Acute CEEG modifications after clozapine and haloperidol administration in schizophrenics

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179

necessary to prevent schizophrenic relapses [I]. The 1-123IBZM-(3-iodo6-methoxybenzamide, Cygne BV) SPECT has the potential to develop as an objective and sensitive method for the assessment of an optimal dose finding below high D2 receptor blockade. The aim of this study was to optimize the analysis of the D2 dopamine receptor occupancy by superimposition of corresponding 1-123 IBZM-SPECT and MR (magnetic resonance)-data. The results were compared with the conventional analysis. We performed 1-123IBZM-SPECT and MRI in 9 schizophrenic patients. An exact conformity was achieved by an three-dimensional and interactive fusion algorithm. Our results show that the combination of IBZM-SPECT data and MR-data allows the exact definition of the RaJ's. This analysis is superior to the conventional one, especially in cases of higher D2 receptor blockade (60-80%). The location and size of the RaJ's can be defined in an objective and reproducible manner. An overestimation of the SPECT-data can be avoided by the neuroanatomic delineation of the MR-data. This will be an advantage for follow-up studies concerning D2 occupancy to evaluate the optimal neuroleptic dose. n

SPECT

MR-fusion

2.03

Medium

3 3

high blockade

3

1.92 1.6 1.33

SIFC ratio Normal

1.56 1.13

[I] NybergS, Farde L, HalldinC, Dahl ML, BertilssonL, Am. J. Psychiatry 152:2 (1995) 173-178

IP-17-91

Neuroleptic DoseRelated 02 Receptor Occupancy Measured by IBZM Spect

R. Coppola, M.B Knable, A. Heinz, 1. Gorey, DR Weinberger. CBDB, NIMH, Washington, DC

Previous studies have estimated receptor occupancy by comparing the specific to nonspecific binding ratio in patients to a normal control group mean. The purpose of the present study was to use IBZM SPECT to determine a relationship between dose or serum concentration levels and occupancy for haloperidol and resperidone treated schizophrenic patients. Patients were scanned at two different dose levels approximately three weeks apart. A 30 minute SPECT scan was obtained 90 minutes after IBZM injection. Specific to nonspecific ratio was determined by measuring activity in basal ganglia minus cerebellum and cerebellum alone. The same measure was determined in a larger normal control group and occupancy estimated as [l-patientlnormmean 100. A two parameter hyperbolic function was fit to determine the relation between observed occupancy and dose or blood level. Haloperidol showeda higher occupancy (up to 80%) and better fit (R2 = 0.87) than resperidone. Fit was better for serum concentration than for dose in both cases. The data suggest that it may be possible to individually adjust dose levels.

r

I P-17-10 I Pharmaco EEG Effects of 5(+) DN·2327 Enantiomer and DN-2327 Racemate

B. Dietrich. LA.B. GmbH & Co, Neu-Ulm, Germany

DN-2327 is a new non-benzodiazepine compound with anxiolytic properties. Analytical studies showed different characteristics of the two enantiomers. This study was performed to explore the central nervous effects of 0.5, I, 2 and 4 mg of the S(+) DN-2327 enantiomer in comparison with I, 2, 4 and 8 mg of the DN-2327 racemate with the help of Pharmaco EEG (PEEG). Results of 34 healthy male volunteers could be analyzed. With intervals of one week each volunteers received 4 different single doses of the investigational compounds, 2 of the racemate and 2 of the S(+) enantiomer, and additionally placebo. Treatment assignment was randomized approaching a balanced incomplete block design as closely as possible. PEEG was recorded pre-dose and 2 and 5 hrs post-dose. Absolute and relative power values of 7 predefined frequency bands were determined. Both compounds showed dose dependent PEEG effects: decrease of absolute power in the theta and both alpha bands frontocentrally and occipitotemporally: increase of power in the beta bands frontocentrally and a decrease occipitotemporally; decrease of delta power only with higher doses. The relative potency of the

enantiomer in comparison with the racemate showed a ratio of I:2, thus indicating that the S(+) DN-2327 enantiomer is the pharmaco-dynamic active part of the DN-2327 racemate.

I P-17-11 I Quantita~ive Electroencephalography in Primary Dysthymia

A. Ravindran, V. Knott, Y. Charbonneau. University of Ottawa, Royal Ottawa Hospital, Ottawa, Canada Previous quantitative EEG (QEEG) studies have identified greater right frontal activation in patients with major depression. There are no reported QEEG investigations in dysthymia, a mood disorder with significant morbidity. Twenty-nine patients who fulfilled DSM III-R criteria for primary early onset dysthymia were investigated with QEEG before and after treatment with either placebo and sertraline both groups also receiving cognitive therapy. Fourteen age and sex matched healthy volunteers served as normal controls. Monopolar EEG was recorded from a double banana 16 site montage and processed by Fast Fournier analysis for computation of absolute and relative amplitude and coherence indices in delta, theta, alpha, beta I , beta-, and beta., frequency bands. Preliminary analysis focussed on pre-treatment absolute amplitude measures evidenced a three way interaction with patients exhibiting reduced alpha amplitudes in left anterior recording sites (relative to homologous right anterior sites) while normal controls evidenced similar asymmetry but at central and posterior temporal sites. No significant differences were seen post treatment. The results indicate that inter-hemispheric relationships may be distorted in patients with dysthymia and that the neuroelectric disturbances may differ from those observed in major depression. Additional findings of the relationship between QEEG measures and other biological markers, symptom measures, and treatment responses will also be presented.

I P-17-121 EEG Coherence Analysis Shows Hypofrontality in SChizophrenic Patients 1. Tauscher, P.Rappelsberger, A. Neumeister,S. Kasper. Dept. of General Psychiatry and lnst. for Neurophysiology, Univ. of Vienna, Austria Reduced blood flow in the dorsolateral prefrontal cortex during cognitive activation requiting "workingmemory" lead to the concept of hypofrontality in schizophrenia. The objective of our study was to investigate whether EEG coherence analysis can be used to depict information-processing deficits in schizophrenic patients. EEG were recorded of 15 medicationfree schizophrenic patients and 16 healthy controls. Averaged power- and cross-power-spectra were computed for six standard frequency bands, as well as coherence and mean amplitudes. During the recordings the subjects had to perform a shape recognition task and mental arithmetic. The obtained spectralparameters were compared with baseline activity with open eyes at rest. Differences were presented in spectralparametermaps and results of statistical evaluations (paired Wilcoxon tests) in probability maps. During the shape recognitiontask, an increase of coherence in the theta-band parietally was seen in both groups. However, a significant coherence decrease in frontal regions during both tasks was seen only in the control-group. This lack of frontal involvement during cognitive activation requiring "workingmemory" supports the concept of hypofrontality in schizophrenia. This study was done in the framework of the BIOMED-I concerted action ANNDEE (BMHI-CT94-I129) sponsored by the E. c., DG XII, and the Austrian Fed. Min. of Science, Research and the Arts.

I P-17-131 Acute CEEG Modifications After Clozapine and Haloperidol Administration in Schizophrenics G.F.Marchesi, B. Nardi, G. Pannelli, G. Santone, P. Ianni, M. Brandoni. Institute of Psychiatry, University ofAncona, Ancona, Italy It is well known that atypical neuroleptics, such clozapine, show few similarities with traditional neuroleptics, such haloperidol: different receptors affinity, low extrapyramidal side effects and good efficacy in the treatment of both positive and negative symptoms of schizophrenia are

P Poster Presentations

180 points in agreement with their specifical pharmacodynamical mechanism [I]. The aim of this study was to evaluate the acute electroencephalografic modifications induced by oral administration of clozapine and haloperidol in subjects affected by schizophrenia. according DSM-IV criteria. Eighteen schizophrenic patients, hospitalised during an acute exacerbation (9 males, mean age: 37.5 years, range: 21-54 years; 9 females, mean age: 34 years, range: 27-41 years), were randomlydivided into two groups of 9 subjects each. The first group received 25 mgfd of clozapine, and the second group 6 mgld of haloperidol. The acute pharmacodynamical effects of clozapine and haloperidol were investigated using a computerised quantitative eiectrophysiological approach (computerised electroencephalography, CEEG): each subject underwent a CEEG recording during psychosensorial rest in a drug free condition and 1/2 hr, I hr, 3 hrs, 6 hrs and 24 hrs after drug administration. Data concerning the relative power of delta (0.5- 4 Hz), theta (4-8 Hz). alpha (8- 12 Hz) and beta (12-3 1 Hz) were statistically evaluated (Friedman test. Wilcoxon test. Linear Regression and Correlation test). Both c1ozapine and haloperidol induced a small increase of beta activity; on the other hand, data concerning slow activity were not univocal. With respect to alpha acitivity, a significant reduction was observed in the clozapine group (p = 0.01) and it was more evident between 30 min and I hr after the drug administration (p = 0.05); between 6 and 24 hrs after the drug administration. alpha activity increased again (p = 0.05). At the same time delta activity showed an initial increase that was reduced after 24 hrs. A significant correlation between alpha and delta modifications was observed (p < 0.01). Such a pattern was not observed in the haloperidol group. In conclusion. CEEG was useful in monitoring the different acute pharmacodynamical effects of the two drugs. [I ] Stille G.• Hippius H.: Kritische Stellungnahme zum Begriff der Neuroleptika (und vonpharmakologischen und klinischen Befunden mit Clozapin). Pharmacopsychiatrie, 4: 182- 191, 1971.

1P-17-1 4 1 EEG Mapping Longitudinal Evaluation of Patients Affected by Schlzophrenlform Disorder G.F. Marchesi, B. Nardi. G. Pannelli, F. Poletti. C. Pierini, S. Biagiotti. Institute of Psychiatry. University of Ancona, Ancona, Italy The aim of this study was to evaluatetopographicaland e1ectrophysiological aspects in subjects affectedby schizophreniformdisorder. Twenty-one patients (13 males, mean age: 21.3 yrs, range: 16-31 yrs; 8 females, mean age 25.3 yrs, range: 18-36 yrs) were selected according DSM IV criteria for schizophreniform disorder and underwent a clinicalevaluation (integrated with SANS and SAPS) and two EEG Mapping (EEGM) recordings (at the onset, after 6 months and after 1 year). Data obtained were statistically evaluated with t-test and Friedman's test. Twelve patients were re-examined after 6 months from the onset, and 7 after I year. After 6 months, the clinical evolution of the disorder was as follows: Schizophrenia (n = 4); Mood Disorder (n ::: I); Personality Disorders (n ::: 7 ). Considering SANS and SAPS results. all patients showed a significant reduction of both negative and positive symptoms (p < 0.(02). With regard to EEGM results, according to our previousstudy [1] at the onset 17 patients showed a "normal-like" pattern and 4 a "slow" pattern (i.e.. evidence of delta and theta activity). After 6 months, the 12 subjects showed an improvement in their EEGM patterns: in general. a significant increase of alpha activity (p < 0.(08 ) and a significant decrease of beta and theta activity (p < 0.008 in both cases) were observed. Furthermore. the "normal-like" pattern (n ::: 10) showed an better topographic localisation of alpha activity in the temporo-occipital region (more of evident in the subject with a Mood Disorder) and a tendency of alpha activity to spread to the anterior regions in 2 of the 4 patients with Schizophrenia. Finally, a modification from the "slow" to "normal-like" pattern was observed in the other 2 schizophrenic patients. After I year. the 7 subjects re-examined showed a substantial stability both in their EEGM pattern ("normal-like") and in their diagnostic evaluation. [Il Marchesi G.P. Nardi, B.: Clinical and electroencephalogram mapping investigations in aeute schizophrenic patients. In: Ravizza L.. Boggetto P.. Zanalda E. (Eds.), Psychiatry and Advanced Technologies, 43-59, Raven Press, New York, 1993.

