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Originally published as JCO Early Release 10.1200/JCO.2009.22.1523 on May 11 2009 © 2009 American Society of Clinical Oncology.
Care of the Caregiver: Stress and Dysregulation of Inflammatory Control in Cancer CaregiversUniversity of Iowa, Iowa City, IA
University of Colorado Denver School of Medicine, Aurora, CO Substantial research has examined the psychosocial distress experienced by cancer patients; however, much less attention has been paid to the experiences of caregivers, who provide much of the social support and home-based outpatient care for patients. The article by Rohleder et al1 in this issue of Journal of Clinical Oncology highlights these topics and also addresses the question of whether the distress from caregiving for a cancer patient takes a biologic toll on the caregiver. A 2004 survey by the National Alliance for Caregiving and AARP estimated that there are 44.4 million unpaid caregivers in the United States, of whom approximately 8% provide care to someone with cancer.2,3 Among the terminally ill, 96% of caregivers are family members.4 Cancer caregiving involves a variety of challenges. These include many practical concerns related to the physical day-to-day needs of the patient, such as managing symptoms and adverse effects, transporting the patient to medical appointments, administering medication, handling insurance, and communication with health care providers. As most caregivers (59%) are working either full- or part-time, caregiving may add an additional burden,3 and many caregivers have to contend with lost time at work or career disruption along with the financial burdens of the patient's treatment. Often caregivers must also manage child care or care of aging parents. Emotionally, effects may include personal distress concerning the diagnosis or effects of treatment in a loved one, concerns regarding disability or the potential loss of the loved one, and the challenge of emotionally supporting the patient despite the caregiver's own distress.5 Caregivers may have less time to spend with friends who might otherwise provide important emotional support. Caregivers often report exhaustion and fatigue, and feel captive in their role, particularly when the patient has high levels of physical or emotional demands.6 Depression is a common problem7 and is underdiagnosed in caregivers.8 A meta-analysis found equivalent levels of distress in caregivers as in the patients themselves.5 These issues may be more profound among caregivers with low socioeconomic status or less education because of limited resources and/or flexibility.7,9,10 Not only does caregiving entail a psychological burden, but the stress of caregiving often has a biologic impact also, as shown by Rohleder et al.1 Most previous studies examining biologic effects of caregiving have studied caregivers of dementia and Alzheimer's patients. Caregiving for Alzheimer's patients has been associated with wide-ranging effects on physiology, including poorer cellular immune function,11–13 cytokine dysregulation,14,15 slower wound healing,16 greater autonomic and neuroendocrine dysregulation,17 and poorer response to influenza vaccine,11,18,19 with the impact of caregiving worsening with increased distress. Caregiving for children with chronic illnesses has also been shown to have significant effects on telomere length and aging processes.20 Alzheimer's caregivers who were experiencing emotional or physical strain were found to have a 63% greater mortality than caregivers without strain or noncaregivers.21 In contrast, social support has been shown to help reduce the experience of stress among caregivers. For example, prostate cancer caregivers who had high levels of social support had less compromise to their cellular immune response than caregivers with lower levels of social support.22 In this context, the article by Rohleder et al1 adds substantially to understanding how the stress response in a group such as cancer caregivers can contribute to dysregulation of bodily systems. The authors have used a well-chosen panel of biomarkers, enabling them to characterize the interplay of important aspects of inflammatory control, for example, the output of neuroendocrine hormones, extent of systemic inflammation, pro- and anti-inflammatory signaling pathways, and tissue sensitivity to glucocorticoids. During the