Aggression, Social Stress, and the Immune System in Humans and Animal Models

Social stress can lead to the development of psychological problems ranging from
exaggerated anxiety and depression to antisocial and violence-related behaviors.
Increasing evidence suggests that the immune system is involved in responses to
social stress in adulthood. For example, human studies show that individuals with
high aggression traits display heightened inflammatory cytokine levels and dysregulated
immune responses such as slower wound healing. Similar findings have been observed in
patients with depression, and comorbidity of depression and aggression was correlated
with stronger immune dysregulation. Therefore, dysregulation of the immune system
may be one of the mediators of social stress that produces aggression and/or
depression. Similar to humans, aggressive animals also show increased levels of
several proinflammatory cytokines, however, unlike humans these animals are more
protected frominfectious organisms and have faster wound healing than animals with low
aggression. On the other hand, subordinate animals that receive repeated social defeat
stress have been shown to develop escalated and dysregulated immune responses
such as glucocorticoid insensitivity in monocytes. In this review we synthesize the
current evidence in humans, non-human primates, and rodents to show a role for the
immune system in responses to social stress leading to psychiatric problems such as
aggression or depression. We argue that while depression and aggression represent
two fundamentally different behavioral and physiological responses to social stress,
it is possible that some overlapped, as well as distinct, pattern of immune signaling
may underlie both of them. We also argue the necessity of studying animal models of
maladaptive aggression induced by social stress (i.e., social isolation) for understanding
neuro-immune mechanism of aggression, which may be relevant to human aggression