- Email: [email protected]
A study of motor dysfunction associated with schizophrenia based on analyses of movement-related cerebral potentials and motor conduction time
A Study of Motor Dysfunction Associated with Schizophrenia Based on Analyses of Movement-Related Cerebral Potentials and Motor Conduction Time Fumio Kubota, Hiroshi Miyata, Nobuyoshi Shibata, and Hiroshi Yarita Background: Several reports have shown that schizophrenics have motor dysfunction. The aim of this study was to identify the site of the nerve damage responsible for the motor dysfunction in schizophrenics by measuring both movement-related cerebral potentials (MRCPs) and motor conduction times. Methods: The subjects were 27 patients and 31 controls. There was no significant difference in age, nor in the length of the subjects’ arms between the two groups. MRCPs were recorded during voluntary self-paced index movements of the thumb. The motor nerve conduction time was determined by magnetically stimulating the motor cortex and the spinal root. Results: Six of 27 schizophrenics had normal MRCPs, but the remaining 21 showed abnormal MRCPs. Of the 31 controls, 27 were normal, whereas 4 showed abnormal MRCPs. The difference between the two groups was significant; however, no significant differences were found in the motor conduction times, the motor root conduction times, or the central motor conduction times between the two groups. Conclusions: Our results suggest that the responsible focus of motor nerve disorder in schizophrenia lies in the motor-integrating system in frontal lobe, and not in the nervous conduction system from the brain to the muscles. Biol Psychiatry 1999;45:412– 416 © 1999 Society of Biological Psychiatry Key Words: Magnetic stimulation, motor conduction time, motor dysfunction, movement-related cerebral potentials, schizophrenia
been several reports on schizophrenia-associated motor dysfunction, which has been studied on the basis of analyses of parameters such as SPEM (smooth-pursuit eye movements), button-pushing reaction times, and tapping speeds (Manschreck et al 1982; Kornhuber 1983; Robert et al 1989; Schwartz et al 1989; Porter 1990). These studies have revealed abnormalities in schizophrenics in each of the parameters. It is thought that these abnormalities exist mainly in the central nervous system. There are a few reports of the peripheral neuron disorder, alpha neuron dysfunction, or morphologic abnormality of skeletal muscle fibers (Crayton et al 1977; Ross-Stanton et al 1980). The aim of this study was to identify the sites of damage in the nervous system responsible for the motor dysfunction in schizophrenics. No other trials have attempted to do this. It was for that purpose that we measured two parameters, movement-related cortical potentials (MRCPs) and the motor conduction times (MCTs). There are various tests for central motor nerve dysfunction. We used MRCPs as a index of it, because we can rule out the effect of motivation, attention, or other psychomotor factors. MRCPs have little relationship to the subject’s attention capacity, because they do not require exogenous stimuli. Furthermore, since MRCPs can be measured at the patient’s own pace, MRCPs are also less likely to suffer from poor patient motivation to participate in the test.
Methods and Materials Introduction
Subjects
C
The subjects of this study were 27 schizophrenics (12 men and 15 women: the schizophrenic group) and 31 healthy volunteers (16 men and 15 women: the control group). All 27 of the schizophrenics (16 inpatients and 11 outpatients) were patients receiving major tranquilizers and antiparkinson agents at the psychiatry department of Gunma University Hospital, and satisfied the DSM-IV criteria for the diagnosis of schizophrenia. Major tranquilizers administered were levomepromazine (100 – 500 mg/day, 9 patients), chlorpromazine (150 – 600 mg/day, 12 patients), haloperidol (4.5–24 mg/day, 16 patients), sulpiride (150 – 600 mg/day, 4 patients), mosapramine hydrochloride
onsidering the retarded speed of movement of schizophrenics, it is plausible to assume that schizophrenia is associated with motor function disturbances. There have
From the Department of Neuropsychiatry, Gunma University School of Medicine, Gunma, Japan (FK, HM, NS); and Tatebayashi General Hospital, Gunma, Japan (HY). Address reprint requests to Dr. Fumio Kubota, Department of Neuropsychiatry, Gunma University School of Medicine, 39-15, Showa-sho 3 Chome, Maebashishi Gunma 371, Japan. Received December 17, 1996; revised June 30, 1997; revised October 3, 1997; accepted November 12, 1997.
