Role of serotonergic 1A receptor dysfunction in depression associated with Parkinson's disease§

Authors

  • Benedicte Ballanger PhD,

    1. CNRS, UMR 5229, Centre de Neurosciences Cognitives, Bron, France
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  • Helene Klinger PsyD,

    1. Hospices Civils de Lyon, Hôpital Neurologique, Neurologie C and Université Lyon I, Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Lyon, France
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  • Julien Eche MD,

    1. Hospices Civils de Lyon, Hôpital Neurologique, Service de Psychiatrie de Liaison, Lyon, France
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  • Jérôme Lerond MD,

    1. Hospices Civils de Lyon, Hôpital Neurologique, Service de Psychiatrie de Liaison, Lyon, France
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  • Anne-Evelyne Vallet MD,

    1. Hospices Civils de Lyon, Hôpital Neurologique, Neurologie C and Université Lyon I, Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Lyon, France
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  • Didier Le Bars PharmD, PhD,

    1. CERMEP, Imagerie du Vivant, Bron, France and Université Lyon I, Hospices Civils de Lyon, Lyon, France
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  • Leon Tremblay PhD,

    1. CNRS, UMR 5229, Centre de Neurosciences Cognitives, Bron, France
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  • Véronique Sgambato-Faure PhD,

    1. CNRS, UMR 5229, Centre de Neurosciences Cognitives, Bron, France
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  • Emmanuel Broussolle MD, PhD,

    1. CNRS, UMR 5229, Centre de Neurosciences Cognitives, Bron, France
    2. Hospices Civils de Lyon, Hôpital Neurologique, Neurologie C and Université Lyon I, Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Lyon, France
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  • Stéphane Thobois MD, PhD

    Corresponding author
    1. CNRS, UMR 5229, Centre de Neurosciences Cognitives, Bron, France
    2. Hospices Civils de Lyon, Hôpital Neurologique, Neurologie C and Université Lyon I, Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Lyon, France
    • Hôpital Neurologique Pierre Wertheimer, Neurologie C, 59 Bd Pinel, 69677 Bron, France
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  • Funding agencies: This work has been supported by a grant from the ANR (ANR-09-MNPS-018) and a grant from the Fédération Française des Groupements de Parkinsoniens.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Depression is frequent in Parkinson's disease, but its pathophysiology remains unclear. Two recent studies have investigated the role of serotonergic system at the presynaptic level. The objective of the present study was to use positron emission tomography and [18F]MPPF to investigate the role of postsynaptic serotonergic system dysfunction in the pathophysiology of depression in Parkinson's disease. Four parkinsonian patients with depression and 8 parkinsonian patients without depression were enrolled. Each patient underwent a scan using [18F]MPPF, a selective serotonin 1A receptor antagonist. Voxel-by-voxel statistical comparison of [18F]MPPF uptake of the 2 groups of parkinsonian patients and with 7 matched normal subjects was made using statistical parametric mapping (P uncorrected < .001). Compared with nondepressed parkinsonian patients, depressed patients exhibited reduced tracer uptake in the left hippocampus, the right insula, the left superior temporal cortex, and the orbitofrontal cortex. Compared with controls, nondepressed parkinsonian patients presented reduced [18F]MPPF uptake bilaterally in the inferior frontal cortex as well as in the right ventral striatum and insula. Compared with controls, [18F]MPPF uptake was decreased in depressed parkinsonian patients in the left dorsal anterior cingulate and orbitofrontal cortices, in the right hippocampic region, and in the temporal cortex. The present imaging study suggests that abnormalities in serotonin 1A receptor neurotransmission in the limbic system may be involved in the neural mechanisms underlying depression in patients with Parkinson's disease. © 2011 Movement Disorder Society

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