Khairova Rushaniya A, Machado-Vieira Rodrigo, Du Jing, Manji Husseini K
Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Neuropsychopharmacol. 2009 May;12(4):561-78. doi: 10.1017/S1461145709009924. Epub 2009 Feb 19.
A growing body of data suggests that hyperactivation of the immune system has been implicated in the pathophysiology of major depressive disorder (MDD). Several pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been found to be significantly increased in patients with MDD. This review focuses on these two cytokines based on multiple lines of evidence from genetic, animal behaviour, and clinical studies showing that altered levels of serum TNF-alpha and IL-1 are associated with increased risk of depression, cognitive impairments, and reduced responsiveness to treatment. In addition, recent findings have shown that centrally expressed TNF-alpha and IL-1 play a dual role in the regulation of synaptic plasticity. In this paper, we review and critically appraise the mechanisms by which cytokines regulate synaptic and neural plasticity, and their implications for the pathophysiology and treatment of MDD. Finally, we discuss the therapeutic potential of anti-inflammatory-based approaches for treating patients with severe mood disorders. This is a promising field for increasing our understanding of the mechanistic interaction between the immune system, synaptic plasticity, and antidepressants, and for the ultimate development of novel and improved therapeutics for severe mood disorders.
越来越多的数据表明，免疫系统的过度激活与重度抑郁症（MDD）的病理生理学有关。已发现几种促炎细胞因子，如肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1），在MDD患者中显著增加。本综述基于来自基因、动物行为和临床研究的多条证据，聚焦于这两种细胞因子，这些证据表明血清TNF-α和IL-1水平的改变与抑郁症风险增加、认知障碍以及治疗反应性降低有关。此外，最近的研究发现，中枢表达的TNF-α和IL-1在突触可塑性调节中起双重作用。在本文中，我们回顾并批判性地评估细胞因子调节突触和神经可塑性的机制，及其对MDD病理生理学和治疗的影响。最后，我们讨论基于抗炎方法治疗重症情绪障碍患者的治疗潜力。这是一个很有前景的领域，有助于增进我们对免疫系统、突触可塑性和抗抑郁药之间机制性相互作用的理解，并最终开发出用于治疗重症情绪障碍的新型和改良疗法。
