Generalized anxiety disorder is associated with overgeneralization of classically conditioned fear

Shmuel Lissek, Antonia N. Kaczkurkin, Stephanie Rabin, Marilla Geraci, Daniel S. Pine, Christian Grillon

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301 Scopus citations


Background Meta-analytic results of fear-conditioning studies in the anxiety disorders implicate generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of anxiety pathology. Due to the absence of conditioning studies assessing generalization in generalized anxiety disorder (GAD), results of this meta-analysis do not reveal whether such generalization abnormalities also apply to GAD. The current study fills this gap by behaviorally and psychophysiologically assessing levels of conditioned fear generalization across adults with and without GAD. Methods Twenty-two patients with a DSM-IV-Text Revision diagnosis of GAD and 26 healthy comparison subjects were recruited and tested. The employed generalization paradigm consisted of quasi-randomly presented rings of gradually increasing size, with extreme sizes serving as conditioned danger cues (CS+) and conditioned safety cues. The rings of intermediary size served as generalization stimuli, creating a continuum of similarity between CS+ and conditioned safety cues across which to assess response slopes, referred to as generalization gradients. Primary outcome variables included slopes for fear-potentiated startle (electromyography) and self-reported risk ratings. Results Behavioral and psychophysiological findings demonstrated overgeneralization of conditioned fear among patients with GAD. Specifically, generalization gradients were abnormally shallow among GAD patients, reflecting less degradation of the conditioned fear response as the presented stimulus differentiated from the CS+. Conclusions Overgeneralization of conditioned fear to safe encounters resembling feared situations may contribute importantly to the psychopathology of GAD by proliferating anxiety cues in the individual's environment that are then capable of evoking and maintaining anxiety and worry associated with GAD.

Original languageEnglish (US)
Pages (from-to)909-915
Number of pages7
JournalBiological psychiatry
Issue number11
StatePublished - Jun 1 2014

Bibliographical note

Funding Information:
This work was supported by the Intramural Research Program of the National Institute of Mental Health and by a grant to SL from the Extramural Research Program of the National Institute of Mental Health (K99 MH080130).


  • Fear conditioning
  • fear-potentiated startle
  • generalized anxiety disorder
  • interpretation bias
  • pathophysiology
  • stimulus generalization


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