Interferon-alpha-induced changes in tryptophan metabolism: Relationship to depression and paroxetine treatment
Interferon-alpha-induced changes in tryptophan metabolism: Relationship to depression and paroxetine treatment
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DOI：
10.1016/s0006-3223(03)00173-2
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发表时间：
2003-11-01
影响因子：
10.6
通讯作者：
Miller, AH
中科院分区：
文献类型：
--
作者：
Capuron, L;Neurauter, G;Miller, AH
背景资料：色氨酸（TRP）在免疫激活过程中被吲哚胺-2，3-双加氧酶降解为犬尿氨酸（KYN）可能有助于干扰素（IFN）-α治疗期间抑郁症状的发展。26名恶性黑色素瘤患者以双盲方式随机分配接受安慰剂或帕罗西汀治疗，在IFN-α治疗前2周开始，并持续IFN-α治疗的前12周。在治疗开始时，并在2，4和12周的IFN-α治疗，TRP，KYN和新蝶呤（免疫激活的标志物）的测量，获得，沿着结构化评估抑郁症，焦虑症，和neurotoxicity.Results：无论抗抑郁药治疗状态，所有患者表现出显着增加KYN，新蝶呤，和KYN/TRP比值在IFN-α治疗。在无抗抑郁药的患者中，与无抑郁药的非抑郁患者相比，发展为重度抑郁症的患者的KYN和新蝶呤浓度显著增加，TRP浓度下降时间更长。此外，在无抗抑郁药的患者中，TRP的降低与抑郁、焦虑和认知症状相关，但与植物神经或躯体症状无关。在抗抑郁药治疗的patients.Conclusions：结果表明，TRP的可用性降低发挥了作用，在IFN-α诱导的抑郁症状，和帕罗西汀，虽然不改变KYN或新蝶呤响应IFN-α，减弱IFN-α介导的TRP耗尽的行为后果之间的相关性。(C)2003生物精神病学学会。
Background: Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-alpha therapy.Methods: Twenty-six patients with malignant melanoma were randomly assigned in double-blind fashion to receive either placebo or paroxetine, beginning 2 weeks before IFN-alpha treatment and continuing for the first 12 weeks of IFN-alpha therapy. At treatment initiation and at 2, 4, and 12 weeks of IFN-alpha treatment, measurements of TRP, KYN, and neopterin (a marker of immune activation), were obtained, along with structured assessments of depression, anxiety, and neurotoxicity.Results: Regardless of antidepressant treatment status, all patients exhibited significant increases in KYN, neopterin, and the KYN/TRP ratio during IFN-alpha therapy. Among antidepressant-free patients, patients who developed major depression exhibited significantly greater increases in KYN and neopterin concentrations and more prolonged decreases in TRP concentrations than did nondepressed, antidepressant-free patients. Moreover, in antidepressant-free patients, decreases in TRP correlated with depressive, anxious, and cognitive symptoms, but not neurovegetative or somatic symptoms. No correlations were found between clinical and biological variables in antidepressant-treated patients.Conclusions: The results suggest that reduced TRP availability plays a role in IFN-alpha-induced depressive symptoms, and paroxetine, although not altering the KYN or neopterin response to IFN-alpha, attenuates the behavioral consequences of IFN-alpha-mediated TRP depletion. (C) 2003 Society of Biological Psychiatry.