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

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.

Hydrocortisone impairs hippocampal-dependent trace eyeblink conditioning in post-traumatic stress disorder.

Trace eyeblink conditioning is a hippocampal-dependent associative learning task that could help evaluate hippocampal function in Post-traumatic stress disorder (PTSD). Since preclinical research has demonstrated that trace eyeblink conditioning can be pharmacologically manipulated by glucocorticoids, this task may shed light on glucocorticoid sensitivity in PTSD. This study assessed baseline and hydrocortisone-mediated changes in trace eyeblink conditioning in patients with PTSD and in healthy controls. A total of 12 patients with PTSD and 12 age- and sex-matched healthy controls participated in a trace eyeblink test 6 h following intravenous administration of 30 mg of hydrocortisone. Spontaneous blink rates were similar between PTSD patients and healthy controls. There was no significant difference in the mean conditioned response between PTSD subjects and healthy controls under placebo conditions. Following hydrocortisone administration, only the PTSD patients demonstrated a significant reduction in conditioned response in contrast to healthy subjects who did not demonstrate any change. Patients with PTSD had increased glucocorticoid sensitivity in the focal brain regions mediating trace eyeblink conditioning.