Karaoulanis S E, Angelopoulos N V
Department of Psychiatry, University of Thessaly, Medical School, University Hospital of Larissa, Larissa, Greece.
Psychiatriki. 2010 Jan;21(1):17-30.
Although there are many papers which examine the role of immune system in the pathophysiology of depression, it is not clear the relationship between depression and immune system. It seems that inflammation is strongly related with depression. Proinflammatory cytokines play crucial role in thepresence of depression. Administration of proinflammatory cytokines to treat medical diseases induce depressive symptoms in humans. Patients diagnosed with depression tend to have high levels of cytokine activity and impaired immune response, as well as those patients suffering from inflammatory processes. Proinflammatory cytokines interfere with the body's feedback loop to reduce circulating corticosteroids during the stress response. Proinflammatory cytokines may also diminish neurotrophic support and monoamine neurotransmission that can lead to neuronal apoptosis and glial damage. This happens because cytokines cause reduction of the levels of brain derived neurotrophic factor (BDNF), which is the primary neurotrophin of the hippocampus. They also induce the enzyme indoleamine 2,3 dioxygenase (IDO), which breaks down tryptophan, the primary amino acid precursor of serotonin, into kynurenine. Consequently, serotonin is reduced in the brain. Stress, which can precipitate depression, can also promote inflammatory responses through effects on sympathetic and parasympathetic nervous system pathways. The antidepressant drugs reduce the serum levels of proinflammatory cytokines. 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. Except from cytokines, there are other factors of immune system which play crucial role in the pathogenesis of depression. These factors include free radicals of oxygen, the balance between ω3and ω6 lipid acids, the increased levels of positive acute phase proteins and the reduction of negative acute phase proteins. The research in the domain of psychoneuroimmunology suggest that targeting proinflammatory cytokines and their signaling pathways might represent a novel strategy to treat depression.
尽管有许多论文探讨了免疫系统在抑郁症病理生理学中的作用，但抑郁症与免疫系统之间的关系尚不清楚。炎症似乎与抑郁症密切相关。促炎细胞因子在抑郁症的发生中起关键作用。在治疗医学疾病时使用促炎细胞因子会在人类中诱发抑郁症状。被诊断为抑郁症的患者往往具有高水平的细胞因子活性和受损的免疫反应，患有炎症性疾病的患者也是如此。促炎细胞因子会干扰身体的反馈回路，以在应激反应期间降低循环皮质类固醇水平。促炎细胞因子还可能减少神经营养支持和单胺神经传递，从而导致神经元凋亡和神经胶质损伤。这是因为细胞因子会导致脑源性神经营养因子（BDNF）水平降低，而BDNF是海马体的主要神经营养因子。它们还会诱导吲哚胺2,3-双加氧酶（IDO），该酶将色氨酸（血清素的主要氨基酸前体）分解为犬尿氨酸。因此，大脑中的血清素会减少。能够引发抑郁症的压力也可通过对交感神经和副交感神经系统途径的影响来促进炎症反应。抗抑郁药物可降低促炎细胞因子的血清水平。有趣的是，已发现炎症生物标志物升高的抑郁症患者更有可能表现出治疗抵抗性，并且在多项研究中，抗抑郁治疗与炎症反应降低有关。除了细胞因子外，免疫系统的其他因素在抑郁症的发病机制中也起关键作用。这些因素包括氧自由基、ω-３和ω-６脂肪酸之间的平衡、正急性期蛋白水平的升高以及负急性期蛋白的减少。心理神经免疫学领域的研究表明，针对促炎细胞因子及其信号通路可能代表一种治疗抑郁症的新策略。
