This application is submitted to the NIMH DATR Mood/Sleep Research Program A2-AID. Depressive disorders occur at a high rate in patients with inflammatory disorders, with a point prevalence of 15-29%, which is two to three times greater than that observed in the general population. Substantial evidence has shown that inflammation and increases in proinflammatory cytokine activity play a critical role in the onset and perpetuation of depression and depressive symptoms (e.g. insomnia, fatigue) in those who are co-morbid for inflammatory disorders (Miller et al., 2009). Consistent with this, experimental work has shown that an inflammatory challenge can increase depressed mood in an otherwise healthy sample (Reichenberg et al., 2001). Based on these findings, there has been a growing interest in whether inflammatory processes can contribute to depression in a causal manner and how these effects might occur. Given the observation that inflammatory processes trigger social withdrawal (Dantzer, 2001;Hart, 1988), coupled with evidence that feelings of 'social disconnection'play a critical role in the onset and perpetuation of (non-inflammatory forms of) depression (Heinrich &Gullone, 2006), it is surprising that the social psychological consequences of inflammation and their contribution to depression have not been more fully explored. Here, we suggest that inflammation may increase feelings of social disconnection and that these social psychological changes may be an important contributor to inflammation-associated depression. Indeed, preliminary data demonstrated that an experimentally-induced inflammatory challenge (endotoxin) led to increases in self-reported feelings of social disconnection (e.g., """"""""I feel disconnected from others"""""""") in addition to increases in depressed mood (Eisenberger et al., 2009b). Aside from these findings, however, there are no studies that have explored the effect of inflammatory processes on social experience in humans. The over- arching objective of this proposal is to explore the experiential and neural correlates of inflammatory- induced changes in social experience (e.g., feelings of social disconnection), which may provide a critical missing link in understanding the relationship between inflammation and depression. Participants (n=100) will be randomly assigned to receive either endotoxin or placebo and will then be monitored for the next six hours. Blood draws to assess cytokine levels as well as self-reported feelings of social disconnection and depressed mood will be collected hourly. In addition, at the time of peak cytokine response, participants will complete a neuroimaging session to examine the effect of inflammatory challenge on neural sensitivity to social rejection and social acceptance. It is hypothesized that endotoxin will increase feelings of social disconnection over time, and that the underlying neural sensitivities that give rise to these feelings (e.g., increased neural sensitivity to social rejection;decreased neural sensitivity to social acceptance) will contribute to inflammatory-induced depressed mood.

Public Health Relevance

Although substantial evidence has demonstrated links between inflammation and depression, the mechanisms underlying this relationship are poorly understood. Based on the observation that inflammation triggers social withdrawal, coupled with evidence that feelings of social disconnection play a critical role in depression, the proposed research will examine the social psychological consequences of inflammation and their relation to depressive symptoms for the first time. In addition, the proposed research will examine the neural correlates that underlie these social psychological changes to better understand the central mechanisms that contribute to inflammatory-induced depressive symptoms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH091352-04
Application #
8429495
Study Section
Social Psychology, Personality and Interpersonal Processes Study Section (SPIP)
Program Officer
Muehrer, Peter R
Project Start
2010-07-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
4
Fiscal Year
2013
Total Cost
$394,868
Indirect Cost
$138,098
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Muscatell, Keely A; Moieni, Mona; Inagaki, Tristen K et al. (2016) Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback. Brain Behav Immun 57:21-9
Cho, H J; Eisenberger, N I; Olmstead, R et al. (2016) Preexisting mild sleep disturbance as a vulnerability factor for inflammation-induced depressed mood: a human experimental study. Transl Psychiatry 6:e750
Moieni, Mona; Irwin, Michael R; Jevtic, Ivana et al. (2015) Sex differences in depressive and socioemotional responses to an inflammatory challenge: implications for sex differences in depression. Neuropsychopharmacology 40:1709-16
Moieni, Mona; Irwin, Michael R; Jevtic, Ivana et al. (2015) Trait sensitivity to social disconnection enhances pro-inflammatory responses to a randomized controlled trial of endotoxin. Psychoneuroendocrinology 62:336-42
Moieni, Mona; Irwin, Michael R; Jevtic, Ivana et al. (2015) Inflammation impairs social cognitive processing: A randomized controlled trial of endotoxin. Brain Behav Immun 48:132-8
Cho, Hyong Jin; Seeman, Teresa E; Kiefe, Catarina I et al. (2015) Sleep disturbance and longitudinal risk of inflammation: Moderating influences of social integration and social isolation in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Brain Behav Immun 46:319-26
Cho, H J; Kivimäki, M; Bower, J E et al. (2013) Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study. Psychol Med 43:1773-83
Eisenberger, Naomi I (2013) Social ties and health: a social neuroscience perspective. Curr Opin Neurobiol 23:407-13
Eisenberger, Naomi I (2013) An empirical review of the neural underpinnings of receiving and giving social support: implications for health. Psychosom Med 75:545-56
Eisenberger, Naomi I (2012) The pain of social disconnection: examining the shared neural underpinnings of physical and social pain. Nat Rev Neurosci 13:421-34

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