past 30 years, the field of psychoneuroimmunology has characterized extensive connections between the CNS and cells involved in the immune response.23 Some of these links involve hard-wired connections between neurons of the sympathetic nervous system and lymphocytes within the spleen and other secondary lymphoid organs.24 Neuroendocrine stress hormones such as cortisol also modulate the activities of lymphocytes and serve to downregulate the cellular immune response and control inflammation. The article by Rohleder et al1 demonstrates how high levels of chronic stress associated with caring for a glioblastoma patient may be translated into general dysregulation of inflammatory control by the hypothalamic-pituitary-adrenal axis, particularly at a cellular level. One of the strengths of this article is that dynamic patterns of change were examined over time, allowing the authors to capture alterations from before the patient's radiation treatment to 4 months after treatment. They report that caregivers show increased general systemic inflammation, as assessed by C-reactive protein, and that inflammation increases over time. Caregivers demonstrate a variety of specific anomalies in inflammatory control. Although levels of cortisol secretion among caregivers do not differ from those of controls, potential cortisol effects on the body are blunted by receptor changes. These include differences in the ratio of the active to the nonactive isoform of the glucocorticoid receptor, suggesting poorer ability of this receptor to mediate anti-inflammatory processes; decreases in the anti-inflammatory molecule inhibitory factor–kappaB over time; and decreased tissue sensitivity to glucocorticoids over time (although the latter finding was not statistically significant). The fact that these patterns of change are observed over time suggests that inflammatory control continues to deteriorate with time spent caregiving. Although not all results were as hypothesized, (eg, the pro-inflammatory nuclear factor–kappaB proteins increased over time in controls and decreased over time in the caregivers, and there was no difference in levels of cortisol secretion between caregivers and controls), these initial results in a small sample are quite intriguing. The study by Rohleder et al1 has important implications for the mental and physical well-being of caregivers of patients with cancer, as it demonstrates increasing inflammation and dysregulation of inflammatory control over time. As inflammatory processes are involved in etiology of a variety of conditions, such as cardiovascular disease, caregivers may be at increased risk for health concerns over time. The time course of this study extended to only to 4 months post-treatment; for many caregivers, their roles go on for years and may become more demanding over time. Thus, research is needed to determine the extent and reversibility of biologic changes in the caregiver that may accompany the ultimate improvement, stabilization, or death of the patient. For example, one previous report noted that 2 years after the death of an Alzheimer's patient, caregivers still demonstrated significant blunting of the immune response.25 These findings also suggest the importance of attention to caregiver distress by medical providers, and the need for research into development of interventions and programs to support caregivers. The US Surgeon General has made suggestions for interventions for caregiver well-being,26 including addressing issues around depression and anxiety; identifying sources of support within the community for the caregivers; focusing on the role of the caregiver's health in their care of the patient; sensitizing the caregivers to their stress and its effect on them; learning more about the illness their loved one is experiencing; and training in a variety of stress management options. As a dyadic interaction, improving the well-being of the caregiver has the potential to improve patient outcomes, and this should also be tested in future well-designed randomized controlled trials. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. AUTHOR CONTRIBUTIONS Conception and design: Susan K. Lutgendorf Collection and assembly of data: Susan K. Lutgendorf Manuscript writing: Susan K. Lutgendorf, Mark L. Laudenslager Final approval of manuscript: Susan K. Lutgendorf, Mark L. Laudenslager Acknowledgment Supported by National Cancer Institute Grants No. CA88293 and CA104825 (S.K.L.) and CA12967 (M.L.L.). REFERENCES
