Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.
Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.
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DOI：
10.1016/j.biopsych.2008.11.029
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发表时间：
2009-05-01
影响因子：
10.6
通讯作者：
Raison, Charles L.
中科院分区：
文献类型：
--
作者：
Miller, Andrew H.;Maletic, Vladimir;Raison, Charles L.
关键词：
认识到炎症可能是一种常见的疾病机制，已经扩展到包括神经精神疾病，包括严重的抑郁症。已发现重度抑郁症患者外周血炎性生物标志物增加，包括炎性细胞因子，已被证明进入大脑并与几乎所有已知的与抑郁症有关的病理生理领域相互作用，包括神经递质代谢、神经内分泌功能和神经可塑性。事实上，脑内炎症通路的激活被认为是神经营养支持减少、谷氨酸释放/再摄取改变以及氧化应激的汇合，导致兴奋毒性和神经胶质细胞成分的丧失，这与抑郁症的神经病理学结果一致。进一步例证炎症和抑郁之间联系的数据表明，心理社会应激是一种众所周知的情绪障碍的诱因，它能够刺激炎症信号分子，包括核因子kappa B，部分是通过激活交感神经系统流出通路。有趣的是，炎症生物标志物增加的抑郁症患者更有可能表现出治疗耐药，在几项研究中，抗抑郁治疗与炎症反应减少有关。最后，来自炎症性疾病患者以及医学上健康的抑郁症患者的初步数据表明，抑制促炎症细胞因子或其信号通路可能会改善抑郁情绪，并提高对传统抗抑郁药物的治疗反应。这些发现的翻译含义包括识别相关患者群体、应用免疫靶向治疗以及在免疫系统和行为水平上监测治疗效果的独特机会。
Recognition that inflammation may represent a common mechanism of disease has been extended to include neuropsychiatric disorders including major depression. Patients with major depression have been found to exhibit increased peripheral blood inflammatory biomarkers, including inflammatory cytokines, which have been shown to access the brain and interact with virtually every pathophysiologic domain known to be involved in depression, including neurotransmitter metabolism, neuroendocrine function, and neural plasticity. Indeed, activation of inflammatory pathways within the brain is believed to contribute to a confluence of decreased neurotrophic support and altered glutamate release/reuptake, as well as oxidative stress, leading to excitotoxicity and loss of glial elements, consistent with neuropathologic findings that characterize depressive disorders. Further instantiating the link between inflammation and depression are data demonstrating that psychosocial stress, a well-known precipitant of mood disorders, is capable of stimulating inflammatory signaling molecules, including nuclear factor kappa B, in part, through activation of sympathetic nervous system outflow pathways. Interestingly, depressed patients with increased inflammatory biomarkers have been found to be more likely to exhibit treatment resistance, and in several studies, antidepressant therapy has been associated with decreased inflammatory responses. Finally, preliminary data from patients with inflammatory disorders, as well as medically healthy depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood and increase treatment response to conventional antidepressant medication. Translational implications of these findings include the unique opportunity to identify relevant patient populations, apply immune-targeted therapies, and monitor therapeutic efficacy at the level of the immune system in addition to behavior.
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