© 1999 Society of Biological Psychiatry
0006-3223/99/$19.00 PII S0006-3223(97)00523-4
Motor Dysfunction in Schizophrenia
(100 mg/day, 1 patient), bromperidol (18 –24 mg/day, 2 patients), fluphenazine (9 –18 mg/day, 3 patients), nemonapride (18 –36 mg/day, 2 patients), and oxypertine (80 mg/day, 1 patient). Antiparkinson agents administered were biperiden hydrochloride (3– 6 mg/day, 15 patients), trihexyphenidyl hydrochloride (6 –12 mg/day, 12 patients), and promethazine hydrochloride (75 mg/ day, 3 patients). The schizophrenic group was composed of the following subtypes: catatonic, 3 patients; disorganized, 10 patients; paranoid, 11 patients; and undifferentiated, 3 patients. The Positive and Negative Syndrome Scale (PANSS) clinical score averaged 72.3 6 16.2 (positive score, 14.6 6 5.4; negative score, 21.2 6 6.3; general psychopathology score, 37.7 6 10.1) in the schizophrenic group. Most of the control volunteers were hospital employees. The average age of the schizophrenic group (30.5 6 6.4 years) and the control group (29.6 6 5.5 years) did not differ significantly, nor was there any significant difference in arm length between the two groups. The illness onset age in the schizophrenic group was 20.8 6 3.2 years, and the illness duration was 9.7 6 5.8 years. None of the subjects had any evidence of neurological or spinal cord disease. Although several patients gave the impression of being slightly slow in their movements, there was no evidence of drug-induced neurological phenomena (parkinsonism, drowsiness, etc.). Informed consent was obtained in writing from each subject prior to the study. All were right-handed subjects.
BIOL PSYCHIATRY 1999;45:412– 416
413
them “negative” waves) that continued to be negative, even after the start of the exercise, were judged to be abnormal. MCT was measured using a magnetic stimulator type Magstim 200 (maximum output: 1500 V, Magstim Co.) composed of a circular coil with a diameter of 12.5 cm. The subject’s head or neck was stimulated once, and the latency of motor evoked potentials (MEPs) from the abductor muscle of the right thumb was measured. The head was stimulated with the coil placed on the scalp. The neck was stimulated by placing the center of the coil on the skin above the spinal process of the seventh cervical vertebra during flexion of the rest. The magnitude of stimulation was gradually increased, until the latency had become almost completely stable, and then the minimal values yielded from three measurements were used as the latency for a given subject. A Nippon Kohden Neuropack 8 was used to measure the MEP latency. The MEP latency produced by cortex stimulation is called the MCT, while that produced by cervical stimulation is called the motor root conduction time (MRCT). The difference in the MEP latency during simultaneous stimulation of both the head and neck was held to be the central motor conduction time (CMCT). In statistical tests for comparison of the two groups, age, the illness onset age, the illness duration, the dose of major tranquilizers, the PANSS score, and the MCT were examined using the unpaired t test. The sex of the subject, the type of schizophrenia, the number of subjects with normal or abnormal MRCPs, and the number of major tranquilizers were examined using the chisquare test. p , .05 was considered to be significant.
Methods MRCPs were tested in a shielded room. Each subject assumed a recumbent position and gently held a response button during the test. To eliminate artifacts caused by eye movements, the subjects were asked to try not to move their eyes. The subjects either closed their eyes or gazed at a light placed 1 m above their eyes. MRCPs during voluntary movements were measured as follows. The subject pushed the button by flexing the right thumb and then extended the thumb as rapidly as possible. The patients repeated this sequence of movements, i.e., rapidly flexing and extending the thumb, at their own pace at irregular intervals (about every 5 sec). One session was composed of 50 movement cycles. Each subject performed two sessions, with a 5-min break between them, to allow the reproducibility of the data to be examined. Pulses