Almulla Abbas F, Thipakorn Yanin, Vasupanrajit Asara, Abo Algon Ali Abbas, Tunvirachaisakul Chavit, Hashim Aljanabi Ashwan Abdulzahra, Oxenkrug Gregory, Al-Hakeim Hussein K, Maes Michael
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq.
Brain Behav Immun Health. 2022 Oct 21;26:100537. doi: 10.1016/j.bbih.2022.100537. eCollection 2022 Dec.
There is now evidence that affective disorders including major depressive disorder (MDD) and bipolar disorder (BD) are mediated by immune-inflammatory and nitro-oxidative pathways. Activation of these pathways may be associated with activation of the tryptophan catabolite (TRYCAT) pathway by inducing indoleamine 2,3-dioxygenase (IDO, the rate-limiting enzyme) leading to depletion of tryptophan (TRP) and increases in tryptophan catabolites (TRYCATs).
To systematically review and meta-analyze central and peripheral (free and total) TRP levels, its competing amino-acids (CAAs) and TRYCATs in MDD and BD.
This review searched PubMed, Google Scholar and SciFinder and included 121 full-text articles and 15470 individuals, including 8024 MDD/BD patients and 7446 healthy controls.
TRP levels (either free and total) and the TRP/CAAs ratio were significantly decreased (p < 0.0001) in MDD/BD as compared with controls with a moderate effect size (standardized mean difference for TRP: SMD = -0.513, 95% confidence interval, CI: -0.611; -0.414; and TRP/CAAs: SMD = -0.558, CI: -0.758; -0.358). Kynurenine (KYN) levels were significantly decreased in patients as compared with controls with a small effect size (p < 0.0001, SMD = -0.213, 95%CI: -0.295; -0.131). These differences were significant in plasma (p < 0.0001, SMD = -0.304, 95%CI: -0.415, -0.194) but not in serum (p = 0.054) or the central nervous system (CNS, p = 0.771). The KYN/TRP ratio, frequently used as an index of IDO activity, and neurotoxicity indices based on downstream TRYCATs were unaltered or even lowered in MDD/BD.
Our findings suggest that MDD and BD are accompanied by TRP depletion without IDO and TRYCAT pathway activation. Lowered TRP availability is probably the consequence of lowered serum albumin during the inflammatory response in affective disorders.
目前有证据表明，包括重度抑郁症（MDD）和双相情感障碍（BD）在内的情感障碍是由免疫炎症和硝基氧化途径介导的。这些途径的激活可能与色氨酸分解代谢产物（TRYCAT）途径的激活有关，通过诱导吲哚胺2,3-双加氧酶（IDO，限速酶）导致色氨酸（TRP）耗竭和色氨酸分解代谢产物（TRYCATs）增加。
系统评价和荟萃分析MDD和BD患者中枢和外周（游离和总）TRP水平、其竞争性氨基酸（CAA）和TRYCATs。
本综述检索了PubMed、谷歌学术和SciFinder，纳入121篇全文文章和15470名个体，包括8024例MDD/BD患者和7446名健康对照。
与对照组相比，MDD/BD患者的TRP水平（游离和总水平）以及TRP/CAA比值显著降低（p<0.0001），效应量中等（TRP的标准化均数差：SMD=-0.513，95%置信区间，CI：-0.611；-0.414；TRP/CAA：SMD=-0.558，CI：-0.758；-0.358）。与对照组相比，患者的犬尿氨酸（KYN）水平显著降低，效应量较小（p<0.0001，SMD=-0.213，95%CI：-0.295；-0.131）。这些差异在血浆中显著（p<0.0001，SMD=-0.30,4，95%CI：-0.415，-0.194），但在血清中不显著（p=0.054）或中枢神经系统中不显著（CNS，p=0.771）。常用作IDO活性指标的KYN/TRP比值以及基于下游TRYCATs的神经毒性指标在MDD/BD中未改变甚至降低。
我们的研究结果表明，MDD和BD伴有TRP耗竭，而无IDO和TRYCAT途径激活。TRP可用性降低可能是情感障碍炎症反应期间血清白蛋白降低的结果。
