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Thirty Parkinson's disease (PD) patients were divided into three equal groups according to their disease duration while 10 normal healthy volunteers matched for age and sex served as a control group. Striatal and extrastriatal serotonergic function was studied with (11)C-DASB PET, a marker of serotonin transporter availability. (11)C-DASB binding was correlated with disease disability and exposure to dopaminergic therapy. We found significant (11)C-DASB binding reductions in striatal, brainstem, and cortical regions in PD but no correlations were evident between (11)C-DASB binding and UPDRS scores, Hoehn &Yahr staging, disease duration and level of exposure to dopaminergic therapy. Our results suggest that progressive non-linear serotonergic dysfunction occurs in PD but it does not determine levels of disability. Additionally, chronic exposure to dopaminergic therapy does not appear to influence SERT binding.

More than 50% of patients with Parkinson's disease (PD) are expected to show abnormalities with their weight in a process that starts several years before the diagnosis. The serotonergic (5-HT) system has been proposed to regulate appetite and the 5-HT transporter (SERT) is a key modulator of 5-HT metabolism. Here, we hypothesized that a dysfunctional 5-HT system could be responsible for alterations of weight in PD and we sought to investigate this in vivo. Thirty four PD patients had Body Mass Index (BMI) changes monitored over a 12-month period and one positron emission tomography (PET) brain scan with (11)C-DASB, a selective marker of SERT availability, during their second clinical assessment. Results were compared with those of a group of 10 normal controls. Half (17) of the PD patients showed abnormal BMI changes over the 12-month period; 12 lost while 5 gained weight. PD patients with abnormal BMI changes showed significantly raised (11)C-DASB binding in rostral raphe nuclei, hypothalamus, caudate nucleus and ventral striatum compared to cases with no significant BMI changes. (11)C-DASB binding in other regions was similarly decreased in the PD BMI subgroups compared to normal controls. BMI gainers showed significantly raised (11)C-DASB binding in anterior cingulate cortex (ACC) compared to BMI losers. Our findings suggest that abnormal BMI changes over a 12-month period are linked with relatively raised SERT availability in PD on an overall background of decreased 5-HT function. The regions implicated are the rostral raphe nuclei and its connections to limbic and cognitive areas. It is conceivable that 5-HT agents could help alleviate abnormal changes in BMI in PD.