Dataset Information

The reach-to-grasp movement in infants later diagnosed with autism spectrum disorder: a high-risk sibling cohort study.

ABSTRACT:

Background

Although autism spectrum disorder (ASD) is characterized by impairments in social communication and the presence of repetitive behavior and/or restricted interests, there is evidence that motor impairments may be a contributing factor to the ASD phenotype. The purpose of this study was to examine the motor act of reaching-to-grasp in children at high risk (HR; with an older sibling diagnosed with ASD) and low-risk (LR; no family history of ASD) for ASD.

Methods

Children were compared for differences in reaching-to-grasp based on sibling status and diagnostic outcome. Children were enrolled between 6 and 12?months of age and the reach-to-grasp movement was scored at 6, 9, (where available) 12, 15, 18, 24, and 36?months of age using the qualitative Skilled Reaching Rating Scale to determine the presence of any group-, age-, or sex-related differences in the mechanics of the reach-to-grasp movement using a Mixed Models analysis. At 36?months, all children underwent a gold-standard diagnostic assessment, which resulted in three outcome groups: HR children diagnosed with ASD (HR-ASD; n?=?10), HR children not diagnosed with ASD (HR-N; n?=?10), and low-risk children not diagnosed with ASD (LR; n?=?10).

Results

The group of children who were later diagnosed with ASD (HR-ASD group) showed higher (worse) total scores on the reach-to-grasp movement, as well as higher scores on the components of Orient, Lift, and Pronate compared to children in the LR and HR-N groups.

Conclusions

Our results support the growing literature indicating that children who are later diagnosed with ASD show impaired early motor performance. These results highlight the importance of early surveillance of children who are at elevated risk for ASD, and early initiatives should focus on early signs of the phenotype, including both movement and sensory differences (prodromal signs) prior to the emergence of diagnostic characteristics.

SUBMITTER: Sacrey LR

PROVIDER: S-EPMC6307213 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

The reach-to-grasp movement in infants later diagnosed with autism spectrum disorder: a high-risk sibling cohort study.

Sacrey Lori-Ann R LR Zwaigenbaum Lonnie L Bryson Susan S Brian Jessica J Smith Isabel M IM

Journal of neurodevelopmental disorders 20181227 1

<h4>Background</h4>Although autism spectrum disorder (ASD) is characterized by impairments in social communication and the presence of repetitive behavior and/or restricted interests, there is evidence that motor impairments may be a contributing factor to the ASD phenotype. The purpose of this study was to examine the motor act of reaching-to-grasp in children at high risk (HR; with an older sibling diagnosed with ASD) and low-risk (LR; no family history of ASD) for ASD.<h4>Methods</h4>Children ...[more]

PMID: 30587102

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Project description:Reaching and grasping (prehension) is one of the earliest developing motor skills in humans, but continued prehension development in childhood and adolescence enables the performance of increasingly complex manual tasks. In individuals with autism spectrum disorder (ASD) atypical unimanual reaching and grasping has been reported, but to date, no studies have investigated discrete bimanual movements. We examined unimanual and bimanual reach to grasp tasks in youth with ASD to better understand how motor performance might change with increasing complexity. Twenty youth with ASD (10.1 ± 2.4 years) and 17 youth with typical development (TD) (9.6 ± 2.6 years) were instructed to reach and grasp cubes that became illuminated. Participants were asked to reach out with the right and/or left hands to grasp and lift targets located at near (18 cm) and/or far (28 cm) distances. For the unimanual (simplest) condition, participants grasped one illuminated cube (with either the left or right hand). For the bimanual conditions, participants grasped two illuminated cubes located at the same distance from the start position (bimanual symmetric condition) or two illuminated cubes located at different distances (bimanual asymmetric condition). Significant interactions among diagnostic group, task complexity, and age were found for initiation time (IT) and movement time (MT). Specifically, the older children in both groups initiated and performed their movements faster in the unimanual condition than in the bimanual conditions, although the older children with ASD produced slower ITs and MTs compared to typically developing peers across all three conditions. Surprisingly, the younger children with ASD had similar ITs and MTs as their peers for the unimanual condition but did not considerably slow these times to adjust for the complexity of the bimanual tasks. We hypothesize that they chose to re-use the motor plans that were generated for the unimanual trials rather than generate more appropriate motor plans for the bimanual tasks. An atypical spatiotemporal relationship between MT and peak aperture (PA) was also found in the ASD group. Together, our results suggest deficits in motor planning that result in subtle effects on performance in younger children with ASD that become more pronounced with age.

Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. The neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development and influence future health outcomes. We performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth. Samples were split into discovery and replication sets and stratified by sex, and their DNA methylation profiles were tested for differentially methylated regions (DMRs) between ASD and typically developing control cord blood samples. DMRs were mapped to genes and assessed for enrichment in gene function, tissue expression, chromosome location, and overlap with prior ASD studies. DMR coordinates were tested for enrichment in chromatin states and transcription factor binding motifs. Results were compared between discovery and replication sets and between males and females. We identified DMRs stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development. At birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD and provides novel insights for early diagnosis and therapy.

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Project description:ImportanceAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are believed to partially share genetic factors and biological influences. As the number of children with these diagnoses rises, so does the number of younger siblings at presumed risk for ADHD and ASD; reliable recurrence risk estimates within and across diagnoses may aid screening and early detection efforts and enhance understanding of potential shared causes.ObjectiveTo examine within-diagnosis sibling recurrence risk and sibling cross-aggregation of ADHD and ASD among later-born siblings of children with either disorder.Design, setting, and participantsUsing data extracted from medical records of 2 large health care systems in the United States, estimates of recurrence risk and cross-aggregation in later-born siblings of children with ADHD or ASD were compared with later-born siblings of children without these diagnoses. One data set included children seen between January 1, 1995, and December 31, 2013; the other included children born between January 1, 1998, and May 17, 2010. Participants included 15 175 later-born siblings of children with ADHD, ASD, and no known diagnosis. The study was conducted from October 2, 2017, to August 14, 2018.Main outcomes and measuresDiagnoses of ASD or ADHD in the later-born sibling, ascertained from medical records, were the primary outcomes of interest; moderators included sex, gestational age, and maternal age.ResultsA total of 15 175 later-born siblings were classified by familial risk status based on the older child's diagnostic status: ADHD risk (n = 730; male [51.92%]), ASD risk (n = 158; male [48.10%]), and no known risk (n = 14 287; male [50.73%]). Compared with later-born siblings of children without ADHD or ASD, later-born siblings of children with ASD were more likely to be diagnosed with ASD (odds ratio [OR], 30.38; 95% CI, 17.73-52.06) or ADHD in the absence of ASD (OR, 3.70; 95% CI, 1.67-8.21). Compared with later-born siblings of children without a diagnosis, later-born siblings of children with ADHD were more likely to be diagnosed with ADHD (OR, 13.05; 95% CI, 9.86-17.27) or ASD in the absence of ADHD (OR, 4.35; 95% CI, 2.43-7.79).Conclusions and relevanceLater-born siblings of children with ASD or ADHD appear to be at elevated risk for the same disorder, but also of being diagnosed with the other disorder. These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies. Later-born siblings of children with ADHD or ASD should be monitored for both conditions.

Project description:BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. The neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development and influence future health outcomes.MethodsWe performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth. Samples were split into discovery and replication sets and stratified by sex, and their DNA methylation profiles were tested for differentially methylated regions (DMRs) between ASD and typically developing control cord blood samples. DMRs were mapped to genes and assessed for enrichment in gene function, tissue expression, chromosome location, and overlap with prior ASD studies. DMR coordinates were tested for enrichment in chromatin states and transcription factor binding motifs. Results were compared between discovery and replication sets and between males and females.ResultsWe identified DMRs stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development.ConclusionsAt birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD and provides novel insights for early diagnosis and therapy.

Dataset Information

The reach-to-grasp movement in infants later diagnosed with autism spectrum disorder: a high-risk sibling cohort study.

Background

Methods

Results

Conclusions

Publications

The reach-to-grasp movement in infants later diagnosed with autism spectrum disorder: a high-risk sibling cohort study.

Similar Datasets

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