The Immunology of Stress and the Impact of Inflammation on the Brain and Behavior.

ABSTRACT

Exposure to acute versus chronic stressors and threats activates the immune system in adaptive and maladaptive manners, respectively. While acute activation of the immune system in response to threat is homeostatically regulated by glucocorticoid negative feedback, chronic activation of the immune system arising from persistent stress exposure can contribute to an allostatic load with an inflammatory diathesis that has been implicated in stress-related psychopathology, including of depression and anxiety. Increased inflammation in the periphery and in the brain arising from chronic stress exposure can alter neurotransmitter metabolism and impact activation of brain regions to increase adverse behavioral health symptoms (e.g. anhedonia, anxiety, fatigue) and emotion dysregulation. While interventions targeting the immune system and its downstream effects on the brain for the treatment of depression and other psychiatric disorders has been of great interest as they have shown some efficacy in treating stress-related behavioral health disorders, future studies are necessary to better characterize the contexts under which anti-inflammatory agents should be used to treat stress-related psychopathology.