Folk wisdom has long suggested that stressful events take a toll on health. The field of psychoneuroimmunology (PNI) is now providing key mechanistic evidence about the ways in which stressors--and the negative emotions that they generate--can be translated into physiological changes. PNI researchers have used animal and human models to learn how the immune system communicates bidirectionally with the central nervous and endocrine systems and how these interactions impact on health.

Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. To describe the pattern of change in IL-6 over 6 years among older adults undergoing a chronic stressor, this longitudinal community study assessed the relationship between chronic stress and IL-6 production in 119 men and women who were caregiving for a spouse with dementia and 106 noncaregivers, with a mean age at study entry of 70.58 (SD ‫؍‬ 8.03) for the full sample. On entry into this portion of the longitudinal study, 28 of the caregivers' spouses had already died, and an additional 50 of the 119 spouses died during the 6 years of this study. Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years. Caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers. Moreover, the mean annual changes in IL-6 among former caregivers did not differ from that of current caregivers even several years after the death of the impaired spouse. There were no systematic group differences in chronic health problems, medications, or health-relevant behaviors that might have accounted for caregivers' steeper IL-6 slope. These data provide evidence of a key mechanism through which chronic stressors may accelerate risk of a host of age-related diseases by prematurely aging the immune response.

Can psychotherapy reduce the incidence of health problems? A general model of psychosomatics assumes that inhibiting or holding back one's thoughts, feelings, and behaviors is associated with long-term stress and disease. Actively confronting upsetting experiences-through writing or talking-is hypothesized to reduce the negative effects of inhibition. Fifty healthy undergraduates were assigned to write about either traumatic experiences or superficial topics for 4 consecutive days. Two measures of cellular immune-system function and health center visits suggested that confronting traumatic experiences was physically beneficial. The implications for psychotherapy as a preventive treatment for health problems are discussed.

Negative emotions can intensify a variety of health threats. We provide a broad framework relating negative emotions to a range of diseases whose onset and course may be influenced by the immune system; inflammation has been linked to a spectrum of conditions associated with aging, including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, Alzheimer's disease, frailty and functional decline, and periodontal disease. Production of proinflammatory cytokines that influence these and other conditions can be directly stimulated by negative emotions and stressful experiences. Additionally, negative emotions also contribute to prolonged infection and delayed wound healing, processes that fuel sustained proinflammatory cytokine production. Accordingly, we argue that distress-related immune dysregulation may be one core mechanism behind a large and diverse set of health risks associated with negative emotions. Resources such as close personal relationships that diminish negative emotions enhance health in part through their positive impact on immune and endocrine regulation.

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Providing long-term care for a demented relative profoundly affects caregivers' lives. We assessed changes in depression, immune function, and health in 69 spousal caregivers who had already been caregiving for an average of five years and 69 sociodemographically matched control subjects. Between the initial sample ("intake") and the follow-up data collected an average of 13 months later, caregivers showed decrements relative to controls on three measures of cellular immunity. Caregivers also reported significantly more days of infectious illness, primarily upper respiratory tract infections. Caregivers had a much greater incidence of depressive disorders than controls, with 25% of caregivers meeting syndromal criteria at intake and 32% at follow-up, compared with no cases among controls at intake and 6% at follow-up. Caregivers who reported lower levels of social support at intake and who were most distressed by dementia-related behaviors showed the greatest and most uniformly negative changes in immune function at follow-up.

These data provide further mechanistic evidence of the sensitivity of wound healing to everyday stressors. Moreover, more frequent and amplified increases in proinflammatory cytokine levels could accelerate a range of age-related diseases. Thus, these data also provide a window on the pathways through which hostile or abrasive relationships affect physiological functioning and health.