Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms
Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms
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DOI：
10.1016/j.biopsych.2010.12.006
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发表时间：
2011-07-15
影响因子：
10.6
通讯作者：
Fuchs, Dietmar
中科院分区：
文献类型：
--
作者：
Capuron, Lucile;Schroecksnadel, Sebastian;Fuchs, Dietmar
背景：神经精神症状是老年人的常见主诉。最近的数据表明，慢性低度炎症是衰老的一个基本特征，它起到了一定的作用。这些效应可能依赖于炎症对吲哚-2，3-双加氧酶(IDO)和鸟苷-三磷酸-环水解酶-1(GTP-CH1)两条途径活性的影响，这两条途径参与单胺的生物合成。本研究对来自三城队列的284名健康老年受试者进行了评估。方法：测定作为炎症标志物的血清白介素6和C反应蛋白；作为IDO活性指标的色氨酸、犬尿氨酸及其比值；作为GTP-CH1活性标志物的新喋呤、苯丙氨酸、酪氨酸和亚硝酸盐。此外，还对抑郁症状、疲劳和一般行为/神经植物性症状进行了结构化评估。结果：正如预期的那样，年龄与免疫标记物浓度和神经精神症状显著相关。炎症增加与色氨酸浓度降低和犬尿氨酸水平升高有关，提示IDO诱导的色氨酸分解代谢增加。此外，炎症与新喋呤和亚硝酸盐水平的增加以及苯丙氨酸浓度的增加有关，而酪氨酸的增加是代价。有趣的是，色氨酸分解代谢增加与疲倦、动力减弱、厌食和悲观等抑郁症状有关。相反，GTP-CH1活性标志物的变化更多地与神经植物症状相关，包括睡眠障碍、消化症状、疲劳、恶心和运动症状。结论：这些发现表明老年慢性低度炎症与参与单胺代谢的酶途径的改变有关，提示这些变化可能参与了老年人神经精神症状的病理生理学。
Background: Neuropsychiatric symptoms are common complaints of elderly persons. Recent data suggest that chronic low-grade inflammation, a fundamental characteristic of aging, plays a role. Effects might rely on the influence of inflammation on the activity of two enzymatic pathways, the indoleamine-2,3-dioxygenase (IDO) and the guanosine-triphosphate-cyclohydrolase-1 (GTP-CH1) pathways, which are involved in the biosynthesis of monoamines. The present study assessed this possibility in 284 healthy elderly subjects drawn from the Three-City cohort.Methods: Assays included the measurement of serum interleukin-6 and C-reactive-protein, as inflammatory markers; tryptophan, kynurenine, and their ratio as index of IDO activity; and neopterin, phenylalanine, tyrosine, and nitrite, as markers of GTP-CH1 activity. In addition, structured assessments of depressive symptomatology, fatigue, and general behavioral/neurovegetative symptoms were performed.Results: As expected, age correlated significantly with concentrations of immune markers and neuropsychiatric symptoms. Increased inflammation was related to reduced tryptophan concentrations and increased kynurenine levels, suggestive of IDO-induced increased tryptophan catabolism. In addition, inflammation was associated with increases in neopterin and nitrite levels and in phenylalanine concentrations at the expense of tyrosine. Interestingly, increased tryptophan catabolism was associated with the depressive symptoms of lassitude, reduced motivation, anorexia, and pessimism. In contrast, variations in markers of GTP-CH1 activity correlated more with neurovegetative symptoms, including sleep disturbance, digestive symptoms, fatigue, sickness, and motor symptoms.Conclusions: These findings show that chronic low-grade inflammation in aging is associated with alterations in enzymatic pathways involved in monoamine metabolism and suggest that these alterations might participate in the pathophysiology of neuropsychiatric symptoms in elderly persons.