4.8 Article

IDO and interferon-α-induced depressive symptoms:: a shift in hypothesis from tryptophan depletion to neurotoxicity

期刊

MOLECULAR PSYCHIATRY
卷 10, 期 6, 页码 538-544

出版社

SPRINGERNATURE
DOI: 10.1038/sj.mp.4001600

关键词

interferon-alpha; depressive symptoms; kynurenine pathway; neurotoxicity; quinolinic acid; kynurenic acid

向作者/读者索取更多资源

Studies show that administration of interferon ( IFN)-alpha causes a significant increase in depressive symptoms. The enzyme indoleamine 2,3- dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine ( KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-alpha induced depressive symptoms, first by decreasing the TRP availability to the brain and second by the induction of the KYN pathway resulting in the production of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of psychiatric disorders and eligible for IFN-alpha treatment, were recruited. Depressive symptoms were measured using the Montgomery Asberg Depression Rating Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance through the blood - brain barrier, KYN and kynurenic acid (KA), a neuroprotective metabolite, were performed using high-performance liquid chromatography. All assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. The MADRS score significantly increased during IFN-alpha treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA ratio, reflecting the neurotoxic challenge. The TRP/CAA ( competing amino acids) ratio, reflecting TRP availability to the brain, did not significantly change during treatment. Total MADRS score was significantly associated over time with the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found that IDO decreases TRP availability to the brain, this study does support a role for IDO activity in the pathophysiology of IFN-alpha-induced depressive symptoms, through its induction of neurotoxic KYN metabolites.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据