Neurophysiologie Clinique/Clinical Neurophysiology (2007) 37, 89—96

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ORIGINAL ARTICLE/ARTICLE ORIGINAL

Mismatch negativity in paranoid, schizotypal,

and antisocial personality disorders
La négativité de discordance dans les désordres
de personnalité de types paranoı̈de, schizotypique
et antisocial
Y. Liu a, X. Shen a, Y. Zhu a, Y. Xu a, W. Cai a, M. Shen b, R. Yu a, W. Wang a,∗

a
Departments of Clinical Psychology and Psychiatry, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China
b
Department of Psychology and Behavioral Sciences, Zhejiang University School of Science, Hangzhou, Zhejiang 310058, China
Available online 2 April 2007

KEYWORDS Abstract
Antisocial; Aims. — The mismatch negativity (MMN) to frequency deviant tones has yielded conflicting
Mismatch negativity results in patients with schizophrenia. This might be because Axis I schizophrenia overlaps with
(MMN); Axis II diagnoses such as paranoid or schizotypal personality disorders. This study was designed
Paranoid; to address this issue.
Personality disorder; Methods. — We evaluated the auditory MMN to frequency deviance in 17 patients with paranoid,
Schizophrenia; 15 schizotypal, and 16 antisocial personality disorders. These were compared to 25 healthy
Schizotypal subjects.
Results. — N1 to both deviant and standard tones was shorter in the paranoid group when
compared to healthy controls. MMN latencies were shorter at Fz, Cz, and Pz in the paranoid
group when compared to healthy controls, schizotypal, and antisocial groups. MMN amplitudes
were higher at Fz and Cz in the schizotypal and antisocial groups when compared to healthy
controls and the paranoid group.
Conclusions. — Patients with paranoid personality disorder had faster automatic detection
of auditory stimuli and of their change, but normal inhibition of irrelevant stimuli. By con-
trast, patients with schizotypal and antisocial personality disorders had normal discrimination
of the auditory stimuli, but might have a deficit in inhibition on irrelevant stimuli. Our
results might help differentiate these personality types, and clarify some MMN findings in
schizophrenia.
© 2007 Elsevier Masson SAS. All rights reserved.

∗ Corresponding author.
E-mail addresses: wangmufan@msn.com, DrWang@Doctor.com (W. Wang).

0987-7053/$ — see front matter © 2007 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.neucli.2007.03.001
90 Y. Liu et al.

MOTS CLÉS Résumé

But de l’étude. — Dans la schizophrénie, les études des modifications de la négativité de dis-
Personnalité
cordance (mismatch negativity : MMN) en réponse à des tons déviants en fréquence ont fourni
antisociale ;
des résultats discordants. Nous testons l’hypothèse selon laquelle cela s’expliquerait par un
Négativité de
chevauchement nosologique des diagnostics selon les axes 1 et 2 du DSM.
discordance ;
Méthodes. — La MMN en réponse à des tons déviants en fréquence a été étudiée chez 17
MMN ;
patients de type paranoı̈de, 15 présentant une personnalité schizotypique et 16 une personnalité
Paranoı̈de ;
antisociale. Ils étaient comparés à 25 sujets témoins en bonne santé.
Troubles de
Résultats. — La N1 en réponse aux stimuli standard et déviants était plus précoce dans le
personnalité ;
groupe paranoı̈de que chez les témoins. Le temps de latence de la MMN était plus court dans
Schizophrénie ;
le groupe paranoı̈de que dans les trois autres groupes. Son amplitude était plus importante en
Schizotypique
Fz et Cz dans les groupes schizotypique et antisocial par comparaisons au groupe paranoı̈de et
aux témoins.
Conclusions. — La personnalité paranoı̈de est associée à une détection plus rapide des stimuli
auditifs et de leurs changements mais à une inhibition normale des stimuli non pertinents. Par
contre, les personnalités schizotypiques et antisociales seraient associées à une discrimina-
tion correcte des stimuli auditifs mais à un déficit d’inhibition des stimuli non pertinents. Ces
résultats contribuent à différencier ces différents types de personnalité et, ainsi, à clarifier les
résultats d’études antérieures de la MMN dans la schizophrénie.
© 2007 Elsevier Masson SAS. All rights reserved.

Introduction

Among human event-related potentials (ERPs), the mis-
match negativity (MMN) is a frontal negativity, which occurs
when a deviant stimulus does not match a sensory trace left
by the preceding standard stimuli. It is described in the audi-
tory [34] and visual [48] modalities. In the auditory modality,
MMN peaks at about 100—250 ms. As an orienting response,
its presence indicates that the subject is able to discrimi-
nate environmental stimuli in a passive mode. MMN latency
reflects the onset of auditory stimulus change in structure,
while its amplitude reflects the magnitude of the change and
saturates with the increment of perceived discrimination
[31,40]. As some investigators showed that its amplitude
increases when active attention is involved [35,54], MMN
has sometimes been considered to reflect an attentive acti-
vation of the human brain [47]. The supratemporal area and
the frontal lobe, which are interconnected with each other,
are both involved in the generation of the MMN. Morpho-
logically, the MMN is typically largest at the frontocentral
electrodes in adults, and thus overlaps with other ERP com-
ponents such as N1 and N2. In non-passive paradigms, it also
overlaps with the N2b component. In order to identify MMN
more clearly, many investigators use passive conditions, in
which no specific task performance is required during the
test. Therefore, the MMN paradigm is considered as a pow-
erful tool for examining the early involuntary or automatic
processing.
Since the first MMN trials to duration [43] and fre-
quency [16] deviance, robust results were obtained in
schizophrenia (reviewed in [28,32]). The reduced MMN
(especially in the frontal region) in schizophrenia was sub-
sequently replicated for duration —– (for recent studies
see [3,11]) and partly for frequency deviance (for recent
studies see [4,44,51,52]). Such reduced MMN amplitude
might reflect deteriorated auditory perception (reviewed
in [28,32]). However, several studies failed to evidence
any MMN reduction to frequency deviance in schizophre-
nia [19,29,37,38]. Neurophysiologic studies show that brain
neurons responsible for the detection of frequency and
duration changes might be different [23,24], and, indeed,
frequency deviance could produce better and more reli-
able MMN than duration deviance [17]. Some schizophrenic
patients who produced a reduced duration MMN displayed
an increased frequency MMN instead [29]. In addition, MMN
was larger in the treatment-refractory schizophrenics [30],
while patients with paranoid schizophrenia (some of these
might be diagnosed as paranoid personality disorder) had
smaller frequency MMN at Fz [41].
According to the DSM system [1], personality disorders
like the paranoid and schizotypal types (Axis II) share sim-
ilar clinical features with schizophrenia (Axis I). Genetic
and neurochemical studies also suggest that paranoid [2,49]
or schizotypal [5,20,45] personality disorders might be a
milder variant of schizophrenia. Since patients with per-
sonality disorders are less affected by such confounding
factors as hospitalization and psychosis, studies were often
conducted in some forms of personality disorder in order
to clarify the discrepancy issues reported in schizophre-
nia. Thus, voluntary cerebral processing, as reflected by
the ERP P3 component in an active paradigm, was stud-
ied in schizotypal [18,25], antisocial [10], and borderline
[6,25] personality disorders. All these studies demonstrated
a reduced P3 amplitude, that is, a similar result as that
obtained in schizophrenia [14,46]. Therefore, one might
wonder whether earlier automatic processing, as reflected
by the frequency MMN, could vary among different forms
of personality disorders that are close to schizophrenia in
terms of the spectrum of disorders. The answer to this ques-
tion would help clarify the frequency MMN issues that are
reported in schizophrenia.
To address this issue, we evaluated the frequency MMN
in patients with schizotypal and paranoid personality dis-
orders. We also included a group of antisocial personality
disorders, as an increased MMN has been demonstrated in
individuals at high risk for alcoholism [55], and alcoholism
MMN in personality disorders
predisposition is linked to several factors including the anti-
social personality disorder [13]. Considering together the
larger MMN in treatment-refractory schizophrenia [30] and
the smaller one in paranoid schizophrenia [41], we hypoth-
esized that the frequency MMN would be larger in both
antisocial and schizotypal personality disorders, but smaller
in paranoid personality disorder.
Methods and materials
Subjects
This study was carried out in 73 subjects: 25 healthy volunteers
(9 women, mean age: 28.1 years ± 8.4 (S.D); range: 18—51 years)
were recruited among students, hospital staff or paid volunteers
from the general population. Forty-eight outpatients were diag-
nosed as suffering from either paranoid (n = 17, 6 women; mean
age: 32.3 years ± 12.0; range 18—55 years), schizotypal (n = 15,
11 women; mean age: 30.5 years ± 12.7; range: 18—62 years), or
antisocial (n = 16, 1 woman; mean age: 29.3 years ± 11.5; range:
18—63 years) personality disorder, based on the DSM-IV-TR criteria
[1]. Since the present study was focused on the Axis II diagnoses, we
did not quantify the anxiety or depression severity of our subjects.
However, it appeared from clinical evaluation that most patients
had suffered from Axis I disorders such as mild to moderate anx-
iety or depression or both. The Axis II diagnoses were confirmed
using the Personality Measure [39]. This questionnaire designed for
assessing the disordered personality functioning styles has proven
reliable in Chinese culture [53]. A semi-structured interview was
performed for each healthy control in order to ascertain that they
were not suffering or had not suffered from any psychiatric prob-
lems. Each patient was diagnosed with one type of personality
disorder only; and patients receiving more than one Axis II diag-
noses were excluded from the study. Some patients might have
trends of obsession-compulsion, but failed to meet the diagnoses
of the obsessive-compulsive personality disorder alone. A recent CT
scan or MRI was available, in order to ensure that all patients were
free from any organic brain lesions. Though about 50% of patients
had received anxiolytics or antidepressants before presenting to our
clinic, all were free from any drug or alcohol for at least 72 h prior
to the test. Patients with any drug or alcohol abuse were excluded
from the study. All subjects gave their written informed consents
to be included in the study. There were no significant age differ-
ences between the different groups (one-way ANOVA, main effect,
F [3,69] = .53, p = .66).
Stimuli and recording parameters
Subjects were seated in an armchair in a quiet room. Binaural tone
stimuli of 80 dB SPL (50 ms in duration; rise/fall times of 5 ms) were
delivered through headphones at an interstimulus interval of 0.625 s
(1.6 Hz). The frequencies of frequent (90%) and rare (10%) tones
were 1.1 KHz and 1.2 KHz, respectively. These were presented in
random order. When compared to our studies, other studies used
higher (e.g., [29]), lower [41,44], or similar [30,52] frequencies.
Artifact-free recordings to 900 frequent and 100 deviant tones were
selected for averaging. With a pen in their dominant hand, sub-
jects were instructed to arrange series of seven randomized digits
(selected from 0 to 9) in an ascending order. This approach was
chosen to keep attention away from the auditory stimuli.
Although both frontal and temporal generators contribute to
MMN morphology, some studies showed that MMN amplitudes are
reduced at the midline electrodes, including Fz, Cz and Pz, but not
at mastoid sites [4,41]. Moreover, because of our limited number of
amplifier channels, we recorded ERPs with cup electrodes placed at
Fz, Cz, and Pz according to the 10—20 System. We used an earlobe
91
reference, in keeping with other studies [27,36]. Bipolar record-
ings of the electrooculogram (EOG) were made with electrodes at
the outer canthus and above the right eye. Ground electrode was
fixed to one arm. Electrode impedance was kept ≤10 K. All record-
ings were made on a Nihon Kohden Neuropack-sigma device using a
band-pass of .01—30 Hz, and a sampling rate of 500 Hz. The config-
uration baud rate was set at 9600 bit/s, and the data configuration
length was set at 8 bits in the hardware of the device. Connections
were set such that a negative activity produced an upward deflec-
tion. Traces with an EOG of amplitude exceeding ±100 ␮V (which
indicates blink or ocular movement) were automatically rejected.
Only artifact-free sweeps were automatically selected for averag-
ing. About 1100 tones were delivered in each trial but only 1000
sweeps were finally selected for averaging. The sampling epoch was
100 ms pre-stimulus and 500 ms post-stimulus.
Both latencies and peak-to-baseline amplitudes of the maximal
negative deflection within a specified latency ranges were mea-
sured, based on visual inspection. N1 was measured within a latency
range of 50—150 ms. Difference waves were obtained by subtracting
the frequent from the deviant tone ERPs, as proposed in [31]. The
MMN was measured on the difference waveforms within a latency
range of 100—250 ms [31].
Statistical analyses
MANOVA (group×gender×electrode sites) was used to study laten-
cies and amplitudes of N1 to standard tones (N1-standard), N1 to
deviant tones (N1-deviant), and MMN at the three midline elec-
trodes in the four groups. Whenever a significant main effect was
found, post-hoc analyses (Duncan’s multiple new range tests) were
performed to evaluate between-group differences for the corre-
sponding parameter. Moreover, the Cohen’s d (effect size) was
calculated as a supplement indicator for the magnitude of vari-
ations. We used Spearman’s rank order correlation to search for
possible relationships between age and latencies or amplitudes. A
p-value < .05 was considered significant.
Results
All subjects showed clear N1 components to standard and deviant
tones at each electrode site. The MMN component in the difference
waves was clearer at Fz and Cz compared to Pz in all subjects. The
grand averages of original and difference waves in each group are
shown in Figure 1.
N1
MANOVA showed significant between-group differences for N1 laten-
cies, both to standard and deviant stimuli (Table 1). Post-hoc
analyses showed that the mean latencies of N1-deviant were shorter
in the paranoid, when compared to the healthy control group, at
Fz (98.0 ms vs 110.0 ms), Cz (96.7 ms vs 108.6 ms), and Pz (96.8 ms
vs 108.4 ms) (Table 2). However, there were no statistical signifi-
cances between any pair of patient groups. Similarly, post-hoc tests
on N1-standard showed that main latencies were shorter in the
paranoid versus healthy control group at Fz (92.7 ms vs 105.1 ms),
Cz (91.5 vs 105.6) and Pz (94.1 vs 105.9). Additionally, there was a
significant difference between the antisocial (94.0 ms) and healthy
control groups, but only at Fz.
There were no significantly between-group differences when
considering amplitudes of either N1-deviant or N1-standard
(Table 1).
92 Y. Liu et al.

Figure 1 Superimposed grand averages of ERPs elicited by deviant tones (thin solid lines), standard tones (dashed lines), difference
waveforms (thick solid lines) at the three midline electrodes, and electrooculogram (EOG) in healthy subjects and patients with
paranoid, schizotypal and antisocial personality disorders.

Mismatch negativity
MANOVA also showed significant between-group differences for
MMN latencies at the three electrode sites (Table 1). Post-hoc
tests showed that the mean latencies of the paranoid group at
Fz (154.7 ms), Cz (154.7 ms) and Pz (152.6 ms) were significantly
shorter than those of the healthy controls (174.4, 173.4 and
173.4 ms, respectively), schizotypal (177.8, 178.5, and 177.5 ms
respectively), and antisocial (169.3, 168.9 and 168.6 ms, respec-
tively) groups. Cohen’s d-values indicated that the related effect
sizes were moderate to strong (Table 2).
Contrary to N1, MANOVA also showed a significant between-
group difference in MMN amplitudes. Post-hoc analyses demon-
strated that the mean amplitudes in both schizotypal and antisocial
groups were significantly higher than in the healthy controls at Fz
(schizotypal: 5.6 ␮V; antisocial: 4.5 ␮V; controls: 3.0 ␮V) and Cz
(schizotypal: 4.8 ␮V; antisocial: 3.7 ␮V; controls: 2.4 ␮V), but not
at Pz. Mean MMN amplitudes in the schizotypal group at Fz (5.6 ␮V)
and Cz, (4.8 ␮V) and those in the antisocial group at Fz (4.5 ␮V)

Figure 2 Scatter-plot of individual MMN amplitudes at Fz in healthy subjects and patients with paranoid, schizotypal and antisocial
personality disorders. Group means and standard deviations are given in Table 2.
MMN in personality disorders 93

Table 1 MANOVA results on latencies and amplitudes of standard and deviant N1, and the mismatch negativity (MMN) in the
four groups of subject

df,error F value p value

Latency
N1 deviant
Group 3,65 3.19 .03
Gender 1,65 4.80 .03
Electrode 2,130 3.54 .03
Group×Gender×Electrode 6,130 .62 .71
N1 standard
Group 3,65 3.46 .02
Gender 1,65 .21 .65
Electrode 2,130 5.40 .01
Group×Gender×Electrode 6,130 1.90 .09
MMN
Group 3,66 4.29 .01
Gender 1,66 .01 .91
Electrode 2,130 .43 .65
Group×Gender×Electrode 6,130 1.20 .31

Amplitude
N1 deviant
Group 3,65 .78 .51
Gender 1,65 2.02 .16
Electrode 2,130 30.91 .00
Group×Gender×Electrode 6,130 1.85 .09

N1 standard
Group 3,65 2.32 .08
Gender 1,65 .07 .79
Electrode 2,130 19.09 .00
Group×Gender×Electrode 6,130 .71 .64

MMN
Group 3,65 4.11 .01
Gender 1,65 .78 .38
Electrode 2,130 32.29 .00
Group×Gender×Electrode 6,130 .54 .77

were also significantly higher than in the paranoid group (Fz: 3.2 ␮V;
Cz: 2.7 ␮V). Cohen’s d-values indicated that these size effects were
moderate to strong at Fz, and weak to moderate at Cz (Table 2).
Since many auditory MMN studies were interested in the frontal
region [40], the individual MMN amplitudes at Fz in the four groups
are shown in Figure 2. MMN amplitudes in the patient groups were
more scattered than in controls, but they were no apparent outliers
or sub-clusters in either group.
Gender effects were only found for N1-deviant latencies at
Fz, (males: 100.7 ms ± 14.9; females: 108.2 ms ± 20.9, p < .05;
d = −.36), Cz (males 99.6 ms ± 14.5; females 107.6 ms ± 20.3,
p < .05; d = −.39), and Pz (males 100.2 ms ± 15.0; females 107.3
ms ± 20.4, p < .05, d = −.34), with weak effect sizes. No correlations
between age and latencies or amplitudes of any ERP parameter were
found in either group or in all subjects pooled together.
Discussion
The MMN to frequency deviant tones was earlier at the
three midline electrodes in patients with paranoid personal-
ity disorder when compared to healthy controls and patients
with schizotypal and antisocial personality disorders. It
was higher at Fz and Cz in patients with schizotypal and
antisocial personality disorders when compared to healthy
controls and patients with paranoid personality disorder.
Additionally, both deviant and standard tones elicited ear-
lier N1s in patients with paranoid personality disorder than
healthy subjects. The mean MMN latencies in our healthy
subjects were comparable to those previously reported
[11,12,50]. The mean MMN amplitudes in the four groups
were maximal at Fz, which is also in line with previous
reports [31,40]. Noteworthy, the reference in this study was
the linked earlobes and not the mastoids, so that there could
be some doubt on whether N2b contributed to the MMN.
Although the distractive task we used should in principle
warrant inattentiveness and absence of N2b, the compliance
to the task of our subjects, especially patients, was poorly
monitored. This issue deserves further investigation for a
clearer identification of MMN and N2b in these subjects.
94 Y. Liu et al.

