Ires Ghielen

13 General introduction developing a dopamine dysregulation syndrome (DDS) is worth noticing, which refers to compulsive PD medication overuse. DDS is associated with wearing-off related anxiety and can develop after continually taking extra PD medication (which can be described as avoidance behavior) to prevent the debilitating ‘off’ state [48]. Since anxiety in PD is complex due to its reciprocal interactions with motor symptoms, treatment should preferably be multidisciplinary and integrated. Current treatment options seem inadequate and there is a need for further investigation and development [8, 13, 14, 49]. Not only the treatment of anxiety symptoms, but also the diagnosis, phenomenology, origin, contributing factors, and underlying mechanisms of anxiety in PD are in high need of further research. Aims & outline thesis The overall aim of this thesis was to investigate the phenomenology, associations and interactions, and treatment of anxiety in relation to motor and other non-motor symptoms in PD patients. Part 1 (chapters 2 through 5) focuses on understanding the complex associations and interactions between anxiety, motor and other non-motor symptoms in PD. This can contribute to an improvement of the diagnosis of anxiety and help developing adequate treatment options for PD related anxiety. Subsequently, part 2 (chapters 6 through 8) focuses on the role of psychotherapy for reducing symptoms of psychological distress (including anxiety) in PD patients, and investigates a newly developed multidisciplinary treatment to address interacting motor and anxiety symptoms. Part 1 In chapter 2 we investigate the phenomenology of anxiety in PD by performing a principal component analysis to explore underlying symptom dimensions of anxiety as measured with the BAI [50]. These symptom dimensions can be considered subscales of anxiety. We also describe the associations of the resulting subscales with motor, autonomic, and depressive symptoms. Insight in the phenomenology of anxiety in PD patients, and its relatedness to other motor and non-motor symptoms, can improve recognition and diagnosis of anxiety in clinical practice. To investigate the generalizability of the findings in chapter 2, chapter 3 describes the replication of the principal component analysis in a PD patient population referred for neuropsychiatric evaluation to a specialized psychiatric outpatient department [Ghielen et al., 2020 (under review)]. In order to investigate the clinical 1