Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention
Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention
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DOI：
10.1186/1744-9081-6-32
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发表时间：
2010-06-09
影响因子：
5.1
通讯作者：
Schwarz, Markus J.
中科院分区：
文献类型：
--
作者：
Oades, Robert D.;Myint, Aye-Mu;Schwarz, Markus J.
背景：与抑郁症和精神病的研究相比，本研究的第一部分显示，健康儿童和合并型注意缺陷/多动障碍（ADHD）儿童的血清细胞因子和色氨酸代谢物水平没有重大差异。然而，在亚组中，潜在毒性犬尿氨酸代谢物的少量减少和细胞因子的明显增加。因此，我们研究了与主要症状群、注意力和反应变异性的生化关联的预测。方法：我们系统地探讨了8种细胞因子（促/抗炎功能指标）和5种色氨酸代谢物与症状评分（如焦虑、对立、注意力不集中）和连续表现测试（CPT）指标（如运动、反应时间（RT）、变异性）在35名ADHD儿童（14名服药儿童）和21名对照儿童中的相关性。线性回归（由错误发现率控制）的预测证实或不证实了考虑到年龄、体重和社会经济地位的部分相关性。结果：(1)总症状评分与白细胞介素IL-16、IL-13升高相关，其中IL-16（伴S100B下降）与多动、IL-13与注意力不集中关系显著。通过ADHD患儿IL-2和对照组患儿IL-6的升高预测对立评分。(2)在CPT中，IL-16与运动措施和委托错误相关，IL-13与遗漏错误相关。增加的RT变异性与较低的tnf - α有关，但与较高的ifn - γ水平有关。(3)色氨酸代谢物与症状无显著相关性。但色氨酸的增加预示着遗漏的错误，它的分解预示着完成的错误，而犬尿氨酸水平与更快的RTs有关。结论：在诊断组中发现了许多关联，即使它们在一组中更为明显。这证实了这些特征的数量性状性质。从概念上讲，促炎和抗炎细胞因子的关系区分了与认知或运动控制相关的行为。进一步的研究应该扩大免疫学和代谢标志物的数量，以证实或反驳本文报道的趋势，并在纵向设计中检查它们从童年到青春期的稳定性。
Background: In contrast to studies of depression and psychosis, the first part of this study showed no major differences in serum levels of cytokines and tryptophan metabolites between healthy children and those with attention-deficit/hyperactivity disorder of the combined type (ADHD). Yet, small decreases of potentially toxic kynurenine metabolites and increases of cytokines were evident in subgroups. Therefore we examined predictions of biochemical associations with the major symptom clusters, measures of attention and response variability.Methods: We explored systematically associations of 8 cytokines (indicators of pro/anti-inflammatory function) and 5 tryptophan metabolites with symptom ratings (e. g. anxiety, opposition, inattention) and continuous performance test (CPT) measures (e. g. movement, response time (RT), variability) in 35 ADHD (14 on medication) and 21 control children. Predictions from linear regressions (controlled by the false discovery rate) confirmed or disconfirmed partial correlations accounting for age, body mass and socio-economic status.Results: (1) Total symptom ratings were associated with increases of the interleukins IL-16 and IL-13, where relations of IL-16 (along with decreased S100B) with hyperactivity, and IL-13 with inattention were notable. Opposition ratings were predicted by increased IL-2 in ADHD and IL-6 in control children. (2) In the CPT, IL-16 related to motor measures and errors of commission, while IL-13 was associated with errors of omission. Increased RT variability related to lower TNF-alpha, but to higher IFN-gamma levels. (3) Tryptophan metabolites were not significantly related to symptoms. But increased tryptophan predicted errors of omission, its breakdown predicted errors of commission and kynurenine levels related to faster RTs.Conclusions: Many associations were found across diagnostic groups even though they were more marked in one group. This confirms the quantitative trait nature of these features. Conceptually the relationships of the pro-and antiinflammatory cytokines distinguished between behaviours associated more with cognitive or more with motor control respectively. Further study should extend the number of immunological and metabolic markers to confirm or refute the trends reported here and examine their stability from childhood to adolescence in a longitudinal design.