generated by pushing the button served as triggers. Reference electrodes were attached to both earlobes, and potentials were recorded from C3, Cz, and C4 electrodes using a band-pass filter in a frequency range of 0.05–50 Hz. The analysis time was 3 sec. A Nippon Kohden Neuropack 8 (measurement equipment with an arithmetic unit) was used for summation and averaging. Eye movements were simultaneously recorded. Electroencephalography (EEG) data that included artifacts caused by eye movements were rejected. The MRCP waveforms recorded were classified into “normal” or “abnormal” according to the Tismit-Berthier classification (Tismit-Bertheir et al 1973). Waves that satisfied both of the following requirements were regarded as being normal: 1) waves that appeared 1–1.5 sec before the start of the exercise; and 2) waves that changed rapidly from negative to positive in approximate synchrony with the appearance of the trigger pulses. Flat waves and waves (we call
Results MRCP waves without artifacts were recorded. A small number of waves had to be rejected (18 out of 1368 in the schizophrenic group; 20 out of 1570 in the control group). An example of normal MRCP waveforms is shown in Figure 1. Examples of abnormal MRCP waveforms are shown in Figures 2 and 3. In the schizophrenic group (n 5 27), normal MRCPs were recorded from 6 subjects and abnormal MRCPs from 21 subjects. In the control group (n 5 31), normal MRCPs were recorded from 27 subjects and abnormal MRCPs from 4 subjects. The incidence of abnormal MRCPs was significantly higher in the schizophrenic group than in the control group (P , .01). Abnormal MRCPs in the schizophrenic group consisted of 19 flat waves (catatonic, n 5 1; disorganized, n 5 10; paranoid, n 5 7; undifferentiated, n 5 1) and 2 “negative” waves (paranoid, n 5 1; undifferentiated, n 5 1). All abnormal MRCPs in the control group consisted of flat waves. The 6 patients with normal MRCPs were 3 men and 3 women, consisting of 4 inpatients and 2 outpatients. They were receiving levomepromazine (100 mg/day, 1 patient), chlorpromazine (150 – 400 mg/day, 4 patients), haloperidol (4.5–18 mg/day, 4 patients), sulpiride (300 mg/day, 1 patient), mosapramine hydrochloride (100 mg/day, 1 patient), and bromperidol (18 mg/day, 1 patient). The dose and type of major tranquilizers administered to the 6
414
F. Kubota et al
BIOL PSYCHIATRY 1999;45:412– 416
Figure 1. An example of normal MRCPs.
patients were not different from those administered to the other 21 patients. There was no significant difference in the age, illness onset age, and illness duration between these 6 patients and the other 21 patients. The PANSS
Figure 3. An example of abnormal MRCPs (waves that continued to be negative even after the start of exercise).
score of the 6 MRCP normal patients averaged 63.2 6 17.2 (positive score, 15.5 6 5.6; negative score, 17.3 6 5.7; general psychopathology score, 33.8 6 9.9), while that of the other 21 patients averaged 74.8 6 17.4 (positive score, 14.4 6 5.6; negative score, 22.3 6 6.2; general psychopathology score, 38.7 6 10.2). In the PANSS score, including subscores, there were no significant differences between the 6 MRCP normal patients and the other 21 patients. No significant differences were found between the two groups in the statistical tests in any of the measured variables stated above. Examples of MEPs during stimulation of the head and neck are shown in Figure 4. In the schizophrenic group, the nerve conduction time (NCT) was 21.07 6 1.42 ms, the MRCT was 12.25 6 0.99 ms, and the CMCT was 9.26 6 0.80 ms. In the control group, the NCT was 21.30 6 1.34 ms, the MRCT was 12.04 6 0.81 ms, and the CMCT was 8.82 6 0.71 ms. None of these parameters differed significantly between the two groups. Moreover there were no significant differences between these parameters in the subtypes. Also there was no relationship between the PANSS score, including subscores, and these parameters.
Discussion Figure 2. An example of abnormal MRCPs (flat waves).
Our study revealed that 78% of the schizophrenic group had abnormal MRCPs, compared to 14% in the control
Motor Dysfunction in Schizophrenia
Figure 4. Examples of MEPs.
