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Spontaneous slow and fast MEG activity in male schizophrenics treated with clozapine
International Congress Series 1232 (2002) 733 – 735
Spontaneous slow and fast MEG activity in male schizophrenics treated with clozapine Wolfgang Sperling a,*, Johannes Kornhuber a
Department of Psychiatry, Freidrich Alexander University, Erlangen Nu¨rnberg, Schwabachanlage 6, 91054, Erlangen, Germany
Abstract The atypical neuroleptic clozapine induces specific electroencephalogram changes, which have not been investigated by the use of the technique of Magnetoencephalography (MEG). A 2*37 channel biomagnetic system (Magnes II, Biomagnetic Technologies, San Diego, CA) was used to record spontaneous magnetic activity for the frequency ranges (2 – 6 Hz), (7.5 – 12 Hz), (12.5 – 30 Hz) in schizophrenic patients and controls in two trials within 3 weeks. Our results lend strong support to the assumption of a significant elevation of absolute dipole values (dipole density maximum [Dmax], dipole number [Dtotal], absolute and relative dipole density) in the fast frequency range (12.5 – 30 Hz) over the left hemisphere, especially in the temporoparietal region by clozapine. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Magnetoencephalography; Clozapine; Haloperidole
1. Introduction Clozapine, an atypical antipsychotic drug, is widely used in refractory schizophrenia. It is well known that psychotropic drugs can induce EEG alterations [1,2]. So far, the spontaneous magnetoencephalogram (MEG) has not been deeply investigated in either normal subjects or psychiatric patients (i.e., schizophrenics). The present article reports the findings of changed spontaneous MEG activity in schizophrenic patients treated with clozapine in comparison with healthy controls and schizophrenics treated with haloperidol.
*
Corresponding author.
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 2 ) 0 0 1 4 3 - 7
734
W. Sperling, J. Kornhuber / International Congress Series 1232 (2002) 733–735
Table 1 Variance analysis 2 – 6 Hz for absolute dipole values [Dmax, Dtotal, Ttotal, relative dipole density (Dmax/Dtotal), absolute dipole density (Dmax/Ttotal)] dependent on Sensor (A,B) and group (clozapine-, haloperidole-treated schizophrenics, healthy controls) and dipole localisation) Clozapine group, n=10
DtotalF DmaxF Dmax/DtotalF Dmax/TtotalF TtotalF Dipole localisation
Haloperidol group, n=10
Control group, n=10
Sensor A
Sensor B
Sensor A
Sensor B
Sensor A
Sensor B
2196 (332) 51.3 (24.2) 0.023 (0.001) 4.47 (2.01) 11.46 (1.34) temporoparietal 80%
2067 (286) 47.3 (21.33) 0.022 (0.002) 3.83 (1.98) 12.34 (1.96) temporoparietal 80%
2231 (305) 50.3 (26.47) 0.022 (0.001) 4.77 (2.11) 10.54 (1.12) temporoparietal 80%
2198 (241) 46.9 (20.12) 0.022 (0.001) 4.01 (2.23) 11.67 (2.12) temporoparietal 80%
2004 (210) 51.5 (23.66) 0.021 (0.001) 4.87 (2.10) 10.56 (1.43) central 90%
2231 (253) 47.8 (20.11) 0.021 (0.001) 4.63 (2.33) 10.32 (1.23) central 90%
2. Methods and subjects Spontaneous magnetic brain activity was measured in a magnetically shielded room, using a 2*37 channel biomagnetic system (Magnes II, Biomagnetic Technologies, San Diego, CA). For each subject, the processed data were digitally filtered using a 2 –6- and 7.5– 12-Hz bandpass filter with a steep roll-off (slope of 40 dB/Hz and a flat from 2 to 6 Hz and 7.5 to 12 Hz) or 12.5– 30-Hz bandpass filter with a steep roll-off (slope of 40 dB/ Hz and a flat from 12.5 to 30 Hz) for the analysis of slow, alpha and fast wave activities, respectively. A total of 20 schizophrenic male patients (10 treated with clozapine, 10 treated with haloperidol) and 20 male control subjects were investigated. For the evaluation of the psychopathological status, the PANSS and BPRS rating scales were applied at the first and second examination.
Table 2 Variance analysis frequency 12.5 – 30 Hz for absolute dipole values (Dtotal, Dmax, Ttotal, relative dipole density [Dmax/Dtotal], absolute dipole density [Dmax/Ttotal] dependent on sensor (sensor A, sensor B), group (clozapine group, haloperidole group, healthy controls) and dipole localisation Clozapine group, n=10
DtotalF DmaxF Dmax/DtotalF Dmax/TtotalF TtotalF Dipole localisation *
( p<0.01).
