Care of the Caregiver: Stress and Dysregulation of Inflammatory Control in Cancer Caregivers

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 al 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. Among the terminally ill, 96% of caregivers are family members. Cancer caregiving involves a variety of challenges. These include many practical concerns related to the physical day-today 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 fullor part-time, caregiving may add an additional burden, 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. 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. Depression is a common problem and is underdiagnosed in caregivers. A meta-analysis found equivalent levels of distress in caregivers as in the patients themselves. These issues may be more profound among caregivers with low socioeconomic status or less education because of limited resources and/or flexibility. 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. 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, cytokine dysregulation, slower wound healing, greater autonomic and neuroendocrine dysregulation, and poorer response to influenza vaccine, 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. Alzheimer’s caregivers who were experiencing emotional or physical strain were found to have a 63% greater mortality than caregivers without strain or noncaregivers. 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. In this context, the article by Rohleder et al 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, proand 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. 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. 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 al 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 JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 27 NUMBER 18 JUNE 2