Institute of Immunology and Physiology, Ural Division of the Russian Academy of Sciences, Ekaterinburg, Russia.
Institute of Molecular Physiology and Genetics, Centre for Biosciences, Slovak Academy of Sciences, Bratislava, Slovakia.
Stress. 2020 Nov;23(6):651-661. doi: 10.1080/10253890.2020.1766020. Epub 2020 May 22.
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和应激相关障碍的患者的血浆皮质醇浓度可能升高或降低；这种状态的确切病理生理机制尚不清楚。已经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和/或水平降低的机制。然而，在所提出的几乎所有理论中都存在一个可能的缺陷：对炎症过程的关注不足，而炎症过程无疑存在于几种应激相关障碍中，包括创伤后应激障碍（PTSD）。以前的研究只是简要提到了 PTSD 中炎症反应的存在，但没有给予足够的重视，尽管他们认识到它可能会影响疾病的进程。因此，不仅在 PTSD 中，而且在冠心病和全身性慢性炎症性疾病（类风湿关节炎）中，也可能观察到以低糖皮质激素、糖皮质激素受体抵抗和持续炎症（循环细胞因子水平升高）为特征的生化变化状态。这就是为什么本综述旨在描述由于炎症刺激作用导致 PTSD 中糖皮质激素减少的病理生理机制。我们描述了糖皮质激素系统和炎症反应的变化作为一个完整系统的一部分，其中糖皮质激素和糖皮质激素受体位于阻止几个炎症途径的调节网络的顶点，而糖皮质激素信号和/或水平的降低导致不受控制的炎症反应，从而促进 PTSD 等疾病的发生。
有证据表明，患有抑郁症和相关焦虑症和应激相关障碍的患者的血浆皮质醇浓度可能升高或降低；这种状态的确切病理生理机制尚不清楚。已经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和/或水平降低的机制。然而，在所提出的几乎所有理论中都存在一个可能的缺陷：对炎症过程的关注不足，而炎症过程无疑存在于几种应激相关障碍中，包括创伤后应激障碍（PTSD）。以前的研究只是简要提到了 PTSD 中炎症反应的存在，但没有给予足够的重视，尽管他们认识到它可能会影响疾病的进程。因此，不仅在 PTSD 中，而且在冠心病和全身性慢性炎症性疾病（类风湿关节炎）中，也可能观察到以低糖皮质激素、糖皮质激素受体抵抗和持续炎症（循环细胞因子水平升高）为特征的生化变化状态。这就是为什么本综述旨在描述由于炎症刺激作用导致 PTSD 中糖皮质激素减少的病理生理机制。我们描述了糖皮质激素系统和炎症反应的变化作为一个完整系统的一部分，其中糖皮质激素和糖皮质激素受体位于阻止几个炎症途径的调节网络的顶点，而糖皮质激素信号和/或水平的降低导致不受控制的炎症反应，从而促进 PTSD 等疾病的发生。
