Neuroendocrine-Immune Mechanisms of Behavioral Comorbidities in Patients With Cancer

Abstract

Patients with cancer experience a host of behavioral alterations that include depression, fatigue, sleep disturbances and cognitive dysfunction. These behavioral co-morbidities 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 co-morbidities in patients with cancer including impaired quality of life, reduced treatment adherence and increased diseaserelated 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, impact central nervous system functions including neurotransmitter metabolism, neuropeptide function, sleep-wake cycles, regional brain activity and ultimately behavior. Further understanding of these immunological 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.

High-Dose Asian Ginseng (Panax Ginseng) for Cancer-Related Fatigue

“…Recent studies suggest the dysregulation of inflammatory cytokines cause and intensify CRF and its related symptoms. 11,12,[57][58][59] In our study, 63% of the patients perceived moderate to vast improvement of improvement in CRF with PG treatment.…”

Short Sleep Duration and Its Correlates among Cancer Survivors in Korea: the Korea National Health and Nutrition Examination Surveys

“…Notwithstanding the limits of knowledge on the exact mechanism across the cancer trajectory, cancer-related sleep problems covering difficulties initiating or maintaining sleep, dissatisfaction with sleep quality, and/or short sleep duration appear to begin with cancer diagnosis, inducing emotional challenges (i.e., anxiety and distress), and are easily exacerbated during cancer treatments such as chemotherapy, which continue through cancer survivorship (Palesh et al, 2012;Garland et al, 2014). Biologically, these negative consequences are assumed to underlie the inflammatory mechanism: a negative feedback loop where substantial increases in proinflammatory cytokine activity induced by cancer treatments can lead to sleep problems, which in turn may feedback to alter immune profiles, activating chronic inflammatory processes among cancer survivors, and finally progress to long-term sleep disturbance throughout the survivorship (Lee et al, 2004;Miller et al, 2008;Irwin et al, 2013). Further investigations concerning both sleep modalities and biology dynamics in longitudinal follow-up studies will help to clarify the hidden mechanism behind cancer-related sleep problems in Korean cancer survivors.…”

Inflammation and the Silent Sequelae of Stroke

“…While stroke itself can lead to dynamic alterations in the metabolism of neurotransmitters (e.g., glutamate), inflammation also leads to major changes in the metabolism of these neurochemicals [80][81][82]. Cytokines (like IFN) alter the metabolism of monoamines (including dopamine and serotonin) and may contribute to fatigue [83,84]. Based on these kinds of data, it appears that all of the major potential causes of fatigue following stroke are therefore intimately related and may share a common denominator in the immune system [85][86][87][88].…”