Dataset Information

Saliva MicroRNA Differentiates Children With Autism From Peers With Typical and Atypical Development.

ABSTRACT: 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.

SUBMITTER: Hicks SD

PROVIDER: S-EPMC6764899 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Saliva MicroRNA Differentiates Children With Autism From Peers With Typical and Atypical Development.

Hicks Steven D SD Carpenter Randall L RL Wagner Kayla E KE Pauley Rachel R Barros Mark M Tierney-Aves Cheryl C Barns Sarah S Greene Cindy Dowd CD Middleton Frank A FA

Journal of the American Academy of Child and Adolescent Psychiatry 20190327 2

<h4>Objective</h4>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.<h4>Method</h4>This multicenter, prospective, case-control study enrolled 443 children (2-6 years ...[more]

PMID: 30926572

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Project description:In families raising a child with an autism spectrum disorder (ASD), infant siblings are at elevated risk for ASD and other developmental concerns, including elements of the broader autism phenotype (BAP). Typically, the BAP is indexed using standardized developmental assessments; however, these measures do not capture a number of social difficulties commonly associated with the BAP. The present study aims to expand our developmental understanding of the BAP by comparing children exhibiting the BAP to their typically developing peers on, (a) standardized measures of development, and (b) social behaviors exhibited during dyadic play interactions. As part of a prospective study, dyads were recruited from families with at least one older child with ASD (high-risk, n = 36), and families with no history of ASD (low-risk, n = 38). During laboratory visits at 12, 15, 18, and 24 months of age, infants completed a series of standardized assessments and a mother-child play interaction. Dyadic play interactions were micro-analytically coded for gaze, positive affect, and vocalizations to create theory-driven composites to index dyadic synchrony and responsiveness. Videos were also coded with an existing rating scheme for joint engagement and child responsiveness. Multilevel models revealed significant group differences on select constructs within the first 2 years. Language and cognitive differences emerged by 24 months of age, whereas dyadic differences were evident as early as 15 months. Recognizing the increasing demand for elevated-risk interventions, these findings highlight several social constructs through which interventions may identify risk and promote optimal development. Autism Res 2019, 12: 469-481 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In families raising children with an autism spectrum disorder (ASD), younger siblings are at an increased risk for social and developmental difficulties that characterize a "broader autism phenotype." The present study explored the emergence of social, language, and cognitive differences in the first 2 years of life. Social differences were evident as early as 15 months of age for several play-based measures, and language and cognitive differences emerged by 24 months of age. For infant siblings of children with ASD, some of the earliest behavioral marks for subclinical features of ASD are evident within the first 2 years of life.

Project description:The Featurally Underspecified Lexicon (FUL) theory predicts that [coronal] is the language universal default place of articulation for phonemes. This assumption has been consistently supported with adult behavioral and event-related potential (ERP) data; however, this underspecification claim has not been tested in developmental populations. The purpose of this study was to determine whether children demonstrate [coronal] underspecification patterns similar to those of adults. Two English consonants differing in place of articulation, [labial] /b/ and [coronal] /d/, were presented to 24 children (ages 4-6 years) characterized by either a typically developing phonological system (TD) or a phonological disorder (PD). Two syllables, /b?/ and /d?/, were presented in an ERP oddball paradigm where both syllables served as the standard and deviant stimulus in opposite stimulus sets. Underspecification was examined with three analyses: traditional mean amplitude measurements, cluster-based permutation tests, and single-trial general linear model (GLM) analyses of single-subject data. Contrary to previous adult findings, children with PD demonstrated a large positive mismatch response (PMR) to /b?/ while the children with TD exhibited a negative mismatch response (MMN); significant group differences were not observed in the /d?/ responses. Moreover, the /b?/ deviant ERP response was significantly larger in the TD children than in the children with PD. At the single-subject level, more children demonstrated mismatch responses to /d?/ than to /b?/, though some children had a /b?/ mismatch response and no /d?/ mismatch response. While both groups of children demonstrated similar responses to the underspecified /d?/, their neural responses to the more specified /b?/ varied. These findings are interpreted within a proposed developmental model of phonological underspecification, wherein children with PD are functioning at a developmentally less mature stage of phonological acquisition than their same-aged TD peers. Thus, phonological underspecification is a phenomenon that likely develops over time with experience and exposure to language.

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Saliva MicroRNA Differentiates Children With Autism From Peers With Typical and Atypical Development.

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Saliva MicroRNA Differentiates Children With Autism From Peers With Typical and Atypical Development.

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