Short CommunicationInflammation and social experience: An inflammatory challenge induces feelings of social disconnection in addition to depressed mood
Introduction
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. We also 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.
Section snippets
Participants and procedures
Thirty-nine healthy participants (20 female; mean age: 21.8 + 3.4 years; range: 18–36 years) completed the study. Sample size was based on previous studies of experimentally-induced inflammatory challenge (Reichenberg et al., 2001). Participants were recruited from flyers posted at the UCLA Medical Center and advertisements posted in the campus newspaper. Prospective participants with the following conditions were excluded from participation through a structured telephone interview: claustrophobia,
Physiological responses to endotoxin
As reported previously (Eisenberger et al., 2009), endotoxin induced a significant increase in IL-6 levels from one to 5 h post-injection (reflected by significant time by condition interactions at each time point compared to baseline: T1 (1 h post-injection) through T5 (5 h post-injection): F(1, 37) = 23.19, 144.14, 177.11, 63.67, 11.36, p’s < .005; Fig. 1a, previously displayed in Eisenberger et al. (2009)). Endotoxin also induced a significant increase in TNF-α levels from baseline to 2 h
Discussion
Findings from this study extend previous work on endotoxin-induced depressed or negative mood (Harrison et al., 2009, Reichenberg et al., 2001, Wright et al., 2005) by demonstrating that an inflammatory challenge can have social consequences as well. Thus, in addition to endotoxin (vs. placebo) leading to significant increases in depressed mood, it also led to significant increases in feelings of social disconnection. Moreover, increases in social disconnection mediated the relationship between
Acknowledgments
The authors have no financial gain related to the outcome of this research, and there are no potential conflicts of interest. We would like to thank the staff and support of the UCLA General Clinical Research Center as well as Anthony Suffredini, M.D. and George Grimes, R.P. at the National Institutes of Health, Warren Grant Magnuson Clinical Center, for providing the standard reference endotoxin and Thanh Luu and Elizabeth Breen for performing the cytokine assays. This research was funded by a
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