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The Journal of Neuroscience, July 25, 2007, 27(30):8080-8087; doi:10.1523/JNEUROSCI.0805-07.2007

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Neurobiology of Disease
Elevated [¹⁸F]Fluorodopamine Turnover in Brain of Patients with Schizophrenia: An [¹⁸F]Fluorodopa/Positron Emission Tomography Study

Yoshitaka Kumakura,^1,2 Paul Cumming,¹ Ingo Vernaleken,³ Hans-Georg Buchholz,⁴ Thomas Siessmeier,⁴ Andreas Heinz,⁵ Thorsten Kienast,⁵ Peter Bartenstein,⁴ and Gerhard Gründer³

¹Centre for Functionally Integrative Neuroscience, Aarhus University, DK-8000 Aarhus C, Denmark, ²Department of Nuclear Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8656, Japan, ³Department of Psychiatry and Psychotherapy, Rheinisch-Westfälische Technische Hochschule, Aachen University, 52062 Aachen, Germany, ⁴Department of Nuclear Medicine, University of Mainz, D-55099 Mainz, Germany, and ⁵Department of Psychiatry, Charité University Medical Center, Charité Campus Mitte, D-10117 Berlin, Germany

Correspondence should be addressed to Yoshitaka Kumakura, Centre for Functionally Integrative Neuroscience, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. Email: yoshi.kumakura{at}gmail.com

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.

Key words: FDOPA; PET; schizophrenia; dopamine; turnover; steady-state storage

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Received Sept. 28, 2006; revised June 6, 2007; accepted June 7, 2007.

Correspondence should be addressed to Yoshitaka Kumakura, Centre for Functionally Integrative Neuroscience, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. Email: yoshi.kumakura{at}gmail.com

This article has been cited by other articles:

				Y. Kumakura and P. Cumming PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches Neuroscientist, December 1, 2009; 15(6): 635 - 650. [Abstract] [PDF]

				G. J. Lyon, A. Abi-Dargham, H. Moore, J. A. Lieberman, J. A. Javitch, and D. Sulzer Presynaptic Regulation of Dopamine Transmission in Schizophrenia Schizophr Bull, June 12, 2009; (2009) sbp010v1. [Abstract] [Full Text] [PDF]

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