Table 2 Latencies and amplitudes (mean ±S.D.) of N1 (to both standard and deviant stimuli) and mismatch negativity (MMN) at
the three midline electrode sites in healthy subjects and patients with paranoid, schizotypal, and antisocial personality disorders

Healthy Paranoid Schizotypal Antisocial

Data Data Significance Data Significance Data Significance

Latency (ms)
N1 deviant
Fz 110.0 ± 18.3 98.0 ± 16.0 a (−.66) 103.0 ± 17.4 99.5 ± 16.6
Cz 108.6 ± 18.6 96.7 ± 15.2 a (−.63) 103.0 ± 17.7 99.0 ± 15.6
Pz 108.4 ± 18.3 96.8 ± 15.9 a (−.64) 103.5 ± 17.9 99.7 ± 15.7
N1 standard
Fz 105.1 ± 12.1 92.7 ± 11.8 a (−1.02) 99.7 ± 15.9 94.0 ± 12.7 a (−.92)
Cz 105.6 ± 13.5 91.5 ± 12.5 a (−1.04) 98.9 ± 16.7 93.6 ± 12.2
Pz 105.9 ± 13.8 94.1 ± 14.4 a (−.89) 99.9 ± 18.1 94.4 ± 12.6
MMN
Fz 174.4 ± 19.1 154.7 ± 24.6 a (−1.03) 177.8 ± 16.5 b (.94) 169.3 ± 21.8 b (.37)
Cz 173.4 ± 19.1 154.7 ± 25.4 a (−.98) 178.5 ± 16.4 b (.94) 168.9 ± 23.0 b (.56)
Pz 173.4 ± 19.5 152.6 ± 26.7 a (−1.07) 177.5 ± 18.8 b (.93) 168.6 ± 22.7 b (.60)

Amplitude (␮V)
N1 deviant
Fz 4.9 ± 3.6 4.5 ± 2.3 5.3 ± 2.6 5.3 ± 2.3
Cz 4.7 ± 2.8 4.3 ± 2.3 5.1 ± 2.7 5.4 ± 2.0
Pz 3.4 ± 2.0 2.8 ± 2.1 3.8 ± 2.4 4.0 ± 2.0
N1 standard
Fz 3.5 ± 2.3 2.5 ± 1.5 2.4 ± 1.7 2.8 ± 1.2
Cz 3.3 ± 1.9 2.5 ± 1.2 2.4 ± 1.8 3.0 ± 1.5
Pz 2.5 ± 1.7 1.5 ± .9 1.5 ± 1.3 2.4 ± 1.6
MMN
Fz 3.0 ± 2.1 3.2 ± 2.1 5.6 ± 2.2 a (1.23), b (1.14) 4.5 ± 2.1 a (.71), b (.62)
Cz 2.4 ± 2.5 2.7 ± 2.2 4.8 ± 2.4 a (.96), b (.95) 3.7 ± 1.9 a (.52)
Pz 1.6 ± 2.6 1.6 ± 1.8 3.1 ± 2.1 2.3 ± 1.7
Note: a, p < .05 vs healthy group; b, p < .05 vs paranoid group; numbers in parentheses after a or b indicates the respective effect size
(Cohen’s d).

Our finding of an earlier MMN in patients with paranoid
personality disorder was also in accordance with a previous
study of paranoid schizophrenia [41], which clearly showed
a frequency MMN at Fz peaking at about 135—140 ms. This
finding, together with the shorter latencies of N1-deviant
and N1-standard, suggest that our patients with paranoid
personality disorders would perceive both types of tones
faster than healthy subjects or other patients, that is, they
would be more readily alerted by environmental acoustic
stimuli. By contrast, the fact that their amplitudes of N1-
deviant, N1-standard, and MMN were similar to those of
healthy subjects suggests that our patients with schizoty-
pal and paranoid personality disorders would display normal
alertness to both type of tones and their contrast.
It has been suggested that N1 and MMN would reflect
sensory gating and its neuronal correlates in temporopari-
etal and prefrontal areas [15,33]. Consequently, higher MMN
amplitudes would imply that subjects have difficulty to
filter out irrelevant stimuli [21,26]. Whether or not the
higher MMN found in our study denotes deficient inhibition
in patients with schizotypal and antisocial personality dis-
orders remains unknown, as our experimental protocol was
not designed to test sensory gating. This hypothesis might be
addressed in further studies, all the more as two lines of evi-
dence make it conceivable. Firstly, given that P3 amplitude
represents the inhibition of regional cortical activity and
reflects the utilization of resources at a more central level of
information processing [22,42], the P3 reduction in schizo-
typal and antisocial personality disorders [10,18,25] could
imply that the cortical areas were less inhibited in these
patients. Secondly, other neurophysiologic studies showed
that patients with schizotypal personality disorder have a
decreased prepulse inhibition of the startle reflex [8], and
of antisaccade and ocular motor responses [7].
The higher MMN amplitude, which was observed in
patients with antisocial personality disorder, is also in keep-
ing with the MMN increment that is observed in subjects
at high risk for alcoholism [55]. This might imply a lack of
inhibition on the irrelevant stimuli per se.
By contrast, we found normal MMN amplitude, instead
of a reduced one, in patients with paranoid personality
disorder, which is similar to a previous study of paranoid
schizophrenic patients [41]. This result would indicate that
patients with paranoid personality disorder do not manifest
impaired context processing and have a normal capacity to
filter our irrelevant stimuli. This group displayed more alert-
MMN in personality disorders
ness, as suggested by the shorter latencies of both standard
and deviant N1s.
The increase in MMN amplitude is in accordance with
some previous results on chronic schizophrenia [29,30], but
contrasts with other reports [3,44,51,52]. This supports our
hypotheses and our findings might help explain the discrep-
ancies of results on MMN to frequency-deviant tones that are
reported in schizophrenia.
In our study, males displayed earlier N1 to deviant tones
than women. There is currently no plausible explanation
for it. As N1 latency to deviant tones denotes a time set
of cerebral perception [31], an earlier N1 would indicate
that males be more alerted than females. However, effect
sizes between both genders were weak, so that those results
should be interpreted with caution. On the other hand,
although it was previously demonstrated that MMN peaks
earlier in younger than older subjects [9], we failed to evi-
dence any correlation between age and MMN latency or
amplitude. This might be due to the small sample size.
These results are preliminary and there are some limi-
tations in our design. Firstly, patient samples were small,
which may be due to the low prevalence of these person-
ality disorders. Secondly, we recorded ERPs only at three
midline electrodes, which results in a poor spatial reso-
lution. Thirdly, we did not enroll patients with schizoid
personality disorders, although they are also closely related
to schizophrenia; hence, such study on schizoid patients
would further to understand the complexity of MMN findings
in schizophrenia. Fourthly, we only used a one-frequency
paradigm; hence, a study using more frequency deviances
could present a clearer picture of MMN variation in these
patients.
Conclusion
To conclude, we did not evidence any decrease in MMN
amplitude in any patient group. Nevertheless, patients with
paranoid personality disorder had faster automatic detec-
tion of the tones and their change, but normal inhibition
of irrelevant stimuli. By contrast, patients with schizoty-
pal and antisocial personality disorders had normal tone
discrimination, but might have a deficit in inhibition of
irrelevant stimuli. Therefore, our results help to delineate
different personality types, which might present similar Axis
I phenomena in clinics. This could help to explain the dis-
crepancies that are observed in the results of studies of MMN
