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Funded Studies

PET Neuroimaging Study of the Brain Serotonin Transporter in Parkinson's Disease: Relationship to Clinical Depression

Approximately 40% of patients with Parkinson's disease (PD) suffer from depression, which in many cases is more disabling than the impairment of motor function. Since the original discovery by Oleh Hornykiewicz 40 years ago of low serotonin concentrations in autopsied brain of some patients with PD, it has been hypothesized that the cause of the depression is not a reaction by the patient to the fact that he/she has a progressive brain disorder but rather a degeneration of brain neurons utilizing serotonin as a neurotransmitter. Recent data also suggest that a serotonin deficiency could explain some of the cognitive and sleep problems in PD, both of which can significantly affect treatment of the patient with PD. We recently developed the first radioligand, [11C]-DASB, which can be used by positron emission tomography (PET) to bind specifically and with high signal to the serotonin transporter (SERT), a marker for serotonin neurones, in living human brain. This makes it possible to establish, for the first time in vivo, whether any or all of these clinically significant non-motor abnormalities in PD might be caused by a loss of brain serotonin neurones. In this study, our major goal will be to establish whether brain SERT is decreased in patients with PD relative to controls and in depressed patients with PD relative to non-depressed PD patients. [11C]-DASB binding to SERT by PET will be compared in groups of non-depressed and depressed patients with PD, and in a matched control group. All subjects will receive an in-depth structured neuropsychiatric interview by a research psychiatrist to establish the presence or absence of depression as well as a formal battery of tests to assess presence of any cognitive or sleep disturbances. The unique data from this investigation will help us to understand the etiology of depression in PD.


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