Article

Overgeneralization of Conditioned Fear as a Pathogenic Marker of Panic Disorder

Mood and Anxiety Disorders Program, NIMH Intramural Research Program, Bethesda, MD, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 11/2009; 167(1):47-55. DOI: 10.1176/appi.ajp.2009.09030410
Source: PubMed

ABSTRACT

Classical conditioning features prominently in many etiological accounts of panic disorder. According to such accounts, neutral conditioned stimuli present during panic attacks acquire panicogenic properties. Conditioned stimuli triggering panic symptoms are not limited to the original conditioned stimuli but are thought to generalize to stimuli resembling those co-occurring with panic, resulting in the proliferation of panic cues. The authors conducted a laboratory-based assessment of this potential correlate of panic disorder by testing the degree to which panic patients and healthy subjects manifest generalization of conditioned fear.
Nineteen patients with a DSM-IV-TR diagnosis of panic disorder and 19 healthy comparison subjects were recruited for the study. The fear-generalization paradigm consisted of 10 rings of graded size presented on a computer monitor; one extreme size was a conditioned danger cue, the other extreme a conditioned safety cue, and the eight rings of intermediary size created a continuum of similarity from one extreme to the other. Generalization was assessed by conditioned fear potentiating of the startle blink reflex as measured with electromyography (EMG).
Panic patients displayed stronger conditioned generalization than comparison subjects, as reflected by startle EMG. Conditioned fear in panic patients generalized to rings with up to three units of dissimilarity to the conditioned danger cue, whereas generalization in comparison subjects was restricted to rings with only one unit of dissimilarity.
The findings demonstrate a marked proclivity toward fear overgeneralization in panic disorder and provide a methodology for laboratory-based investigations of this central, yet understudied, conditioning correlate of panic. Given the putative molecular basis of fear conditioning, these results may have implications for novel treatments and prevention in panic disorder.

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Available from: Daniel S Pine, Dec 16, 2013
    • "The steepness of this gradient indexes generalization, with flatter downward gradients indicating greater generalization (Armony et al., 1997;Greenberg et al., 2013a) (Fig. 1). Recent studies in subjects suffering from generalized anxiety disorder (GAD) and panic disorder (PD) demonstrated that generalization gradients were abnormally shallow among these patients, reflecting stronger transfer of fear to stimuli resembling the CS (Lissek et al., 2014bLissek et al., , 2010). In both of these studies the participants were presented with rings of gradually increasing size with extremes serving as the conditioned danger cue (CS+) and conditioned safety cue (CS−), and the intermediately sized rings as GSs. "
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    • "Subjects often take some time to learn the safety value of such cues, initially attributing the occurrence of the UCS to any stimulus present, and their ability to finally discriminate between actual UCS predictors (CS+) and safety cues (CS-) may also predict positive health outcomes (Britton et al., 2011;Craske et al., 2012;Gazendam et al., 2013). Similar reappraisal abilities may be needed when learning to distinguish a UCS predictor from physically similar but non-predictive cues (Vervliet et al., 2006;Lissek et al., 2009) or when learning that the context in which conditioning occurs is not in itself a good UCS predictor (Grillon et al., 2006;Kaouane et al., 2012). Assessing discrimination learning has the desirable quality that it can be done as part of a fear conditioning paradigm used to measure PC 1 . "
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    • "Indeed, the unrestricted generalization or ''overgeneralization'' of maladaptive fear and avoidance is now widely considered to be a defining feature of anxiety disorders (American Psychiatric Association, 2013). Overgeneralization of conditioned fear has been observed in panic disorder (Lissek et al., 2010), generalized anxiety disorder (Lissek et al., 2014; Tinoco-González et al., in press) and post-traumatic stress disorder (Lissek and Grillon, 2012). Yet, surprisingly little research has been conducted on the generalization of avoidance with healthy participants (Lommen et al., 2010; van Meurs et al., 2014; see also, Geschwind et al., 2015). "
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