Laboratory of Molecular Psychiatry, Center for Genes and Behavior, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Laboratory of Molecular Psychiatry, Center for Genes and Behavior, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Brain Behav Immun. 2018 Aug;72:2-13. doi: 10.1016/j.bbi.2017.10.025. Epub 2017 Nov 2.
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.
压力是精神障碍的一个主要风险因素，包括重性抑郁障碍（MDD），并可引发炎症，而抑郁症中炎症通常是失调的。一些临床和临床前研究表明，抑郁症状与增加炎症的因素的表达之间存在很强的关联。相反，给予抗炎药物已被证明可以改善抑郁症状，这表明炎症作为抑郁症的中介物的重要性。尽管很明显炎症在抑郁症的病理生理学中起作用，但炎症在心境障碍中被激活的机制仍不清楚。为了解决这个问题，研究已经调查了模式识别受体（PRR）激活在应激诱导的炎症和心境障碍中的作用。然而，激活这些受体的内源性因子，即所谓的危险相关分子模式（DAMP）的鉴定仍研究不足。在这里，我们回顾了 DAMPs 在抑郁症中的作用，并强调了 DAMP 信号在 MDD 患者和抑郁症的临床前动物应激模型中升高的临床证据。