group. Previous studies have found abnormal MRCPs in 71–78% of schizophrenics (including some psychotics), compared to 12–16% of a control group (Tismit-Berthier et al 1973; Dongier 1973; Kousaka et al 1980; Terayama et al 1985; Kaku et al 1993). The incidence of abnormal MRCPs in our schizophrenic and control groups agreed with reports to date. Our patients with abnormal MRCPs exhibited mostly flat MRCPs. This result is also in agreement with reports to date (Tismit-Berthier et al 1973; Dongier 1973; Kousaka et al 1980; Terayama et al 1985; Kaku et al 1993). It has been reported that few schizophrenics display “negative” waves (Tismit-Berthier et al 1973; Dongier 1973; Takasaka et al 1980; Terayama et al 1985). Two of our schizophrenic group exhibited “negative” waves. The MRCP test is easy and useful to examine patients exhibiting central motor dysfunction, who have been reported to have flat MRCPs (Shibasaki et al 1982). Although it is thought that flat MRCPs indicate reduced motor function, we cannot conjecture the physiological basis for “negative” MRCPs found only in schizophrenics. Although there were no significant differences between the 6 MRCP-abnormal patients and the other 21 patients, the tendency for the 21 MRCP-abnormal patients to have lower scores in the PANSS negative score is found across all of the variables measured. The reason may be that the sample size was small. Twenty-one patients with abnormal MRCPs had raised negative symptoms measured by the PANSS negative score, compared to the other 6 patients. Negative symptoms may result partially from motor dysfunction. We think that 2 out of the 3 catatonic type patients had normal MRCPs, because the 2 patients exhibited few negative symptoms. It
BIOL PSYCHIATRY 1999;45:412– 416
415
has been reported that most schizophrenics in the chronic or disorganized subtype had flat MRCPs (Terayama et al 1985; Kaku et al 1993), but their sample size was too small to support the claim. No other studies have examined the relationships between MRCPs and the variables of schizophrenics (such as type of schizophrenia, major tranquilizers, PANSS score, and so on). It is presumed that MRCPs develop from such areas as the supplementary motor area, or the whole frontal lobe, and so on. The exact generator of the MRCP is unclear, and we have not been able to determine the dissective site of motor dysfunction in schizophrenics. This is the limitation of this method. It is, however, clear that MRCPs develop from the frontal lobe, because of the scrap topography on the head (Shibasaki et al 1980). Our MRCP results suggest that schizophrenics have abnormalities in the motor integration area of the frontal lobe. MCTs have not yet been measured in schizophrenics. The present study revealed no significant differences in the MCT, the MRCT, or the CMCT between the schizophrenic group and the control group, which suggests the absence of any abnormalities in the motor nerve conduction system from the brain to the muscles in schizophrenia. It is well known that major tranquilizers sometimes affect motor function, especially drug-induced parkinsonism. We assessed parkinsonism using the following five symptoms: masked countenance, tremor, rigidity, parkinsonian gait, and excess secretion of sputum. None of the patients exhibited any of these five symptoms. We think that major tranquilizers did not affect the motor functions of our patients. On the basis of these results, we can conclude that the motor dysfunction associated with schizophrenia is probably attributable to damage to the motor integration center of the brain, and that the neural conduction system from the brain to the muscles is usually intact in schizophrenics.
References Crayton JW, Meltzer HY, Goode DJ (1977): Motoneuron excitability in psychiatric patients. Biol Psychiatry 12:545– 561. Dongier M (1973): Event related slow potential changes in psychiatry. In: Bogoch S, editor. Biological Diagnosis of Brain Disorders. New York: Spectrum, pp 47–59. Kaku T, Shiba M, Suzuki E, Momotani Y, Higasi Y (1993): Movement related cortical potential of schizophrenics. Seisin Igaku 5:273–279. Kornhuber HH (1983): Chemistry physiology and neuropsychology of schizophrenia: Towards an earlier diagnosis of schizophrenia I. Arch Psychiatr Nervenkr, 233:415– 422. Manschreck TC, Maher BA, Rucklos ME, Vereen DR (1982): Disturbed voluntary motor activity in schizophrenic disorder. Psychol Med 12:73– 84.
416
BIOL PSYCHIATRY 1999;45:412– 416
Porter R (1990): The Kugelberg lecture. Brain mechanisms of voluntary motor commands—A review. Electroencephalogr Clin Neurophysiol 76:282–293. Robert DC, Richard WL, Larry JS (1989): The relationship between smooth pursuit eye movement impairment and psychological measures of psychopathology. Psychol Med 19: 343–358. Ross-Stanton J, Schlessinger S, Meltzer HY (1980): Multiple neuromuscular abnormalities in a paranoid schizophrenic. Psychiatry Res 3:53– 67. Schwartz F, Carr AC, Munich RL, Glauber S, Lesser BA, Murray J (1989): Reaction time impairment in schizophrenia and affective illness: The role of attention. Boil Psychiatry 25:540 –548. Shibasaki H, Barrett G, Halliday E, Halliday AM (1980): Components of the movement-related cerebral potential and
F. Kubota et al
their scalp topography. Electroencephalogr Clin Neurophysiol 49:213–226. Shibasaki H, Sakai T, Nishimura H, Sato Y, Goto I, Kuroiwa Y (1982): Involuntary movements in chorea-acanthocytosis. A comparison with Huntington’s chorea. Ann Neurol 12:311– 314. Takasaka Y, Yamauti T, Kataoka N, Kudou T, Hirabayashi Y (1980): Movement-related cerebral potentials in psychiatric patients. Rinsyou Nouha 22:471– 476. Terayama K, Kumashiro H, Kaneko Y, Suzuki S, Aono T (1985): Readiness potential in chronic schizophrenics—Physiological approach for the interhemispheric functional disorder. Rinsyou Nouha 27:381–385. Timsit-Berthier M, Delaunoy J, Rousseau J (1973): Slow potential changes in psychiatry. II. Motor potential. Electroencephalogr Clin Neurophysiol 35:363–367.