amplitude in schizophrenia.
Acknowledgements
The study was partly supported by grants from the Depart-
ment of Science and Technology of Zhejiang Province
(No. 2005C33022), the Department of Health of Zhejiang
Province (No. 2005QN011), the 151 Intelligence Fund of the
Department of Personnel of Zhejiang Province, and the
Research Center of Language and Cognition of Zhejiang Uni-
versity to the Dr W. Wang, and by a Neuroscience Research
Grant of Zhejjiang University School of Medicine to Dr X.
Shen. Drs Y. Liu, X. Shen and Y. Zhu contributed equally to
the paper.
95
References
[1] American Psychiatric, Association. Diagnostic and Statistical
Manual of Mental Disorders, text revision. 4th ed. Washington
DC: American Psychiatric Association; 2000.
[2] Asarnow RF, Nuechterlein KH, Subotnik KL, Fogelson DL,
Torquato RD, Payne DL, et al. Neurocognitive impairment
in nonpsychotic parents of children with schizophrenia and
attention-deficit/hyperactivity disorder: the University of
California Los Angeles Family Study. Arch Gen Psychiatry
2002;59:1053—60.
[3] Baldeweg T, Klugman A, Gruzelier JH, Hirsch SR. Impair-
ment in frontal but not temporal components of mismatch
negativity in schizophrenia. Int J Psychophysiol 2002;43:
111—22.
[4] Baldeweg T, Klugman A, Gruzelier J, Hirsch SR. Mismatch neg-
ativity and cognitive impairment in schizophrenia. Schizophr
Res 2004;69:203—17.
[5] Battaglia M, Torgersen S. Schizotypal disorder: at the
crossroads of genetics and nosology. Acta Psychiatr Scand
1996;94:303—10.
[6] Blackwood DH, St Clair DM, Kutler SP. P300 event-related
potential abnormalities in borderline personality disorder. Biol
Psychiatry 1986;21:560—4.
[7] Brenner C, McDowell JE, Cadenhead KS, Clementz BA. Saccadic
inhibition among schizotypal personality disorder subjects.
Psychophysiology 2001;38:399—403.
[8] Cadenhead KS, Geyer MA, Braff DL. Impaired startle prepulse
inhibition and habituation in schizotypal personality disordered
patients. Am J Psychiatry 1993;150:1862—7.
[9] Cooper RJ, Todd J, McGill K, Michie PT. Auditory sensory mem-
ory and the aging brain: A mismatch negativity study. Neurobiol
Aging 2006;27:752—62.
[10] Costa L, Bauer L, Kuperman S, Porjesz B, O’Connor S,
Hesselbrock V, et al. Frontal P300 decrements, alcohol depen-
dence, and antisocial personality disorder. Biol Psychiatry
2000;47:1064—71.
[11] Davalos DB, Kisley MA, Polk SD, Ross RG. Mismatch negativity
in detection of interval duration deviation in schizophrenia.
Neuroreport 2003;14:1283—6.
[12] Dick BD, Connolly JF, McGrath PJ, Finley GA, Stoink G, Houlihan
ME, et al. The disruptive effect of chronic pain on mismatch
negativity. Clin Neurophysiol 2003;114:1497—506.
[13] Finn PR, Sharkansky EJ, Brandt KM, Turcott N. The effects of
familial risk, personality, and expectancies on alcohol use and
abuse. J Abnorm Psychol 2000;109:122—33.
[14] Ford JM. Schizophenia: the broken P300 and beyond. Psy-
chophysiology 1999;36:667—82.
[15] Grunwald T, Boutros NN, Pezer N, von Oertzen J, Fernadez G,
Schaller C, et al. Neural substrates of sensory gating within the
human brain. Biol Psychiatry 2003;53:511—9.
[16] Javitt DC, Doneshka P, Zylberman I, Ritter W, Vaughan HG.
Impairment of early cortical processing in schizophrenia: an
event-related potential confirmation study. Biol Psychiatry
1993;33:513—9.
[17] Jemel B, Achenbach C, Muller BW, Roepcke B, Oades RD. Mis-
match negativity results from bilateral asymmetrical dipole
sources in the frontal and temporal lobe. Brain Topogr
2002;15:13—27.
[18] Kalus O, Horvath TB, Peterson A, Coccaro EF, Mitropoulou
V, Davidson M, et al. Event-related potentials in schizoty-
pal personality disorder and schizophrenia. Biol Psychiatry
1991;29:137A.
[19] Kathman N, Wagner M, Rendtorff N, Engel RR. Delayed peak
latency of the mismatch negativity in schizophrenics and alco-
holics. Biol Psychiatry 1995;37:754—7.
[20] Kendler KS, Gruenberg AM, Kinney DK. Independent diagnoses
of adoptees and relatives as defined by DSM-III in the provin-
96
cial and national samples of the Danish adoption study of
schizophenia. Arch Gen Psychiatry 1994;51:456—68.
[21] Kisley M, Olincy A, Robbins E, Polk SD, Adler LE, Waldo MC,
et al. Sensory gating impairment associated with schizophre-
nia persists into REM sleep. Psychophysiology 2003;40:29—
38.
[22] Kok A. Event-related potential (ERP) reflections of mental
resources: a review and synthesis. Biol Psychol 1997;45:19—56.
[23] Kraus N, McGee T, Carrell T, King C, Littman T, Nicol T. Discrim-
ination of speech-like signals in auditory thalamus and cortex.
J Acoust Soc Am 1994;96:2758—68.
[24] Kraus N, McGee T, Littman T, Nicol T, King C. Encoding of
acoustic change involves non-primary auditory thalamus. J
Neurophysiol 1994;72:1270—7.
[25] Kutcher SP, Blackwood DH, Gaskell DF, Muir WJ, St Clair
DM. Auditory P300 does not differentiate borderline person-
ality from schizotypal personality disorder. Biol Psychiatry
1989;26:766—74.
[26] Light G, Braff D. Do self-reports of perceptual anomalies
reflect gating deficits in schizophrenia patients? Biol Psychiatry
