Ires Ghielen

11 General introduction Debilitating neuropsychiatric symptoms are common, also without fulfillment of the criteria for specific disorders. Clinically relevant anxiety and depressive symptoms occur in 11-26% [19, 20] and 35% of patients [21], respectively. The neurodegenerative process whereby neurotransmitter systems are extensively affected, and the high prevalence and impact of neuropsychiatric symptoms indicate that non-motor symptoms are an important part of the disease, in addition to the motor symptoms on which the PD diagnosis is mainly based. Anxiety in PD Currently, up to 45% of PD patients experience either clinically relevant anxiety symptoms or fulfill the criteria for an anxiety disorder, including generalized anxiety disorder, panic attacks, and social phobia [20, 22, 23]. According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [24], anxiety disorders are characterized by certain affective, cognitive, physical, and behavioral symptoms. Affective symptoms include feeling nervous, fear of losing control, and feeling scared. Cognitive symptoms include ruminating, negative bias, and poor concentration. Physical symptoms include muscle tension, sweating, trembling, shortness of breath, and heart palpitations, amongst many others. Lastly, behavioral symptoms include avoidance and safety behaviors. Diagnosing anxiety in PD is complicated. Physical symptoms of anxiety can be interpreted as motor or autonomic symptoms as part of the disease itself (e.g., tremor, rigidity, freezing, excessive daytime sweating) [25, 26]. In addition, anxiety frequently occurs comorbid or secondary to depression, psychosis, and cognitive decline [23, 27-29]. Detecting and quantifying anxiety can be done with self-report questionnaires, such as the Beck Anxiety Inventory (BAI) [30]. However, due to overlapping anxiety and PD-specific symptoms, and comorbidity with other neuropsychiatric symptoms, the interpretation of the total score on such self-report questionnaires in PD is complicated [25, 26] and raises the question whether these measures are suitable for investigating anxiety in PD [31]. Since it appears to be a complicated construct in PD, anxiety can be both over- as well as underdiagnosed in clinical practice [32, 33]. 1