Inflammation-Induced Depressed Mood: The Role of Social Neurocognitive Mechanisms
Status:
Completed
Trial end date:
2013-08-01
Target enrollment:
Participant gender:
Summary
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. Consistent with this, experimental work has shown that an
inflammatory challenge can increase depressed mood in an otherwise healthy sample. 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, coupled with
evidence that feelings of 'social disconnection' play a critical role in the onset and
perpetuation of (non-inflammatory forms of) depression, 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. 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.