been several reports on schizophrenia-associated motor dysfunction, which has been studied on the basis of analyses of parameters such as SPEM (smooth-pursuit eye movements), button-pushing reaction times, and tapping speeds (Manschreck et al 1982; Kornhuber 1983; Robert et al 1989; Schwartz et al 1989; Porter 1990). These studies have revealed abnormalities in schizophrenics in each of the parameters. It is thought that these abnormalities exist mainly in the central nervous system. There are a few reports of the peripheral neuron disorder, alpha neuron dysfunction, or morphologic abnormality of skeletal muscle fibers (Crayton et al 1977; Ross-Stanton et al 1980). The aim of this study was to identify the sites of damage in the nervous system responsible for the motor dysfunction in schizophrenics. No other trials have attempted to do this. It was for that purpose that we measured two parameters, movement-related cortical potentials (MRCPs) and the motor conduction times (MCTs). There are various tests for central motor nerve dysfunction. We used MRCPs as a index of it, because we can rule out the effect of motivation, attention, or other psychomotor factors. MRCPs have little relationship to the subject’s attention capacity, because they do not require exogenous stimuli. Furthermore, since MRCPs can be measured at the patient’s own pace, MRCPs are also less likely to suffer from poor patient motivation to participate in the test.
Methods and Materials Introduction
Subjects
C
The subjects of this study were 27 schizophrenics (12 men and 15 women: the schizophrenic group) and 31 healthy volunteers (16 men and 15 women: the control group). All 27 of the schizophrenics (16 inpatients and 11 outpatients) were patients receiving major tranquilizers and antiparkinson agents at the psychiatry department of Gunma University Hospital, and satisfied the DSM-IV criteria for the diagnosis of schizophrenia. Major tranquilizers administered were levomepromazine (100 – 500 mg/day, 9 patients), chlorpromazine (150 – 600 mg/day, 12 patients), haloperidol (4.5–24 mg/day, 16 patients), sulpiride (150 – 600 mg/day, 4 patients), mosapramine hydrochloride
onsidering the retarded speed of movement of schizophrenics, it is plausible to assume that schizophrenia is associated with motor function disturbances. There have
From the Department of Neuropsychiatry, Gunma University School of Medicine, Gunma, Japan (FK, HM, NS); and Tatebayashi General Hospital, Gunma, Japan (HY). Address reprint requests to Dr. Fumio Kubota, Department of Neuropsychiatry, Gunma University School of Medicine, 39-15, Showa-sho 3 Chome, Maebashishi Gunma 371, Japan. Received December 17, 1996; revised June 30, 1997; revised October 3, 1997; accepted November 12, 1997.
© 1999 Society of Biological Psychiatry
0006-3223/99/$19.00 PII S0006-3223(97)00523-4
Motor Dysfunction in Schizophrenia
(100 mg/day, 1 patient), bromperidol (18 –24 mg/day, 2 patients), fluphenazine (9 –18 mg/day, 3 patients), nemonapride (18 –36 mg/day, 2 patients), and oxypertine (80 mg/day, 1 patient). Antiparkinson agents administered were biperiden hydrochloride (3– 6 mg/day, 15 patients), trihexyphenidyl hydrochloride (6 –12 mg/day, 12 patients), and promethazine hydrochloride (75 mg/ day, 3 patients). The schizophrenic group was composed of the following subtypes: catatonic, 3 patients; disorganized, 10 patients; paranoid, 11 patients; and undifferentiated, 3 patients. The Positive and Negative Syndrome Scale (PANSS) clinical score averaged 72.3 6 16.2 (positive score, 14.6 6 5.4; negative score, 21.2 6 6.3; general psychopathology score, 37.7 6 10.1) in the schizophrenic group. Most of the control volunteers were hospital employees. The average age of the schizophrenic group (30.5 6 6.4 years) and the control group (29.6 6 5.5 years) did not differ significantly, nor was there any significant difference in arm length between the two groups. The illness onset age in the schizophrenic group was 20.8 6 3.2 years, and the illness duration was 9.7 6 5.8 years. None of the subjects had any evidence of neurological or spinal cord disease. Although several patients gave the impression of being slightly slow in their movements, there was no evidence of drug-induced neurological phenomena (parkinsonism, drowsiness, etc.). Informed consent was obtained in writing from each subject prior to the study. All were right-handed subjects.
