Measuring approach-avoidance behavior in patients with panic disorder using the human elevated plus maze in mixed reality.

BACKGROUND

Avoidance behavior is a hallmark of panic disorder (PD), yet experimental evidence remains limited due to challenges in assessing unconditioned avoidance without specific threats. The human Elevated Plus Maze (EPM), implemented in mixed reality, provides an ecologically valid paradigm to measure approach-avoidance behavior under controlled conditions.

METHODS

Twenty PD patients and 20 healthy controls (HC) were tested on the human EPM. Approach-avoidance behavior was assessed alongside subjective anxiety, tension, and cardiovascular responses across multiple time points. Hormonal markers (copeptin, ACTH, cortisol) were analyzed in a subgroup.

RESULTS

PD patients showed significantly higher anticipatory anxiety, tension, and heart rate responses than HC, indicating heightened emotional and physiological reactivity. Contrary to our hypothesis, no significant group differences emerged in approach-avoidance behavior. Sensation seeking emerged as the strongest inverse predictor of both avoidance and subjective anxiety. Across groups, higher anxiety in the EPM center robustly predicted avoidance. Subgroup analyses suggested antidepressant use may attenuate avoidance behavior in PD.

DISCUSSION: The EPM elicited ecologically valid subjective and physiological anxiety responses, supporting its translational utility. However, avoidance behavior was more strongly shaped by trait factors than by diagnostic status. In particular, sensation seeking may represent a protective trait promoting approach tendencies and extinction learning, offering a potential target for personalized interventions. The human EPM thus provides a promising tool to investigate transdiagnostic mechanisms of avoidance and to inform tailored treatment strategies in PD.