kbo-Isar-Amper-Klinikum München Ost, Vockestraße 72, 85540 Haar, Germany.
Technical University of Munich, Department of Gynecology and Obstetrics, Schneckenburgerstrasse 6, 81675 Munich, Germany.
Psychoneuroendocrinology. 2021 Jul;129:105242. doi: 10.1016/j.psyneuen.2021.105242. Epub 2021 May 3.
This study aimed to identify yet unavailable blood biomarkers for the responsive and the hyporesponsive hypothalamic-pituitary-adrenal (HPA) axis subtypes of posttraumatic stress disorder (PTSD). As, I, we recently discovered the intranasal neuropeptide oxytocin to reduce experimentally provoked PTSD symptoms, II, expression of its receptor (OXTR) has hitherto not been assessed in PTSD patients, and III, oxytocin and OXTR have previously been related to the HPA axis, we considered both as suitable candidates. During a Trier Social Stress Test (TSST), we compared serum oxytocin and blood OXTR mRNA concentrations between female PTSD patients, their HPA axis reactivity subtypes and sex and age-matched healthy controls (HC). At baseline, both candidates differentiated the hyporesponsive HPA axis subtype from HC, however, only baseline OXTR mRNA discriminated also between subtypes. Furthermore, in the hyporesponsive HPA axis subgroup, OXTR mRNA levels correlated with PTSD symptoms and changed markedly during the TSST. To assess the influence of (traumatic) stress on the cerebral expression of oxytocin and its receptor and to test their suitability as biomarkers for the mouse PTSD-like syndrome, we then analyzed oxytocin, its mRNA (Oxt) and Oxtr mRNA in three relevant brain regions and Oxt in blood of a PTSD mouse model. To further explore the HPA axis reactivity subtype dependency of OXTR, we compared cerebral OXTR protein expression between mice exhibiting two different HPA axis reactivity traits, i.e., FK506 binding protein 51 knockout vs. wildtype mice. In summary, blood OXTR mRNA emerged as a potential biomarker of the hyporesponsive HPA axis PTSD subtype and prefrontal cortical Oxtr and Oxt of the mouse PTSD-like syndrome. Moreover, we found first translational evidence for a HPA axis responsivity trait-dependent regulation of OXTR expression. The lack of a cohort of the (relatively rare) hyporesponsive HPA axis subtype of HC is a limitation of our study.
这项研究旨在确定创伤后应激障碍（PTSD）下丘脑-垂体-肾上腺（HPA）轴反应性和低反应性亚类中尚未发现的血液生物标志物。由于我最近发现鼻内神经肽催产素可减少实验诱发的 PTSD 症状，II、PTSD 患者尚未评估其受体（OXTR）的表达，III、催产素和 OXTR 先前与 HPA 轴有关，因此我们认为两者都是合适的候选者。在特里尔社会应激测试（TSST）期间，我们比较了女性 PTSD 患者、她们的 HPA 轴反应性亚型以及性别和年龄匹配的健康对照者（HC）的血清催产素和血液 OXTR mRNA 浓度。在基线时，这两个候选者都将低反应性 HPA 轴亚型与 HC 区分开来，但只有基线 OXTR mRNA 也能区分亚型。此外，在低反应性 HPA 轴亚组中，OXTR mRNA 水平与 PTSD 症状相关，并在 TSST 期间明显变化。为了评估（创伤）应激对催产素及其受体的大脑表达的影响，并测试它们作为类似 PTSD 的小鼠模型的生物标志物的适用性，我们然后分析了三个相关脑区的催产素、其 mRNA（Oxt）和 Oxtr mRNA 以及 PTSD 小鼠模型的血液中的 Oxt。为了进一步探索 OXTR 对 HPA 轴反应性亚型的依赖性，我们比较了表现出两种不同 HPA 轴反应性特征的小鼠的大脑 OXTR 蛋白表达，即 FK506 结合蛋白 51 敲除与野生型小鼠。总之，血液 OXTR mRNA 似乎是低反应性 HPA 轴 PTSD 亚型的潜在生物标志物，而前额叶皮质的 Oxtr 和 Oxt 则是类似 PTSD 的小鼠综合征的生物标志物。此外，我们首次发现了 OXTR 表达与 HPA 轴反应性特征依赖性的转化证据。缺乏（相对罕见的） HPA 轴低反应性亚类 HC 的队列是我们研究的一个局限性。
