NeuralCipher Research overview
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BackgroundThe pathophysiology and neural substrates of depression in Parkinson's disease remain unclear. It has been associated with dysregulation of the monoaminergic systems. Furthermore, functional abnormalities within the mesolimbic-basal ganglia reward circuit may be involved in the pathogenesis of Parkinson's disease-related depression.ObjectivesWe aimed to investigate monoaminergic deficits and the corresponding changes within the striatum-mesolimbic circuitry in patients with Parkinson's disease and depression.MethodsThis study included eight depressed and 18 non-depressed patients with Parkinson's disease and 28 matched healthy controls. We simultaneously obtained 18F-fluoropropyl-dihydrotetrabenazine positron emission tomography (18F-FP-DTBZ PET) and resting-state functional magnetic resonance images (rs-fMRI). We also recruited additional patients with Parkinson's disease (nine depressed and 20 non-depressed) for the validation of the rs-fMRI analysis. The 18F-FP-DTBZ standardized uptake value ratio relative to the occipital lobe was used to quantify monoaminergic deficits in the striatum-mesolimbic subregion. Voxel- and volume-of-interest-based analyses were performed to investigate the functional connectivity changes in the striatum-mesolimbic circuitry of depressed patients.ResultsPatients who were depressed exhibited greater monoaminergic deficits in the anterior dorsal and ventral putamen and the nucleus-accumbens than non-depressed patients did. Depression severity was negatively correlated with standardized uptake value ratio in the anterior ventral putamen and the nucleus-accumbens of patients with Parkinson's disease. Compared with non-depressed patients, higher functional connectivity was noted within the striatum-mesolimbic circuit in depressed patients.ConclusionsIn depressed Parkinson's disease patients, monoaminergic deficits are present alongside abnormally increased connectivity within the striatum-mesolimbic circuitry, highlighting this pathway as a potential target for treatment.
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