A large body of epidemiologic data indicates that feelings of social isolation are strongly associated with human physical health (Cacioppo and Hawkley, 2003
; Seeman, 1996
). Those who report feeling socially isolated have increased risk of all-cause mortality (Cacioppo and Hawkley, 2003
; Seeman, 1996
), as well as several specific infectious, neoplastic, cardiovascular, and inflammation-related diseases (Caspi et al., 2006
; Cohen et al., 1997
; Cole et al., 2003
; Kroenke et al., 2006
Although the biological basis for these links are not known, inflammatory processes may be involved. One study found that the leukocytes of socially isolated older adults (defined by feelings of loneliness) evidenced activation of inflammatory response genes along with increased activity of the nuclear factor (NF) κB pathway, a critical signal for the inflammatory cascade (Cole et al., 2007
). Together, these cross-sectional data point toward an association between social isolation and inflammation. However, it is not known whether subjective feelings of social isolation—which we call ‘social disconnection’—activate inflammatory markers, whether inflammatory dynamics contribute to social disconnection, or some combination of both.
Research on neuroimmune signaling has shown that proinflammatory cytokines initiate “sickness behavior,” a coordinated motivational response that includes symptoms such as fatigue, anorexia, and social withdrawal, and is thought to facilitate recovery and recuperation from illness (Dantzer, 2001
; Hart, 1988
). Although a principal component of sickness behavior is social withdrawal, the psychological experience that accompanies these social changes has been largely overlooked. To the extent that there is a correlational relationship between feelings of social disconnection and inflammation, it is possible that cytokines may also increase feelings of social disconnection even in the absence of any overt changes in social behavior.
In addition, exploring the effect of inflammation on social disconnection may improve understanding of the emerging relationship between inflammation and depression (Miller et al., 2009
) as both social disconnection and inflammation have been shown to play a role in depressive symptomatology. Thus, feelings of social disconnection (loneliness) have been shown to contribute to the development and maintenance of depression (Heinrich and Gullone, 2006
), and cytokines have been shown to play a causal role in the onset of depressed or negative mood (Harrison et al., 2009
; Reichenberg et al., 2001
; Wright et al., 2005
). As a result, it is possible that inflammatory-induced feelings of social disconnection may play a role in the link between inflammation and depressive symptoms. To date, however, these relationships have not been examined.
In this study, we examined the effect of endotoxin, an inflammatory challenge, vs. placebo on circulating levels of the proinflammatory cytokines—interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)1
—and on self-reported social disconnection and depressed mood. We hypothesized that endotoxin, compared to placebo, would lead to increases in social disconnection in addition to increases in depressed mood. In addition, we examined whether increases in social disconnection mediated the relationship between inflammation and depressed mood by examining whether controlling for increases in social disconnection eliminated the relationship between exposure to inflammatory challenge and increases in depressed mood.