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Am J Psychiatry. 2016 Jul 1;173(7):714-21. doi: 10.1176/appi.ajp.2015.15040518. Epub 2016 Feb 19.

Phosphodiesterase 10A in Schizophrenia: A PET Study Using [(11)C]IMA107.

Author information

1
From the Department of Psychosis Studies, the Neurodegeneration Imaging Group, the Department of Basic and Clinical Neuroscience, and the Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London; the Division of Brain Sciences, Department of Medicine, and the Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Institute of Clinical Science, Imperial College London, London; and Imanova Ltd., Centre for Imaging Sciences, Hammersmith Hospital, London.

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.

PMID:
26892941
DOI:
10.1176/appi.ajp.2015.15040518
[Indexed for MEDLINE]
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