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 Table of Contents  
Year : 2015  |  Volume : 36  |  Issue : 2  |  Page : 112-117

Auditory mismatch negativity, P300, and disability among first-episode schizophrenia patients without auditory hallucinations

1 Department of Psychiatry, ENT, Zagazig University, Zagazig, Egypt
2 Department of Audiology Unit, ENT, Zagazig University, Zagazig, Egypt

Date of Submission04-Jan-2015
Date of Acceptance03-Apr-2015
Date of Web Publication4-Jun-2015

Correspondence Address:
Nagy Fawzy
Department of Psychiatry, Zagazig University, Zagazig, Sharkia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1110-1105.158120

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The aim of this study was to determine the functional deficits, including the inter-related domains of attention, memory, and information processing, among first-episode schizophrenia patients without auditory hallucinations. Such deficits could be evaluated objectively utilizing measurements of auditory-evoked potentials.
Patients and methods
The study sample consisted of two groups: group I included 58 first-episode schizophrenia patients without auditory hallucinations recruited from the psychiatric outpatient's clinics of Zagazig University Hospitals and group II included 53 participants selected randomly from Zagazig University Hospitals' visitors. Patients were subjected to a semistructured psychiatric interview using DSM-IV criteria for diagnosis, and auditory mismatch negativity (MMN) and P300 were assessed in schizophrenia patients before and after treatment. The degree of disability was assessed and its correlation with auditory processing function was determined.
Our study showed no statistically significant difference as regards MMN measures with any observable effect of atypical antipsychotics; the P300 component showed delayed latency and smaller amplitude before treatment and markedly enhanced after treatment, and there was statistically significant correlation between the degree of disability and MMN, as well as P300 measures, before and after treatment.
The current study concluded that the attention-dependent processes reflected in P300 measures are already defective during the early stage of schizophrenia and could be improved with the use of an atypical antipsychotic medication.

Keywords: auditory mismatch negativity, disability, P300, schizophrenia

How to cite this article:
Fawzy N, Gado O, Abdalla AM, Ibrahim WM. Auditory mismatch negativity, P300, and disability among first-episode schizophrenia patients without auditory hallucinations. Egypt J Psychiatr 2015;36:112-7

How to cite this URL:
Fawzy N, Gado O, Abdalla AM, Ibrahim WM. Auditory mismatch negativity, P300, and disability among first-episode schizophrenia patients without auditory hallucinations. Egypt J Psychiatr [serial online] 2015 [cited 2023 Dec 11];36:112-7. Available from: https://new.ejpsy.eg.net//text.asp?2015/36/2/112/158120

