There is evidence that plasma cortisol concentration can be either increased or decreased in patients with depression and related anxiety and stress-related disorders; the exact pathophysiological mechanisms of this state are not almost clear. Several distinct theories were proposed and mechanisms, which could lead to decreased glucocorticoid signaling and/or levels, were described. However, there is a possible drawback in almost all the theories proposed: insufficient attention to the inflammatory process, which is undoubtedly present in several stress-related disorders, including post-traumatic stress disorder (PTSD). Previous studies only briefly mentioned the presence of an inflammatory reaction’s signs in PTSD, without giving it due importance, although recognizing that it can affect the course of the disease. With that, the state of biochemical changes, characterized by the low glucocorticoids, glucocorticoid receptor’s resistance and the signs of the persistent inflammation (with the high levels of circulating cytokines) might be observed not only in PTSD but in coronary heart diseases and systemic chronic inflammatory diseases (rheumatoid arthritis) as well. That is why the present review aims to depict the pathophysiological mechanisms, which lead to a decrease in glucocorticoids in PTSD due to the action of inflammatory stimuli. We described changes in the glucocorticoid system and inflammatory reaction as parts of an integral system, where glucocorticoids and the glucocorticoid receptor reside at the apex of a regulatory network that blocks several inflammatory pathways, while decreased glucocorticoid signaling and/or level leads to unchecked inflammatory reactions to promote pathologies such as PTSD.

Lay summary: This review emphasizes the importance of inflammatory reaction in the development of puzzling conditions sometimes observed in severe diseases including post-traumatic stress disorder —the decreased levels of glucocorticoids in the blood. Following the classical concepts, one would expect an increase in glucocorticoid hormones, since they are part of the feedback mechanism in the immune system, which reduces stress and inflammation. However, low levels of glucocorticoid hormones are also observed. Thus, this review describes potential mechanisms, which can lead to the development of such a state.

有证据表明，患有抑郁症和相关焦虑症以及与压力有关的疾病的患者血浆皮质醇浓度可以升高或降低。这种状态的确切病理生理机制尚不清楚。提出了几种不同的理论，并描述了可能导致糖皮质激素信号传导和/或水平降低的机制。但是，几乎所有提出的理论都有可能存在缺陷：对炎症过程的关注不足，炎症过程无疑存在于多种与压力有关的疾病中，包括创伤后应激障碍（PTSD）。先前的研究仅简要提及了PTSD中炎症反应迹象的存在，但没有给予应有的重视，尽管认识到它可以影响疾病的进程。接着就，随即，不仅在PTSD中而且在冠心病和全身性慢性炎症性疾病（类风湿病）中均观察到以低糖皮质激素，糖皮质激素受体的抵抗力和持续性炎症（循环细胞因子水平高）为特征的生化变化状态关节炎）。这就是为什么本综述旨在描述病理生理机制，由于炎症刺激的作用导致PTSD中糖皮质激素的减少。我们将糖皮质激素系统的变化和炎症反应描述为一个整体系统的一部分，其中糖皮质激素和糖皮质激素受体位于阻断多种炎症途径的调节网络的顶点，

总结：这篇评论强调了炎症反应在令人困惑的疾病发展中的重要性，这种疾病有时在包括创伤后应激障碍（血液中糖皮质激素水平降低）在内的严重疾病中观察到。遵循经典概念，人们可以预期糖皮质激素的增加，因为它们是免疫系统反馈机制的一部分，可以减少压力和炎症。但是，也观察到了低水平的糖皮质激素。因此，这篇综述描述了可能导致这种状态发展的潜在机制。