2000;47:463—7.
[27] Micheyl C, Carlyon RP, Shtyrov Y, Hauk O, Dodson T,
Pullvermueller F. The neurophysiological basis of auditory con-
tinuity illusion: a mismatch negativity study. J Cogn Neurosci
2003;15:747—58.
[28] Michie PT. What has MMN revealed about the auditory system
in schizophrenia? Int J Psychophysiol 2001;42:177—94.
[29] Michie PT, Budd TW, Todd J, Rock D, Wichmann H, Box J, et al.
Duration and frequency mismatch negativity in schizophrenia.
Clin Neurophysiol 2000;111:1054—65.
[30] Milovan DL, Baribeau J, Roth RM, Stip E. ERP study of
pre-attentive auditory processing in treatment-refractory
schizophenia. Brain Cogn 2004;55:355—7.
[31] Näätänen R. Attention and Brain Function. Hillsdale, NJ:
Lawrence Erlbaum; 1992.
[32] Näätänen R. Mismatch negativity: clinical research and possible
applications. Int J Psychophysiol 2003;48:179—88.
[33] Näätänen R, Picton TW. The N1 wave of the human electric
and magnetic response to sound: a review and an analysis if
the component structure. Psychophysiology 1987;24:375—425.
[34] Näätänen R, Gaillard AWK, Mantysalo S. Early selective-
attention effect on evoked potential reinterpreted. Acta
Psychol (Amst) 1978;42:313—29.
[35] Näätänen R, Paavilainen P, Tiitinen H, Jiang D, Alho K. Attention
and mismatch negativity. Psychophysiology 1993;24:375—425.
[36] Näätänen R, Pakarinen S, Rinne T, Takegata R. The mismatch
negativity (MMN): toward the optimal paradigm. Clin Neuro-
physiol 2004;115:140—4.
[37] O’Donnell BF, Hokama M, McCarley RW, Smith RS, Salisbury
DF, Mondrow E, et al. Auditory ERPs to non-target stimuli in
schizophrenia: relationship to probability, task-demands, and
target ERPs. Int J Psychophysiol 1994;17:219—31.
[38] Oades RD, Dittman-Balcar A, Zerbin D, Grzella I. Impaired
attention-dependent augmentation of MMN in nonparanoid vs
paranoid schizophrenic patients: a comparison with obsessive-
compulsive disorder and healthy subjects. Biol Psychiatry
1997;41:1121—96.
Y. Liu et al.
[39] Parker G, Hadzi-Pavlovic D. A questionnaire of style: refining
the dimensions of personality disorder style. J Personal Disord
2001;15:300—18.
[40] Picton TW, Alain C, Otten L, Ritter W, Achinm A. Mismatch
negativity: Different waters in the same river. Audiol Neurootol
2000;5:111—39.
[41] Sato Y, Yabe H, Todd J, Michie P, Shinozaki N, Sutoh T, et al.
Impairment in activation of frontal attention-switch mecha-
nism in schizophrenic patients. Biol Psychol 2002;62:49—63.
[42] Schupp HT, Lutzenberger W, Rau H, Birbaumer N. Positive shifts
of event-related potentials: a state of cortical disfacilitation as
reflected by the startle reflex probe. Electroencephalogr Clin
Neurophysiol 1994;90:135—44.
[43] Shelley AM, Ward PB, Catts SV, Michie PT, Andrews S,
McConaghy N. Mismatch negativity: an index of preat-
tentive processing deficit in schizophrenia. Biol Psychiatry
1991;30:1059—62.
[44] Shinozaki N, Yabe H, Sato Y, Hiruma T, Sutoh T, Nashida T,
et al. The difference in mismatch negativity between the
acute and post-acute phase of schizophrenia. Biol Psychol
2002;59:105—19.
[45] Siever LJ, Amin F, Coccaro EF, Trestman R, Silverman J, Hor-
vath TB, et al. CSF homovanillic acid in schizotypal personality
disorder. Am J Psychiatry 1993;150:149—51.
[46] Squires-Wheeler E, Friedman D, Skodol AE, Erlenmeyer-Kimling
L. A longitudinal study relating P3 amplitude to schizophre-
nia spectrum disorders and global personality functioning. Biol
Psychiatry 1993;33:774—85.
[47] Sussman ES. Is MMN truly pre-attentive? In: Shtyrov Y, Pulver-
mullerF F., editors. Programme and Abstract Book of the Fourth
Conference on Mismatch Negativity (MMN) and its Clinical and
Scientific Applications, Cambridge. April 22—26, 2006. S1.2.
[48] Tales A, Newton P, Troscianko T, Butler S. Mismatch negativity
in the visual modality. Neuroreport 1999;10:3363—7.
[49] Tienari P, Wynne LC, Lasky K, Moring J, Nieminen P, Sorri A,
et al. Genetic boundaries of the schizophrenia spectrum: evi-
dence from the Finnish Adoptive Family Study of Schizophrenia.
Am J Psychiatry 2003;160:1587—94.
[50] Todd J, Michie PT, Jablensky AV. Association between
duration mismatch negativity (MMN) and raised temporal dis-
crimination thresholds in schizophrenia. Clin Neurophysiol
2003;114:2061—70.
[51] Umbricht D, Krljes S. Mismatch negativity in schizophrenia: a
meta-analysis. Schizophr Res 2005;76:1—23.
[52] Umbricht D, Koller R, Schmid L, Skrabo A, Grubel C, Huber T, et
al. How specific are deficits in mismatch negativity generation
to schizophrenia? Biol Psychiatry 2003;53:1120—31.
[53] Wang W, Hu L, Mu L, Chen D, Song Q, Zhou M, et al. Func-
tioning styles of personality disorders and five-factor normal
personality traits: a correlation study in Chinese students. BMC
Psychiatry 2003;3:11.
[54] Woldorff M, Hackley S, Hillyard SA. The effects of channel-
selective attention on mismatch negativity wave elicited by
deviant tones. Psychophysiology 1991;28:30—42.
[55] Zhang XL, Cohen HL, Porjesz B, Begleitner H. Mismatch nega-
tivity in subjects at high risk for alcoholism. Alcohol Clin Exp
Res 2001;25:330—7.