  Introduction Top

Schizophrenia is a complex illness that is characterized by significant impairment of social, psychological, and cognitive functioning (Adler et al., 2004). Poor executive functions, together with defective attention and echoic memory, are the main cognitive deficits encountered in schizophrenic patients (Ehrenreich et al., 2007; Ranganath et al., 2008). These deficits are mostly subtle and are often detected with specific neurophysiological tests. Among these tests are the measurements of auditory mismatch negativity (MMN) and P300. Schizophrenic patients mostly have a deficit in auditory sensory processing as reflected by the reduction in MMN and P300 amplitudes (Kircher et al., 2004; Arnfred, 2006; Salisbury et al., 1998). Many authors have reported that these deficits appear to be unmodulated with the utilization of the typical antipsychotic medication (Light et al., 2000). Nowadays, with the introduction of atypical antipsychotics into the mainstream treatment of schizophrenia, it is important to fully explore its neurobiological and clinical effects in such patients. This work was designed to assess the inter-related domains of auditory sensory processing, memory, and attention in schizophrenic patients before and following the use of an atypical antipsychotic medication. The auditory MMN can occur in response to deviance in pitch, intensity, or duration. The auditory MMN is a frontocentral negative potential with sources in the primary and nonprimary auditory cortex and a typical latency of 150-250 ms after the onset of the deviant stimulus. Sources could also include one from the right opercular part of the inferior frontal gyrus. The amplitude and latency of the MMN is related to how different the deviant stimulus is from the standard. Large deviances elicit MMN at earlier latencies. For very large deviances, the MMN can even overlap the N100 (Campbell et al., 2007). Auditory event-related potentials are averaged neural responses that are time locked to some specified auditory event (Stapells, 2004). Such an event could be a physical stimulus, a change in a train of stimuli, a missing stimulus, or a stimulus that has been designated to be a target one. These potentials could be divided into two major categories: Sensory-evoked potentials and processing-contingent potentials (PCPs) (Steinschneider et al., 1992). Sensory-evoked potentials represent the obligatory sensory processing stage, which depend upon the presence of auditory stimuli, and are sensitive to changes in the physical characteristics of the stimuli (Martin et al.,2006). In contrast, PCPs are associated with further processing of the sensory stimuli beyond the obligatory stage (Martin et al., 2006). These potentials are associated with active, attention-dependent, perceptual, or cognitive processes and with automatic processing that is not under volitional control (Stapells, 2004). MMN and P300 are the two main components of PCPs. Both refer to the ability to compare a deviant stimulus from a previously stored set of identical stimuli. Odatsch et al. (2011) found that MMN durations were reduced in a group of schizophrenia patients who later went on to have psychotic episodes, suggesting that MMN durations may predict future psychosis. MMN is an automatic preattentive response that is thought to reflect the short-term memory and is independent of higher-level cognitive processes (Kircher et al., 2004). However, P3b component of the P300 response cannot be elicited without selective activation of the attention-triggering mechanisms; thus, it reflects the conscious perception of the stimulus change (Stapells, 2004).

  Patients and methods Top

This study was carried out in the psychiatry outpatient clinics of Zagazig University Hospitals between April 2013 and June 2014. The study sample consisted of 58 patients with the diagnosis of first-episode schizophrenia, who were recruited from the psychiatric outpatient clinic of Zagazig University Hospitals, and 53 healthy volunteers as a control group recruited from Zagazig University Hospitals' visitors. Inclusion criteria were as follows: patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. criteria for schizophrenia in the patient group, age between 16 and 40 years, both sexes, and individuals from all educational and socioeconomic classes. The exclusion criteria were as follows: patients with other psychiatric or physical disorders, auditory hallucinations, mental retardation, substance dependence, history of documented learning disability, metabolic disorders, patients previously treated with antipsychotic medication, and those with hearing loss. All participants provided written informed consent before the start of the study. Approval was obtained from the Institutional Review Board (IRB) and the Department of Psychiatry, Zagazig University.

Detection of schizophrenia and other psychotic disorders was based on the semistructured psychiatric interview with resultant DSM-IV-TR diagnosis (American Psychiatric Association, 2000) Disability was measured with the help of the WHO Disability Assessment Schedule, version 2.0 (WHO/DAS II). It is a 36-item semistructured interview that measures the self-reported difficulty of functioning in six major domains, which are considered to be important in most cultures.


A two-channel audiometer Orbiter model 922 connected to a sound-treated booth.

A middle ear analyzer Interacoustic model AT 235h.

Auditory evoked potential system, Intelligent hearing systems model Smart EP, version 2.39.

Measurements of auditory evoked potentials: For every patient, both MMN and P300 were measured twice, at two different sessions, just before and 3 months after treatment. The following procedure was used:

