Phosphodiesterase 10A in Schizophrenia: A PET Study Using [(11)C]IMA107.
File(s)
Author(s)
Type
Journal Article
Abstract
OBJECTIVE: Phosphodiesterase 10A (PDE10A) is an enzyme present in striatal medium spiny neurons that degrades the intracellular second messengers triggered by dopamine signaling. The pharmaceutical industry has considerable interest in PDE10A inhibitors because they have been shown to have an antipsychotic-like effect in animal models. However, the status of PDE10A in schizophrenia is unknown. Using a newly developed and validated radioligand, [(11)C]IMA107, the authors report the first in vivo assessment of PDE10A brain expression in patients with schizophrenia. METHOD: The authors compared PDE10A availability in the brains of 12 patients with chronic schizophrenia and 12 matched healthy comparison subjects using [(11)C]IMA107 positron emission tomography (PET). Regional estimates of the binding potential (BPND) of [(11)C]IMA107 were generated from dynamic PET scans using the simplified reference tissue model with the cerebellum as the reference tissue for nonspecific binding. RESULTS: There was no significant difference in [(11)C]IMA107 BPND between schizophrenia patients and comparison subjects in any of the brain regions studied (thalamus, caudate, putamen, nucleus accumbens, globus pallidus, and substantia nigra). There was also no significant correlation between [(11)C]IMA107 BPND and the severity of psychotic symptoms or antipsychotic dosage. CONCLUSIONS: Patients with schizophrenia have normal availability of PDE10A in brain regions thought to be involved in the pathophysiology of this disorder. The findings do not support the proposal of an altered PDE10A availability in schizophrenia. The implication of this finding for future drug development is discussed.
Date Issued
2016-02-19
Date Acceptance
2015-11-20
Citation
American Journal of Psychiatry, 2016, 173 (7), pp.714-721
ISSN
1535-7228
Publisher
American Psychiatric Publishing -
Start Page
714
End Page
721
Journal / Book Title
American Journal of Psychiatry
Volume
173
Issue
7
Copyright Statement
Copyright © American Psychiatric Association. All rights reserved. The official published article is available online at https://dx.doi.org/10.1176/appi.ajp.2015.15040518
Subjects
Psychiatry
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Publication Status
Published