Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder

Abstract

BackgroundOnly 40–60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of “personalized medicine.” Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder.Methods/designWe are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder–7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods.DiscussionThis protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome.Trial registrationThe study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results.

Test–retest reliability of approach‐avoidance conflict decision‐making during functional magnetic resonance imaging in healthy adults

“…Overall, this study characterized several specific behavioral variables and brain ROIs that may be optimal to use in future applications of this approach-avoidance conflict task. For example, such variables could be of interest in examining individual differences (e.g., in relation to clinical symptom severity or prediction of treatment outcome) or for examining mechanisms of intervention effects (i.e., in conjunction with randomized clinical trials for anxiety disorders [Santiago et al, 2020]). Additionally, this study presents a framework for how other task paradigms might comprehensively examine these mechanisms in order to identify findings that are both reproducible and reliable.…”

Reduced neural differentiation of rewards and punishment during passive avoidance learning in adolescents with generalized anxiety disorder

“…It has been claimed that disrupted computations related to approach-avoidance decision-making are implicated in the pathophysiology of GAD (Aupperle & Paulus, 2010;Santiago et al, 2020).…”

“…It has been claimed that disrupted computations related to approach‐avoidance decision‐making are implicated in the pathophysiology of GAD (Aupperle & Paulus, 2010; Santiago et al, 2020). However, we found no regions showing significant atypical activity during approach‐avoidance decisions in the adolescents with GAD relative to the TD adolescents.…”

“…This difficulty likely contributes to nonoptimal real‐world decision‐making that potentially exacerbates worry and anxiety. It is certainly likely to disrupt approach‐avoidance decision‐making—an impairment that has been implicated in the pathophysiology of GAD (Aupperle & Paulus, 2010; Santiago et al, 2020). Indeed, the adolescents showed some degree in approach/avoidance decision‐making on the current task; the participants with GAD were more likely to respond to the stimuli probabilistically associated with punishment (commission errors) than the TD participants.…”

“…It has been proposed that disrupted computations related to approach‐avoidance decision‐making are implicated in the pathophysiology of GAD (Aupperle & Paulus, 2010; Santiago et al, 2020). GAD may reflect conflicting motivations to approach or avoid anxiogenic situations that also contain potential gains, leading to chronic distress, uncertainty, and the use of maladaptive coping mechanisms (i.e., avoidance, worry) (Aupperle & Paulus, 2010).…”