title: Acute hydrocortisone treatment increases anxiety but not fear in healthy volunteers: a fear-potentiated startle study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  Hydrocortisone affected neither baseline nor short-duration, fear-potentiated startle but increased long-duration anxiety-potentiated startle.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-2670, USA. Christian.grillon@nih.gov
authors.forename: Christian
authors.initials: C
authors.lastname: Grillon
authors.forename: Randi
authors.initials: R
authors.lastname: Heller
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hirschhorn
authors.forename: Mitchel A
authors.initials: MA
authors.lastname: Kling
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.forename: Jay
authors.initials: J
authors.lastname: Schulkin
authors.forename: Meena
authors.initials: M
authors.lastname: Vythilingam
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000187:drug effects; D018592:Cross-Over Studies; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004576:Electromyography; D004597:Electroshock / Q000009:adverse effects; D005239:Fear / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects* / Q000378:metabolism; D008297:Male; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012189:Retrospective Studies; D012463:Saliva / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D006854:Hydrocortisone