Glucocorticoids Enhance in Vivo Exposure-Based Therapy of Spider Phobia

Soravia, Leila M.; Heinrichs, Markus; Winzeler, Livia; Fisler, Melanie Sarah; Schmitt, W; Horn, Helge; Dierks, Thomas; Strik, Werner; Hofmann, S.; Quervain, Dominique J.‐F. de

doi:10.1002/da.22219

Cited by 93 publications

(78 citation statements)

References 39 publications

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“…We utilized fMRI to record the neural activity in response to pictures of spiders in patients with spider phobia, who received either cortisol or placebo, and in control subjects who did not receive any medication. As shown in previous studies (Aerni et al, 2004;Soravia et al, 2014), cortisol treatment improves phobic symptoms, but patients still exhibits a significant level of phobic response. To investigate neural correlates of residual symptoms, we compared the phobic patient groups with the healthy controls.…”

Section: Introductionsupporting

confidence: 68%

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Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia

Nakataki

Soravia

Schwab

et al. 2016

Neuropsychopharmacol

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Glucocorticoids reduce phobic fear in patients with anxiety disorders. Previous studies have shown that fear-related activation of the amygdala can be mediated through the visual cortical pathway, which includes the fusiform gyrus, or through other pathways. However, it is not clear which of the pathways that activate the amygdala is responsible for the pathophysiology of a specific phobia and how glucocorticoid treatment alleviates fear processing in these neural networks. We recorded the brain activity with functional magnetic resonance imaging in patients with spider phobia, who received either 20 mg of cortisol or a placebo while viewing pictures of spiders. We also tested healthy participants who did not receive any medication during the same task. We performed dynamic causal modelling (DCM), a connectivity analysis, to examine the effects of cortisol on the networks involved in processing fear and to examine if there was an association between these networks and the symptoms of the phobia. Cortisol administration suppressed the phobic stimuli-related amygdala activity to levels comparable to the healthy participants and reduced subjective phobic fear. The DCM analysis revealed that cortisol administration suppressed the aberrant inputs into the amygdala that did not originate from the visual cortical pathway, but rather from a fast subcortical pathway mediated by the pulvinar nucleus, and suppressed the interactions between the amygdala and fusiform gyrus. This network changes were distinguishable from healthy participants and considered the residual changes under cortisol administration. We also found that the strengths of the aberrant inputs into the amygdala were positively correlated with the severity of spider phobia. This study demonstrates that patients with spider phobia show an aberrant functional connectivity of the amygdala when they are exposed to phobia-related stimuli and that cortisol administration can alleviate this fear-specific neural connectivity.

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Section: Introductionsupporting

confidence: 68%

“…The patients were selected from a cohort of our previous clinical trial, investigating the effectiveness of cortisol treatment and cognitive behavioral therapy on spider phobia treatment (Soravia et al, 2014;clinicaltrials.gov NCT01574014). The subjects were recruited via advertisement.…”

Section: Subjectsmentioning

confidence: 99%

Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia

Nakataki

Soravia

Schwab

et al. 2016

Neuropsychopharmacol

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“…Repeated or prolonged unreinforced retrievals can lead to extinction learning (Merlo et al, 2014; but see Cai et al (2006) for single-trial extinction). GCs and stress have been shown to enhance exposure-based psychotherapy (de Quervain et al, 2011;Soravia et al, 2006;Soravia et al, 2014) and extinction learning (Hamacher-Dang et al, 2013), presumably by enhancing the consolidation of the newly acquired extinction memory (de Quervain and Margraf, 2008). In their rodents fear conditioning study, Cai et al (2006) demonstrated that postreactivation corticosterone can impair recall of established contextual fear memory, presumably through enhancement of extinction learning, even after a single trial.…”

Section: Discussionmentioning

confidence: 99%

Effects of Cortisol on Reconsolidation of Reactivated Fear Memories

Drexler

Merz

Hamacher-Dang

et al. 2015

Neuropsychopharmacol

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The return of conditioned fear after successful extinction (eg, following exposure therapy) is a significant problem in the treatment of anxiety disorders and posttraumatic stress disorder (PTSD). Targeting the reconsolidation of fear memories may allow a more lasting effect as it intervenes with the original memory trace. Indeed, several pharmacological agents and behavioral interventions have been shown to alter (enhance, impair, or otherwise update) the reconsolidation of reactivated memories of different types. Cortisol is a stress hormone and a potent modulator of learning and memory, yet its effects on fear memory reconsolidation are unclear. To investigate whether cortisol intervenes with the reconsolidation of fear memories in healthy males and how specific this effect might be, we built a 3-day reconsolidation design with skin conductance response (SCR) as a measure of conditioned fear: Fear acquisition on day 1; reactivation/no-reactivation of one conditioned stimulus and pharmacological intervention on day 2; extinction learning followed by reinstatement and reinstatement test on day 3. The groups differed only in the experimental manipulation on day 2: Reactivation+Cortisol Group, Reactivation+Placebo Group, or No-reactivation+Cortisol Group. Our results revealed an enhancing effect of cortisol on reconsolidation of the reactivated memory. The effect was highly specific, strengthening only the memory of the reactivated conditioned stimulus and not the non-reactivated one. Our findings are in line with previous findings showing an enhancing effect of behavioral stress on the reconsolidation of other types of memories. These results have implications for the understanding and treatment of anxiety disorders and PTSD.

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“…16 Indeed, stress and associated elevated cortisol levels increase extinction memory consolidation, 59 and the administration of glucocorticoids enhances the effects of exposure therapy for anxiety disorders. 60, 61, 62 Accordingly, FKBP5 genotype might influence the initial fear memory strength as well as the process of extinction learning.…”

Section: Discussionmentioning

confidence: 99%

The role of FKBP5 genotype in moderating long-term effectiveness of exposure-based psychotherapy for posttraumatic stress disorder

et al. 2014

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Exposure-based therapies are considered the state-of-the-art treatment for Posttraumatic Stress Disorder (PTSD). Yet, a substantial number of PTSD patients do not recover after therapy. In the light of the well-known gene × environment interactions on the risk for PTSD, research on individual genetic factors that influence treatment success is warranted. The gene encoding FK506-binding protein 51 (FKBP5), a co-chaperone of the glucocorticoid receptor (GR), has been associated with stress reactivity and PTSD risk. As FKBP5 single-nucleotide polymorphism rs1360780 has a putative functional role in the regulation of FKBP5 expression and GR sensitivity, we hypothesized that this polymorphism influences PTSD treatment success. We investigated the effects of FKBP5 rs1360780 genotype on Narrative Exposure Therapy (NET) outcome, an exposure-based short-term therapy, in a sample of 43 survivors of the rebel war in Northern Uganda. PTSD symptom severity was assessed before and 4 and 10 months after treatment completion. At the 4-month follow-up, there were no genotype-dependent differences in therapy outcome. However, the FKBP5 genotype significantly moderated the long-term effectiveness of exposure-based psychotherapy. At the 10-month follow-up, carriers of the rs1360780 risk (T) allele were at increased risk of symptom relapse, whereas non-carriers showed continuous symptom reduction. This effect was reflected in a weaker treatment effect size (Cohen's D=1.23) in risk allele carriers compared with non-carriers (Cohen's D=3.72). Genetic factors involved in stress response regulation seem to not only influence PTSD risk but also responsiveness to psychotherapy and could hence represent valuable targets for accompanying medication.

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Glucocorticoids Enhance in Vivo Exposure-Based Therapy of Spider Phobia

Abstract: These findings indicate that adding cortisol to in vivo exposure-based group therapy of spider phobia enhances treatment outcome.

Cited by 93 publications

References 39 publications

Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia

Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia

Effects of Cortisol on Reconsolidation of Reactivated Fear Memories

The role of FKBP5 genotype in moderating long-term effectiveness of exposure-based psychotherapy for posttraumatic stress disorder

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