1P-17-151 Difference of Processing among Parts-of-Speech Using Event-Related Potentials A. Takashima I , K. Ohta I • M. Yoshino 2, T. Ohkura 2, K. Hara I , E. Matsushima 1. M. Toru 1. I Department of Neuropsychiatry, Tokyo Medical and Dental University School of Medicine, Tokyo, Japan; 2 Onda-daini Hospital, Chiba, Japan Previous studies have reported the differences that appear in event-related potentials (ERPs) between congruous and incongruous word completion of sentences. The differences in the process of recognition and integration among the parts-of-speech in Japanese have not yet been studied. In this study, we presented 3 sets of sentences on a screen, word by word each lasting 1.2 sec, and measured ERPs for a epoch of 1000 msec. beginning 100 msec before the onset of word presentation. Only verbs, nouns, auxiliary verbs and particles were selected and analysed. Words with more than 2 characters were omitted. Each group elicited a positive component starting at around 150 msec and reached a peak at approximately 200 msec. There was a statistical significant difference among the mean amplitudes for this range of the 4 groups. The noun and the verb group showed the largest amplitude followed by the auxiliary verb and the particle group respectively. For the particle group, this positive component disappeared the earliest at about 500 msec. No significant difference for the noun and the verb group was found. This suggests that content word class (noun. verb) mobilized more processing resources for recognition and integration compared with functional word class (auxiliary verb, particle).

I P-17-161 ..

Audito.ry P300 in Depression with Silent Cerebral Infarction

1. Yanai I, Y. Otagaki 1, Y. Touhouda I . T. Fujikawa2, M. Osada 2, S. Yamawaki 2. I Department of Psychiatry and Neurology, Hiroshima Prefectural Hiroshima Hospital, Hiroshima, Japan; 2 Departmentof Psychiatry and Neurosciences, Hiroshima University School of Medicine, Hiroshima, Japan Purpose The auditory P300 component of the event-related potentials is associated with cognitive processing. The aim of this study is to investigate the influence of silent cerebral infarction (SCI) detected by magnetic resonance imaging (MRI) on P300 component of patients with major depression. Subjects and Methods Patients who met the DSM-III-R criteria for major depression (n = 16) were measured P300 component using oddball task before and after medical treatment. They were classified based on MRI findings into the SCI+ (n = 7) or SCI- (n = 9) group. Data recorded before medical treatment were compared with that of controls (n::: 17). Effects of medical treatment on P300 component were studied between the SCI+ and the SCI- group. Patients with stroke or focal neurological symptoms were excluded. Informed consent was obtained according to institutional guidelines. Results P300 amplitude in patients was significantly smaller than that of controls (p < 0.01 ). P300 latency in the SCI+ group was significantly longer than that of controls (p < 0.05). P300 amplitude after medical treatment increased significantly in the SCI-group (p < 0.05), but not in the SCI+ group. P300 latency did not change significantly by medical treatment in both groups. Conclusion Our findings suggest that depressed patients·have some cognitive dysfunctionand that SCI may interfere with recovery from such dysfunction in depression.

1P-17-171 Contextual Effects and Repetition Effects on N400 and LatePositive Component K. Ohta 1, A. Takashima I, M. Yoshino 2. T. Ohkura 2, K. Hara 1, E. Matsushima I • M. Toru I . I Departmentof Neuropsychiatry, Tokyo Medical and Dental UniversitySchool of Medicine, Tokyo, Japan; 2 Onda-daini Hospital, Chiba, Japan N400 and late positive components (LPCs) have been shown to be sensitive to congruity, expectancy, frequency, repetition. and task. In order to clarify contextual effects and repetition effects in Japanese. the present