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Ketatmin reduces the neuromagnetic mismatch reaction
148
A.276. KETATMIN NEUROMAGNETIC REACTION
REDUCES THE MISMATCH
H. Sauer l, I. K r e i t s c h m a n n - A n d e r m a h r 1, E. G a s e r 2, H. N o w a k 3, U. D e m m e 4, T. R o s b u r g 1
Departments of Psychiatry ~, Anesthesiology z, Neurology (Biomagnetic Center) 3 and Forensic Medicine4, University of ,lena, D-07740 Jena, Germany This mismatch field (MMF), the neuromagnetic correlate of the electrophysiological mismatch negativity (MMN), reflects early preconcious information processing. In schizophrenia, the MMF is impaired (Kreitschmann-Andermahr, 1999). In animal experiments, the N-methyl-d-aspartate (NMDA)receptor subtype of the excitatory glutamate receptor system has been linked to the generation of MMN. In order to further elucidate the role of NMDA in the generation of the mismatch reaction, the MMFs of 10 healthy volunteers were investigated before and after i.v. application of the NMDA-receptor antagonist ketamine (0.3mg/kg body weight continuously over 5 minutes). Monaural stimulation was performed using an oddball paradigm with a 1000 Hz standard tone and three different kinds of mismatch (frequency, duration and intensity deviant), each occurring at a 10% pseudorandom probability. Ketamine blood levels were obtained at 20 and 35 minutes after i.v. application. Stable neuromagnetic fields could be elicited and psychotropic effects of ketamine were reported by all participants during the investigation. The strength of the neuromagnetic mismatch field decreased highly significantly after the administration of ketamine, while the strength of the N 100m remained stable. The latency of the MMF was found to be significantly increased under ketamine. The finding of a reduced MMF after ketamine underlies the crucial role of the NMDA-receptor for this kind of information processing and supports the hypoglutamergic hypotheses schizophrenia.
Reference Kreitschmann-Andermahr 1. et al. (1999) Schizophrenia Research 35, 121 129.
A,277. EFFECTS OF TYPICAL AND ATYPICAL ANTI-PSYCHOTICS ON PPI IN SCHIZOPHRENIC PATIENTS B. Oranje, C.J. van Oel, C.C. Gispen-de Wied, M.N. Verbaten, R.S. K a h n
Department of Ps:vchiatrv, University Hospital Utrecht, P.O. Box 85500. 3508 GA, Utrecht, The Netherlands Background: Schizophrenic patients show a loss of sensory gating, which is reflected in a reduced prepulse inhibition of
the startle reflex (PPI). Previous reports on the influence of anti-psychotic medication on PPI are inconclusive. Methods: 50 schizophrenic patients, consisting of 26 with typical and 20 with atypical anti-psychotics, and fifty matched controls were tested in a PPI paradigm. The prepulse and startle stimuli were pure tones of 1500Hz (duration 40ms, intensity 80 dB and I 10 dB respectively), with a fixed interstimulus interval of 120ms. Post-hoc, the data were divided into three blocks of twelve stimuli each. In a MANOVA. PPI blockeffects were analyzed over the three groups, using co-medication (i.e. sedatives) as covariate. Results: Main effects of group (F[2.90] =3.93; p <0.05) and block (F[2.182] =4.99; p<0.01 ) were found, while the effect of co-medication was not significant. Further analysis displayed significant differences between the patients with typical antipsychotics and the control group, regarding the PPI of blocks 1 (t =2.46;p<0.05) and 3 (t--2.57;p<0.05) and total PPI (t= 2.14; p<0.05). No differences were found between the other groups, implicating an improved PPI in the atypical but not in the typical group of patients. In addition, the PPI dropped significantly from block 1 to block 2 and 3 (taken together) in the control (t = 2.91; p < 0.01 ) and atypical (t = 2.57; p < 0.05), but not in the typical group. Conclusion: Atypical anti-psychotics appear to be more effective in restoring sensory gating in schizophrenic patients than typical anti-psychotics.
A.278. DIFFERENTIAL LATENT INHIBITION VOLUNTEERS
DRUG EFFECTS IN HEALTHY
ON
D. M c C a r t a n , C. Campbell, R. Bell*, J.F. Green, K. Trimble, D.J. King
Dept. Therapeutics & Pharm., Whitla Medical Bld, The Queens University, Belfast BT9 7BL, *Dept. Psychology (QUB), David Keir Bld, Malone Road, Belfast BT9 Latent inhibition, a measure of the ability to ignore irrelevant stimuli, may be a model for attentional deficits in schizophrenia (Lubow and Gerwirtz, 1995; Psychol. Bull. 117, 87-103). Inconsistent evidence of LI disruption in schizophrenia, is confounded by antipsychotic drug effects. In healthy volunteers haloperidol (HPL) disrupted LI in an auditory paradigm but enhanced it in a visual paradigm (Williams et al., 1997; Jrnl. Psychopharmacol., 11,247-252). In two studies where n=48, we measured the effects of: SI) HPL (1 mg, i.v.), paroxetine (PAR) (20rag) and placebo (PL1), and $2) chlorpromazine (CPZ) (100 rag), lorazepam (LOR) (2 mg) and placebo (PL2), on LI in healthy volunteers. Designs were double-blind, doubledummy, with parallel groups. Measures included an auditory LI paradigm, the Barnes Akathisia Rating Scale (BARS), eye movement tests and Visual Analogue Rating Scales (VARS). In S1, neither HPL nor PAR influenced LI (p<0.05) (a trend towards disruption was recorded), and no sedation was observed. BARS was highly significant (p<0.001), with 75% of the HPL group reporting akathisia. Therefore, the trend towards disrupted LI may be due to akathisia associated with
A.276. KETATMIN NEUROMAGNETIC REACTION
REDUCES THE MISMATCH
H. Sauer l, I. K r e i t s c h m a n n - A n d e r m a h r 1, E. G a s e r 2, H. N o w a k 3, U. D e m m e 4, T. R o s b u r g 1
Departments of Psychiatry ~, Anesthesiology z, Neurology (Biomagnetic Center) 3 and Forensic Medicine4, University of ,lena, D-07740 Jena, Germany This mismatch field (MMF), the neuromagnetic correlate of the electrophysiological mismatch negativity (MMN), reflects early preconcious information processing. In schizophrenia, the MMF is impaired (Kreitschmann-Andermahr, 1999). In animal experiments, the N-methyl-d-aspartate (NMDA)receptor subtype of the excitatory glutamate receptor system has been linked to the generation of MMN. In order to further elucidate the role of NMDA in the generation of the mismatch reaction, the MMFs of 10 healthy volunteers were investigated before and after i.v. application of the NMDA-receptor antagonist ketamine (0.3mg/kg body weight continuously over 5 minutes). Monaural stimulation was performed using an oddball paradigm with a 1000 Hz standard tone and three different kinds of mismatch (frequency, duration and intensity deviant), each occurring at a 10% pseudorandom probability. Ketamine blood levels were obtained at 20 and 35 minutes after i.v. application. Stable neuromagnetic fields could be elicited and psychotropic effects of ketamine were reported by all participants during the investigation. The strength of the neuromagnetic mismatch field decreased highly significantly after the administration of ketamine, while the strength of the N 100m remained stable. The latency of the MMF was found to be significantly increased under ketamine. The finding of a reduced MMF after ketamine underlies the crucial role of the NMDA-receptor for this kind of information processing and supports the hypoglutamergic hypotheses schizophrenia.
Reference Kreitschmann-Andermahr 1. et al. (1999) Schizophrenia Research 35, 121 129.
A,277. EFFECTS OF TYPICAL AND ATYPICAL ANTI-PSYCHOTICS ON PPI IN SCHIZOPHRENIC PATIENTS B. Oranje, C.J. van Oel, C.C. Gispen-de Wied, M.N. Verbaten, R.S. K a h n
Department of Ps:vchiatrv, University Hospital Utrecht, P.O. Box 85500. 3508 GA, Utrecht, The Netherlands Background: Schizophrenic patients show a loss of sensory gating, which is reflected in a reduced prepulse inhibition of
the startle reflex (PPI). Previous reports on the influence of anti-psychotic medication on PPI are inconclusive. Methods: 50 schizophrenic patients, consisting of 26 with typical and 20 with atypical anti-psychotics, and fifty matched controls were tested in a PPI paradigm. The prepulse and startle stimuli were pure tones of 1500Hz (duration 40ms, intensity 80 dB and I 10 dB respectively), with a fixed interstimulus interval of 120ms. Post-hoc, the data were divided into three blocks of twelve stimuli each. In a MANOVA. PPI blockeffects were analyzed over the three groups, using co-medication (i.e. sedatives) as covariate. Results: Main effects of group (F[2.90] =3.93; p <0.05) and block (F[2.182] =4.99; p<0.01 ) were found, while the effect of co-medication was not significant. Further analysis displayed significant differences between the patients with typical antipsychotics and the control group, regarding the PPI of blocks 1 (t =2.46;p<0.05) and 3 (t--2.57;p<0.05) and total PPI (t= 2.14; p<0.05). No differences were found between the other groups, implicating an improved PPI in the atypical but not in the typical group of patients. In addition, the PPI dropped significantly from block 1 to block 2 and 3 (taken together) in the control (t = 2.91; p < 0.01 ) and atypical (t = 2.57; p < 0.05), but not in the typical group. Conclusion: Atypical anti-psychotics appear to be more effective in restoring sensory gating in schizophrenic patients than typical anti-psychotics.
A.278. DIFFERENTIAL LATENT INHIBITION VOLUNTEERS
DRUG EFFECTS IN HEALTHY
ON
D. M c C a r t a n , C. Campbell, R. Bell*, J.F. Green, K. Trimble, D.J. King
Dept. Therapeutics & Pharm., Whitla Medical Bld, The Queens University, Belfast BT9 7BL, *Dept. Psychology (QUB), David Keir Bld, Malone Road, Belfast BT9 Latent inhibition, a measure of the ability to ignore irrelevant stimuli, may be a model for attentional deficits in schizophrenia (Lubow and Gerwirtz, 1995; Psychol. Bull. 117, 87-103). Inconsistent evidence of LI disruption in schizophrenia, is confounded by antipsychotic drug effects. In healthy volunteers haloperidol (HPL) disrupted LI in an auditory paradigm but enhanced it in a visual paradigm (Williams et al., 1997; Jrnl. Psychopharmacol., 11,247-252). In two studies where n=48, we measured the effects of: SI) HPL (1 mg, i.v.), paroxetine (PAR) (20rag) and placebo (PL1), and $2) chlorpromazine (CPZ) (100 rag), lorazepam (LOR) (2 mg) and placebo (PL2), on LI in healthy volunteers. Designs were double-blind, doubledummy, with parallel groups. Measures included an auditory LI paradigm, the Barnes Akathisia Rating Scale (BARS), eye movement tests and Visual Analogue Rating Scales (VARS). In S1, neither HPL nor PAR influenced LI (p<0.05) (a trend towards disruption was recorded), and no sedation was observed. BARS was highly significant (p<0.001), with 75% of the HPL group reporting akathisia. Therefore, the trend towards disrupted LI may be due to akathisia associated with