Effects of yohimbine and hydrocortisone on panic symptoms, autonomic responses, and attention to threat in healthy adults

Abstract

Rationale: Research in rodents and non-human primates implicates the noradrenergic system and hypothalamic-pituitary-adrenal axis in stress, anxiety, and attention to threat. Few studies examine how these two neurochemical systems interact to influence anxiety and attention in humans.

Objective: The objective of this paper is to examine the effects of exogenous yohimbine and hydrocortisone, as well as their combination (Y + H), on panic symptoms and attention to social threat cues.

Methods: Thirty-two healthy adults underwent a pharmacological challenge in which they were blindly randomized to either yohimbine, hydrocortisone, Y + H, or placebo. Thirty minutes after drug infusion, attention to threat was measured using the dot probe task, a visual attention task that presents angry, happy, and neutral faces and measures the degree of attention allocated towards or away from the emotional faces. Panic and autonomic measures were assessed before and 30 min after drug infusion.

Results: There was a significant increase in panic symptoms in the yohimbine and Y + H groups, but not in the hydrocortisone or placebo groups. Yohimbine resulted in a greater increase in panic symptoms than Y + H. On the dot probe task, the placebo group exhibited an attention bias to angry faces, whereas this bias was absent after yohimbine. When collapsing across groups, increased panic symptoms was associated with less attention to angry faces.

Conclusions: Exogenous hydrocortisone may attenuate noradrenergic-induced panic symptoms. The inverse relationship between panic symptoms and attention to angry faces extends prior research demonstrating attention modulation by stressful conditions.

Figure 1

Illustration of congruent and incongruent trials in the dot probe task.

Figure 2

Mean change in panic symptom scale scores across medication groups* *Mean change in panic symptom scores and standard error bars are presented for each condition. Panic symptoms were measured immediately after the dot probe task was administered. The mean change in panic symptoms (from baseline to 30 minutes) was significant for yohimbine (p = .001, d = 2.84) and Y+H (p = .012, d = 1.42) but not hydrocortisone or placebo. The mean change in panic symptoms for yohimbine was significantly greater than Y+H (p < .01, d = 1.56).

Figure 3

Mean change in systolic blood pressure across medication groups* *Mean change in blood pressure and standard error bars are presented for each condition. Blood pressure was taken after the dot probe task. Within group comparisons showed that yohimbine was the only group that had a significant increase in SBP (p < .01, d = 1.40). The mean change in SBP did not differ between yohimbine and Y+H (p = .37).

Figure 4

Mean threat bias scores on the dot probe task administered 30 minutes after drug infusion* * Mean threat bias scores and standard error bars are presented for each condition. Mean threat bias scores were calculated by subtracting the mean reaction time for angry-congruent trials from the mean reaction time for angry-incongruent trials. Positive values reflect an attention bias towards threat cues. Significant group differences are indicated (*p < .05, **p < .01).

Figure 5

Scatterplot illustrating the relationship between mean threat bias scores and mean panic symptoms scores in the whole group (n = 30). A significant inverse correlation between these two variables was present (p < .01).