Clinic for Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, 45147 Essen, Germany.
Behav Brain Funct. 2010 Jun 9;6:32. doi: 10.1186/1744-9081-6-32.
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.
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.
(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.
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.
与抑郁和精神病研究相比，本研究的第一部分并未显示健康儿童和注意力缺陷/多动障碍混合型（ADHD）儿童之间的细胞因子和色氨酸代谢物血清水平存在重大差异。然而，在亚组中，潜在有毒犬尿氨酸代谢物的减少和细胞因子的增加是显而易见的。因此，我们检查了生化关联与主要症状群、注意力和反应变异性测量值的预测。
我们系统地研究了 8 种细胞因子（炎症功能的指标）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）和连续性能测试（CPT）测量值（如运动、反应时间（RT）、变异性）之间的关联在 35 名 ADHD（14 名服用药物）和 21 名对照儿童中。线性回归（通过虚假发现率控制）的预测结果证实或否定了考虑年龄、体重和社会经济地位的偏相关。
（1）总症状评分与白细胞介素 IL-16 和 IL-13 的增加有关，其中 IL-16（与 S100B 降低有关）与多动有关，而 IL-13 与注意力不集中有关。对立评分由 ADHD 中 IL-2 的增加和对照组中 IL-6 的增加预测。（2）在 CPT 中，IL-16 与运动测量和冲动错误有关，而 IL-13 与遗漏错误有关。RT 变异性增加与 TNF-alpha 降低有关，但与 IFN-gamma 水平升高有关。（3）色氨酸代谢物与症状无显著相关性。但是，色氨酸增加预测遗漏错误，其分解物预测冲动错误，犬尿氨酸水平与更快的 RT 有关。
即使在一个组中更为明显，跨诊断组也发现了许多关联。这证实了这些特征的定量特征性质。从概念上讲，促炎和抗炎细胞因子的关系将与认知相关的行为与与运动控制相关的行为区分开来。进一步的研究应该扩展免疫和代谢标志物的数量，以确认或反驳这里报告的趋势，并在纵向设计中检查它们从儿童期到青春期的稳定性。
