Association of exaggerated HPA axis response to the initial injection of interferon-alpha with development of depression during interferon-alpha therapy

Am J Psychiatry. 2003 Jul;160(7):1342-5. doi: 10.1176/appi.ajp.160.7.1342.


Objective: The authors assessed the relationship between the hypothalamic-pituitary-adrenal (HPA) axis response to interferon-alpha (IFN-alpha) and the development of major depression during IFN-alpha treatment.

Method: Adrenocorticotropic hormone (ACTH), cortisol, and interleukin-6 (IL-6) plasma concentrations were measured in 14 patients with malignant melanoma at regular intervals during the first 12 weeks of IFN-alpha therapy, both immediately before and 1, 2, and 3 hours after IFN-alpha administration. Symptom criteria for major depression were also evaluated at each visit.

Results: ACTH and cortisol responses but not IL-6 responses to the initial administration of IFN-alpha were significantly higher in the seven patients who subsequently developed symptom criteria for major depression than in those who did not. No differences in hormonal or cytokine responses were found between these two groups during chronic IFN-alpha administration.

Conclusions: The HPA axis response to the acute administration of IFN-alpha reveals a vulnerability to IFN-alpha-induced depression, possibly due to sensitization of corticotropin-releasing factor pathways.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Depressive Disorder / blood
  • Depressive Disorder / chemically induced*
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology
  • Injections, Subcutaneous
  • Interferon-alpha / adverse effects*
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Interleukin-6 / blood
  • Male
  • Melanoma / blood*
  • Melanoma / drug therapy*
  • Melanoma / psychology
  • Middle Aged
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / physiology


  • Interferon-alpha
  • Interleukin-6
  • Adrenocorticotropic Hormone
  • Hydrocortisone