title: Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study.
abstract: 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 (BPND) 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 BPNDto 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 (BPND) 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 BPNDof [11C]Lu AE92686 in striatum (P=0.003) than healthy controls. The striatal BPNDsignificantly 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 BPNDfor [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.
authors.affiliation: Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Bodén
authors.affiliation: Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Persson
authors.affiliation: Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Wall
authors.affiliation: Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lubberink
authors.affiliation: Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Ekselius
authors.affiliation: Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
authors.forename: E-M
authors.initials: EM
authors.lastname: Larsson
authors.affiliation: Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Antoni
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D003069:Coffee; D003071:Cognition; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017072:Neostriatum / Q000378:metabolism*; D009929:Organ Size; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000473:pathology; D011725:Pyridines; D019275:Radiopharmaceuticals; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D012565:Schizophrenic Psychology; D012907:Smoking; D013997:Time Factors; D014230:Triazoles; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D003069:Coffee; C000614657:Lu AE92686; D011725:Pyridines; D019275:Radiopharmaceuticals; D014230:Triazoles; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases