, JHarms, LSchall, UMichie, PTMismatch negativity: translating the potential. Front Psychiatry 4 2013 171
[35]Shelley, AMWard, PBCatts, SVMichie, PTAndrews, SMcConaghy, NMismatch negativity: an index of a preattentive processing deficit in schizophrenia. Biol Psychiatry 1991;30(10):10591062.
[36]Takei, YKumano, SMaki, YHattori, SKawakubo, YKasai, Ket al.Preattentive dysfunction in bipolar disorder: a MEG study using auditory mismatch negativity. Prog Neuropsychopharmacol Biol Psychiatry 2010;34(6):903912.
[37]Jahshan, CWynn, JKMathis, KIAltshuler, LLGlahn, DCGreen, MFCross-diagnostic comparison of duration mismatch negativity and P3a in bipolar disorder and schizophrenia. Bipolar Disord 2012;14(3):239248.
[38]Kaur, MLagopoulos, JWard, PBWatson, TLNaismith, SLHickie, IBet al.Mismatch negativity/P3a complex in young people with psychiatric disorders: a cluster analysis. PLoS One 2012;7(12):e51871
[39]Chang, YXu, JPang, XSun, YZheng, YLiu, YMismatch negativity indices of enhanced preattentive automatic processing in panic disorder as measured by a multi-feature paradigm. Biol Psychol 2015;105: 7782.
[40]Park, HJKwon, JSYoun, TPae, JSKim, JJKim, MSet al.Statistical parametric mapping of LORETA using high density EEG and individual MRI: application to mismatch negativities in schizophrenia. Hum Brain Mapp 2002;17(3):168178.
[41]Oknina, LBWild-Wall, NOades, RDet al.Frontal and temporal sources of mismatch negativity in healthy controls, patients at onset of schizophrenia in adolescence and others at 15 years after onset. Schizophr Res 2005;76(1):2541.
[42]Takahashi, HRissling, AJPascual-Marqui, RKirihara, KPela, MSprock, Jet al.Neural substrates of normal and impaired preattentive sensory discrimination in large cohorts of nonpsychiatric subjects and schizophrenia patients as indexed by MMN and P3a change detection responses. Neuroimage 2013;66: 594603.
[43]van Lutterveld, ROranje, BKemner, Cet al.Increased psychophysiological parameters of attention in non-psychotic individuals with auditory verbal hallucinations. Schizophr Res 2010;121(1–3):153159.
[44]Rössler, WAjdacic-Gross, VMüller, MRodgers, SHaker, HHengartner, MPAssessing sub-clinical psychosis phenotypes in the general population--a multidimensional approach. Schizophr Res 2015;161(2–3):194201.
[45]Ajdacic-Gross, VMüller, MRodgers, Set al.The ZInEP Epidemiology Survey: background, design and methods. Int J Methods Psychiatr Res 2014;23(4):451–68.
[46]Angst, JDobler-Mikola, ABinder, JThe Zurich study-a prospective epidemiological study of depressive, neurotic and psychosomatic syndromes. I. Problem, methodology. Eur Arch Psychiatry Neurol Sci 1984;234(1):1320.
[47]Angst, JGamma, ANeuenschwander, MAjdacic-Gross, VEich, DRössler, Wet al.Prevalence of mental disorders in the Zurich Cohort Study: a twenty year prospective study. Epidemiol Psychiatr Soc 2005;14(2):6876.
[48]Hardt, JEgle, UTKappis, BHessel, ABrähler, ESymptom Checklist SCL-27. Psychother Psychosom Med Psychol 2004;54(5):214223.
[49]Derogatis, LSymptom Checklist 90, R-Version Manual I: Scoring, Administration, and Procedures for the SCL-90 Baltimore, MD: Johns Hopkins Press; 1977.
[50]Oldfield, RCThe assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971;9(1):97113.
[51]Fazio, RCoenen, CDenney, RLThe original instructions for the Edinburgh Handedness Inventory are misunderstood by a majority of participants. Laterality 2012;17(1):7077.
[52]Veale, JFEdinburgh Handedness Inventory - Short Form: a revised version based on confirmatory factor analysis. Laterality 2014;19(2):164177.
[53]Breetvelt, EJBoks, MPNumans, MESelten, JPSommer, IEGrobbee, DEet al.Schizophrenia risk factors constitute general risk factors for psychiatric symptoms in the population. Schizophr Res 2010;120(1–3):184190.
