Complex anxiety disorders : Risk factors, underlying mechanisms, and treatment enhancement

This thesis aims to address lacunas in the current knowledge of complex anxiety disorders. This is an important topic since complex anxiety disorders tend to develop a chronic course and because current guidelines are incomplete. In this thesis, several studies are presented regarding the various aspects of complex anxiety disorders. This includes research on a putative risk factor for complex anxiety disorders (comorbidity), on a potential underlying mechanism of complex anxiety disorders (the tendency to overestimate threat; expectancy bias), and on a potential new treatment enhancer (d-cycloserine; DCS). In Chapters 2.1, 2.2, and 2.3, we present three studies regarding comorbidity in anxiety disorders. These three studies were based on samples derived from two longitudinal studies, which are the Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands OCD Association (NOCDA) study. These studies demonstrate the clinical relevance of comorbidity regardless of the etiology of comorbidity. These findings are but into a broader perspective against the current debate and ongoing research on possible shared etiology. The study presented in Chapter 3 aimed to enhance current knowledge on a potentially underlying mechanism of complex anxiety, which is the expectancy bias (the tendency to overestimate the association between fear-(ir)relevant stimuli and the aversive stimuli). This is the first study to investigate the predictive value of expectancy bias on treatment outcome in patients with a panic disorder and agoraphobia. Based on one earlier study on spider phobia,50 we hypothesised that higher expectancy ratings before treatment would be associated with worse treatment outcome. However, our results demonstrates that higher expectancy rates do not predict treatment outcome in the patient group. In Chapter 4, we present the RCT we performed to investigate the additional effect of d-cycloserine (DCS) in exposure therapy for patients with a panic disorder with agoraphobia. We tested 57 patients from three Dutch institutions who received 125 mg of DCS or placebo as addition to 6 exposure sessions within a 12-session exposure protocol. 19 patients received DCS prior to exposure, 19 patients received DCS after exposure, and 19 patients received placebo. We found no differences between DCS and placebo. These ‘null’ findings are discussed and compared to recent literature