Department of Psychosomatic Medicine and Psychotherapy, Medical Park Chiemseeblick, Rasthausstr, 25, 83233 Bernau am Chiemsee, Germany.
Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
Curr Neuropharmacol. 2024;22(5):904-915. doi: 10.2174/1570159X21666230811141557.
Major depressive disorder (MDD) is a stress-related mental disorder with a lifetime prevalence of 20% and, thus, is one of the most prevalent mental health disorders worldwide. Many studies with a large number of patients support the notion that abnormalities of the hypothalamus-pituitaryadrenal (HPA) axis are crucial for the development of MDD. Therefore, a number of strategies and drugs have been investigated to target different components of the HPA axis: 1) corticotrophinreleasing hormone (CRH) 1 receptor antagonists; 2) vasopressin V receptor antagonists, 3) glucocorticoid receptor antagonists, and 4) FKBP5 antagonists. Until now, V receptor antagonists and GR antagonists have provided the most promising results. Preclinical data also support antagonists of FKBP5, which seem to be partly responsible for the effects exerted by ketamine. However, as HPA axis alterations occur only in a subset of patients, specific treatment approaches that target only single components of the HPA axis will be effective only in this subset of patients. Companion tests that measure the function of the HPA axis and identify patients with an impaired HPA axis, such as the dexamethasone-corticotrophin-releasing hormone (dex-CRH) test or the molecular dexamethasonesuppression (mDST) test, may match the patient with an effective treatment to enable patient-tailored treatments in terms of a precision medicine approach.
重度抑郁症（MDD）是一种与压力相关的精神障碍，终身患病率为 20%，因此是全球最常见的精神健康障碍之一。许多研究表明，大量患者的 HPA 轴异常对 MDD 的发展至关重要。因此，已经研究了许多针对 HPA 轴不同成分的策略和药物：1）促皮质素释放激素（CRH）1 受体拮抗剂；2）血管加压素 V 受体拮抗剂，3）糖皮质激素受体拮抗剂，和 4）FKBP5 拮抗剂。到目前为止，V 受体拮抗剂和 GR 拮抗剂提供了最有希望的结果。临床前数据也支持 FKBP5 的拮抗剂，这些拮抗剂似乎部分负责氯胺酮的作用。然而，由于 HPA 轴的改变仅发生在一部分患者中，仅针对 HPA 轴单一成分的特定治疗方法仅对这部分患者有效。伴行测试，如地塞米松-促皮质素释放激素（dex-CRH）测试或分子地塞米松抑制（mDST）测试，可以测量 HPA 轴的功能并识别 HPA 轴受损的患者，将患者与有效的治疗方法相匹配，从而实现基于精准医学方法的个体化治疗。
