Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-2670, USA.
Biol Psychiatry. 2011 Mar 15;69(6):549-55. doi: 10.1016/j.biopsych.2010.12.013. Epub 2011 Jan 31.
The debilitating effects of chronic glucocorticoids excess are well-known, but comparatively little is understood about the role of acute cortisol. Indirect evidence in rodents suggests that acute cortisone could selectively increase some forms of long-duration aversive states, such as "anxiety," but not relatively similar, briefer aversive states, such as "fear." However, no prior experimental studies in humans consider the unique effects of cortisol on anxiety and fear, using well-validated methods for eliciting these two similar but dissociable aversive states. The current study examines these effects, as instantiated with short- and long-duration threats.
Healthy volunteers (n = 18) received placebo or a low (20 mg) or a high (60 mg) dose of hydrocortisone in a double-blind crossover design. Subjects were exposed repeatedly to three 150-sec duration conditions: no shock; predictable shocks, in which shocks were signaled by a short-duration threat cue; and unpredictable shocks. Aversive states were indexed by acoustic startle. Fear was operationally defined as the increase in startle reactivity during the threat cue in the predictable condition (fear-potentiated startle). Anxiety was operationally defined as the increase in baseline startle from the no shock to the two threat conditions (anxiety-potentiated startle).
Hydrocortisone affected neither baseline nor short-duration, fear-potentiated startle but increased long-duration anxiety-potentiated startle.
These results suggest that hydrocortisone administration in humans selectively increases anxiety but not fear. Possible mechanisms implicated are discussed in light of prior data in rodents. Specifically, hydrocortisone might increase anxiety via sensitization of corticotrophin-releasing hormones in the bed nucleus of the stria terminalis.
慢性糖皮质激素过量的衰弱效应是众所周知的，但相对而言，人们对急性皮质醇的作用知之甚少。啮齿动物的间接证据表明，急性可的松可能会选择性地增加某些形式的长时间厌恶状态，如“焦虑”，但不会增加相对相似的、短暂的厌恶状态，如“恐惧”。然而，之前没有在人类中进行的实验研究考虑皮质醇对焦虑和恐惧的独特影响，也没有使用有效方法来诱发这两种相似但可分离的厌恶状态。本研究通过使用短期和长期威胁来检验这些影响。
健康志愿者（n=18）在双盲交叉设计中接受安慰剂或低（20mg）或高（60mg）剂量的氢可的松。受试者反复暴露于三种 150 秒持续时间的条件下：无电击；可预测的电击，其中电击由短持续时间的威胁线索提示；和不可预测的电击。厌恶状态通过声学惊吓来指数化。恐惧被操作性地定义为在可预测条件下威胁线索期间惊吓反应的增加（恐惧增强的惊吓）。焦虑被操作性地定义为从无电击到两个威胁条件的基础惊吓的增加（焦虑增强的惊吓）。
氢可的松既不影响基线也不影响短时间的、恐惧增强的惊吓，但增加了长时间的焦虑增强的惊吓。
这些结果表明，氢可的松给药在人类中选择性地增加焦虑而不是恐惧。讨论了可能涉及的机制，并结合了先前在啮齿动物中的数据。具体而言，氢化可的松可能通过增加终纹床核中的促肾上腺皮质激素释放激素的敏感性来增加焦虑。
