Myo-inositol mediates the effects of traffic-related air pollution on generalized anxiety symptoms at age 12 years
Myo-inositol mediates the effects of traffic-related air pollution on generalized anxiety symptoms at age 12 years
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DOI：
10.1016/j.envres.2019.05.009
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发表时间：
2019-08-01
影响因子：
8.3
通讯作者：
Cecil, Kim M.
中科院分区：
文献类型：
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作者：
Brunst, Kelly J.;Ryan, Patrick H.;Cecil, Kim M.
背景：暴露于交通相关的空气污染（TRAP）与儿童焦虑症状有关。焦虑症患者的神经影像学显示神经化学改变。目的：在辛辛那提儿童过敏和空气污染研究（CCAAPS）中评估TRAP对脑代谢的影响及其与儿童焦虑症状的关系。方法：对145名青少年进行磁共振波谱检查。脑代谢物，包括肌醇、n -乙酰天冬氨酸、肌酸、胆碱、谷氨酸、谷氨酸加谷氨酰胺和谷胱甘肽在前扣带皮层测量。使用斯宾塞儿童焦虑量表评估焦虑症状。使用经过验证的土地利用回归模型估计了早期生活、童年平均和成像前12个月的TRAP暴露。使用线性回归和自举方法评估TRAP暴露、脑代谢和焦虑症状之间的关联，以测试脑代谢物水平的中介作用。结果：与低水平TRAP暴露相比，近期暴露于高水平TRAP与肌醇显著增加相关（β = 0.26; 95%CI 0.01, 0.51）。近期TRAP暴露升高（β = 4.71; 95% CI 0.95, 8.45）和肌醇水平升高（β = 2.98; 95% CI 0.43, 5.52）也与广泛性焦虑症状增加显著相关，其中12%的TRAP和广泛性焦虑症状之间的总效应是由肌醇水平介导的。结论：这是第一个利用神经影像学来联系TRAP暴露、大脑代谢物失调和其他健康儿童的广泛性焦虑症状的儿童研究。TRAP可能引起非典型兴奋性神经传递和胶质炎症反应，导致代谢物水平升高和随后的焦虑症状。
Background: Exposure to traffic-related air pollution (TRAP) has been linked to childhood anxiety symptoms. Neuroimaging in patients with anxiety disorders indicate altered neurochemistry.Objectives: Evaluate the impact of TRAP on brain metabolism and its relation to childhood anxiety symptoms in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS).Methods: Adolescents (n = 145) underwent magnetic resonance spectroscopy. Brain metabolites, including myoinositol, N-acetylaspartate, creatine, choline, glutamate, glutamate plus glutamine, and glutathione were measured in the anterior cingulate cortex. Anxiety symptoms were assessed using the Spence Children's Anxiety Scale. TRAP exposure in early-life, averaged over childhood, and during the 12 months prior to imaging was estimated using a validated land use regression model. Associations between TRAP exposure, brain metabolism, and anxiety symptoms were estimated using linear regression and a bootstrapping approach for testing mediation by brain metabolite levels.Results: Recent exposure to high levels of TRAP was associated with significant increases in myo-inositol (beta = 0.26; 95%CI 0.01, 0.51) compared to low TRAP exposure. Recent elevated TRAP exposure (beta = 4.71; 95% CI 0.95, 8.45) and increased myo-inositol levels (beta = 2.98; 95% CI 0.43, 5.52) were also significantly associated with increased generalized anxiety symptoms with 12% of the total effect between TRAP and generalized anxiety symptoms being mediated by myo-inositol levels.Conclusions: This is the first study of children to utilize neuroimaging to link TRAP exposure, metabolite dysregulation in the brain, and generalized anxiety symptoms among otherwise healthy children. TRAP may elicit atypical excitatory neurotransmission and glial inflammatory responses leading to increased metabolite levels and subsequent anxiety symptoms.