Background:The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions.

Exposure-based psychological interventions currently represent the empirically best established first line form of cognitive-behavioural therapy for all types of anxiety disorders. Although shown to be highly effective in both randomized clinical and other studies, there are important deficits: (1) the core mechanisms of action are still under debate, (2) it is not known whether such treatments work equally well in all forms of anxiety disorders, including comorbid diagnoses like depression, (3) it is not known whether an intensified treatment with more frequent sessions in a shorter period of time provides better outcome than distributed sessions over longer time intervals. This paper reports the methods and design of a large-scale multicentre randomized clinical trial (RCT) involving up to 700 patients designed to answer these questions. Based on substantial advances in basic research we regard extinction as the putative core candidate model to explain the mechanism of action of exposure-based treatments. The RCT is flanked by four add-on projects that apply experimental neurophysiological and psychophysiological, (epi)genetic and ecological momentary assessment methods to examine extinction and its potential moderators. Beyond the focus on extinction we also involve stakeholders and routine psychotherapists in preparation for more effective dissemination into clinical practice.

Abstract. As a core component of cognitive-behavioral therapies (CBT), behavioral exposure is an effective treatment for anxiety disorders. Still, recent treatment studies demonstrate relatively high rates of treatment dropout, nonresponse, and relapse, indicating a substantial need for optimizing and personalizing existing treatment procedures. In the present article, we aim to address current challenges and future demands for translational research in CBT for the anxiety disorders, including (a) a better understanding of those mechanisms conferring behavioral change, (b) identifying important sources of individual variation that may act as moderators of treatment response, and (c) targeting practical barriers for dissemination of exposure therapy to routine care. Based on a recursive process model of psychotherapy research we will describe distinct steps to systematically translate basic and clinical research “from bench to bedside” to routine care, but also vice versa. Some of these aspects may stimulate the future roadmap for evidence-based psychotherapy research in order to better target the treatment of anxiety disorders as one core health challenge of our time.

Extinction learning is suggested to be a central mechanism during exposure-based cognitive behavioral psychotherapy. A positive association between the patients' pretreatment extinction learning performance and treatment outcome would corroborate the hypothesis. Indeed, there is first correlational evidence between reduced extinction learning and therapy efficacy. However, the results of these association studies may be hampered by extinction-training protocols that do not match treatment procedures. Therefore, we developed an extinction-training protocol highly tailored to the procedure of exposure therapy and tested it in two samples of 46 subjects in total. By using instructed fear acquisition training, including a consolidation period overnight, we wanted to ensure that the conditioned fear response was well established prior to extinction training, which is the case in patients with anxiety disorders prior to treatment. Moreover, the extinction learning process was analyzed on multiple response levels, comprising unconditioned stimulus (US) expectancy ratings, autonomic responses, defensive brain stem reflexes, and neural activation using functional magnetic resonance imaging. Using this protocol, we found robust fear conditioning and slow-speed extinction learning. We also observed within-group heterogeneity in extinction learning, albeit a stable fear response at the beginning of the extinction training. Finally, we found discordance between different response systems, suggesting that multiple processes are involved in extinction learning. The paradigm presented here might help to ameliorate the association between extinction learning performance assessed in the laboratory and therapy outcomes and thus facilitate translational science in anxiety disorders.

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