Increased anxiety during anticipation of unpredictable aversive stimuli in posttraumatic stress disorder but not in generalized anxiety disorder

Abstract

Background: Uncontrollability and unpredictability are key concepts related to re-experiencing, avoidance, and hypervigilance symptoms of posttraumatic stress disorder (PTSD). However, little is known about the differential sensitivity of PTSD individuals to unpredictable stressors, relative to either healthy individuals or individuals with other anxiety disorders. This study tested the hypothesis that elevated anxious reactivity, specifically for unpredictable aversive events, is a psychophysiological correlate of PTSD.

Methods: Sixteen patients with PTSD (34.5 +/- 12.4 years) were compared with 18 patients with generalized anxiety disorder (GAD) (34.0 +/- 10.5 years) and 34 healthy control subjects (30.2 +/- 8.5 years). Participants were exposed to three conditions: one in which predictable aversive stimuli were signaled by a cue, a second in which aversive stimuli were administered unpredictably, and a third in which no aversive stimuli were anticipated. Startle magnitude was used to assess anxious responses to the threat cue and to contexts associated with each condition.

Results: Posttraumatic stress disorder and GAD patients showed normative enhancement of fear to the predictable threat cue, but the PTSD group displayed elevated anxiety during the unpredictable condition compared with participants with GAD and healthy control subjects.

Conclusions: Anxious reactivity to unpredictable aversive events was heightened in PTSD but not in GAD and healthy subjects. Prior works also found signs of increased reactivity to unpredictable threat in panic disorder (PD), suggesting that PTSD and PD may involve shared vulnerability. As such, the current results inform understandings of classification, pathophysiology, and psychopharmacology of anxiety disorders, generally, and PTSD and panic disorder specifically.

Figure 1

Schematic of the experiment. Subjects were presented with three neutral (N), two predictable (P), and two unpredictable (U) contexts (order U N P N P N U as shown or P N U N U N P). Each N, P, and U condition contained four 8-s duration cues. In the P condition, the aversive stimulus was administered only in the presence of the cue. In the U condition, the aversive stimulus was administered randomly during cue-free periods. In the N condition, no aversive stimulus was administered. Startle stimuli were delivered during the cues (blue arrow pointing up) or during cue free-periods (green arrow pointing up).

Figure 2

Startle magnitudes in the cue-free periods in the no aversive event (N), predictable (P), and unpredictable (U) conditions among the control, PTSD, and PD groups. Error bars reflect SEM. There was a significant (F[1,14]=8.4, p<.01) increase in startle magnitude from N to U in PTSD only. There were also significant group differences when contrasting startle during N to startle during U. # Control vs. PTSD: F[1,46] =9.3, p<.004); ^ GAD vs. PTSD: F[1,30] =4.4, p<.04.