Cognitive flexibility mediates the relation between intolerance of uncertainty and safety signal responding in those with panic disorder

There is a growing literature associating anxiety disorders with an inability to inhibit defensive responding during safety conditions of threatening tasks. However, investigations on the relation between panic disorder (PD) and defensive responding to safety have yielded mixed results. A recent study from our laboratory revealed that intolerance of uncertainty (IU) moderates this association, such that only individuals with PD and a high IU exhibit heightened startle potentiation during safety. The mechanism underlying this relationship is unknown. Given that safety conditions typically alternate with periods of threat, cognitive flexibility (i.e., the ability to adjust one's habitual responding to a situation, given the input of new information) may be involved in the ongoing reappraisal of danger and adjustment of defensive responding. Thus, the present study sought to investigate whether deficits in cognitive flexibility mediate the association between IU and defensive responding to safety among a sample of 71 adults diagnosed with PD. As hypothesised, cognitive flexibility mediated the relationship between IU and heightened startle potentiation during safety conditions. This finding suggests that within this subgroup, a failure to inhibit defensive responding during safety conditions may be due to deficits in cognitive flexibility.