1. ¹Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
2. ²Department of Neurology and Neurosurgery, Washington University School of Medicine, St Louis, MO, USA
3. ³Department of Radiology and Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA
4. ⁴APDA Advanced Research Center for Parkinson Disease, Washington University School of Medicine, St Louis, MO, USA
5. ⁵Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO, USA
6. ⁶Program in Physical Therapy, Washington University School of Medicine, St Louis, MO, USA

Correspondence: Dr KJ Black, Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, 660 S Euclid Ave. St Louis, MO 63110-1093, USA. Tel: +1 314 362 6281; Fax: +1 314 362 0168; E-mail: kevin@wustl.edu

Received 20 February 2004; Revised 28 September 2004; Accepted 26 October 2004; Published online 15 December 2004.

Abstract

Some patients with advanced Parkinson's disease (PD) develop dose-related fluctuations in mood. This may reflect alterations in dopamine-influenced brain circuits that mediate emotion. However, there is no available information to localize which dopamine-influenced neurons may be most affected. Eight patients with PD and clinically significant levodopa-related mood fluctuations (mania, depression, or anxiety) were compared to 13 patients with similarly severe PD and fluctuations of motor function but not of mood. Regional cerebral blood flow (rCBF) was measured with positron emission tomography before and after levodopa (in the presence of carbidopa). The rCBF response to levodopa in medial frontal gyrus and posterior cingulate cortex (PCC) significantly differed between mood fluctuators and control patients (corrected p<0.02). Other regions with uncorrected p<0.001 in this comparison were cortical Brodmann areas 22, 40, 13, 11, and 28, hippocampus, and claustrum. The levodopa activation paradigm detected group differences not evident in a comparison of resting rCBF. Abnormalities of dopamine innervation may produce mood fluctuations via effects on PCC, an area strongly linked to mood and anxiety and with known rCBF responsiveness to levodopa or D2-like dopamine receptor agonists. We speculate that mood fluctuations may arise in parkinsonian patients who have abnormal dopaminergic modulation of caudate nucleus, anterior cingulate cortex, or orbital frontal cortex, all of which innervate PCC. The findings require confirmation in larger and better-matched groups.