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The Japanese Journal of Psychiatry

and Neurology, Vol. 48, No. 3, 1994

Missing Peaks in Auditory Brainstem Responses


and Negative Symptoms in Schizophrenia

Masayuki Igata, M.D., Mikio Ohta, M.D., Yoshiaki Hayashida, M.D.,*


and Kazuhiko Abe, M.D.

Department of Psychiatry, University of Occupational and


Environmental Health, Kitakyushu
*Department of Systems Physiology, University of Occupational and
Environmental Health, Kitakyushu

Abstract: Auditory brainstem responses (ABRs) were examined in 30 schizophrenic pa-


tients and 29 normal subjects. The psychotic symptoms were assessed by the Brief Psychi-
atric Rating Scale (BPRS) and the Scale for Assessment of Negative Symptoms (SANS) in
the patients. At least one of the waves I, I1 or I11 was found missing on either side at 80
dBHL (hearing level) in 8 (27%) of the patients but in only one (3%)of the normal sub-
jects. There was a significant association between the missing peaks and the BPRS nega-
tive symptom cluster or the total score of the SANS. These results suggest that some
schizophrenics, especially those with negative symptoms, have an abnormality of input
processing of auditory information in the lower brainstem.

Key Words: auditory brainstem response, schizophrenia, negative symptoms


Jpn J Psychiatry Neurol48: 571-578,1994.

INTRODUCTION amining the early processing of incoming au-


ditory information and is neurophysiologi-
Numerous studies have reported abnormal cally superior in three features to other AEPs.
auditory evoked potentials (AEPs) in First, the pattern of the ABR in a normal popu-
schizophrenics. These results include de- lation is very stable, both in and between indi-
creased amplitudes27z9, reduced latenciesz829 ~ i d n a 1 s .Secondly,
l~ the ABR has the advan-
and high variability26of cortical AEPs, as well tages of being quite insensitive to attention24,
as a shorter latency/smaller amplitude P50 arousal8, sleep33, and drug administra-
wave". Abnormalities in the early processing tion7 30. Thirdly, the generators of each wave
could potentially affect later information pro- of the ABR are fairly well understood5 l 4 3 1 .
cessing in schizophrenics. However, there It has been reported that schizophrenics
have been relatively few studies of earlier have abnormal ABRs such as missing peaks
evoked potentials. The ABR is useful for ex- or a decreased amplitude12, missing peaks or
prolonged latencies19 *O and a prolonged la-
Received for publication on Feb. 7, 1994. tencyI7 18. The relationship between ABR ab-
Mailing address: Masayuki Igata, M.D., Depart-
ment of Psychiatry, University of Occupational and normalities and clinical characteristics of
Environmental H e a l t h , Yahata-Nishiku, schizophrenic patients have not been fully ex-
Kitakyushu 807, Japan. plored.
572 M. Igata er ti/

