D1-Dopamine Receptor Availability in First-Episode Neuroleptic Naive Psychosis Patients

Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be...

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Published inThe international journal of neuropsychopharmacology Vol. 22; no. 7; pp. 415 - 425
Main Authors Stenkrona, Per, Matheson, Granville J, Halldin, Christer, Cervenka, Simon, Farde, Lars
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.07.2019
Subjects
Adult
Antipsychotic agents
Antipsychotics
Bayesian analysis
Benzazepines
Brain
Brain - diagnostic imaging
Brain - metabolism
Brain Mapping
Brain research
Cardiotonic agents
D-1 dopamine receptor
Diagnostic imaging
Dopamine
dorsolateral prefrontal cortex
drug naive
Female
Follow-Up Studies
Health aspects
Humans
Hypotheses
Magnetic Resonance Imaging
Male
Medical research
Middle Aged
Phenols (Class of compounds)
Physiological aspects
Positron emission tomography
Psychosis
Psychotic disorders
Psychotic Disorders - diagnostic imaging
Psychotic Disorders - metabolism
Radiopharmaceuticals
Receptors, Dopamine D1 - metabolism
Regular s
Schizophrenia
Schizophrenia - diagnostic imaging
Schizophrenia - metabolism
Tomography
Young Adult
Sweden
D1 dopamine receptor
schizophrenia
positron emission tomography
dorsolateral prefrontal cortex
drug naïve
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Abstract Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs. Here, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [11C]SCH23390. We observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum. This investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.
AbstractList Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs.BACKGROUNDPositron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs.Here, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [11C]SCH23390.METHODSHere, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [11C]SCH23390.We observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum.RESULTSWe observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum.This investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.CONCLUSIONSThis investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.
Background: Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs. Methods: Here, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [[.sup.11]C]SCH23390. Results: We observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum. Conclusions: This investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus. Key words: schizophrenia, drug naive, positron emission tomography, [D.sub.1] dopamine receptor, dorsolateral prefrontal cortex
Background Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs. Methods Here, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [11C]SCH23390. Results We observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum. Conclusions This investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.
Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs. Here, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [11C]SCH23390. We observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum. This investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.
Background: Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs. Methods: Here, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [C-11]SCH23390. Results: We observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum. Conclusions: This investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.
Audience Academic
Author Matheson, Granville J
Halldin, Christer
Cervenka, Simon
Stenkrona, Per
Farde, Lars
AuthorAffiliation 1 Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden
2 PET Science Centre, Precision Medicine, R&D Oncology, AstraZeneca, Karolinska Institutet, Sweden
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Issue 7
Keywords D1 dopamine receptor
schizophrenia
positron emission tomography
dorsolateral prefrontal cortex
drug naïve
Language English
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PublicationCentury 2000
PublicationDate 2019-07-01
PublicationDateYYYYMMDD 2019-07-01
PublicationDate_xml – month: 07
  year: 2019
  text: 2019-07-01
  day: 01
PublicationDecade 2010
PublicationPlace England
PublicationPlace_xml – name: England
– name: Oxford
– name: US
PublicationTitle The international journal of neuropsychopharmacology
PublicationTitleAlternate Int J Neuropsychopharmacol
PublicationYear 2019
Publisher Oxford University Press
Publisher_xml – name: Oxford University Press
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Snippet Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been...
Background: Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia...
Background Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia...
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StartPage 415
SubjectTerms Adult
Antipsychotic agents
Antipsychotics
Bayesian analysis
Benzazepines
Brain
Brain - diagnostic imaging
Brain - metabolism
Brain Mapping
Brain research
Cardiotonic agents
D-1 dopamine receptor
Diagnostic imaging
Dopamine
dorsolateral prefrontal cortex
drug naive
Female
Follow-Up Studies
Health aspects
Humans
Hypotheses
Magnetic Resonance Imaging
Male
Medical research
Middle Aged
Phenols (Class of compounds)
Physiological aspects
Positron emission tomography
Psychosis
Psychotic disorders
Psychotic Disorders - diagnostic imaging
Psychotic Disorders - metabolism
Radiopharmaceuticals
Receptors, Dopamine D1 - metabolism
Regular s
Schizophrenia
Schizophrenia - diagnostic imaging
Schizophrenia - metabolism
Tomography
Young Adult
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Title D1-Dopamine Receptor Availability in First-Episode Neuroleptic Naive Psychosis Patients
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Volume 22
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