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


METHODS
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.
Capuron
Lucile
L
Department of Psychiatry and Behavioral Sciences and the Winship Cancer Institute, Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Raison
Charles L
CL
Musselman
Dominique L
DL
Lawson
David H
DH
Nemeroff
Charles B
CB
Miller
Andrew H
AH
D000324:Adrenocorticotropic Hormone / Q000097:blood; D003866:Depressive Disorder / Q000097:blood / Q000139:chemically induced*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology
D016898:Interferon-alpha; D015850:Interleukin-6; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone