The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BP ND) of the new validated PDE10A ligand [ 11C]Lu AE92686 between patients with schizophrenia and healthy controls. Furthermore, we aimed to assess the correlation of PDE10A BP ND to cortical thickness. Sixteen healthy male controls and 10 male patients with schizophrenia treated with clozapine, olanzapine or quetiapine were investigated with positron emission tomography (PET) and magnetic resonance imaging (MRI). Striatal binding potential (BP ND) of [ 11C]Lu AE92686 was acquired through dynamic PET scans and cortical thickness by structural MRI. Clinical assessments of symptoms and cognitive function were performed and the antipsychotic dosage was recorded. Patients with schizophrenia had a significantly lower BP ND of [ 11C]Lu AE92686 in striatum ( P=0.003) than healthy controls. The striatal BP ND significantly correlated to cortical thickness in the medial prefrontal cortex and superior frontal gyrus across patients with schizophrenia and healthy controls. No significant correlation was observed between the BP ND for [ 11C]Lu AE92686 in striatum and age, schizophrenia symptoms, antipsychotic dosage, coffee consumption, smoking, duration of illness or cognitive function in the patients. In conclusion, PDE10A may be important for functioning in the striato-cortical interaction and in the pathophysiology of schizophrenia.