Fear Extinction and Relapse: State of the Art

Vervliet, Bram; Craske, Michelle G.; Hermans, Dirk

doi:10.1146/annurev-clinpsy-050212-185542

Cited by 570 publications

(498 citation statements)

References 136 publications

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“…Processes underlying clinical relapse are modeled in the laboratory using classical conditioning paradigms and return of fear (ROF) manipulations following extinction training in animals and humans (Bouton, 2002;Vervliet, Craske, & Hermans, 2013). Thereby, extinction is thought to generate competing inhibitory extinction memories that co-exist with fear memories (Bouton, 2004;Myers & Davis, 2007) rather than erase them.…”

Section: Introductionmentioning

confidence: 99%

“…Thereby, extinction is thought to generate competing inhibitory extinction memories that co-exist with fear memories (Bouton, 2004;Myers & Davis, 2007) rather than erase them. Insufficient expression of extinction memories upon re-confrontation with the conditioned stimulus at a later time thus results in ROF (Bouton, 2002), a suggested experimental analog of clinical relapse (Vervliet et al, 2013). Experimentally, ROF can be induced by the mere passage of time (spontaneous recovery), a contextual change (renewal) and the unexpected re-exposure to the unconditioned stimulus or another aversive event (reinstatement, RI) (Bouton, 2004;Vervliet et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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State anxiety modulates the return of fear

Kuhn

Mertens

Lonsdorf

2016

International Journal of Psychophysiology

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Current treatments for anxiety disorders are effective but limited by the high frequency of clinical relapse. Processes underlying relapse are thought to be experimentally modeled in fear conditioning experiments with return fear (ROF) inductions. Thereby reinstatementinduced ROF might be considered a model to study mechanisms underlying adversity-induced relapse. Previous studies have reported differential ROF (i.e. specific for the danger stimulus) but also generalized ROF (i.e. for safe and danger stimuli), but reasons for these divergent findings are not clear yet. Hence, the response pattern (i.e. differential or generalized) following reinstatement may be of importance for the prediction of risk or resilience for ROF.The aim of this study was to investigate state anxiety as a potential individual difference factor contributing to differentiability or generalization of return of fear.Thirty-six participants underwent instructed fear expression, extinction and ROF induction through reinstatement while physiological (skin conductance response, fear potentiated startle) and subjective measures of fear and US expectancy were acquired. Our data show that, as expected, high state anxious individuals show deficits in SCR discrimination between dangerous and safe cues after reinstatement induced ROF (i.e. generalization) as compared to low state anxious individuals.The ability to maintain discrimination under aversive circumstances is negatively associated with pathological anxiety and predictive of resilient responding while excessive generalization is a hallmark of anxiety disorders. Therefore, we suggest that experimentally induced ROF might prove useful in predicting relapse risk in clinical settings and might have implications for possible interventions for relapse prevention.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

State anxiety modulates the return of fear

Kuhn

Mertens

Lonsdorf

2016

International Journal of Psychophysiology

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“…There is an extensive literature on contextual modulation of extinction and return of fear in patients with anxiety disorders (e.g., Vervliet et al 2013) and some evidence of altered contextual modulation of extinction in PTSD patients (Rougemont-Bücking et al 2011). …”

Section: Do Ptsd Patients Have Altered Contextual Fear Learning?mentioning

confidence: 99%

“…Theoretically, drugs that improve pattern completion and separation could be used prophylactically during or immediately following trauma to improve specificity of learning and prevent overgeneralization of contextual or discrete fear (Glenn et al 2014). Conversely, such drugs may be contraindicated for use in conjunction with exposure therapy for PTSD and other anxiety disorders given concerns that greater contextual specificity of fear extinction learning increases the probability of contextually mediated renewal of fear (Bouton et al 2006;Vervliet et al 2013). …”

Section: Are Contextual Fear Learning and Fear Generalizationmentioning

confidence: 99%

“…An additional concern in terms of drugs effects on fear extinction is whether inhibitory learning processes are expedited (i.e., faster reduction in fear) or made more robust to relapse. It has recently been noted that in exposure therapy, the extent to which reductions in fear are long-lasting and resistant to relapse may be of greater clinical value than the sheer magnitude of decrease in fear (Vervliet et al 2013). …”

Section: Practical Considerations When Using Learned Fear Processes Amentioning

confidence: 99%

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On the Road to Translation for PTSD Treatment: Theoretical and Practical Considerations of the Use of Human Models of Conditioned Fear for Drug Development

Risbrough

Glenn²,

Baker

2015

Translational Neuropsychopharmacology

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The use of quantitative, laboratory-based measures of threat in humans for proof-of-concept studies and target development for novel drug discovery has grown tremendously in the last 2 decades. In particular, in the field of posttraumatic stress disorder (PTSD), human models of fear conditioning have been critical in shaping our theoretical understanding of fear processes and importantly, validating findings from animal models of the neural substrates and signaling pathways required for these complex processes. Here, we will review the use of laboratorybased measures of fear processes in humans including cued and contextual conditioning, generalization, extinction, reconsolidation, and reinstatement to develop novel drug treatments for PTSD. We will primarily focus on recent advances in using behavioral and physiological measures of fear, discussing their sensitivity as biobehavioral markers of PTSD symptoms, their response to known and novel PTSD treatments, and in the case of d-cycloserine, how well these findings have translated to outcomes in clinical trials. We will highlight some gaps in the literature and needs for future research, discuss benefits and limitations of these outcome measures in designing proof-of-concept trials, and offer practical guidelines on design and interpretation when using these fear models for drug discovery.

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