犬尿氨酸代谢与炎症诱发的抑郁情绪：一项人体实验研究。
Kynurenine metabolism and inflammation-induced depressed mood: A human experimental study.
机构信息
Cousins Center for Psychoneuroimmunology, University of California Los Angeles, United States; Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, United States.
Cousins Center for Psychoneuroimmunology, University of California Los Angeles, United States; Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, United States.
出版信息
Psychoneuroendocrinology. 2019 Nov;109:104371. doi: 10.1016/j.psyneuen.2019.104371. Epub 2019 Jul 3.
Inflammation has an important physiological influence on mood and behavior. Kynurenine metabolism is hypothesized to be a pathway linking inflammation and depressed mood, in part through the impact of kynurenine metabolites on glutamate neurotransmission in the central nervous system. This study evaluated whether the circulating concentrations of kynurenine and related compounds change acutely in response to an inflammatory challenge (endotoxin administration) in a human model of inflammation-induced depressed mood, and whether such metabolite changes relate to mood change. Adults (n = 115) were randomized to receive endotoxin or placebo. Mood (Profile of Mood States), plasma cytokine (interleukin-6, tumor necrosis factor-α) and metabolite (kynurenine, tryptophan, kynurenic acid, quinolinic acid) concentrations were repeatedly measured before the intervention, and at 2 and 6 h post-intervention. Linear mixed models were used to evaluate relationships between mood, kynurenine and related compounds, and cytokines. Kynurenine, kynurenic acid, and tryptophan (but not quinolinic acid) concentrations changed acutely (p's all <0.001) in response to endotoxin as compared to placebo. Neither kynurenine, kynurenic acid nor tryptophan concentrations were correlated at baseline with cytokine concentrations, but all three were significantly correlated with cytokine concentrations over time in response to endotoxin. Quinolinic acid concentrations were not correlated with cytokine concentrations either before or following endotoxin treatment. In those who received endotoxin, kynurenine (p = 0.049) and quinolinic acid (p = 0.03) positively correlated with depressed mood, although these findings would not survive correction for multiple testing. Changes in tryptophan and kynurenine pathway metabolites did not mediate the relationship between cytokines and depressed mood. Further work is necessary to clarify the pathways leading from inflammation to depressed mood in humans.
炎症对情绪和行为有重要的生理影响。色氨酸代谢被认为是连接炎症和抑郁情绪的途径之一，部分原因是色氨酸代谢物对中枢神经系统谷氨酸神经递质传递的影响。本研究评估了在炎症诱导的抑郁情绪的人类模型中，炎症刺激是否会导致色氨酸和相关化合物的循环浓度急性变化，以及这种代谢物变化是否与情绪变化相关。将 115 名成年人随机分为接受内毒素或安慰剂组。在干预前、干预后 2 小时和 6 小时，反复测量了情绪（心境状态问卷）、血浆细胞因子（白细胞介素-6、肿瘤坏死因子-α）和代谢物（色氨酸、犬尿氨酸、犬尿氨酸酸、喹啉酸）浓度。线性混合模型用于评估情绪、犬尿氨酸和相关化合物与细胞因子之间的关系。与安慰剂相比，内毒素组犬尿氨酸、犬尿氨酸酸和色氨酸（但不是喹啉酸）浓度急性变化（p 值均<0.001）。犬尿氨酸、犬尿氨酸酸和色氨酸浓度在基线时与细胞因子浓度无相关性，但在接受内毒素后，这三种浓度均与细胞因子浓度呈显著相关。在接受内毒素治疗前后，喹啉酸浓度与细胞因子浓度均无相关性。在内毒素组中，犬尿氨酸（p=0.049）和喹啉酸（p=0.03）与抑郁情绪呈正相关，尽管这些发现不会在经过多次测试校正后仍然存在。色氨酸和犬尿氨酸途径代谢物的变化不能介导细胞因子与抑郁情绪之间的关系。需要进一步研究来阐明人类炎症导致抑郁情绪的途径。
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