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Cited by 272Posttraumatic Stress Disorder ResearchAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesPsychoanalysis and Psychopathology Research

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

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Grillon, Christian, Pine, Daniel S., Lissek, Shmuel, Rabin, Stephanie, Bonne, Omer, Vythilingam, Meena·2009·Biological Psychiatry
DOI 10.1016/j.biopsych.2008.12.028PMC PMC2696581
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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.

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  • This interpretation matches our finding that mildly aversive stimuli do not produce contextual anxiety.

    “This interpretation is consistent with our observation that mildly aversive stimuli do not induce contextual anxiety (Grillon et al, 2004, 2009b).”

    From Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety (2010) · cites this paper as Grillon et al, 2009b

    The Discussion reports that the less noxious stimuli did not produce contextual startle potentiation in healthy controls or the GAD group. But it also reports heightened contextual anxiety in the PTSD group, so the unqualified claim that mildly aversive stimuli do not induce contextual anxiety is too broad. Page numbers were not available in our copy. (LLM, conf=0.88)

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  • No relation has been found between physiological measures of response to uncertainty and GAD symptoms.

    “However, no such relation has been found with GAD symptoms (Gorka et al., 2017a; Grillon et al., 2009).”

    From Aversive response to uncertainty as a mediator for the effect of a mindfulness intervention on symptoms of anxiety (2022) · cites this paper as Grillon et al., 2009

    The Results (Startle magnitude; page unavailable) found no significant difference in startle reactivity between the GAD and healthy-control groups across conditions, and the Discussion reports no heightened anxiety during unpredictable aversive events in GAD. This supports the claim for the study’s physiological measure and experimental condition, but the paper compares diagnostic groups rather than testing a relation between physiological responses and GAD symptom severity. (LLM, conf=0.85)

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Research works printed but not linked: 2

  1. [33]Charney DS Bremner DJ Charney DS Nestler EJ Bunney BS The neurobiology of anxiety disorders Neurobiology of Mental Illness New York Oxford University Press 1999 494 517
  2. [38]Lissek S Baas JMP Pine DS Airpuff startle probes: an efficacious and less aversive alternative to white-noise Biological Psychology 2005 68 283 297 15620795

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Authors
Grillon, C., Pine, D. S., Lissek, S., Rabin, S., Bonne, O., & Vythilingam, M.
Affiliations
  • National Institutes of Health (US)
  • Hadassah Medical Center (IL)
Corresponding author
Grillon, Christian
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2009-07
Volume
66
Issue
1
Pages
47-53
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2008.12.028
PMC
PMC2696581
OpenAlex
W2094911181
Cited by
272
References
57
Citations by year
2026: 10 · 2025: 8 · 2024: 9 · 2023: 12 · 2022: 14 · 2021: 18 · 2020: 17 · 2019: 24 · 2018: 17 · 2017: 19 · 2016: 30 · 2015: 19 · 2014: 20 · 2013: 17 · 2012: 15
FWCI
13.47
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (Z01MH002798)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
Keywords
post-traumatic stress disorder, generalized anxiety disorder, threat anticipation, startle response, fear conditioning, uncontrollability, panic disorder, anxiety disorders
MeSH terms
Acoustic Stimulation, Adult, Anxiety Disorders, Avoidance Learning, Conditioning, Classical, Cues, Female, Humans, Male, Middle Aged, Physical Stimulation, Reflex, Startle, Stress Disorders, Post-Traumatic, Young Adult

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