[54]Hoechstetter, KBerg, PScherg, MBESA Research Tutorial 3: batch scripts, multiple subjects & conditions BESA Research Tutorials: MATLAB-Interface; 2010. 148.
[55]Berg, PScherg, MDipole models of eye movements and blinks. Electroencephalogr Clin Neurophysiol 1991;79(1):3644.
[56]Giard, MHPerrin, FPernier, JBouchet, PBrain generators implicated in the processing of auditory stimulus deviance: a topographic event-related potential study. Psychophysiology 1990;27(6):627640.
[57]Näätänen, RThe mismatch negativity: a powerful tool for cognitive neuroscience. Ear Hear 1995;16(1):618.
[58]Michie, PTBudd, TWTodd, JRock, DWichmann, HBox, Jet al.Duration and frequency mismatch negativity in schizophrenia. Clin Neurophysiol 2000;111(6):10541065.
[59]Baldeweg, TKlugmann, AGruzelier, JHHirsch, SRImpairment in frontal but not temporal components of mismatch negativity in schizophrenia. Int J Psychophysiol 2002;43(2):111122.
[60]Sato, YYabe, HTodd, Jet al.Impairment in activation of a frontal attention-switch mechanism in schizophrenic patients. Biol Psychol 2003;62(1):4963.
[61]O’Donnell, BFHokama, HMcCarley, RWSmith, RSSalisbury, DFMondrow, Eet al.Auditory ERPs to non-target stimuli in schizophrenia: relationship to probability, task-demands, and target ERPs. Int J Psychophysiol 1994;17(3):219231.
[62]Kathmann, NWagner, MRendtorff, NEngel, RRDelayed peak latency of the mismatch negativity in schizophrenics and alcoholics. Biol Psychiatry 1995;37(10):754757.
[63]Kirino, EInoue, RThe relationship of mismatch negativity to quantitative EEG and morphological findings in schizophrenia. J Psychiatr Res 1999;33(5):445456.
[64]Damaso, KAMichie, PTTodd, JPaying attention to MMN in schizophrenia. Brain Res 2015;1626: 267279.
[65]Näätänen, RPaavilainen, PRinne, TAlho, KThe mismatch negativity (MMN) in basic research of central auditory processing: a review. Clin Neurophysiol 2007;118(12):25442590.
[66]Paavilainen, PMikkonen, MKilpeläinen, MLehtinen, RSaarela, MTapola, LEvidence for the different additivity of the temporal and frontal generators of mismatch negativity: a human auditory event-related potential study. Neurosci Lett 2003;349(2):7982.
[67]Atkinson, RJMichie, PTSchall, UDuration mismatch negativity and P3a in first-episode psychosis and individuals at ultra-high risk of psychosis. Biol Psychiatry 2012;71(2):98104.
[68]Nagai, TTada, MKirihara, KYahata, NHashimoto, RAraki, Tet al.Auditory mismatch negativity and P3a in response to duration and frequency changes in the early stages of psychosis. Schizophr Res 2013;150(2–3):547554.
[69]Perez, VBWoods, SWRoach, BJFord, JMMcGlashan, THSrihari, VHet al.Automatic auditory processing deficits in schizophrenia and clinical high-risk patients: forecasting psychosis risk with mismatch negativity. Biol Psychiatry 2014;75(6):459469.
[70]Brockhaus-Dumke, ATendolkar, IPukrop, RSchultze-Lutter, FKlosterkötter, JRuhrmann, SImpaired mismatch negativity generation in prodromal subjects and patients with schizophrenia. Schizophr Res 2005;73(2–3):297310.


Type Description Title
Supplementary materials

Döring et al. supplementary material
Table S1

 Word (21 KB)
21 KB

Mismatch negativity: Alterations in adults from the general population who report subclinical psychotic symptoms

  • C Döring (a1) (a2), M Müller (a1) (a2), F Hagenmuller (a1) (a2), V Ajdacic-Gross (a1) (a2), H Haker (a1) (a3), W Kawohl (a1) (a2), W Rössler (a1) (a4) and K Heekeren (a1) (a2)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.

Mismatch negativity: Alterations in adults from the general population who report subclinical psychotic symptoms

  • C Döring (a1) (a2), M Müller (a1) (a2), F Hagenmuller (a1) (a2), V Ajdacic-Gross (a1) (a2), H Haker (a1) (a3), W Kawohl (a1) (a2), W Rössler (a1) (a4) and K Heekeren (a1) (a2)...
Submit a response


No Comments have been published for this article.


Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *