D1-Dopamine Receptor Availability in First-Episode Neuroleptic Naive Psychosis Patients.
Adult
Benzazepines
Brain
/ diagnostic imaging
Brain Mapping
Female
Follow-Up Studies
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Positron-Emission Tomography
Psychotic Disorders
/ diagnostic imaging
Radiopharmaceuticals
Receptors, Dopamine D1
/ metabolism
Schizophrenia
/ diagnostic imaging
Young Adult
D1 dopamine receptor
dorsolateral prefrontal cortex
drug naïve
positron emission tomography
schizophrenia
Journal
The international journal of neuropsychopharmacology
ISSN: 1469-5111
Titre abrégé: Int J Neuropsychopharmacol
Pays: England
ID NLM: 9815893
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
received:
10
01
2019
revised:
12
03
2019
accepted:
05
04
2019
pubmed:
9
4
2019
medline:
9
4
2020
entrez:
9
4
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 30958880
pii: 5432304
doi: 10.1093/ijnp/pyz017
pmc: PMC6600463
doi:
Substances chimiques
Benzazepines
0
DRD1 protein, human
0
Radiopharmaceuticals
0
Receptors, Dopamine D1
0
SCH 23390
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
415-425Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of CINP.
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