Distinct Responses to Predictable and Unpredictable Threat in Anxiety Pathologies: Effect of Panic Attack

Christian Grillon, Katherine O'Connell, Lynne Lieberman, Gabriella Alvarez, Marilla Geraci, Daniel S. Pine, Monique Ernst

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background Delineating specific clinical phenotypes of anxiety disorders is a crucial step toward better classification and understanding of these conditions. The present study sought to identify differential aversive responses to predictable and unpredictable threat of shock in healthy comparisons and in nonmedicated anxiety patients with and without a history of panic attacks (PAs). Methods In this study, 143 adults (72 healthy control subjects; 71 patients with generalized, social, or both generalized and social anxiety disorders, 24 with and 47 without PAs) were exposed to three conditions: 1) predictable shocks signaled by a cue, 2) unpredictable shocks, and 3) no shock. Startle magnitude was used to assess aversive responses. Results Across disorders, a history of PAs was specifically associated with hypersensitivity to unpredictable threat. By disorder, social anxiety disorder was associated with hypersensitivity to predictable threat, whereas generalized anxiety disorder was associated with exaggerated baseline startle. Conclusions These results identified three physiological patterns. The first is hypersensitivity to unpredictable threat in individuals with PAs. The second is hypersensitivity to predictable threat, which characterizes social anxiety disorder. The third is enhanced baseline startle in generalized anxiety disorder, which may reflect propensity for self-generated anxious thoughts in the absence of imminent danger. These results inform current thinking by linking specific clinical features to particular physiology profiles.

Original languageEnglish (US)
Pages (from-to)575-581
Number of pages7
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number7
StatePublished - Oct 2017
Externally publishedYes


  • Anxiety
  • Anxiety disorder
  • Fear
  • Panic attack
  • Predictability
  • Startle

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cognitive Neuroscience
  • Clinical Neurology
  • Biological Psychiatry


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