1. Rohleder N, Marin TJ, Ma R, et al: Biological cost of caring for a cancer patient: Dysregulation of pro- and anti-inflammatory signaling pathways. J Clin Oncol 27:2909–2915, 2009. 2. National Alliance for Caregiving, AARP. Caregiving in the U.S. 2004. http://www.caregiving.org/data/04finalreport.pdf. 3. Northouse L: Helping families of patients with cancer. Oncol Nurs Forum 32:743–750, 2005.[CrossRef][Medline] 4. Emanuel EJ, Fairclough DL, Slutsman J, et al: Assistance from family members, friends, paid caregivers, and volunteers in the care of terminally ill patients. N Engl J Med 341:956–963, 1999. 5. Hodges LJ, Humphris GM, Macfarlane G: A meta-analytic investigation of the relationship between the psychological distress of cancer patients and their carers. Soc Sci Med 60:1–12, 2005.[CrossRef][Medline] 6. Gaugler JE, Hanna N, Linder JG, et al: Cancer caregiving and subjective stress: A multi-site, multi-dimensional analysis. Psychooncology 14:771–785, 2005.[CrossRef][Medline] 7. Nijboer C, Tempelaar R, Triemstra M, et al: The role of social and psychologic resource in caregiving of cancer patients. Cancer 91:1029–1039, 2001.[CrossRef][Medline] 8. Kozachik S, Given C, Given B, et al: Improving depressive symptoms among caregivers of patients with cancer: Results of a randomized clinical trial. Oncol Nurs Forum 28:1149–1157, 2001.[Medline] 9. Oberst M, Scott D: Post-discharge distress in surgically treated cancer patients and their spouses. Res Nurs Health 11:223–233, 1988.[CrossRef][Medline] 10. Phipps S, Dunavant M, Lensing S, et al: Psychosocial predictors of distress in parents of children undergoing stem cell or bone marrow transplantation. J Pediatr Psychol 30:139–153, 2005. 11. Kiecolt-Glaser JK, Glaser R, Gravenstein S, et al: Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci U S A 93:3043–3047, 1996. 12. Kiecolt-Glaser JK, Glaser R, Shuttleworth ED, et al: Chronic stress and immunity in family caregivers of Alzheimer's disease victims. Psychosom Med 49:523–535, 1987. 13. Vitaliano PP, Scanlan JM, Ochs HD, et al: Psychosocial stress moderates the relationship of cancer history with natural killer cell activity. Ann Behav Med 20:199–208, 1998.[Medline] 14. Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, et al: Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci U S A 100:9090–9095, 2003. 15. Lutgendorf S, Garand L, Buckwalter K, et al: Life stress, mood disturbance, and elevated IL-6 in healthy older women. J Gerontol A Biol Sci Med Sci 54:M434–9, 1999.[Medline] 16. Kiecolt-Glaser JK, Marucha PT, Malarkey WB, et al: Slowing of wound healing by psychological stress. Lancet 346:1194–1196, 1995.[CrossRef][Medline] 17. Mills PJ, Ziegler MG, Patterson T, et al: Plasma catecholamine and lymphocyte beta 2-adrenergic receptor alterations in elderly Alzheimer caregivers under stress. Psychosom Med 59:251–256, 1997. 18. Vedhara K, Cox NK, Wilcock GK, et al: Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. Lancet 353:627–631, 1999.[CrossRef][Medline] 19. Vedhara K, McDermott MP, Evans TG, et al: Chronic stress in nonelderly caregivers: Psychological, endocrine and immune implications. J Psychosom Res 53:1153–1161, 2002.[CrossRef][Medline] 20. Epel ES, Blackburn EH, Lin J, et al: Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A 101:17312–17315, 2004. 21. Schulz R, Beach SR: Caregiving as a risk factor for mortality: The Caregiver Health Effects Study. JAMA 282:2215–2219, 1999. 22. Baron R, Cutrona C, Hicklin D, et al: Social support and immune function among spouses of cancer patients. J Pers Soc Psychol 59:344–352, 1990.[CrossRef][Medline] 23. Ader R, Felton DL, Cohen N. Psychoneuroimmunology, ed 3 New York, NY: Academic Press Inc, 2000. 24. Felten S, Felten D. Innervation of lymphoid tissue. R Ader, D Felten, and N Cohen. Psychoneuroimmunology, ed 2 New York, NY: Academic Press Inc, 1991. p.27–71. 25. Esterling B, Kiecolt-Glaser J, Bodnar J, et al: Chronic stress, social support, and persistent alterations in the natural killer cell response to cytokines in older adults. Health Psychol 13:291–298, 1994.[CrossRef][Medline] 26. Ulrich B: Caring for the caregivers. Nephrol Nurs J 33:129; 2006.[Medline]
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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