title: Role of serotonergic 1A receptor dysfunction in depression associated with Parkinson's disease.
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 [(18)F]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 [(18)F]MPPF, a selective serotonin 1A receptor antagonist. Voxel-by-voxel statistical comparison of [(18)F]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 [(18)F]MPPF uptake bilaterally in the inferior frontal cortex as well as in the right ventral striatum and insula. Compared with controls, [(18)F]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.
authors: CNRS, UMR 5229, Centre de Neurosciences Cognitives, Bron, France.
authors: Benedicte
authors: B
authors: Ballanger
authors: Helene
authors: H
authors: Klinger
authors: Julien
authors: J
authors: Eche
authors: Jérôme
authors: J
authors: Lerond
authors: Anne-Evelyne
authors: AE
authors: Vallet
authors: Didier
authors: D
authors: Le Bars
authors: Leon
authors: L
authors: Tremblay
authors: Véronique
authors: V
authors: Sgambato-Faure
authors: Emmanuel
authors: E
authors: Broussolle
authors: Stéphane
authors: S
authors: Thobois
mesh_terms: D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D003863:Depression / Q000000981:diagnostic imaging* / Q000209:etiology*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging; D010879:Piperazines / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics
chemical_list: D000631:Aminopyridines; D005462:Fluorine Radioisotopes; D010879:Piperazines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C099463:4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine