Brain serotonin transporter binding in non-depressed patients with Parkinson's disease.
Early post-mortem data suggest that damage to brain serotonin neurones might play a role in some features (e.g., depression) of Parkinson's disease (PD). However, it is not known whether such damage is a typical characteristic of living patients with PD or whether the changes are regionally widespread. To address this question we measured, by positron emission tomography imaging, levels of the brain serotonin transporter (SERT), a marker for serotonin neurones, as inferred from binding of [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB), a second generation SERT radioligand, in subcortical and cerebral cortical brain areas of clinically advanced non-depressed (confirmed by structured psychiatric interview) patients with PD. SERT binding levels in PD were lower than those in controls in all examined brain areas, with the changes statistically significant in orbitofrontal cortex (-22%), caudate (-30%), putamen (-26%), and midbrain (-29%). However, only a slight non-significant reduction (-7%) was observed in dorsolateral pre-frontal cortex, an area implicated in major depression. Our imaging data suggests that a modest, regionally widespread loss of brain serotonergic innervation might be a common feature of advanced PD. Further investigation will be required to establish whether SERT binding is more or less decreased in those patients with PD who also have major depressive disorder.
Guttman
M
M
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
Boileau
I
I
Warsh
J
J
Saint-Cyr
J A
JA
Ginovart
N
N
McCluskey
T
T
Houle
S
S
Wilson
A
A
Mundo
E
E
Rusjan
P
P
Meyer
J
J
Kish
S J
SJ
D000368:Aged; D001596:Benzylamines; D001667:Binding, Competitive / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology*; D002250:Carbon Radioisotopes; D003866:Depressive Disorder / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D001596:Benzylamines; D015415:Biomarkers; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin