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Phosphodiesterase 10A in Schizophrenia: A PET Study Using [(11)C]IMA107
Tiago Reis Marques1, Sridhar Natesan1, Flavia Niccolini1
1From 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.
This study found normal levels of phosphodiesterase 10A (PDE10A) in the brains of schizophrenia patients. These findings suggest PDE10A availability is not altered in schizophrenia, impacting future antipsychotic drug development.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Phosphodiesterase 10A (PDE10A) is a key enzyme in dopamine signaling pathways.
- PDE10A inhibitors show antipsychotic-like effects in animal models, making PDE10A a drug development target.
- The role of PDE10A in schizophrenia pathophysiology remains unclear.
Purpose of the Study:
- To investigate the in vivo brain expression of PDE10A in patients with schizophrenia.
- To assess PDE10A availability using a novel radioligand, [(11)C]IMA107, and Positron Emission Tomography (PET).
Main Methods:
- Compared PDE10A availability (binding potential, BPND) in 12 schizophrenia patients and 12 healthy controls using [(11)C]IMA107 PET.
- Utilized the simplified reference tissue model with cerebellum as reference tissue.
- Analyzed PDE10A availability in key brain regions including the thalamus, striatum (caudate, putamen, nucleus accumbens), and substantia nigra.
Main Results:
- No significant differences in [(11)C]IMA107 BPND were observed between schizophrenia patients and healthy controls across all studied brain regions.
- PDE10A availability did not correlate with symptom severity or antipsychotic medication dosage.
- The findings indicate normal PDE10A expression in brain areas implicated in schizophrenia.
Conclusions:
- Schizophrenia patients exhibit normal PDE10A availability in relevant brain regions.
- The results do not support the hypothesis of altered PDE10A availability in schizophrenia.
- This study's implications for the development of PDE10A-targeting antipsychotic medications are discussed.
