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Cancer Health Center

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Fatigue (PDQ®): Supportive care - Health Professional Information [NCI] - Pathogenesis of Fatigue


Finally, another theory is that serotonin is negatively impacted through chronic exposure to proinflammatory cytokines. One hypothesis is that the relationship between central nervous system concentrations of serotonin and fatigue have a U-shaped relationship, suggesting that very high and very low levels of serotonin may be associated with cancer-related fatigue.[12] However, studies that have evaluated serotonergic agents have not demonstrated a benefit for fatigue.[2] The role and relationship of many important neurotransmitters such as dopamine, norepinephrine, and serotonin with HPA axis functioning and cytokine expression have yet to be fully understood.


  1. Miaskowski C, Portenoy RK: Update on the assessment and management of cancer-related fatigue. Principles and Practice of Supportive Oncology Updates 1 (2): 1-10, 1998.
  2. Morrow GR, Andrews PL, Hickok JT, et al.: Fatigue associated with cancer and its treatment. Support Care Cancer 10 (5): 389-98, 2002.
  3. Aistars J: Fatigue in the cancer patient: a conceptual approach to a clinical problem. Oncol Nurs Forum 14 (6): 25-30, 1987 Nov-Dec.
  4. Bower JE, Ganz PA, Aziz N, et al.: Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med 64 (4): 604-11, 2002 Jul-Aug.
  5. Evans WJ, Lambert CP: Physiological basis of fatigue. Am J Phys Med Rehabil 86 (1 Suppl): S29-46, 2007.
  6. Bower JE, Ganz PA, Tao ML, et al.: Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. Clin Cancer Res 15 (17): 5534-40, 2009.
  7. Dantzer R: Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 933: 222-34, 2001.
  8. Hart BL: Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 12 (2): 123-37, 1988.
  9. Eisenberger NI, Inagaki TK, Mashal NM, et al.: Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun 24 (4): 558-63, 2010.
  10. Bower JE, Ganz PA, Aziz N: Altered cortisol response to psychologic stress in breast cancer survivors with persistent fatigue. Psychosom Med 67 (2): 277-80, 2005 Mar-Apr.
  11. Bower JE, Ganz PA, Dickerson SS, et al.: Diurnal cortisol rhythm and fatigue in breast cancer survivors. Psychoneuroendocrinology 30 (1): 92-100, 2005.
  12. Jager A, Sleijfer S, van der Rijt CC: The pathogenesis of cancer related fatigue: could increased activity of pro-inflammatory cytokines be the common denominator? Eur J Cancer 44 (2): 175-81, 2008.

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http:// cancer .gov or call 1-800-4-CANCER.

WebMD Public Information from the National Cancer Institute

Last Updated: 8/, 015
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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