Journal
BRAIN
Volume 133, Issue -, Pages 3434-3443Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awq268
Keywords
Parkinson; fatigue; serotonin; F-dopa; DASB; PET
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Funding
- Medical Research Council [MC_U120036861] Funding Source: researchfish
- MRC [MC_U120036861] Funding Source: UKRI
- Medical Research Council [MC_U120036861] Funding Source: Medline
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Disabling fatigue is a symptom in a number of neurological diseases, including multiple sclerosis, stroke and Parkinson's disease. We used F-18-dopa and C-11-DASB [N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine] positron emission tomography, markers of dopamine storage capacity and serotonin transporter availability, to investigate whether fatigue in Parkinson's disease is associated with dopaminergic and serotonergic dysfunction in basal ganglia and limbic circuits. Ten patients with Parkinson's disease and fatigue and 10 patients without fatigue had a F-18-dopa scan. Seven patients with and eight patients without fatigue also had a C-11-DASB scan. The two groups were matched for age, disease duration and severity and daily intake of levodopa equivalent units. None had a history of depression or sleep disturbance. Using a region of interest analytical approach, we found that patients with fatigue had significantly lower serotonin transporter binding than patients without fatigue in the caudate, putamen, ventral striatum and thalamus. Striatal F-18-dopa uptake was similar in the fatigued and non-fatigued groups. Voxel-based analysis localized further relative serotonin transporter binding reductions in the cingulate and amygdala of the fatigue group, and F-18-dopa uptake reductions in the caudate and insula. We conclude that fatigue in Parkinson's disease is associated with reduced serotonergic function in the basal ganglia and limbic structures. Insular dopaminergic dysfunction could also play a role. These findings imply that strategies to increase brain level of serotonin would be a rational approach for relieving fatigue symptoms in Parkinson's disease and may also be relevant to alleviating fatigue in other clinical conditions.
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