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Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer

Miller AH, Ancoli-Israel S, Bower JE, Capuron L, Irwin MR
Journal of Clinical Oncology 2008; 26:971-982 DOI: 10.1200/JCO.2007.10.7805.

Summary

This is a review of accumulated findings from 'modeling' studies conducted by the CDC CFS collaborative research group. Perturbations of the endocrine and immune systems likely play a role in the pathophysiology of CFS but studies to date 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 used in the treatment of hepatitis C, activates the immune system and produces an illness resembling CFS (e.g., fatigue, cognitive complaints, pain, sleep disturbance, and depression) and we are using this to help understand the symptoms and pathophysiology of CFS. This particular publication documents that depression occurs along with other symptoms of CFS following immune activation. This article reviews knowledge to date in this area.

Abstract

Patients with cancer experience a host of behavioral alterations that include depression, fatigue, sleep disturbances, and cognitive dysfunction. These behavioral comorbidities are apparent throughout the process of diagnosis and treatment for cancer and can persist well into the survivorship period. There is a rich literature describing potential consequences of behavioral comorbidities in patients with cancer including impaired quality of life, reduced treatment adherence, and increased disease-related morbidity and mortality. Medical complications of cancer and its treatment such as anemia, thyroid dysfunction, and the neurotoxicity of cancer chemotherapeutic agents account in part for these behavioral changes. Nevertheless, recent advances in the neurosciences and immunology/oncology have revealed novel insights into additional pathophysiologic mechanisms that may significantly contribute to the development of cancer-related behavioral changes. Special attention has been focused on immunologic processes,  specifically activation of innate immune inflammatory responses and their regulation by neuroendocrine pathways, which, in turn, influence CNS functions including neurotransmitter metabolism, neuropeptide function, sleep-wake cycles, regional brain activity, and, ultimately, behavior. Further understanding of these immunologic influences on the brain provides a novel conceptual framework for integrating the wide spectrum of behavioral alterations that occur in cancer patients and may reveal a more focused array of translational targets for therapeutic interventions and future research. Such developments warrant complementary advances in identification of cancer patients at risk as well as those currently suffering, including an increased emphasis on the status of behavior as a “sixth vital sign” to be assessed in all cancer patients throughout their disease encounter.

Page last modified on October 24, 2007

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