The role of Phosphodiesterase 10A in Schizophrenia: A Positron Emission Tomography study using [¹¹C]IMA107

Objectives Phosphodiesterase 10A (PDE10A) is an enzyme present in dopamine D1 and D2 receptor neurons that degrades the intracellular second messengers triggered by dopamine signalling. Although preclinical studies with PDE10A inhibitors show a broad-based 'antipsychotic-like' effect, the status of PDE10A in patients with schizophrenia is still unknown. In this study we have assessed the availability of PDE10A in patients with Schizophrenia using [¹¹C]IMA107 positron emission tomography (PET).

Methods We compared PDE10A availability in the brains of 12 patients with chronic schizophrenia on antipsychotic treatment with 12 healthy controls (HC). Parametric images of [¹¹C]IMA107 binding potential (BP_ND) were generated from the dynamic [¹¹C]IMA107 data using the simplified reference tissue model with the cerebellum as the reference tissue for non-displaceable binding.

Results There was no significant difference in the [¹¹C]IMA107 BP_ND between patients and HC in any of the brain regions studied: putamen (P=.95; 0%), globus pallidus (P=.66; -3%), caudate (P=0.35; -8%), accumbens (P=0.39; -7%), thalamus (P=0.9; -1%), and substancia nigra (P=.34; -11%). No significant correlation was found between [¹¹C]IMA107 BP_ND and severity of psychotic symptoms (p =.71) or exposure to antipsychotics (p =.55).

Conclusions Patients with schizophrenia on antipsychotic medication have similar availability of PDE10A as HC in brain regions thought to be involved in the pathophysiology of this disorder. Our findings do not support the proposal of an altered PDE10A expression in schizophrenia.

Research Support This work was supported by grant MR/L022176/1 from the Medical Research Council, U.K