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

Capuron L, Raison CL, Musselman DL, Lawson DH, Nemeroff CB, Miller AH
Association of exaggerated HPA axis response to the initial injection of interferon-alpha with development of depression during interferon-alpha therapy.
American Journal of Psychiatry 2003;160:1342-1345.

Summary

Emory University Department of Psychiatry and Behavioral Sciences faculty who are also members of the CDC/Emory University Collaborative CFS Research Program published this article under partial support of the CFS research program.

Studies examining the pathophysiology of CFS have been complicated by patient heterogeneity with respect to chronicity and co-morbid illnesses. "Model" systems in which symptom-free subjects develop CFS-like illness following exposure to a known immune system stimulus obviate these problems and permit controlled studies of the pathophysiology of fatigue and associated symptoms as they relate to immune and endocrine activation. Interferon-alpha (IFN-alpha), a cytokine widely used in the treatment of hepatitis C and malignant melanoma, represents a model system of great promise, given that IFN-alpha activates the immune system and produces a high rate of symptoms commonly observed in CFS, including fatigue, cognitive complaints, pain, sleep disturbance and depression. Thus, the CDC/Emory University Collaborative Group has undertaken a series of integrated studies using INF-alpha-associated fatigue to model CFS.

One important question concerns the relationship between depression and CFS. Patients who receive INF-alpha develop CFS-like illness that has overlapping features with major depression. This study sought to determine whether differences in neuroendocrine response to INF-alpha could predict development of major depression apart from other symptoms. They found that patients who developed depression following INF-alpha treatment had subclinical behavioral symptoms before challenge and hypothesize that patients who develop depression associated with CFS-like illness may have a more generalized hyperresponsiveness to stress.

Abstract

Objective: The authors assessed the relationship between the hypothalamic-pituitary-adrenal (HPA) axis response to interferon-alpha (INF-a) and the development of major depression during INF-a 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 INF-a therapy, both immediately before and 1, 2, and 3 hours after INF-a 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 INF-a 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 INF-a administration.

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

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