An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)
An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)
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DOI：
10.1007/s12402-011-0062-2
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发表时间：
2011-12-01
期刊：
影响因子：
--
通讯作者：
Oades, Robert D.
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文献类型：
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作者：
Oades, Robert D.
患有注意力缺陷多动症（ADHD）的儿童特征的个体差异可能反映了突触中神经胶质能量供应的受损。我们最近报道，虽然神经胶质标记物细胞因子 S100B 的血清水平没有发生严重改变，但其他细胞因子和色氨酸代谢物的水平与症状、注意力和变异性相关。在这里，我们通过回归分析探讨这些物质的水平是否与具有潜在病因学意义的妊娠指数特征相关。取自 35 名患有 DSM-IV ADHD 的儿童（其中 14 名正在接受药物治疗）和 21 名典型对照儿童的血清，以测量 8 种细胞因子（S100B、IL-2、IL-6、IL-10、IL-13、IL-16、TNF-α 和 IFN-γ）和 5 种代谢物（色氨酸、犬尿氨酸、犬尿酸盐 [KA]、3-羟基犬尿氨酸 [3HK] 和5-羟基吲哚乙酸[5-HIAA]）。母亲们收到了一份包含 124 项有关怀孕相关特征的调查问卷。 (1) 对于患有 ADHD 的儿童，怀孕时间较短和出生体重较小与 3HK 和 IFN-gamma 升高以及 TNF-α 水平降低的产科问题存在统计学相关性。 (2) 母亲吸烟与ADHD儿童犬尿氨酸降低和3HK和S100B水平升高有关。父亲吸烟与对照组的色氨酸增加和 ADHD 儿童的 IL-6 水平增加有关。 (3)ADHD儿童服用补充剂常与降低TNF-α、升高IL-10和降低5-HIAA水平有关。较少的 5-HIAA 但较多的色氨酸分别与早期和晚期的生活事件相关。 (4) ADHD 组中 IL-16 和 5-HIAA 水平升高与婴儿健康状况较差的报道有关。出乎意料的是，多动症患者比健康家庭需要更多的儿童看护（海鲜和在一起的时间），这与较低的色氨酸水平和促炎细胞因子平衡的改变有关。总的来说，对照组家庭通常表现出与 ADHD 组不显着的关联或相反。在多动症儿童中，与对照组相比，潜在毒性或保护性犬尿氨酸代谢物与促抗炎细胞因子的平衡可能反映了与压力相关的围产期经历，但与孕产妇疾病无关。
Intra-individual variability of the characteristics of children with attention-deficit hyperactivity (ADHD) may reflect compromised glial energy supply in the synapse. We reported recently that while serum levels of a glial marker, the cytokine S100B, were not seriously altered, levels of other cytokines and tryptophan metabolites were related to symptoms, attention and variability. Here, we explore with a regression analysis whether levels of these substances were associated with features of the index pregnancy of potential aetiological significance. Serum was taken from 35 children with DSM-IV ADHD (14 on medication) and 21 typically developing controls to measure 8 cytokines (S100B, IL-2, IL-6, IL-10, IL-13, IL-16, TNF-alpha and IFN-gamma) and 5 metabolites (Tryptophan, Kynurenine, Kynurenate [KA], 3-hydroxy-kynurenine [3HK] and 5-hydroxyindole acetic acid [5-HIAA]). The mothers received a 124-item questionnaire on features surrounding the pregnancy. (1) For children with ADHD, a shorter pregnancy and smaller birth weight were associated statistically with increased 3HK and IFN-gamma and for obstetric problems with decreased TNF-alpha levels. (2) Maternal smoking related to decreasing kynurenine and increasing 3HK and S100B levels in ADHD children. Paternal smoking was associated with increased tryptophan in the controls and increased IL-6 levels in ADHD children. (3) The taking of supplements often related to decreasing TNF-alpha, increasing IL-10 and lower 5-HIAA levels in the ADHD children. Less 5-HIAA but more tryptophan was associated with earlier and later life events, respectively. (4) Increased IL-16 and 5-HIAA levels in the ADHD group related to reports of poorer infant health. Unexpectedly, more child care (seafood and time together) in ADHD than healthy families was implicated by lower tryptophan levels and an altered balance of pro-inflammatory cytokines. Across measures control families generally showed either non-significant associations or the opposite to those of the ADHD group. In ADHD children more than controls, the balance of potentially toxic or protective kynurenine metabolites and of pro-over anti-inflammatory cytokines may reflect the perinatal experience associated with stress, but not with maternal illness.