In the present study, each ABR wave was ders, organic mental disorders, other neuro-
carefully observed by increasing stimulus in- logical disorders, or hearing loss greater than
tensity, as the latter has a profound effect on 20 dBHL. Informed consent was obtained
ABR. Then the obtained findings were exam- from all the participants.
ined in relation to positive and negative symp-
toms of the patients as assessed by BPRS2* METHODS
and SANS’.
The patients’ clinical symptoms were as-
SUBJECTS sessed using BPRS and SANS by a psychia-
trist just before the present study. They were
Table 1 shows the characteristics of schizo- rated by the total score (T-BPRS), the positive
phrenic patients and normal subjects in this symptom cluster (P-BPRS; hallucinatory be-
study. The 30 schizophrenic patients, who havior, unusual thought content and suspi-
were hospitalized at the psychiatric ward of ciousness), the negative symptom cluster (N-
our university and at a private mental hospital, BPRS; blunted affect and emotional with-
were examined. They consisted of 19 males drawal) of the BPRS, and the total score of the
and 1 1 females. Their ages ranged from 17 to SANS (SANS).
46 (mean 31.8) and their duration of illness The ABR recordings were based on a minor
was from 6 months to 21 years (mean 9.1). revision of Pfefferbaum’ s method.23Ag/AgCl
The mean dosage of antipsychotic drugs was disk electrodes were attached to the vertex
534.5 mg (S.D.=330.4) in equivalent doses of (Cz), to the left or right mastoid for reference.
c h l o r p r ~ m a z i n eTheir
.~ diagnoses of schizo- and to the forehead for grounding. The imped-
phrenia according to DSM-111-R1 were: 10 ance of each electrode was checked to be less
cases disorganized, 4 catatonic, 8 paranoid, 4 than 5 kohms. The patients were instructed to
residual and 4 undifferentiated. Five were lie in a comfortable position with eyes closed
classified as subchronic, 14 as chronic, 3 as on an electrically shielded sheet placed on a
subchronic with acute exacerbation, 4 as bed. The following experiments were carried
chronic with acute exacerbation and 4 were in out using an evoked potential recorder system
remission by the classification of course (Neuropack 11, NIHONKOHDEN, JAPAN).
(DSM-111-R). Click stimuli (rectangular, 0.1-msec pulses)
Twenty-nine normal subjects ( 18 males and were delivered binaurally through an electro-
11 females), aged 24 to 46 (mean 29.3) were magnetically shielded headphone (TDH-49,
matched with the patients in age and gender Telephonics, U.S.A.) at a rate of S/sec. The
(Table 1). None of the patients and normal hearing thresholds to the click stimuli were
subjects had any histories of psychoactive tested for each ear and a stimulus intensity
substance-use disorders, developmental disor- paradigm delivered clicks at 60, 70 and 80
dBHL. In all the ABRs, positivity at the vertex
was recorded as an upward deflection. The re-
Table 1 : Characteristics of the Subjects sulting signal was delivered to a bandpass fil-
ter set at 20-3,000 Hz. The analysis time was
Sex Duration Dose of 10 msec after each stimulus and the sampling
Age of Illness Antipsychotic
M F (years) (years) Drugs*(rng) time was 20 psec. The averaged responses to
Schizophrenic Patients (n=30)
2,048 click stimuli were recorded and drawn
19 I 1 3 1.828.1 9.1k6.9 53452330.4 with an X-Y recorder. A typical ABR consists
Normal Subjects (n=29) of a series of waves, designated by the Roman
18 I I 29.3kS.3 ~ - numerals I, 11,111, IV and V within the first 10
’: D a i l y e q u i v a l e n t s of c h l o r p r o r n a r i n e a n d r e l a t e d ms after the onset of the stimulus.lS The ABR
antipsychotic drugs by Davis, J.M. (1976). amplitude rises linearly with increasing stimu-
Auditory Brainstem Responses in Schizophrenia 573

lus intensity over a wide range beginning at


the hearing threshold and eventually saturat- - Absolute Latency
c

ing at an intensity of about 80 dB.25The


stimulus intensity of 80 dBHL was taken as a
sufficient intensity in our preliminary study.
I' *

The ABRs evoked by click stimuli at 80


dBHL intensity were examined in this study.
Because wave IV is often fused with wave V,
we did not consider wave IV. With regard to
the pattern of ABRs, a missing peak was de-
fined either as an indistinct negative trough of
a peak on either side or as the amplitude of a
peak that was less than 0.08 yV at 80 dBHL
intensity. Fig. 1 shows a typical ABR record-
ing and measurements of amplitudes, absolute
latencies and IPIs. The amplitude of wave I
was measured from the baseline to the peak
and the amplitudes of the other waves were
from the negative trough of a wave to the posi-
0 lOrnsec
tive peak of the following wave. The latencies
Fig. 1 : An ABR recording and methods of
were measured from the onset of the stimulus measuring amplitude, absolute latency and
to the peak of each wave (absolute latency of interpeak interval (IPI) of each ABR wave (waves
waves I, 11, I11 and V), and between different I, II,-III and V). Wave IV was not often evoked.

