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


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.

Download full-text


Available from: Daniel S Pine, Dec 16, 2013
1 Follower
40 Reads
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Excessive avoidance behavior, in which an instrumental action prevents an upcoming aversive event, is a defining feature of anxiety disorders. Left unchecked, both fear and avoidance of potentially threatening stimuli may generalize to perceptually related stimuli and situations. The behavioral consequences of generalization mean that aversive learning experiences with specific threats may lead to the inference that classes of related stimuli are threatening, potentially dangerous, and need to be avoided, despite differences in physical form. Little is known however about avoidance generalization in humans and the learning pathways by which it may be transmitted. In the present study, we compared two pathways to avoidance-instructions and social observation-on subsequent generalization of avoidance behavior, fear expectancy and physiological arousal. Participants first learned that one cue was a danger cue (conditioned stimulus, CS+) and another was a safety cue (CS-). Groups were then either instructed that a simple avoidance response in the presence of the CS+ cancelled upcoming shock (instructed-learning group) or observed a short movie showing a demonstrator performing the avoidance response to prevent shock (observational-learning group). During generalization testing, danger and safety cues were presented along with generalization stimuli that parametrically varied in perceptual similarity to the CS+. Reinstatement of fear and avoidance was also tested. Findings demonstrate, for the first time, generalization of socially transmitted and instructed avoidance: both groups showed comparable generalization gradients in fear expectancy, avoidance behavior and arousal. Return of fear was evident, suggesting that generalized avoidance remains persistent following extinction testing. The utility of the present paradigm for research on avoidance generalization is discussed.
    Frontiers in Behavioral Neuroscience 07/2015; 1(9). DOI:10.3389/fnbeh.2015.00159 · 3.27 Impact Factor
  • Source
    • "Explaining individual differences in generalization is one of the central topics in this literature, because these differences presumably explain differences in the vulnerability to, and maintenance of psychopathology (Dymond et al., 2014). For example, Lissek et al. (2010) found more generalization in a group suffering from panic disorder compared to healthy controls. Lommen et al. (2010) found that individuals high in trait neuroticism generalized more than individuals low in trait neuroticism. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A case is made for the use of hierarchical models in the analysis of generalization gradients. Hierarchical models overcome several restrictions that are imposed by repeated measures analysis-of-variance (rANOVA), the default statistical method in current generalization research. More specifically, hierarchical models allow to include continuous independent variables and overcomes problematic assumptions such as sphericity. We focus on how generalization research can benefit from this added flexibility. In a simulation study we demonstrate the dominance of hierarchical models over rANOVA. In addition, we show the lack of efficiency of the Mauchly's sphericity test in sample sizes typical for generalization research, and confirm how violations of sphericity increase the probability of type I errors. A worked example of a hierarchical model is provided, with a specific emphasis on the interpretation of parameters relevant for generalization research.
    Frontiers in Psychology 05/2015; 6(652). DOI:10.3389/fpsyg.2015.00652 · 2.80 Impact Factor
  • Source
    • "During stimulus generalization individuals extrapolate knowledge from one situation to other situations without actually having to experience them. Generalization reduces the risk of missing positive alarms, but goes with the cost of an increased risk to responding to false alarms, and has shown to be a potent predictor of distress outside the pain field [62]. Generalization of pain-related fear has been suggested a mechanism contributing to the spreading of pain. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pain is a biologically relevant signal and response to bodily threat, associated with the urge to restore the integrity of the body. Immediate protective responses include increased arousal, selective attention, escape, and facial expressions, followed by recuperative avoidance and safety-seeking behaviors. To facilitate early and effective protection against future bodily threat or injury, learning takes place rapidly. Learning is the observable change in behavior due to events in the internal and external environmental and includes nonassociative (habituation and sensitization) and associative learning (Pavlovian and operant conditioning). Once acquired, these knowledge representations remain stored in memory and may generalize to perceptually or functionally similar events. Moreover, these processes are not just a consequence of pain; they may directly influence pain perception. In contrast to the rapid acquisition of learned responses, their extinction is slow, fragile, context dependent and only occurs through inhibitory processes. Here, we review features of associative forms of learning in humans that contribute to pain, pain-related distress, and disability and discuss promising future directions. Although conditioning has a long and honorable history, a conditioning perspective still might open new windows on novel treatment modalities that facilitate the well-being of individuals with chronic pain.
    Pain 04/2015; 156 Suppl 1:S86-93. DOI:10.1097/j.pain.0000000000000107 · 5.21 Impact Factor
Show more