Fatigue in Parkinson’s disease is linked to striatal and limbic serotonergic dysfunction

• Published in: Brain (London, England : 1878) Vol. 133; no. 11; pp. 3434 - 3443
• Main Authors: Pavese, Nicola, Metta, Vinod, Bose, Subrata K., Chaudhuri, Kallol Ray, Brooks, David J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-2010
• Subjects: Adult; Aged; Biological and medical sciences; Corpus Striatum - metabolism; Corpus Striatum - physiology; DASB; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; F-dopa; fatigue; Fatigue - complications; Fatigue - metabolism; Fatigue - physiopathology; Female; Humans; Limbic System - metabolism; Limbic System - physiology; Male; Medical sciences; Middle Aged; Neurology; Parkinson; Parkinson Disease - complications; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; PET; Positron-Emission Tomography - methods; serotonin; Serotonin - metabolism; Serotonin - physiology; Nervous system diseases; Serotonin; Parkinson disease; Fatigue; Parkinson; Cerebral disorder; DASB; Dysfunction; Central nervous system disease; Neurotransmitter; Degenerative disease; Dopa; Positron emission tomography; PET; Extrapyramidal syndrome; Emission tomography; F-dopa
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awq268

Disabling fatigue is a symptom in a number of neurological diseases, including multiple sclerosis, stroke and Parkinson’s disease. We used 18F-dopa and 11C-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 18F-dopa scan. Seven patients with and eight patients without fatigue also had a 11C-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 18F-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 18F-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.