Increased Anxiety During Anticipation of Unpredictable Aversive Stimuli in Posttraumatic Stress Disorder but not in Generalized Anxiety Disorder

Christian Grillon, Daniel S. Pine, Shmuel Lissek, Stephanie Rabin, Omer Bonne, Meena Vythilingam

Research output: Contribution to journalArticlepeer-review

207 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)47-53
Number of pages7
JournalBiological psychiatry
Issue number1
StatePublished - Jul 1 2009

Bibliographical note

Funding Information:
Financial support of this study was provided by the Intramural Research Program of the National Institute of Mental Health.


  • Anticipatory anxiety
  • PTSD
  • anxiety
  • fear-potentiated startle
  • generalized anxiety disorder
  • predictability
  • startle
  • threat


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