Effect of Neuroleptics on Altered Cerebral Glucose Metabolism in Schizophrenia

Szechtman, Henry; Nahmias, Claude; Garnett, E. S.; Firnau, Gunther; Brown, Gregory M.; Kaplan, Ronald D.; Cleghorn, John M.

doi:10.1001/archpsyc.1988.01800300019002

Cited by 175 publications

(54 citation statements)

References 44 publications

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“…This suggests that neuroleptic-induced prolactin increases, which are an index of dopamine D: antagonism at the pituitary level, may be a less precise measure of antagonism in the brain itself than the radioligand uptake method described here. Chronic administration of neuroleptics to schizophrenics is reported to increase metabolic rate of glucose in the basal ganglia (DeLisi et al 1985;Buchsbaum et al 1987 ;Szechtman et al 1988). However, our finding of no significant effect of neuroleptic dosage on cerebral blood flow is consistent with previous PET studies of acute neuroleptic administration (Volkow et al 1986).…”

Section: Discussionsupporting

confidence: 92%

Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and11C-raclopride

et al. 1993

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Abstract. Positron emission tomography (PET) and 11C. raclopride were used to measure the occupancy of central dopamine D2 receptors by a new neuroleptic, CP-88,059-1. In a double blind dose escalation study, seven healthy male subjects received a predose of between 2 mg and 60 mg CP-88,059-1, 5 h before PET scanning. One additional subject was assigned to placebo predose. Receptor occupancy was defined as the percentage reduction in binding potential compared with that seen in the subject predosed with placebo and with that seen in seven unmedicated normal volunteers previously studied. Binding of 11C-raclopride decreased in a dose dependent manner, and 85 % dopamine D 2 receptor occupancy was achieved with the highest dose of CP-88,059-1. The findings confirm that brain dopamine D 2 receptors are blocked by CP-88,059-1 and suggest that an effective antipsychotic dose will be between 20 mg and 40 mg. The study highlights the potential of positron emission tomography in the preclinical evaluation of new drugs.

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Section: Discussionsupporting

confidence: 92%

Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and11C-raclopride

et al. 1993

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“…From the viewpoint of the model psychosis paradigm, our results are in line with evidence in favor of an association between acute psychotic episodes and hyperactivity in frontal cortical regions (Wiesel et al 1987;Szechtman et al 1988;Cleghorn et al 1989;Ebmeier et al 1993;Parellada et al 1994). These findings are in contrast with the hypofrontality, which has repeatedly been reported in studies with chronic schizophrenic patients (Buchsbaum et al 1982;Farkas et al 1984;Cohen et al 1987;Volkow et al 1987;Weinberger et al 1988;Wolkin et al 1988;Buchsbaum et al 1990;Andreasen et al 1992;Wolkin et al 1992;Siegel et al 1993).…”

Section: Neurometabolic Effects Of the Drugs And Correlations With Pssupporting

confidence: 88%

Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG

Gouzoulis-Mayfrank

1999

Neuropsychopharmacology

181

100

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The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation taskwere investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n ϭ 8 Experimental studies of cerebral blood flow and metabolism with psychoactive drugs in humans aim to explore the interaction of these drugs with human brain function. Recent studies with hallucinogenic, "mind-expanding" drugs in healthy subjects provided evidence in favor of an altered functional interhemispheric balance From the Department of Psychiatry and Psychotherapy (EG-M, BT, HS), University of Technology (RWTH), Aachen, Germany; Department of Nuclear Medicine (MS, OS, CA, UB), University of Technology (RWTH), Aachen, Germany; Department of Psychiatry (MS), University of Ulm, Ulm, Germany; Pharmaceutical Institute (K-AK), University of Tübingen, Tübingen, Germany; Psychiatric and Neurological Hospital Christophsbad (LH), Göppingen, Germany.Address correspondence to: E. Gouzoulis-Mayfrank, M.D., Department of Psychiatry and Psychotherapy, University of Technology (RWTH), Pauwelsstrasse 30, D-52074 Aachen, Germany.Received March 14, 1998, accepted July 20, 1998 566 E. Gouzoulis-Mayfrank et al. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 6 with right hemispheric dominance and an increased activity in frontocortical regions after acute administration of mescaline, psilocybin, or ketamine (Hermle et al. 1992; Vollenweider et al. 1997a, b). The most profound increase in metabolism was found in the anterior cingulate (Vollenweider et al. 1997a(Vollenweider et al. , 1997b, which is linked to both emotional and attentional functions (Vogt et al. 1992;Devinsky et al. 1995;Murtha et al. 1996). These functions are, in turn, tightly connected to both the effects of hallucinogens and the symptoms of schizophrenic and schizophrenia-spectrum psychoses.Hallucinogenic drug-induced states can be used as models for acute endogenous psychotic states in psychiatric research (Hermle et al. 1992; Vollenweider et al. 1997a, b;Gouzoulis-Mayfrank et al. 1998). Within the framework of this model psychosis paradigm neurometabolic data from the above-mentioned studies can be interpreted in the sense that acute psychotic states with prominent positive symptoms are linked to increased activity in frontal neocortical, and limbic areas. This is in contrast to the majority of functional neuroimaging studies with schizophrenic patients, which demostrate hypofrontality both in resting states (Buchsbaum et al. 1982;Farkas et al. 1984;Wolkin et al. 1988;Siegel et al. 1993) and under cognitive tasks believed to employ frontal brain areas (Cohen et al. 1987;Weinberger et al. 1988;Buchsbaum et al. 1990;Andreasen et al. 1992). However, most of these studies were performed with chronically ill patients on various neuroleptic medications, a...

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“…5 This hyperperfusion correlates positively with at least some acute schizophrenic symptoms and their severity, 30 as imaging studies have shown. 3,5,28,31 This study is the first to demonstrate locally increased CBFV in first-episode acute schizophrenics against agematched normal control subjects with the use of TCD. Increases were most pronounced in the MCA and the ACA on both sides.…”

Section: Discussionmentioning

confidence: 78%

“…[1][2][3] Most studies deal mainly with chronic schizophrenia, and the essential finding is hypoperfusion. Using 133 Xe inhalation, Ingvar and Franzén 4 were the first to report hypofrontality in schizophrenics.…”

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confidence: 99%

Cerebral Blood Flow Velocity in Acute Schizophrenic Patients

Owega

Klingelhöfer

Sabri

et al. 1998

Stroke

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Background and Purpose-The aim of this study was to determine whether acutely psychotic first-episode schizophrenics show an increased cerebral blood flow velocity and whether this condition is reversible on psychopathological improvement. Methods-In the first of two examinations, transcranial Doppler ultrasonography and assessment with the Positive and Negative Syndrome Scale (PANSS) were performed on 28 acutely psychotic, neuroleptically naive, first-episode schizophrenics. In the second examination, the same patients were assessed psychometrically (PANSS) as well as with Doppler ultrasonography after psychopathological improvement. Results-Acutely psychotic first-episode schizophrenics showed a significant increase of the mean velocity on both sides in the middle and anterior cerebral arteries and in the right posterior cerebral artery. Blood flow showed significant correlations with productive psychotic symptoms. After psychopathological improvement there was a bilateral normalization of the mean velocity in the middle, anterior, and posterior cerebral arteries. Conclusions-Acutely psychotic first-episode schizophrenics show a significantly increased bilateral cerebral blood flow velocity, which normalizes on psychopathological improvement. There were significant correlations of cerebral blood flow velocity with psychopathology. 1-3 Most studies deal mainly with chronic schizophrenia, and the essential finding is hypoperfusion. Using 133 Xe inhalation, Ingvar and Franzén 4 were the first to report hypofrontality in schizophrenics. Some recent imaging studies on acute schizophrenia 5 describe hyperperfusion in the supply areas of the MCA and the ACA, occasionally with a left-side predominance. An investigation of brain activity in schizophrenics depends on the profile of the particular target symptom and on how strongly it is pronounced in the patient group. 6 Hoyer and Ö sterreich 7 found that acutely psychotic schizophrenics show an increase in global cerebral perfusion of about twice the normal value, whereas in chronic schizophrenics this parameter is significantly lower than in acute schizophrenics or healthy control subjects, without a significant difference between control subjects and patients with paranoia or schizophrenia simplex. It should thus be possible to demonstrate a correlation between psychotic state and CBFV.TCD is a standard method in neurology and neurosurgery but is not yet widely used in psychiatry, and no systematic neuropsychiatric studies have used this method. CBFV measurements by TCD show a high reliability 8 -11 and correlation with rCBF.12-15 TCD can locate vessels and quantify blood flow velocity with precision, 16 thus allowing an accurate identification of the vessel irrigating the brain area in question. CBFV is the decisive Doppler parameter since flow velocity varies directly with the diameter of the small resistance vessels, whereas the diameter of the basal cerebral arteries remains essentially constant. 17,18 Given that CBF equals CBFV times vessel diameter, where ve...

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Effect of Neuroleptics on Altered Cerebral Glucose Metabolism in Schizophrenia

Cited by 175 publications

References 44 publications

Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and11C-raclopride

Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and11C-raclopride

Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG

Cerebral Blood Flow Velocity in Acute Schizophrenic Patients

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