Fig. 2: A series of ABR


, , , , , , , , , , 10.3uV waveforms from two
schizophrenic patients, a
0 lOmsec
man aged 44 (A) and the
QOdBHL other 41 (B). Wave I1 on
t h e left side in A a nd
waves I and I1 on both
sides in B were not clearly
, , , , , , , , , , 10.3rrV evoked at 80 dBHL (hear-
0 lOmsec ing level).
574 M. Igata ef al.

waves (the 1-11, 1-111, I-V, and 111-V IPIs). The peaks). The mean amplitude of each wave in
mean data of ABR measurements from both these groups and in the normal subjects is pre-
sides were used in the statistical analyses. The sented in Table 2. Group A showed signifi-
significance of any group differences was de- cantly lower amplitudes of wave I (t=2.36,
termined using the two-tailed t-test. p<0.05 by Student’s t-test), I11 (t=2.05, p<0.05
by Student’s t-test) and V (t=4.57, p<O.Ol by
RESULTS Student’s t-test) than the normal subjects,
while group B had a lower amplitude of wave
Fig. 2 shows a series of ABR waveforms V (t=2.09, p<0.05 by Welch’s t-test). The
from two schizophrenic patients, a man aged mean absolute latencies and IPIs in both
44 (A) and the other 41 (B). Wave I1 on the
left side in A and waves I and I1 on both sides
in B were not clearly evoked in spite of an in- Table 2: Amplitudes of Each ABR Wave in
crease in stimulus intensity to 80 dBHL. In B, the Schizophrenic Patients with One or More
these waves were not evoked at 90 dBHL ei- Missing Peaks (Group A) or without
ther. Waves I and I11 on the right side of one any Missing Peaks (Group B)
and in Normal Subjects
patient, wave I1 on the left side of four, wave
I1 on the right side of one, wave I1 on both Amplitude (vV)
sides of one and waves I and I1 on both sides
of one were not clearly evoked at 80 dBHL. I I1 I11 v
Wave I1 on both sides was lacking in one nor- Schizophrenics
mal subject. One or two peaks of ABR wave- Group A (n=8)
mean 0.15* - 0.36* 0.74**
forms were missing in 8 of the 30 schizo-
S.D. 0.03 - 0.13 0.15
phrenic patients (26.7%), but in one of the 29 Group B (n=22)
normal subjects (3.4%). This was a significant mean 0.25 0.38 0.44 0.94*
difference at the 0.05 level (x2=4.48, df=l, S.D. 0.09 0.17 0.16 0.29
p<0.05, after Yate’s correction). Normal Controls (n=29)
The patients were divided into group A mean 0.25 0.44 0.52 1.10
(n=8, those with one or more missing peaks) S.D. 0.10 0.19 0.18 0.20
and group B (n=22, those without any missing ’*: pcO.05, +*: p<O.Ol, compared to normal subjects

Table 3: Absolute Latencies and IPIs of Each ABR Wave in the Schizophrenic Patients with
One or More Missing Peaks (Group A) or without any Missing Peaks (Group B) and in Normal Subjects
_ _ _ _ ~ ~ ~ ~~ ____

Absolute Latency (msec) Interpeak Interval (msec)


I I1 111 V 1-11 1-111 I-v 111-v
Schizophrenics
Group A (n=8)
mean 1.57** - 3.93 5.96 - 2.33* 4.43** 2.03
S.D. 0.12 - 0.23 0.28 - 0.1 I 0.10 0.16
Group B (n=22)
mean 1.63* 2.81* 3.77** 5.75 1.19 2.14 4.13 1.99
S.D. 0.24 0.19 0.21 0.21 0.15 0.18 0.19 0.16
Normal Controls (n=29)
mean 1.74 2.94 3.91 5.88 1.19 2.16 4.13 1.97
S.D. 0.11 0.13 0.15 0.22 0.12 0.15 0.21 0.14
*: p<0.05, * * p<O.Oi, compared to normal subjects.
Auditory Brainstem Responses in Schizophrenia 575

Table 4: Subject’sCharacteristicsand Symptom Clusters in SchizophrenicPatients with One or More


Missing Peaks (Group A) and without any Missing Peaks (Group B)

Subject’s Characteristics Symptom Clusters


Total$
Duration of Doses of
Age (years) illness Antipsyc.otic Total BPRS P-BPRS N-BPRS Total’ SANS
Drugs

