Measuring maladaptive avoidance: from animal models to clinical anxiety

Avoiding stimuli that predict danger is required for survival. However, avoidance can become maladaptive in individuals who overestimate threat and thus avoid safe situations as well as dangerous ones. Excessive avoidance is a core feature of anxiety disorders, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). This avoidance prevents patients from confronting maladaptive threat beliefs, thereby maintaining disordered anxiety. Avoidance is associated with high levels of psychosocial impairment yet is poorly understood at a mechanistic level. Many objective laboratory assessments of avoidance measure adaptive avoidance, in which an individual learns to successfully avoid a truly noxious stimulus. However, anxiety disorders are characterized by maladaptive avoidance, for which there are fewer objective laboratory measures. We posit that maladaptive avoidance behavior depends on a combination of three altered neurobehavioral processes: (1) threat appraisal, (2) habitual avoidance, and (3) trait avoidance tendency. This heterogeneity in underlying processes presents challenges to the objective measurement of maladaptive avoidance behavior. Here we first review existing paradigms for measuring avoidance behavior and its underlying neural mechanisms in both human and animal models, and identify how existing paradigms relate to these neurobehavioral processes. We then propose a new framework to improve the translational understanding of maladaptive avoidance behavior by adapting paradigms to better differentiate underlying processes and mechanisms and applying these paradigms in clinical populations across diagnoses with the goal of developing novel interventions to engage specific identified neurobehavioral targets.