Glucocorticoids reduce phobic fear in humans

Abstract

Phobias are characterized by excessive fear, cued by the presence or anticipation of a fearful situation. Whereas it is well established that glucocorticoids are released in fearful situations, it is not known whether these hormones, in turn, modulate perceived fear. As extensive evidence indicates that elevated glucocorticoid levels impair the retrieval of emotionally arousing information, they might also inhibit retrieval of fear memory associated with phobia and, thereby, reduce phobic fear. Here, we investigated whether acutely administrated glucocorticoids reduced phobic fear in two double-blind, placebo-controlled studies in 40 subjects with social phobia and 20 subjects with spider phobia. In the social phobia study, cortisone (25 mg) administered orally 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation, exposure, and recovery phase of the stressor. Moreover, the stress-induced release of cortisol in placebo-treated subjects correlated negatively with fear ratings, suggesting that endogenously released cortisol in the context of a phobic situation buffers fear symptoms. In the spider phobia study, repeated oral administration of cortisol (10 mg), but not placebo, 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again 2 days after the last cortisol administration, suggesting that cortisol may also have facilitated the extinction of phobic fear. Cortisol treatment did not reduce general, phobia-unrelated anxiety. In conclusion, the present findings in two distinct types of phobias indicate that glucocorticoid administration reduces phobic fear.

Fig. 1.

Social phobia. (A) Study design. Cortisone (25 mg) or placebo was administered orally 1 h before the stressor, and salivary cortisol levels, subjective fear, and mood were repeatedly measured. T, time (min) in relation to the time point of substance administration at T0. (B) Effects of cortisone treatment on fear ratings. Fear ratings were assessed with a visual analog scale ranging from 0 (no fear) to 10 (maximal fear). After substance administration, fear ratings were significantly lower in the cortisone group as compared with the placebo group in the course of the experiment (P = 0.004). Values are depicted as mean ± SEM. Asterisks indicate significant differences at a certain time point: ∗, P < 0.05.

Fig. 2.

Social phobia. Negative correlation between stress-induced cortisol release and fear ratings in placebo-treated subjects. Δcortisol (salivary cortisol levels after TSST minus baseline cortisol levels) correlated negatively (r = −0.616; P = 0.04) with Δfear (fear after TSST minus baseline fear).

Fig. 3.

Spider phobia. (A) The phobic stimulus consisted of a color photograph of a spider. (B) Effect of cortisol on stimulus-induced fear in spider phobia. Fear symptoms were assessed by using a visual analog scale ranging from 0 (no fear) to 10 (maximal fear). On sessions 2–5, subjects were administered either cortisol (10 mg) or placebo 1 h before exposure to the phobic stimulus, whereas no pharmacological treatment was given on sessions 1 and 6. Fear ratings are depicted as mean ± SEM. P values indicate significance of symptom change across sessions for each treatment group.