Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia

Abstract

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.

Glucocorticoid administration restores salience network activity in patients with spider phobia

“…The cortisol and behavioral data has been described in detail in our previous study and is briefly recapitulated here (Nakataki et al, 2017).…”

“…This study consisted of the following three participant groups: patients with spider phobia who received either 20 mg of cortisol or placebo in a double-blind and randomized manner, and healthy participants who did not receive any medication, as described in detail in our previous study (Nakataki et al, 2017). After the fMRI investigation, all patients were offered the opportunity to attend exposure-based group therapy, in which we investigated the effectiveness of the combination of cortisol treatment and cognitive behavioral therapy for spider phobia (Soravia et al, 2014).…”

“…According to our previous study, we used only the data from female participants in the analyses to avoid an imbalanced sex distribution across groups (Nakataki et al, 2017). Two patients and three healthy control participants were excluded due to missing data, and one patient was excluded because of ineffective elevation in the salivary cortisol levels in response to cortisol administration.…”

“…While the release of glucocorticoids enhances memory consolidation (Abercrombie, Kalin, Thurow, glucocorticoids exert fear-reducing effects, including the inhibition of fear memory retrieval, in patients with anxiety disorders. Additionally, it has been recently reported that patients with spider phobia exhibit aberrant functional connectivity of the amygdala when they are exposed to phobia-related stimuli, while cortisol administration can alleviate this fear-specific neural connectivity (Nakataki et al, 2017). Additionally, it has been recently reported that patients with spider phobia exhibit aberrant functional connectivity of the amygdala when they are exposed to phobia-related stimuli, while cortisol administration can alleviate this fear-specific neural connectivity (Nakataki et al, 2017).…”

“…The sample in this study employing network analyses was used previously in a dynamic causal modeling study (Nakataki et al, 2017). Specifically, patients with spider phobia received 20 mg of cortisol or placebo 1 hr before performing a picture task that provoked phobic fear during functional magnetic resonance imaging (fMRI).…”