Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Drug Discov Today. 2023 Apr;28(4):103518. doi: 10.1016/j.drudis.2023.103518. Epub 2023 Feb 8.
Well-established animal models of depression have described a proximal relationship between stress and central nervous system (CNS) inflammation - a relationship mirrored in the peripheral inflammatory biomarkers of individuals with depression. Evidence also suggests that stress-induced proinflammatory states can contribute to the neurobiology of treatment-resistant depression. Interestingly, ketamine, a rapid-acting antidepressant, can partially exert its therapeutic effects via anti-inflammatory actions on the hypothalamic-pituitary adrenal (HPA) axis, the kynurenine pathway or by cytokine suppression. Further investigations into the relationship between ketamine, inflammation and stress could provide insight into ketamine's unique therapeutic mechanisms and stimulate efforts to develop rapid-acting, anti-inflammatory-based antidepressants.
已建立的抑郁症动物模型描述了应激与中枢神经系统（CNS）炎症之间的密切关系——这一关系在抑郁症患者的外周炎症生物标志物中得到了反映。有证据还表明，应激诱导的促炎状态可能导致治疗抵抗性抑郁症的神经生物学改变。有趣的是，氯胺酮是一种快速起效的抗抑郁药，其部分治疗作用可能是通过对下丘脑-垂体肾上腺（HPA）轴、犬尿氨酸途径或细胞因子抑制的抗炎作用发挥的。进一步研究氯胺酮、炎症和应激之间的关系，可以深入了解氯胺酮的独特治疗机制，并促使人们努力开发快速起效的、基于抗炎的抗抑郁药。
