Cortisol suppression by dexamethasone reduces exaggerated fear responses in posttraumatic stress disorder

Abstract

Summary PTSD symptoms are associated with heightened fear responses in laboratory fear conditioning paradigms. This study examined the effects of dexamethasone administration on hypothalamic–pituitary–adrenal (HPA) function and fear-potentiated startle (FPS) in trauma-exposed individuals with and without PTSD. We used an established fear discrimination procedure, in which one visual stimulus (CS+, danger cue) was paired with aversive airblasts to the throat (unconditioned stimulus, US), and another stimulus (CS−, safety cue) was presented without airblasts. In addition to FPS, the dexamethasone suppression test (DST) was performed. The study sample (N = 100) was recruited from a highly traumatized civilian population in Atlanta, GA. Half of the subjects (n = 54, 16 PTSD, 38 controls) underwent conditioning at baseline and the other half (n = 46, 17 PTSD, 29 controls) after DST, in a cross-sectional design. We found a significant interaction effect of diagnostic group and dexamethasone treatment. Under baseline conditions, subjects with PTSD showed more than twice as much fear-potentiated startle to the danger cue compared to traumatized controls, F(1,53) = 8.08, p = 0.006. However, there was no group difference in subjects tested after dexamethasone suppression. Furthermore, there was a significant treatment effect in PTSD subjects but not in controls, with dexamethasone reducing fear-potentiated startle to the CS+, F(1,32) = 4.00, p = 0.05. There was also a positive correlation between PTSD subjects’ FPS and cortisol levels, r = 0.46, p = 0.01. These results suggest that transient suppression of HPA function via dexamethasone suppression may reduce exaggerated fear in patients with PTSD.

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala

“…The SNP rs1360780 A within FKBP5 may be actually contributing to alterations in negative feedback of the HPA axis (Klengel et al, 2013). In a previous study of traumatized civilians with and without PTSD, we demonstrated that dexamethasone administration leads to a transient suppression of HPA function that may, in turn, normalize exaggerated fear in patients with PTSD (Jovanovic et al, 2010;Jovanovic et al, 2011). In the current study, we sought to determine whether controlled dexamethasone suppression would similarly enhance EXT of fear in a mouse model of stress-induced EXT deficits.…”

“…Dexamethasone pretreatment has been shown to modulate fear learning in PTSD patients (Jovanovic et al, 2010;Jovanovic et al, 2011). Thus, we hypothesized that it may enhance fear EXT learning and RET in our model of PTSD fear-related symptoms.…”

Updated Meta-Analysis of Classical Fear Conditioning in the Anxiety Disorders

“…Fail-safe N calculations suggest that 29 nonsignificant effect sizes would be needed to drop any significant pooled effect size from the current meta-analyses below significance. Grillon et al [57] Hermann et al [23] Howe [60] 1958 Cases of severe anxiety [31] in larynx [61] in larynx [44] in larynx Kircher et al [63] Lau et al [64] …”

CGRP antagonist infused into the bed nucleus of the stria terminalis impairs the acquisition and expression of context but not discretely cued fear

“…Because intra-BNST CGRP infusions increase fos immunoreactivity in the paraventricular nucleus of the hypothalamus (Sink et al 2011)-a nodal point in the HPA axis-and because HPA activity can influence fear learning and expression (Roozendaal 2002;Aerni et al 2004;Donley et al 2005;Schelling et al 2006;Soravia et al 2006;Tronel and Alberini 2007;Taubenfeld et al 2009;Jovanovic et al 2011;Zohar et al 2011;Atsak et al 2012;de Oliveira et al 2013), we also examined the contribution of BNST CGRP receptors to shockinduced corticosterone release.…”