Haloperidole group, n=10
Control group, n=10
Sensor A
Sensor B
Sensor A
Sensor B
Sensor A
Sensor B
2462* (903) 52.1* (33.1) 0.022* (0.02) 4.22* (2.58) 12.33 (1.32) temporoparietal 90%
2327* (901) 51.6 (28.3) 0.022 (0.01) 4.49 (2.56) 11.47 (1.89) central 80%
2112 (873) 42.19 (36.3) 0.019 (0.02) 3.15 (1.98) 13.36 (1.22) central 70%
2213 (760) 48.12 (16.6) 0.021 (0.022) 4.17 (2.58) 11.53 (2.34) central 80%
2175 (1013) 42.13 (41.0) 0.019 (0.02) 3.38 (3.15) 12.45 (1.45) central 70%
2146 (739) 49.3 (16.8) 0.022 (0.02) 4.08 (1.47) 12.07 (1.22) central 70%
W. Sperling, J. Kornhuber / International Congress Series 1232 (2002) 733–735
735
3. Results Tables 1 and 2 show the results of the variance analysis of the group (patients, controls)- and sensor (sensor A, sensor B)-specific absolute dipole values (Ttotal, Dtotal, Dmax, absolute dipole density, relative dipole density) after the first MEG measurement for slow and fast frequency ranges. Significant or tendential deviations were found in the clozapine vis-a-vis the haloperidol group of schizophrenics and controls for Dmax, Dtotal ( p<0.01), the absolute and the relative dipole densities ( p<0.01) for sensor A (left hemisphere) only in the fast frequency range. For sensor B (right hemisphere), Dmax was tendentially elevated in the clozapine group ( p<0.08); no statistically significant difference has been found for Dtotal, absolute and relative dipole density between clozapine-/haloperidol-treated patients and the control group.
4. Conclusion Our results lend strong support to the assumption of a significant effect of clozapine on absolute dipole values (Dmax, Dtotal, absolute- and relative dipole density) and dipole localization in the fast frequency range (12.5 – 30 Hz) over the left hemisphere, especially in the temporoparietal region. With regard to the dipole localization in the slow-frequency range (2 –6 Hz), we found no difference between the clozapine- and haloperidol-treated groups, in which dipole concentration predominated in the temporoparietal region in contrast to the central concentration in healthy controls. To gain more insight into this situation, further studies with larger number of cases, and in particular, investigations in untreated schizophrenics, are needed. Already, however, the results presently available point to the differences between clozapine and haloperidol, both with regard to the distribution of absolute dipole values and dipole localisation.
References [1] I.A. Treves, M.Y. Neufeld, EEG abnormalities in clozapine-treated schizophrenic patients, Eur. Neuropsychopharmacol. 6 (1996) 155 – 158. [2] M.Y. Neufeld, J.M. Rabey, E. Orlov, Electroencephalogram findings with low-dose clozapine treatment in psychotic parkinsonian patients, Clin. Neuropharmacol. 19 (1996) 81 – 86.
Spontaneous slow and fast MEG activity in male schizophrenics treated with clozapine Wolfgang Sperling a,*, Johannes Kornhuber a
Department of Psychiatry, Freidrich Alexander University, Erlangen Nu¨rnberg, Schwabachanlage 6, 91054, Erlangen, Germany
Abstract The atypical neuroleptic clozapine induces specific electroencephalogram changes, which have not been investigated by the use of the technique of Magnetoencephalography (MEG). A 2*37 channel biomagnetic system (Magnes II, Biomagnetic Technologies, San Diego, CA) was used to record spontaneous magnetic activity for the frequency ranges (2 – 6 Hz), (7.5 – 12 Hz), (12.5 – 30 Hz) in schizophrenic patients and controls in two trials within 3 weeks. Our results lend strong support to the assumption of a significant elevation of absolute dipole values (dipole density maximum [Dmax], dipole number [Dtotal], absolute and relative dipole density) in the fast frequency range (12.5 – 30 Hz) over the left hemisphere, especially in the temporoparietal region by clozapine. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Magnetoencephalography; Clozapine; Haloperidole
1. Introduction Clozapine, an atypical antipsychotic drug, is widely used in refractory schizophrenia. It is well known that psychotropic drugs can induce EEG alterations [1,2]. So far, the spontaneous magnetoencephalogram (MEG) has not been deeply investigated in either normal subjects or psychiatric patients (i.e., schizophrenics). The present article reports the findings of changed spontaneous MEG activity in schizophrenic patients treated with clozapine in comparison with healthy controls and schizophrenics treated with haloperidol.
*
Corresponding author.