Group A (n=8)
mean 33.0 10.5 599.2 55.1 11.9 10.3** 92.0’
S.D. 11.2 8.5 421.7 8.0 2.2 1.8 20.8
(n=3)
Group B (n=22)
mean 31.4 8.6 51 1 . 1 52.9 10.8 8.2 59.1
S.D. 6.5 6.2 286.6 12.7 3.4 1.7 18.7
(n=10)
9: dosage of antipsychotic drugs in equivalent doses of chlorpromazine (Davis 1976), *: assessment in 13 of 30 schizophrenic patients,
P-BPRS: BPRS positive symptom cluster (hallucinatory behavior, unusual thought content and suspiciousness), N-BPRS: BPRS negative
symptom cluster (blunted affect and emotional withdrawal).
*: p<0.05, **: p<O.OI, Group A vs. Group B

groups and in the normal subjects are given in groups A and B regarding the other clinical
Table 3. Group A showed a significantly features such as total doses of antipsychotic
shorter latency of wave I (t=3.33, p<O.Ol by drugs (599.2k421.7 vs.511.1+286.6mg,
Student’s t-test), and longer 1-111 (t=2.45, t=0.63,0.5cpcl by Student’s t-test).
pc0.05 by Student’s t-test) and I-V (t=3.16,
pcO.01 by Student’s t-test) IPIs than the nor- DISCUSSION
mal subjects. The prolonged I-V IPI was due
to the prolonged 1-111 IPI, as there was no sig- The above results indicate that at least one
nificant prolongation of the 111-V interval. of waves I, I1 or I11 was missing frequently
Group B had a significantly shorter latency of (27%) in the schizophrenic patients. This
wave I (t=2.09, pc0.05 by Welch’s t-test), I1 prevalence approximates that of other investi-
(t=2.57, pc0.05 by Welch’s t-test) and I11 gators, 50%19 and 38.5%*O in which the pa-
(t=2.73, pcO.01 by Student’s t-test) than the thology of absolute latencies or IPIs was in-
normal subjects. The reduced wave I1 and I11 cluded, or 32.5%’* of chronic schizophrenics
latencies were attributed to the reduced wave I selected by the Kraepelin Performance Test.
latency, because of no reduction of 1-11 and I- The prevalence of missing peaks (3.4%) in the
I11 IPIs. normal subjects was in agreement with that of
Table 4 shows the patients’ characteristics other studies.6 l 2
(age, duration of illness and total doses of The schizophrenic patients with one or
antipsychotic drugs) and symptom clusters more missing peaks had decreased amplitudes
(T-BPRS, P-BPRS, N-BPRS and SANS) of of all components and a prolonged 1-111 IPI.
the two schizophrenic groups. The N-BPRS This suggests these patients have a decrement
score was significantly higher in group A than in neuronal activity and/or asynchronization
in group B (t=2.77, pcO.01 by Student’s t-test) in the brainstem and slow transmission in the
and the same tendency (p=0.025 by Wilcoxon auditory pathway in the lower brainstem. The
rank-sum test) was seen in the SANS score. amplitude of evoked responses is thought to
There were no significant differences between reflect the degree of neuronal activities andor
S7h M. Igata et cil.

the synchronization of electrical events', companied by high negative symptoms4 2 ' ) .


while the latency is thought to reflect the neu- From these results one may hypothesize that
rotransmission time. It has been reported that there is an interrelation among negative symp-
unmedicated schizophrenics have prolonged toms, an abnormality of ABR and CSF HVA
latencies of 111, V. 111-V and I-VIx and that in schizophrenics. The missing peaks might
chronic schizophrenics have a delayed wave serve a s a neurophysiological marker of
VI7. Although the ABR latencies sometimes schizophrenics with predominantly negative
increase in schizophrenics, no agreement has symptoms.
been reached among these investigators as to The present study indicates that
which wave is most reliably delayed. All of schizophrenics with predominantly negative
our schizophrenic patients had a decreased symptoms have an abnormal input processing
amplitude of wave V and a reduced latency of of auditory information. Follow-up neuro-
wave I . All of the patients might have had imaging studies may shed more light on the
some common neurophysiological dysfunc- abnormal ABRs which were found to be re-
tion in the midbrain area, from which wave V lated to negative symptoms.
is thought to arise5 l 4 3 1 , and a greater sensitiv-
ity of the auditory sensory organ owing to an
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