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Biol Psychiatry. 2014 Jun 1;75(11):909-15. doi: 10.1016/j.biopsych.2013.07.025. Epub 2013 Aug 31.

Generalized anxiety disorder is associated with overgeneralization of classically conditioned fear.

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Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland; Department of Psychology, University of Minnesota, Minneapolis, Minnesota. Electronic address:
Department of Psychology, University of Minnesota, Minneapolis, Minnesota.
Department of Psychology, Drexel University, Philadelphia, Pennsylania.
Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland.



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.


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.


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+.


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.


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

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