Classical fear conditioning in the anxiety disorders: a meta-analysis

Lissek, Shmuel; Powers, Alice Schade; McClure, Erin B.; Phelps, Elizabeth A.; Woldehawariat, Girma; Grillon, Christian; Pine, Daniel S.

doi:10.1016/j.brat.2004.10.007

Cited by 923 publications

(915 citation statements)

References 86 publications

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“…Though the shape of the generalization gradient in healthy humans resembles that of animals, the elevated tendency of anxiety patients to transfer conditioned fear to a CS-with strong resemblance to the CS+ (Grillon and Morgan, 1999;Lissek et al, 2005) supports the prediction of less steep generalization gradients among those with clinical anxiety, whereby startle magnitudes would remain elevated during presentation of Classes 3, 2, and perhaps 1 before dropping to CS-levels. Additionally, given that anxious individuals are characterized by a heightened tendency to appraise ambiguous stimuli as threatening (for a review, see Richards, 2004), those with clinical anxiety relative to healthy controls would be expected to display elevated risk ratings for shock when presented with classes of rings containing ambiguous threat information (i.e., Classes 4, 3, and 2), but would display approximately equal risk ratings for rings with more certain signal-value (i.e., CS+, CS-).…”

Section: Predictions For Anxiety Patients Generated From Current Resultsmentioning

confidence: 70%

“…A recent meta-analysis of lab-based, fearconditioning studies in the anxiety disorders implicates heightened anxious reactivity to conditioned stimuli (CS's) signaling safety as an important conditioning correlate of clinical anxiety (Lissek et al, 2005). A closer look at this literature reveals that studies of posttraumatic stress disorder (PTSD) contribute prominently to this pattern.…”

Section: Introductionmentioning

confidence: 99%

“…Because of these advantages, FPS is increasingly used to measure psychophysiological correlates of pathologic anxiety and to test the anxiolytic properties of pharmaceutical compounds (for a review, see Grillon, in press). Given the strong relevance of conditioned fear generalization to anxiety disorders (e.g., Foa, Steketee, & Rothbaum, 1989;Grillon & Morgan, 1999;Keane, Zimmering, & Caddell, 1985;Lissek et al, 2005;Mineka, 1992), conditioned startle-potentiated paradigms capable of eliciting continuous gradients of fear generalization may be a particularly powerful translational tool. The current study tests a novel conditioned startle-potentiation paradigm designed for this purpose in 20 healthy participants.…”

Section: Introductionmentioning

confidence: 99%

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Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance

Lissek

Biggs

Rabin

et al. 2008

Behaviour Research and Therapy

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Though generalization of conditioned fear has been implicated as a central feature of pathological anxiety, surprisingly little is known about the psychobiology of this learning phenomenon in humans. Whereas animal work has frequently applied methods to examine generalization gradients to study the gradual weakening of the conditioned-fear response as the test stimulus increasingly differs from the conditioned stimulus (CS), to our knowledge no psychobiological studies of such gradients have been conducted in humans over the last 40 years. The current effort validates an updated generalization paradigm incorporating more recent methods for the objective measurement of anxiety (fear-potentiated startle). The paradigm employs 10, quasi-randomly presented, rings of graduallyincreasing size with extremes serving as CS+ and CS-. The eight rings of intermediary size serve as generalization stimuli (GS's) and create a continuum-of-similarity from CS+ to CS-. Both startle data and online self-report ratings demonstrate continuous decreases in generalization as the presented stimulus becomes less similar to the CS+. The current paradigm represents an updated and efficacious tool with which to study fear generalization-a central, yet understudied conditioningcorrelate of pathologic anxiety.

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Section: Predictions For Anxiety Patients Generated From Current Resultsmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance

Lissek

Biggs

Rabin

et al. 2008

Behaviour Research and Therapy

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350

382

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“…Finally, of all our participants, 29% showed no response to treatment (Non-responders), reporting severe PTSD symptoms at all time points. As other studies recorded a similar non-responders cluster (Allan et al, 2016; Stein et al, 2012), this raises the question whether, for some patients, extinction learning is not feasible (Lissek et al, 2005). …”

Section: Discussionmentioning

confidence: 77%

Intensive prolonged exposure therapy for chronic PTSD patients following multiple trauma and multiple treatment attempts

Hendriks

Kleine

Broekman³

et al. 2018

European Journal of Psychotraumatology

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Background: Suboptimal response and high dropout rates leave room for improvement of trauma-focused treatment (TFT) effectiveness in ameliorating posttraumatic stress disorder (PTSD) symptoms. Objective: To explore the effectiveness and safety of intensive prolonged exposure (iPE) targeting chronic PTSD patients with a likely diagnosis of ICD-11 Complex PTSD following multiple interpersonal trauma and a history of multiple treatment attempts. Method: Participants (N = 73) received iPE in 12 × 90-minute sessions over four days (intensive phase) followed by four weekly 90-minute booster prolonged exposure (PE) sessions (booster phase). The primary outcomes, clinician-rated severity of PTSD symptoms, and diagnostic status (Clinician-Administered PTSD Scale; CAPS-IV) were assessed at baseline, post-treatment, and at three and six months. Treatment response trajectories were identified and predictors of these trajectories explored. Results: Mixed model repeated measures analysis of CAPS-IV scores showed a baseline-to-posttreatment decrease in PTSD symptom severity (p < .001) that persisted during the three- and six-month follow-ups with large effect sizes (Cohen’s d > 1.2); 71% of the participants responded. None of the participants dropped out during the intensive phase and only 5% during the booster phase. Adverse events were extremely low and only a minority showed symptom exacerbation. Cluster analysis demonstrated four treatment response trajectories: Fast responders (13%), Slow responders (26%), Partial responders (32%), and Non-responders (29%). Living condition and between-session fear habituation were found to predict outcome. Participants living alone were more likely to belong to the Partial responders than to the Non-responders cluster, and participants showing more between-session fear habituation were more likely to belong to the Fast responders than to the Non-responders cluster. Conclusions: The results of this open study suggest that iPE can be effective in PTSD patients with multiple interpersonal trauma and after multiple previous treatment attempts. In addition, in this chronic PTSD population iPE was safe.

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“…The underlying neurobehavioral mechanisms supporting this transition from adaptive fear learning to clinical fear, avoidance, and anxiety are now well understood thanks to the fear-conditioning paradigm (Beckers et al, 2013;Lissek et al, 2005;Vervliet & Raes, 2013). But fear learning is rarely (if ever) limited to those specific instances or events in which conditioning occurred.…”

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confidence: 99%

Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research

et al. 2015

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Fear generalization, in which conditioned fear responses generalize or spread to related stimuli, is a defining feature of anxiety disorders. The behavioral consequences of maladaptive fear generalization are that aversive experiences with one stimulus or event may lead one to regard other cues or situations as potential threats that should be avoided, despite variations in physical form. Theoretical and empirical interest in the generalization of conditioned learning dates to the earliest research on classical conditioning in nonhumans. Recently, there has been renewed focus on fear generalization in humans due in part to its explanatory power in characterizing disorders of fear and anxiety. Here, we review existing behavioral and neuroimaging empirical research on the perceptual and non-perceptual (conceptual and symbolic) generalization of fear and avoidance in healthy humans and patients with anxiety disorders. The clinical implications of this research for understanding the etiology and treatment of anxiety is considered and directions for future research described.

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Classical fear conditioning in the anxiety disorders: a meta-analysis

Cited by 923 publications

References 86 publications

Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance

Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance

Intensive prolonged exposure therapy for chronic PTSD patients following multiple trauma and multiple treatment attempts

Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research

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