The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson's disease

SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson's disease. Pathophysiological evidence suggests...

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Published in:Brain (London, England : 1878) England : 1878), 2016-09, Vol.139 (Pt 9), p.2486-2502
Main Authors: Maillet, Audrey, Krack, Paul, Lhommée, Eugénie, Météreau, Elise, Klinger, Hélène, Favre, Emilie, Le Bars, Didier, Schmitt, Emmanuelle, Bichon, Amélie, Pelissier, Pierre, Fraix, Valérie, Castrioto, Anna, Sgambato-Faure, Véronique, Broussolle, Emmanuel, Tremblay, Léon, Thobois, Stéphane
Format: Article
Language:English
Subjects:
Adult
Aged
Anxiety - diagnostic imaging
Anxiety - etiology
Anxiety - metabolism
Anxiety - physiopathology
Apathy - physiology
Cognitive science
Depression - diagnostic imaging
Depression - etiology
Depression - metabolism
Depression - physiopathology
Female
Humanities and Social Sciences
Humans
Life Sciences
Male
Middle Aged
Parkinson Disease - complications
Parkinson Disease - diagnostic imaging
Parkinson Disease - metabolism
Parkinson Disease - physiopathology
Positron-Emission Tomography - methods
Serotonin - metabolism
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Summary:SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson's disease. Pathophysiological evidence suggests that parkinsonian apathy is primarily due to a mesolimbic dopaminergic denervation, but the role of the serotonergic alteration has never been examined, despite its well-known involvement in the pathogenesis of depression and anxiety. To fill this gap, we address here the pure model of de novo Parkinson's disease, without the confounding effects of antiparkinsonian treatment. Fifteen apathetic (Lille Apathy Rating Scale scores ≥ -21) and 15 non-apathetic (-36 ≤ Lille Apathy Rating Scale scores ≤ -22) drug-naïve de novo parkinsonian patients were enrolled in the present study and underwent detailed clinical assessment and positron emission tomography imaging, using both dopaminergic [(11)C-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane (PE2I)] (n = 29) and serotonergic [(11)C-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine (DASB)] (n = 27) presynaptic transporter radioligands. Apathetic parkinsonian patients presented higher depression (P = 0.0004) and anxiety (P = 0.004) scores - as assessed using the Beck Depression Inventory and the part B of the State-Trait Anxiety Inventory, respectively - compared to the non-apathetic ones - who were not different from the age-matched healthy subjects (n = 15). Relative to the controls, the non-apathetic parkinsonian patients mainly showed dopaminergic denervation (n = 14) within the right caudate nucleus, bilateral putamen, thalamus and pallidum, while serotonergic innervation (n = 15) was fairly preserved. Apathetic parkinsonian patients exhibited, compared to controls, combined and widespread dopaminergic (n = 15) and serotonergic (n = 12) degeneration within the bilateral caudate nuclei, putamen, ventral striatum, pallidum and thalamus, but also a specific bilateral dopaminergic disruption within the substantia nigra-ventral tegmental area complex, as well as a specific serotonergic alteration within the insula, the orbitofrontal and the subgenual anterior cingulate cortices. When comparing the two parkinsonian groups, the apathetic patients mainly displayed greater serotonergic alteration in the ventral striatum, the dorsal and the subgenual parts of the anterior cingulate cortices, b
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/aww162