目的:孤独症谱系障碍(ASD)与脂质代谢异常有关,例如多不饱和脂肪酸(PUFA)中omega-6与omega-3的高总比率。PUFA通过细胞色素P450(CYP)代谢为环氧脂肪酸;然后,二羟基脂肪酸是由可溶性环氧化物水解酶产生的。这项研究检查了脐带血中PUFA代谢物与儿童ASD症状和适应功能之间的关系。
方法:本前瞻性队列研究利用脐带血对CYP通路的PUFA代谢物进行定量。自闭症诊断观察时间表(ADOS-2)和Vineland适应行为量表,第二版(VABS-II)用于评估6岁儿童随后的ASD症状和适应功能。分析包括200名儿童和他们的母亲。
结果:花生四烯酸衍生的二醇,发现11,12-diHETrE会影响ASD症状严重程度,影响ADOS-2校准的严重程度评分和VABS-II评估的社会化领域的损害(P=0.0003;P=0.004,分别)。高水平的11,12-diHETrE影响ASD症状的社会影响(P=0.002),而低水平的8,9-diHETrE影响重复/限制性行为(P=0.003)。值得注意的是,diHETrE和ASD症状之间的关联具有特异性,尤其是女孩。
结论:这些发现表明,胎儿期diHETrE的动力学在出生后儿童的发育轨迹中很重要。鉴于二醇代谢物在体内神经发育中的作用完全没有特征,这项研究的结果为diHETrE和ASD病理生理学的作用提供了重要的见解。
OBJECTIVE: Autism spectrum disorder (ASD) is associated with abnormal lipid metabolism, such as a high total ratio of omega-6 to omega-3 in polyunsaturated fatty acids (PUFAs). PUFAs are metabolized to epoxy fatty acids by cytochrome P450 (CYP); then, dihydroxy fatty acid is produced by soluble epoxide hydrolase. This
study examined the association between PUFA metabolites in the cord blood and ASD symptoms and adaptive functioning in children.
METHODS: This prospective cohort
study utilized cord blood to quantify PUFA metabolites of the CYP pathway. The Autism Diagnostic Observation Schedule (ADOS-2) and Vineland Adaptive Behaviors Scales, Second Edition (VABS-II) were used to assess subsequent ASD symptoms and adaptive functioning in children at 6 years. The analysis included 200 children and their mothers.
RESULTS: Arachidonic acid-derived diols, 11,12-diHETrE was found to impact ASD symptom severity on the ADOS-2-calibrated severity scores and impairment in the socialization domain as assessed by the VABS-II (P = 0.0003; P = 0.004, respectively). High levels of 11,12-diHETrE impact social affect in ASD symptoms (P = 0.002), while low levels of 8,9-diHETrE impact repetitive/restrictive behavior (P = 0.003). Notably, there was specificity in the association between diHETrE and ASD symptoms, especially in girls.
CONCLUSIONS: These findings suggest that the dynamics of diHETrE during the fetal period is important in the developmental trajectory of children after birth. Given that the role of diol metabolites in neurodevelopment in vivo is completely uncharacterized, the results of this
study provide important insight into the role of diHETrE and ASD pathophysiology.