Glucocorticoid-induced enhancement of extinction\u2014from animal models to clinical trials

Dominique De Quervain,Oliver T Wolf,Benno Roozendaal

doi:10.1007/s00213-018-5116-0

Abstract

Extensive evidence from both animal model and human research indicates that glucocorticoid hormones are crucially involved in modulating memory performance. Glucocorticoids, which are released during stressful or emotionally arousing experiences, enhance the consolidation of new memories, including extinction memory, but reduce the retrieval of previously stored memories. These memory-modulating properties of glucocorticoids have recently received considerable interest for translational purposes because strong aversive memories lie at the core of several fear-related disorders, including post-traumatic stress disorder and phobias. Moreover, exposure-based psychological treatment of these disorders relies on successful fear extinction. In this review, we argue that glucocorticoid-based interventions facilitate fear extinction by reducing the retrieval of aversive memories and enhancing the consolidation of extinction memories. Several clinical trials have already indicated that glucocorticoids might be indeed helpful in the treatment of fear-related disorders.

Highlights

Stress mediators, including hormones, peptides, and neurotransmitters, promote the organism’s ability to cope with stress by acting on target systems in the periphery and byThis article belongs to a Special Issue on Psychopharmacology of ExtinctionExtensive evidence from studies in animals have indicated that glucocorticoid hormones, in concert with many other stress mediators, are crucially involved in mediating the modulatory effects of stress on both the consolidation and retrieval of memory (Quirarte et al 1997; de Quervain et al 1998; Roozendaal et al 2009)
Because these memory processes are all highly relevant in the pathogenesis, maintenance and treatment of fear-related disorders, the memorymodulatory properties of glucocorticoids are of considerable translational interest
Many of the clinical trials reviewed above suggest that the strategy to enhance extinction-based psychotherapy with a timed glucocorticoid administration is a promising approach to treat fear-related disorders

Summary

Introduction

Stress mediators, including hormones, peptides, and neurotransmitters, promote the organism’s ability to cope with stress by acting on target systems in the periphery and by. A potential mechanism might be that high doses of glucocorticoids—due to the inverted-U-shaped dose-response relationship for the effects of glucocorticoids on consolidation—may have resulted in an impairment of consolidation (Roozendaal et al 1999b), and/or by a reduction of the retrieval of the traumatic memory and thereby interrupting the vicious cycle of retrieving, re-experiencing and reconsolidating aversive memories (de Quervain et al 2009) These effects of glucocorticoid administration on reducing the risk for the development of PTSD are consistent with the findings of other studies indicating that the risk for PTSD is decreased by higher excretion of endogenous cortisol in the first hours after a traumatic event (McFarlane et al 1997; Yehuda et al 1998; Delahanty et al 2000).

Design

Conclusions and future perspectives

Findings

Compliance with ethical standards