Felger Jennifer C
Emory University School of Medicine, Atlanta, GA, USA.
Handb Exp Pharmacol. 2019;250:255-286. doi: 10.1007/164_2018_166.
Approximately one third of depressed patients fail to respond to currently available antidepressant therapies. Therefore, new conceptual frameworks are needed to identify pathophysiologic pathways and neurobiological targets for the development of novel treatment strategies. In this regard, recent evidence suggests that inflammation may contribute to symptoms relevant to a number of psychiatric disorders and particularly depression. Numerous studies (including meta-analyses) have found elevated peripheral and central inflammatory cytokines and acute phase proteins in depression. Chronic exposure to increased inflammation is thought to drive changes in neurotransmitters and neurocircuits that lead to depressive symptoms and that may also interfere with or circumvent the efficacy of antidepressants. Indeed, patients with high inflammation have been shown to exhibit poor response to conventional antidepressant therapies. Recent developments in our ability to understand and measure the effects of inflammation on the brain in patients have opened new doors for the testing of novel treatment strategies that target the immune system or its consequences on neurotransmitter systems. Such recent developments in the field of behavioral immunology and their translational implications for the treatment of depression are discussed herein.
大约三分之一的抑郁症患者对目前可用的抗抑郁疗法没有反应。因此,需要新的概念框架来确定病理生理途径和神经生物学靶点,以开发新的治疗策略。在这方面,最近的证据表明,炎症可能导致与多种精神疾病尤其是抑郁症相关的症状。大量研究(包括荟萃分析)发现,抑郁症患者外周和中枢的炎性细胞因子及急性期蛋白水平升高。长期暴露于炎症增加的环境被认为会导致神经递质和神经回路发生变化,进而引发抑郁症状,还可能干扰或规避抗抑郁药的疗效。事实上,炎症水平高的患者对传统抗抑郁疗法的反应较差。我们理解和测量炎症对患者大脑影响的能力最近取得的进展,为测试针对免疫系统或其对神经递质系统影响的新治疗策略打开了新的大门。本文将讨论行为免疫学领域的这些最新进展及其对抑郁症治疗的转化意义。