Depression and sterile inflammation: Essential role of danger associated molecular patterns

Stress is a major risk factor for psychiatric disorder including major depressive disorder (MDD) and can induce inflammation, which is known to be dysregulated in depression. Several clinical and pre-clinical studies have demonstrated a strong association between depressive symptoms and the expression of factors that increase inflammation. Conversely, administration of anti-inflammatory agents has been shown to ameliorate depressive symptoms, demonstrating the importance of inflammation as a mediator of depression. Although it is clear that inflammation plays a role in the pathophysiology of depression, the mechanism by which inflammation is activated in mood disorders remains unclear. To address this issue, studies have investigated the role of pattern recognition receptor (PRR) activation in stress-induced inflammation and mood disorders. However, the identification of the endogenous factors, referred to as danger-associated molecular patterns (DAMP) that activate these receptors remains understudied. Here we review the role of DAMPs in depression and highlight the clinical evidence for elevation of DAMP signaling in MDD patients and in pre-clinical animal stress models of depression.