title: Elevated [18F]fluorodopamine turnover in brain of patients with schizophrenia: an [18F]fluorodopa/positron emission tomography study.
abstract: Previous positron emission tomography (PET) studies with levodopa analogs have revealed a modestly increased capacity for dopamine synthesis in the striatum of patients with schizophrenia compared with healthy age-matched control subjects. We hypothesized that not just the synthesis but also the turnover of radiolabeled dopamine is elevated in patients. To test the hypothesis, we reanalyzed 2-h-long [18F]fluorodopa (FDOPA)/PET recordings from eight unmedicated patients with schizophrenia and 15 healthy age-matched control subjects, using new methods for the quantification of [18F]fluorodopamine steady-state kinetics. The fractional rate constant for the catabolism and elimination of [18F]fluorodopamine was elevated nearly twofold in striatum, the largest biochemical difference in brain of schizophrenics yet reported. The magnitude of the intrinsic blood-brain FDOPA clearance with correction for this loss of [18F]fluorodopamine metabolites was increased by 20% in caudate and putamen and by 50% in amygdala and midbrain of the patients. However, the magnitude of the steady-state storage of FDOPA and its decarboxylated metabolites (V(d)) was reduced by one-third in the caudate nucleus and amygdala of the schizophrenic group. Thus, reduced steady-state storage of [18F]fluorodopamine occurs in the midst of accelerated synthesis in brain of untreated patients. Positive scores of the positive and negative syndrome scale correlated inversely with the magnitude of V(d) in amygdala, suggesting an association between positive symptoms and impaired steady-state storage of FDOPA metabolites in that structure.
authors.affiliation: Centre for Functionally Integrative Neuroscience, Aarhus University, DK-8000 Aarhus C, Denmark. yoshi.kumakura@gmail.com
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kumakura
authors.forename: Paul
authors.initials: P
authors.lastname: Cumming
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.forename: Thomas
authors.initials: T
authors.lastname: Siessmeier
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kienast
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D012559:Schizophrenia / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism
chemical_list: D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine