(Dis)Inhibition - Imaging Neuropsychiatry in Parkinson’s disease

The aim of this thesis was to gain a better understanding of the neurobiological factors that contribute to the development of anxiety, depression and impulse control disorders (ICD) in Parkinson’s disease (PD) using multiple neuroimaging techniques. In Chapter 1 we provide a general introduction on PD, a short description of its pathophysiology and the neuropsychiatric symptoms of depression, anxiety and impulse control disorders (ICD) that occur frequently in the disease. Chapter 2 describes an investigation on the relation between brain volume and anxiety symptoms in 110 PD patients. We focused on volume of the amygdala and hippocampus, two structures that are important for the processing of emotions. The severity of anxiety symptoms was negatively correlated with volume of the left amygdala. This reduction in left amygdalar volume was independent of the severity of motor symptoms and medication use. These results are consistent with studies in non-PD patients with anxiety disorders. We discuss a number of possible interpretations of these results and tentatively hypothesize that degeneration of the amygdala is caused by the Parkinson pathology and that this subsequently leads to the development of anxiety symptoms. Replication of these results with prospective follow-up studies is, however, necessarily to substantiate this hypothesis. In Chapter 3 we present the results of a study on the relationship between striatal dopamine transporter (DaT) availability and the severity of depressive symptoms in 100 PD patients. Using Single Photon Emission Computed Tomography (SPECT) scans we determined DaT availability in the caudate nucleus and putamen. The caudate nucleus is involved in cognitive and motivational processes and the putamen in motor skills. We replicated previously findings on the association between the severity of motor symptoms in PD and decreased DaT availability in the putamen. Furthermore, we showed that DaT availability in the caudate nucleus but not the putamen was negatively associated with the severity of depressive symptoms. We thuus showed a double association between depressive and motor symptoms on striatal DaT availability that concurs with our understanding of the cortico-striatal-thalamocortical (CSTC) circuits and their functions and showed a role for dopamine depletion in the pathophysiology of PD-related depression. In Chapter 4 we investigate the relation between striatal DaT availability measured with SPECT scans and the development of symptoms of ICD after commencing dopamine replacement therapy. In this study, 31 PD patients underwent a DaT SPECT scan when they were diagnosed and at that time showed no signs of ICD and were naïve for dopamine replacement therapy. Thirty months (on average) after the DaT SPECT scan and after commencing