The Neurobiological Correlates of Anhedonic Depression in Parkinsons Disease: Associations Between Dopamine Function and Functional Pathways
Abstract
Rationale: Parkinsons disease (PD) is a common brain disease, which is characterized by a severe loss of dopamine in specific brain circuits. Dopamine is one of the chemical substances - neurotransmitters - needed to transmit neuronal signals. Frequently, in more than a third of the patients with PD, a depression co-occurs. Core symptoms of depression are a sad mood or anhedonia. Anhedonia is defined as a decreased liking and/or wanting of pleasure. It is linked with differences in dopamine transmission. Depression in Parkinsons disease has a large disease burden, with higher chances of a lower quality of life, more progression of the PD, and earlier mortality. Adequate treatment is therefore important. However, as we still lack biological insight into the exact how and why, i.e., into the underlying mechanisms of depression in PD, patients may not receive the best care they deserve. In the search for underlying causes, previous imaging studies in PD evaluated differences between depressed and non-depressed PD patients in brain areas and in neurotransmitters, like dopamine. However, findings are inconclusive. Importantly, nowadays, new imaging techniques and the combination of several techniques in the same patients enable a more detailed approach. Moreover, studies in depressed patients without PD have taught us that we should consider depression a disease with many variations, which may also reflect distinct underlying mechanisms. Therefore, it is important to study carefully defined subgroups of patients with a depression and likewise in PD. Because of its link with dopamine, the subtype of depression with anhedonia is of particular interest in Parkinsons disease, but it has never been studied in PD. Objective: By combining two imaging techniques (functional Magnetic Resonance Imaging and a new Position Emission Tomography [18F-FE-PE2I]) we aim to study differences in the level of dopamine loss in the brain and how these differences relate to brain function between three groups of patients with PD: 25 PD patients with a psychiatric diagnosis of a depression with anhedonia, 25 PD patients with a depression without anhedonia, and 25 PD patients without depression. We expect to find more dopamine loss in the PD patients with a depression with anhedonia and expect to link more dopamine loss with an altered brain function in specific regions and pathways in the brain. Aims, Clinical Impact, and Focus Area: The current study eventually will improve our understanding of the underlying mechanisms of depression with and without anhedonia in Parkinsons disease, i.e., on the dopaminergic aspects of psychiatric depressive symptoms and their cognitive processing in PD. This can guide the development of new, individualized psychiatric treatment targets for depressive patients. For example, if we find that dopamine loss is most pronounced in PD patients with a depression with anhedonia (while this is less in patients with a depression without anhedonia), this would suggest that medication targeting dopamine dysfunction (i.e., pramipexole) might best be prescribed for these patients, while the common antidepressants (i.e., serotonin reuptake inhibitors) might be better prescribed in patients without anhedonia. However, if we find that in both depression types dopamine is present while the brain function is different, this might indicate a differential approach in treatment, e.g., aiming to interfere with specific brain networks, e.g., with Deep Brain Stimulation or repetitive Transcranial Magnetic Stimulation. Principal Investigator: This project will give me, as Principal Investigator, the opportunity to learn advanced neuro-imaging techniques and combine this with my psychiatric expertise in depression. Moreover, it will strengthen my approach to distinguish depression subtypes in PD. Our research team’s combined knowledge about underlying mechanisms in Parkinsons disease and depression will provide me opportunities to deve
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910713
Entities
People
- Marleen Van Beek
Organizations
- United States Army
- Universitair Medisch Centrum St. Radboud