Clinical Immunology and Infectious Diseases, Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria.
Curr Opin Clin Nutr Metab Care. 2011 Jan;14(1):49-56. doi: 10.1097/MCO.0b013e328340d849.
A high percentage of patients with malignant disease develops mood disorders or even depression. This review provides an overview, how immune activation and tryptophan degradation might contribute to the development of depression.
Neurobiochemical changes caused by immune activation are supposed to be involved in the development of mood disorders, especially depression, in cancer patients. Within Th1-type immune response the enzyme indoleamine 2,3-dioxygenase (IDO) is induced, which degrades the essential amino acid tryptophan to form kynurenine derivatives. Enhanced immune-mediated tryptophan degradation is reflected by decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1-type immune activation marker neopterin. IDO activation has been demonstrated in patients with various kinds of cancer, and it has also been shown to predict a worse outcome of patients. Recent data also indicate strongly, that immune-mediated tryptophan degradation is crucially involved in the development of depression: IDO activation leads to the accumulation of neurotoxic metabolites, which are supposed to induce depressive-like behaviour. Furthermore immune-mediated tryptophan deprivation might also impair serotonin synthesis, as tryptophan is the precursor of this important neurotransmitter.
Immune-mediated tryptophan degradation appears to be crucially involved in the development of depression.
恶性肿瘤患者中很大比例会出现情绪障碍甚至抑郁。本文综述了免疫激活和色氨酸降解如何导致抑郁的发生。
免疫激活引起的神经生化变化可能与癌症患者的情绪障碍（尤其是抑郁）的发生有关。在 Th1 型免疫反应中，诱导酶吲哚胺 2,3-双加氧酶（IDO），它将必需氨基酸色氨酸降解为犬尿氨酸衍生物。增强的免疫介导的色氨酸降解反映为血浆色氨酸水平降低和犬尿氨酸浓度升高，同时 Th1 型免疫激活标志物新蝶呤浓度升高。已经在各种癌症患者中证明了 IDO 的激活，并且已经表明它可以预测患者的预后更差。最近的数据还强烈表明，免疫介导的色氨酸降解在抑郁的发生中起着至关重要的作用：IDO 的激活导致神经毒性代谢物的积累，这些代谢物可能导致类似抑郁的行为。此外，免疫介导的色氨酸剥夺也可能损害 5-羟色胺的合成，因为色氨酸是这种重要神经递质的前体。
免疫介导的色氨酸降解似乎在抑郁的发生中起着关键作用。