BIOL PSYCHIATRY 1999;45:412– 416
413
them “negative” waves) that continued to be negative, even after the start of the exercise, were judged to be abnormal. MCT was measured using a magnetic stimulator type Magstim 200 (maximum output: 1500 V, Magstim Co.) composed of a circular coil with a diameter of 12.5 cm. The subject’s head or neck was stimulated once, and the latency of motor evoked potentials (MEPs) from the abductor muscle of the right thumb was measured. The head was stimulated with the coil placed on the scalp. The neck was stimulated by placing the center of the coil on the skin above the spinal process of the seventh cervical vertebra during flexion of the rest. The magnitude of stimulation was gradually increased, until the latency had become almost completely stable, and then the minimal values yielded from three measurements were used as the latency for a given subject. A Nippon Kohden Neuropack 8 was used to measure the MEP latency. The MEP latency produced by cortex stimulation is called the MCT, while that produced by cervical stimulation is called the motor root conduction time (MRCT). The difference in the MEP latency during simultaneous stimulation of both the head and neck was held to be the central motor conduction time (CMCT). In statistical tests for comparison of the two groups, age, the illness onset age, the illness duration, the dose of major tranquilizers, the PANSS score, and the MCT were examined using the unpaired t test. The sex of the subject, the type of schizophrenia, the number of subjects with normal or abnormal MRCPs, and the number of major tranquilizers were examined using the chisquare test. p , .05 was considered to be significant.
Methods MRCPs were tested in a shielded room. Each subject assumed a recumbent position and gently held a response button during the test. To eliminate artifacts caused by eye movements, the subjects were asked to try not to move their eyes. The subjects either closed their eyes or gazed at a light placed 1 m above their eyes. MRCPs during voluntary movements were measured as follows. The subject pushed the button by flexing the right thumb and then extended the thumb as rapidly as possible. The patients repeated this sequence of movements, i.e., rapidly flexing and extending the thumb, at their own pace at irregular intervals (about every 5 sec). One session was composed of 50 movement cycles. Each subject performed two sessions, with a 5-min break between them, to allow the reproducibility of the data to be examined. Pulses generated by pushing the button served as triggers. Reference electrodes were attached to both earlobes, and potentials were recorded from C3, Cz, and C4 electrodes using a band-pass filter in a frequency range of 0.05–50 Hz. The analysis time was 3 sec. A Nippon Kohden Neuropack 8 (measurement equipment with an arithmetic unit) was used for summation and averaging. Eye movements were simultaneously recorded. Electroencephalography (EEG) data that included artifacts caused by eye movements were rejected. The MRCP waveforms recorded were classified into “normal” or “abnormal” according to the Tismit-Berthier classification (Tismit-Bertheir et al 1973). Waves that satisfied both of the following requirements were regarded as being normal: 1) waves that appeared 1–1.5 sec before the start of the exercise; and 2) waves that changed rapidly from negative to positive in approximate synchrony with the appearance of the trigger pulses. Flat waves and waves (we call
Results MRCP waves without artifacts were recorded. A small number of waves had to be rejected (18 out of 1368 in the schizophrenic group; 20 out of 1570 in the control group). An example of normal MRCP waveforms is shown in Figure 1. Examples of abnormal MRCP waveforms are shown in Figures 2 and 3. In the schizophrenic group (n 5 27), normal MRCPs were recorded from 6 subjects and abnormal MRCPs from 21 subjects. In the control group (n 5 31), normal MRCPs were recorded from 27 subjects and abnormal MRCPs from 4 subjects. The incidence of abnormal MRCPs was significantly higher in the schizophrenic group than in the control group (P , .01). Abnormal MRCPs in the schizophrenic group consisted of 19 flat waves (catatonic, n 5 1; disorganized, n 5 10; paranoid, n 5 7; undifferentiated, n 5 1) and 2 “negative” waves (paranoid, n 5 1; undifferentiated, n 5 1). All abnormal MRCPs in the control group consisted of flat waves. The 6 patients with normal MRCPs were 3 men and 3 women, consisting of 4 inpatients and 2 outpatients. They were receiving levomepromazine (100 mg/day, 1 patient), chlorpromazine (150 – 400 mg/day, 4 patients), haloperidol (4.5–18 mg/day, 4 patients), sulpiride (300 mg/day, 1 patient), mosapramine hydrochloride (100 mg/day, 1 patient), and bromperidol (18 mg/day, 1 patient). The dose and type of major tranquilizers administered to the 6
414
F. Kubota et al
BIOL PSYCHIATRY 1999;45:412– 416
Figure 1. An example of normal MRCPs.
