Inflammation-Induced Depressed Mood: The Role of Social Neurocognitive Mechanisms
Condition: Depression
MeSH terms: Inflammation; Depression
Study type: Interventional
Phase: Early Phase 1

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.
    


Intervention name(s): endotoxin
Intervention type(s): Drug
Intervention description(s): Low-dose endotoxin (0.8 ng/kg of body weight): EC.O:113 administered once
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: inflammation; depression; social cognition; neural activity