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Saliva MicroRNA Differentiates Children With Autism From Peers With Typical and Atypical Development.
Journal of the American Academy of Child and Adolescent Psychiatry ( IF 9.2 ) Pub Date : 2019-03-27 , DOI: 10.1016/j.jaac.2019.03.017
Steven D Hicks 1 , Randall L Carpenter 2 , Kayla E Wagner 3 , Rachel Pauley 4 , Mark Barros 5 , Cheryl Tierney-Aves 6 , Sarah Barns 7 , Cindy Dowd Greene 3 , Frank A Middleton 7
Affiliation  

OBJECTIVE Clinical diagnosis of autism spectrum disorder (ASD) relies on time-consuming subjective assessments. The primary purpose of this study was to investigate the utility of salivary microRNAs for differentiating children with ASD from peers with typical development (TD) and non-autism developmental delay (DD). The secondary purpose was to explore microRNA patterns among ASD phenotypes. METHOD This multicenter, prospective, case-control study enrolled 443 children (2-6 years old). ASD diagnoses were based on DSM-5 criteria. Children with ASD or DD were assessed with the Autism Diagnostic Observation Schedule II and Vineland Adaptive Behavior Scales II. MicroRNAs were measured with high-throughput sequencing. Differential expression of microRNAs was compared among the ASD (n = 187), TD (n = 125), and DD (n = 69) groups in the training set (n = 381). Multivariate logistic regression defined a panel of microRNAs that differentiated children with ASD and those without ASD. The algorithm was tested in a prospectively collected naïve set of 62 samples (ASD, n = 37; TD, n = 8; DD, n = 17). Relations between microRNA levels and ASD phenotypes were explored. RESULT Fourteen microRNAs displayed differential expression (false discovery rate < 0.05) among ASD, TD, and DD groups. A panel of 4 microRNAs (controlling for medical/demographic covariates) best differentiated children with ASD from children without ASD in training (area under the curve = 0.725) and validation (area under the curve = 0.694) sets. Eight microRNAs were associated (R > 0.25, false discovery rate < 0.05) with social affect, and 10 microRNAs were associated with restricted/repetitive behavior. CONCLUSION Salivary microRNAs are "altered" in children with ASD and associated with levels of ASD behaviors. Salivary microRNA collection is noninvasive, identifying ASD-status with moderate accuracy. A multi-"omic" approach using additional RNA families could improve accuracy, leading to clinical application. CLINICAL TRIAL REGISTRATION INFORMATION A Salivary miRNA Diagnostic Test for Autism; https://clinicaltrials.gov/; NCT02832557.

中文翻译:

唾液MicroRNA可将自闭症儿童与具有典型和非典型发育的同伴区分开来。

目的自闭症谱系障碍(ASD)的临床诊断依赖于耗时的主观评估。这项研究的主要目的是研究唾液microRNA在区分ASD儿童与典型发育(TD)和非自闭症发育迟缓(DD)的同伴中的用途。第二个目的是探索ASD表型之间的microRNA模式。方法该多中心,前瞻性,病例对照研究招募了443名儿童(2-6岁)。ASD诊断基于DSM-5标准。对患有ASD或DD的儿童进行了“自闭症诊断观察计划表II”和“葡萄园适应行为量表II”的评估。MicroRNA通过高通量测序进行测量。在ASD(n = 187),TD(n = 125),和DD(n = 69)组在训练集中(n = 381)。多元logistic回归定义了一组microRNA,用于区分患有ASD的儿童和没有ASD的儿童。该算法在前瞻性收集的62个样本的原始集合中进行了测试(ASD,n = 37; TD,n = 8; DD,n = 17)。探索了microRNA水平与ASD表型之间的关系。结果14个microRNA在ASD,TD和DD组之间显示差异表达(错误发现率<0.05)。一组4个microRNA(控制医学/人口统计学协变量)在训练(曲线下面积= 0.725)和验证(曲线下面积= 0.694)组中最佳区分了患有ASD的儿童与没有ASD的儿童。八个microRNA与社会影响相关(R> 0.25,错误发现率<0.05),以及10个microRNA与限制性/重复性行为相关。结论ASD儿童唾液中的微小RNA“改变”,并与ASD行为水平有关。唾液微RNA收集是非侵入性的,可以以中等准确度识别ASD状态。使用其他RNA家族的多“组学”方法可以提高准确性,从而导致临床应用。临床试验注册信息自闭症的唾液miRNA诊断测试;https://clinicaltrials.gov/; NCT02832557。导致临床应用。临床试验注册信息自闭症的唾液miRNA诊断测试;https://clinicaltrials.gov/; NCT02832557。导致临床应用。临床试验注册信息自闭症的唾液miRNA诊断测试;https://clinicaltrials.gov/; NCT02832557。
更新日期:2020-01-23
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