patients were not different from those administered to the other 21 patients. There was no significant difference in the age, illness onset age, and illness duration between these 6 patients and the other 21 patients. The PANSS
Figure 3. An example of abnormal MRCPs (waves that continued to be negative even after the start of exercise).
score of the 6 MRCP normal patients averaged 63.2 6 17.2 (positive score, 15.5 6 5.6; negative score, 17.3 6 5.7; general psychopathology score, 33.8 6 9.9), while that of the other 21 patients averaged 74.8 6 17.4 (positive score, 14.4 6 5.6; negative score, 22.3 6 6.2; general psychopathology score, 38.7 6 10.2). In the PANSS score, including subscores, there were no significant differences between the 6 MRCP normal patients and the other 21 patients. No significant differences were found between the two groups in the statistical tests in any of the measured variables stated above. Examples of MEPs during stimulation of the head and neck are shown in Figure 4. In the schizophrenic group, the nerve conduction time (NCT) was 21.07 6 1.42 ms, the MRCT was 12.25 6 0.99 ms, and the CMCT was 9.26 6 0.80 ms. In the control group, the NCT was 21.30 6 1.34 ms, the MRCT was 12.04 6 0.81 ms, and the CMCT was 8.82 6 0.71 ms. None of these parameters differed significantly between the two groups. Moreover there were no significant differences between these parameters in the subtypes. Also there was no relationship between the PANSS score, including subscores, and these parameters.
Discussion Figure 2. An example of abnormal MRCPs (flat waves).
Our study revealed that 78% of the schizophrenic group had abnormal MRCPs, compared to 14% in the control
Motor Dysfunction in Schizophrenia
Figure 4. Examples of MEPs.
group. Previous studies have found abnormal MRCPs in 71–78% of schizophrenics (including some psychotics), compared to 12–16% of a control group (Tismit-Berthier et al 1973; Dongier 1973; Kousaka et al 1980; Terayama et al 1985; Kaku et al 1993). The incidence of abnormal MRCPs in our schizophrenic and control groups agreed with reports to date. Our patients with abnormal MRCPs exhibited mostly flat MRCPs. This result is also in agreement with reports to date (Tismit-Berthier et al 1973; Dongier 1973; Kousaka et al 1980; Terayama et al 1985; Kaku et al 1993). It has been reported that few schizophrenics display “negative” waves (Tismit-Berthier et al 1973; Dongier 1973; Takasaka et al 1980; Terayama et al 1985). Two of our schizophrenic group exhibited “negative” waves. The MRCP test is easy and useful to examine patients exhibiting central motor dysfunction, who have been reported to have flat MRCPs (Shibasaki et al 1982). Although it is thought that flat MRCPs indicate reduced motor function, we cannot conjecture the physiological basis for “negative” MRCPs found only in schizophrenics. Although there were no significant differences between the 6 MRCP-abnormal patients and the other 21 patients, the tendency for the 21 MRCP-abnormal patients to have lower scores in the PANSS negative score is found across all of the variables measured. The reason may be that the sample size was small. Twenty-one patients with abnormal MRCPs had raised negative symptoms measured by the PANSS negative score, compared to the other 6 patients. Negative symptoms may result partially from motor dysfunction. We think that 2 out of the 3 catatonic type patients had normal MRCPs, because the 2 patients exhibited few negative symptoms. It
BIOL PSYCHIATRY 1999;45:412– 416
415
