Fluegge Keith
Institute of Health and Environmental Research, Cleveland, OH, USA.
J Child Psychol Psychiatry. 2017 Jan;58(1):28-29. doi: 10.1111/jcpp.12649.
Rijlaarsdam et al. (2016) recently published their findings utilizing a longitudinal design showing that prenatal 'unhealthy diet' was positively associated with IGF2 DNA methylation at birth across both youth cohorts. However, only in the EOP youth was prenatal 'unhealthy diet' positively associated with ADHD symptoms presumably through IGF2 DNA hypermethylation. Rijlaarsdam et al.'s () choice to assess high fat and sugar diet with the Food Frequency Questionnaire (FFQ) may offer some indication as to prenatal nutrient status, as the foods identified by the FFQ in their study are relatively low in free choline. It has been shown that gestational choline deficiency in rats leads to hypermethylation of IGF2. Consistent with the literature describing an association between air pollution and cognitive neurodevelopmental impairment, the author of this commentary has previously proposed through empirical investigation that chronic environmental exposure to the trace levels of the pervasive air pollutant, nitrous oxide (N O), may facilitate core features of neurodevelopmental disorders, like ADHD. Impaired acetylcholine synthesis in rats exposed to N O has been shown, with a 53% reduction in [1-2H2,2-2H2] choline. Low-dose N O exposure is also thought to stimulate central release of opioid peptides, like dynorphin, which play a role in significantly increasing food intake behavior and/or modulating sucrose intake. Taken altogether, these studies present a strong confounder to the interpretation made by Rijlaarsdam et al. () that prenatal 'unhealthy diet' may play a role in the onset of ADHD symptoms in youth with EOP conduct problems through induction of IGF2 DNA hypermethylation. While the 'unhealthy diet' may represent possible maternal nutrient deficiencies during gestation, it is also possible that exposure to air pollutants, particularly N O, may not only directly reduce fetal cholinergic status thereby enhancing IGF2 DNA hypermethylation but may also significantly modulate maternal food intake behaviors (i.e. sucrose).
里贾尔斯达姆等人（2016年）最近发表了他们利用纵向设计得出的研究结果，表明产前“不健康饮食”与两个青年队列出生时的IGF2 DNA甲基化呈正相关。然而，只有在早发性精神病理学（EOP）青年中，产前“不健康饮食”才可能通过IGF2 DNA高甲基化与注意力缺陷多动障碍（ADHD）症状呈正相关。里贾尔斯达姆等人选择用食物频率问卷（FFQ）来评估高脂肪和高糖饮食，这可能为产前营养状况提供一些线索，因为他们研究中FFQ所确定的食物中游离胆碱含量相对较低。研究表明，大鼠孕期胆碱缺乏会导致IGF2高甲基化。与描述空气污染和认知神经发育障碍之间关联的文献一致，本评论的作者此前通过实证研究提出，长期环境暴露于普遍存在的微量空气污染物一氧化二氮（N₂O）中，可能会促使神经发育障碍的核心特征出现，如ADHD。已表明暴露于N₂O的大鼠乙酰胆碱合成受损，[1-²H₂,2-²H₂]胆碱减少了53%。低剂量N₂O暴露还被认为会刺激阿片肽的中枢释放，如强啡肽，其在显著增加食物摄入行为和/或调节蔗糖摄入方面发挥作用。综上所述，这些研究给里贾尔斯达姆等人的解释带来了一个强有力的混杂因素，即产前“不健康饮食”可能通过诱导IGF2 DNA高甲基化，在有EOP行为问题的青年ADHD症状发作中起作用。虽然“不健康饮食”可能代表孕期母亲可能存在的营养缺乏，但也有可能接触空气污染物，特别是N₂O，不仅可能直接降低胎儿胆碱能状态，从而增强IGF2 DNA高甲基化，还可能显著调节母亲的食物摄入行为（即蔗糖）。
