Abstract
Glucocorticoids—stress hormones released from the adrenal cortex—reduce phobic fear in anxiety disorders and enhance psychotherapy, possibly by reducing the retrieval of fear memories. Glucocorticoid signaling in the basolateral amygdala can influence connected fear and memory related cortical regions, but this is not fully understood. Previous studies investigated specific pathways moderated by glucocorticoids, for example visual-temporal pathways, however, these analyses are limited to a priori selected regions. Here, we performed whole-brain pattern analysis to localize phobic stimulus decoding related to the fear-reducing effect of glucocorticoids. We analyzed functional magnetic resonance imaging (fMRI) data from a randomized, double-blind, placebo-controlled study with spider-phobic patients while they were looking at spider images. The patients either received oral glucocorticoids (20 mg of hydrocortisone) or a placebo. Patients with phobia had higher decoding in the anterior cingulate cortex (ACC) and the left and right anterior insula compared to controls. Decoding in the ACC and the right insula showed the highest correlations with experienced fear and explained 40% of the variance across all participants. Patients with cortisol reported a reduction of fear by 10–13% and showed decoding of phobic images in the precuneus, the cerebellum and the opercular cortex. Patients in the placebo group with increased fear showed decoding in the insula, the ACC and the right frontal lateral pole which have been shown to be related to the fear circuitry and episodic memory. This study demonstrates phobic decoding in fear-related frontal regions and suggests that cortisol administration alters these fears-specific processing areas.
Footnotes
Conflict of Interest: The authors declare no competing financial interests.