has been reported that most schizophrenics in the chronic or disorganized subtype had flat MRCPs (Terayama et al 1985; Kaku et al 1993), but their sample size was too small to support the claim. No other studies have examined the relationships between MRCPs and the variables of schizophrenics (such as type of schizophrenia, major tranquilizers, PANSS score, and so on). It is presumed that MRCPs develop from such areas as the supplementary motor area, or the whole frontal lobe, and so on. The exact generator of the MRCP is unclear, and we have not been able to determine the dissective site of motor dysfunction in schizophrenics. This is the limitation of this method. It is, however, clear that MRCPs develop from the frontal lobe, because of the scrap topography on the head (Shibasaki et al 1980). Our MRCP results suggest that schizophrenics have abnormalities in the motor integration area of the frontal lobe. MCTs have not yet been measured in schizophrenics. The present study revealed no significant differences in the MCT, the MRCT, or the CMCT between the schizophrenic group and the control group, which suggests the absence of any abnormalities in the motor nerve conduction system from the brain to the muscles in schizophrenia. It is well known that major tranquilizers sometimes affect motor function, especially drug-induced parkinsonism. We assessed parkinsonism using the following five symptoms: masked countenance, tremor, rigidity, parkinsonian gait, and excess secretion of sputum. None of the patients exhibited any of these five symptoms. We think that major tranquilizers did not affect the motor functions of our patients. On the basis of these results, we can conclude that the motor dysfunction associated with schizophrenia is probably attributable to damage to the motor integration center of the brain, and that the neural conduction system from the brain to the muscles is usually intact in schizophrenics.
References Crayton JW, Meltzer HY, Goode DJ (1977): Motoneuron excitability in psychiatric patients. Biol Psychiatry 12:545– 561. Dongier M (1973): Event related slow potential changes in psychiatry. In: Bogoch S, editor. Biological Diagnosis of Brain Disorders. New York: Spectrum, pp 47–59. Kaku T, Shiba M, Suzuki E, Momotani Y, Higasi Y (1993): Movement related cortical potential of schizophrenics. Seisin Igaku 5:273–279. Kornhuber HH (1983): Chemistry physiology and neuropsychology of schizophrenia: Towards an earlier diagnosis of schizophrenia I. Arch Psychiatr Nervenkr, 233:415– 422. Manschreck TC, Maher BA, Rucklos ME, Vereen DR (1982): Disturbed voluntary motor activity in schizophrenic disorder. Psychol Med 12:73– 84.
416
BIOL PSYCHIATRY 1999;45:412– 416
Porter R (1990): The Kugelberg lecture. Brain mechanisms of voluntary motor commands—A review. Electroencephalogr Clin Neurophysiol 76:282–293. Robert DC, Richard WL, Larry JS (1989): The relationship between smooth pursuit eye movement impairment and psychological measures of psychopathology. Psychol Med 19: 343–358. Ross-Stanton J, Schlessinger S, Meltzer HY (1980): Multiple neuromuscular abnormalities in a paranoid schizophrenic. Psychiatry Res 3:53– 67. Schwartz F, Carr AC, Munich RL, Glauber S, Lesser BA, Murray J (1989): Reaction time impairment in schizophrenia and affective illness: The role of attention. Boil Psychiatry 25:540 –548. Shibasaki H, Barrett G, Halliday E, Halliday AM (1980): Components of the movement-related cerebral potential and
F. Kubota et al
their scalp topography. Electroencephalogr Clin Neurophysiol 49:213–226. Shibasaki H, Sakai T, Nishimura H, Sato Y, Goto I, Kuroiwa Y (1982): Involuntary movements in chorea-acanthocytosis. A comparison with Huntington’s chorea. Ann Neurol 12:311– 314. Takasaka Y, Yamauti T, Kataoka N, Kudou T, Hirabayashi Y (1980): Movement-related cerebral potentials in psychiatric patients. Rinsyou Nouha 22:471– 476. Terayama K, Kumashiro H, Kaneko Y, Suzuki S, Aono T (1985): Readiness potential in chronic schizophrenics—Physiological approach for the interhemispheric functional disorder. Rinsyou Nouha 27:381–385. Timsit-Berthier M, Delaunoy J, Rousseau J (1973): Slow potential changes in psychiatry. II. Motor potential. Electroencephalogr Clin Neurophysiol 35:363–367.