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 2 ) 0 0 1 4 3 - 7
734
W. Sperling, J. Kornhuber / International Congress Series 1232 (2002) 733–735
Table 1 Variance analysis 2 – 6 Hz for absolute dipole values [Dmax, Dtotal, Ttotal, relative dipole density (Dmax/Dtotal), absolute dipole density (Dmax/Ttotal)] dependent on Sensor (A,B) and group (clozapine-, haloperidole-treated schizophrenics, healthy controls) and dipole localisation) Clozapine group, n=10
DtotalF DmaxF Dmax/DtotalF Dmax/TtotalF TtotalF Dipole localisation
Haloperidol group, n=10
Control group, n=10
Sensor A
Sensor B
Sensor A
Sensor B
Sensor A
Sensor B
2196 (332) 51.3 (24.2) 0.023 (0.001) 4.47 (2.01) 11.46 (1.34) temporoparietal 80%
2067 (286) 47.3 (21.33) 0.022 (0.002) 3.83 (1.98) 12.34 (1.96) temporoparietal 80%
2231 (305) 50.3 (26.47) 0.022 (0.001) 4.77 (2.11) 10.54 (1.12) temporoparietal 80%
2198 (241) 46.9 (20.12) 0.022 (0.001) 4.01 (2.23) 11.67 (2.12) temporoparietal 80%
2004 (210) 51.5 (23.66) 0.021 (0.001) 4.87 (2.10) 10.56 (1.43) central 90%
2231 (253) 47.8 (20.11) 0.021 (0.001) 4.63 (2.33) 10.32 (1.23) central 90%
2. Methods and subjects Spontaneous magnetic brain activity was measured in a magnetically shielded room, using a 2*37 channel biomagnetic system (Magnes II, Biomagnetic Technologies, San Diego, CA). For each subject, the processed data were digitally filtered using a 2 –6- and 7.5– 12-Hz bandpass filter with a steep roll-off (slope of 40 dB/Hz and a flat from 2 to 6 Hz and 7.5 to 12 Hz) or 12.5– 30-Hz bandpass filter with a steep roll-off (slope of 40 dB/ Hz and a flat from 12.5 to 30 Hz) for the analysis of slow, alpha and fast wave activities, respectively. A total of 20 schizophrenic male patients (10 treated with clozapine, 10 treated with haloperidol) and 20 male control subjects were investigated. For the evaluation of the psychopathological status, the PANSS and BPRS rating scales were applied at the first and second examination.
Table 2 Variance analysis frequency 12.5 – 30 Hz for absolute dipole values (Dtotal, Dmax, Ttotal, relative dipole density [Dmax/Dtotal], absolute dipole density [Dmax/Ttotal] dependent on sensor (sensor A, sensor B), group (clozapine group, haloperidole group, healthy controls) and dipole localisation Clozapine group, n=10
DtotalF DmaxF Dmax/DtotalF Dmax/TtotalF TtotalF Dipole localisation *
( p<0.01).
Haloperidole group, n=10
Control group, n=10
Sensor A
Sensor B
Sensor A
Sensor B
Sensor A
Sensor B
2462* (903) 52.1* (33.1) 0.022* (0.02) 4.22* (2.58) 12.33 (1.32) temporoparietal 90%
2327* (901) 51.6 (28.3) 0.022 (0.01) 4.49 (2.56) 11.47 (1.89) central 80%
2112 (873) 42.19 (36.3) 0.019 (0.02) 3.15 (1.98) 13.36 (1.22) central 70%
2213 (760) 48.12 (16.6) 0.021 (0.022) 4.17 (2.58) 11.53 (2.34) central 80%
2175 (1013) 42.13 (41.0) 0.019 (0.02) 3.38 (3.15) 12.45 (1.45) central 70%
2146 (739) 49.3 (16.8) 0.022 (0.02) 4.08 (1.47) 12.07 (1.22) central 70%
W. Sperling, J. Kornhuber / International Congress Series 1232 (2002) 733–735
735
3. Results Tables 1 and 2 show the results of the variance analysis of the group (patients, controls)- and sensor (sensor A, sensor B)-specific absolute dipole values (Ttotal, Dtotal, Dmax, absolute dipole density, relative dipole density) after the first MEG measurement for slow and fast frequency ranges. Significant or tendential deviations were found in the clozapine vis-a-vis the haloperidol group of schizophrenics and controls for Dmax, Dtotal ( p<0.01), the absolute and the relative dipole densities ( p<0.01) for sensor A (left hemisphere) only in the fast frequency range. For sensor B (right hemisphere), Dmax was tendentially elevated in the clozapine group ( p<0.08); no statistically significant difference has been found for Dtotal, absolute and relative dipole density between clozapine-/haloperidol-treated patients and the control group.
4. Conclusion Our results lend strong support to the assumption of a significant effect of clozapine on absolute dipole values (Dmax, Dtotal, absolute- and relative dipole density) and dipole localization in the fast frequency range (12.5 – 30 Hz) over the left hemisphere, especially in the temporoparietal region. With regard to the dipole localization in the slow-frequency range (2 –6 Hz), we found no difference between the clozapine- and haloperidol-treated groups, in which dipole concentration predominated in the temporoparietal region in contrast to the central concentration in healthy controls. To gain more insight into this situation, further studies with larger number of cases, and in particular, investigations in untreated schizophrenics, are needed. Already, however, the results presently available point to the differences between clozapine and haloperidol, both with regard to the distribution of absolute dipole values and dipole localisation.
References [1] I.A. Treves, M.Y. Neufeld, EEG abnormalities in clozapine-treated schizophrenic patients, Eur. Neuropsychopharmacol. 6 (1996) 155 – 158. [2] M.Y. Neufeld, J.M. Rabey, E. Orlov, Electroencephalogram findings with low-dose clozapine treatment in psychotic parkinsonian patients, Clin. Neuropharmacol. 19 (1996) 81 – 86.