  1. Stimulus parameters: The stimuli were presented binaurally within an odd-ball paradigm, with the frequent stimulus (the phoneme ba for MMN and 1 KHz tone burst for P300) occurring in 80% and the rare stimulus (the phoneme da and 1.5 KHz tone burst) occurring in 20% of the total number of presentations. The stimuli were presented at a rate of 1/s with an intensity of 75 dB nHL.
  2. Recording parameters: A two-channel recording was used with the common electrode on FPz, the two active electrodes on Cz and Pz, and the two reference electrodes on M1 and M2.
  3. Technique: Only for P300 measurement, the patients were instructed to be mentally attentive and to count the number of the rare stimuli. A total of 100 sweeps were presented with averaging of the rare and frequent sweeps on separate traces.
  4. Data analysis: On comparing the frequent and rare waveforms, MMN and P300 responses were identified, with subsequent measurement of their latencies and amplitudes.
Statistical plane

c2 -Test analysis was utilized to compare the sociodemographic characteristics of the study group with that of the control group. Thereafter, the analysis of variance (ANOVA) test was used to detect the differences between the two groups before and after treatment as regards the latency and amplitude of MMN and P300. On the basis of the ANOVA test results, post-hoc comparisons were conducted to determine which groups differ from each other. For such propose, Tukey's studentized range test was used. Such a test yields a value that is called the honestly significant difference (HSD) value.

Statistical analyses

The statistical differences between the mean of the tested groups were compared with the HSD value. If the HSD value was above the statistical differences, the differences were considered to be statistically significant. Significance levels were set at P value of 0.05 or less.

where q is a table value that corresponds to the group number and the degree of freedom at P value of 0.05 or less; n is number of tested values; MS is mean square that is obtained from the already computed ANOVA.

Finally, Pearson's correlation test (R-value) was used to correlate the degree of disability with the measures of both MMN and P300 before and after treatment.

  Results Top

The present study reported the sociodemographics and characteristics of the study group and the control group [Table 1]. For every patient, MMN and P300 components were measured twice, just before and 3 months after the use of medication. The results were compared with that of the control group. As regards the speech elicited MMN, no statistically significant difference was observed between the three measurements without any observed effect of medication [Table 2]. In contrast, the mean latencies and amplitudes of the tonal P300 component are presented in [Table 3]. Patients showed delayed latencies and smaller amplitudes before medication compared with those of the control group. Such difference is proved to be statistically significant [Table 3]. Following treatment, patients still had delayed latencies and smaller amplitudes; however, a statistically significant improvement was observed on comparing the measures before and after treatment [Table 3]. Such improvement with treatment was also noticed for the degree of disability as measured with WHO/DAS II [Table 4]. Furthermore, the amplitude of the P300 component showed a significant negative correlation with the degree of disability, denoting smaller amplitudes with higher degrees of disability. Such finding was observed with and without treatment [Table 5].
Table 1 Sociodemographic characteristics of the study group and the control group

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Table 2 Comparison between mismatch negativity measures in the control group and the study group before and after treatment

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Table 3 Comparison between P300 measures in the control group and the study group before and after treatment

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Table 4 Degree of disability among schizophrenic patients based on the WHO/DAS II score before and after treatment

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Table 5 Correlation between the degree of disability and mismatch negativity, as well as P300 measures, before and after treatment

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  Discussion Top

Cognitive impairment is a common feature in schizophrenic patients, which is thought to reflect the neurophysiological and neurochemical changes in the auditory cortex. The functional state of the neural substrate of auditory information processing for those patients could be objectively probed with measurement of auditory cortical event-related potentials (Korostenskaja and Kahkonen, 2007). For such purpose, an odd-ball paradigm is used to elicit MMN and P300 responses to phoneme and tonal deviants, respectively. Such stimuli could reflect the preattentive and attention-dependent information processing at various levels of difficulty. Patients having effects of previous antipsychotic medications as well as patients with negative symptoms were excluded in order to allow maximum psychological stability during testing. Moreover, patients with predominantly negative symptoms mostly have a more pronounced cognitive impairment (Mubarak et al., 1999). Measurements were carried out just before and 3 months after utilization of risperidone treatment, which is thought to modulate the neurochemical changes in those patients. For speech-elicited MMN, no statistically significant difference could be detected between patients and healthy controls [Table 2]. Utilizing different types of physically deviant tones, Salisbury et al. (2002) and Magnoac et al. (2008) reported similar results. They concluded that the reduction in MMN is usually present in patients with chronic schizophrenia but not with first onset cases. Furthermore, Umbricht and Krljes (2005), on summarizing the results on MMN changes from about 40 published studies, concluded a strong association between a deficient MMN generation and chronic schizophrenia. Recently, Fisher et al. (2008) and Todd et al. (2008) showed specific MMN changes only with the use of duration and intensity deviants. In the current study, phoneme deviants were utilized aiming to detect a different observation among first episode cases. The rationale came from reviewing the study of Korostenskaja et al. (2003), who concluded that the sensitivity of MMN in schizophrenic patients could be improved with other measurement parameters such as the slope of the ascending MMN wave or the MMN area. However, it seems that MMN deficits in schizophrenic patients are progressive and mostly not manifested at the illness onset. In contrast with MMN results, a statistically significant difference was detected in P300 response between schizophrenic patients and healthy controls [Table 3]. P300 studies with unmedicated schizophrenic patients are quite rare (Korostenskaja and Kahkonen, 2007). Jeon and Polich (2003) and Salisbury et al. (1998) observed deficient P300 latency and amplitude, respectively, at initial hospitalization of those patients. Such observation could indicate that the attention-dependent processes reflected in P300 component are already slowed down during the early stages of schizophrenia. This speculation is supported by Mathalonab et al. (2000), who concluded that reduced P300 amplitude may be used as a marker of an early onset variant of schizophrenia. Such amplitude reduction is also associated with an increase in the degree of disability [Table 5]. Iwanami et al. (1999) reported a similar finding and concluded that P300 amplitude could be used as an index for disability of daily life in schizophrenia. Following treatment, both P300 latency and amplitude were significantly enhanced; however, it was still outside the normal values. It is likely that the alleviation of negative symptoms with treatment is responsible for such improvement.

Umbricht et al. (1999) and Iwanami et al. (2001) obtained similar results after 6-9 and 4 weeks of treatment, respectively, utilizing doses between 4 and 6 mg/day. Contrary to these results, Korostenskaja and Kahkonen (2007) showed no changes in P300 parameters with treatment. Their patients were treated only for 2 weeks at a dose of 2.5 ± 1 mg/day. Actually, it seems that, the effect of treatment on active attention as measured by P300 is dose and time dependent. Furthermore, the amplitude of the P300 component showed a significant negative correlation with the degree of disability, denoting smaller amplitudes with higher degrees of disability. The attention-dependent processes reflected in P300 measures are already defective during the early stage of schizophrenia and could be improved with the use of an atypical antipsychotic medication.

  Conclusion Top

The current study concluded that the attention-dependent processes reflected in P300 measures are already defective during the early stage of schizophrenia and could be improved with the use of an atypical antipsychotic medication.


We recommend performing auditory MMN and P300 for schizophrenia patients as a method for the diagnosis and efficacy of treatment. Further studies are required to show the difference between chronic and first-episode schizophrenia.

  Acknowledgements Top

Conflicts of interest

There are no conflicts of interest.[26]

  References Top

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Fisher DJ, Labelle A, Knott VJ (2008). The right profile: mismatch negativity in schizophrenia with and without auditory hallucinations as measured by a multi-feature paradigm. Clin Neurophysiol 119:909-921.  Back to cited text no. 6
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Todd J, Michie PT, Schall U, et al. (2008). Deviant matters: duration, frequency, and intensity deviants reveal different patterns of mismatch negativity reduction in early and late schizophrenia. Biol Psychiatry 63:58-64.  Back to cited text no. 24
Umbricht D, Krljes S (2005). Mismatch negativity in schizophrenia: a meta-analysis. Schizophr Res 76:1-23.  Back to cited text no. 25
Umbricht D, Javitt D, Novak G, Bates J, Pollack S, Lieberman J, Kane J (1999). Effects of risperidone on auditory event-related potentials in schizophrenia. Int J Neuropsychopharmacol 2:299-304.  Back to cited text no. 26


  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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