Atypical Postural Control Variability and Coordination Persist Into Middle and Older Adulthood in Autism Spectrum Disorder / Jingying WANG ; Desirae J. SHIRLEY ; Hanna M. GEMMELL ; Danielle CHRISTENSEN ; Ann-Marie ORLANDO ; Regilda A. ROMERO ; Brandon A. ZIELINSKI ; Zheng WANG in Autism Research, 18-4 (April 2025)  

Public ISBD [article]  inAutism Research > 18-4 (April 2025) . - p.752-764 Titre : Atypical Postural Control Variability and Coordination Persist Into Middle and Older Adulthood in Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Jingying WANG, Auteur ; Desirae J. SHIRLEY, Auteur ; Hanna M. GEMMELL, Auteur ; Danielle CHRISTENSEN, Auteur ; Ann-Marie ORLANDO, Auteur ; Regilda A. ROMERO, Auteur ; Brandon A. ZIELINSKI, Auteur ; Zheng WANG, Auteur Article en page(s) : p.752-764 Langues : Anglais (eng) Mots-clés : aging  autism spectrum disorder  dynamic postural sway  middle aged and older  postural control  static stance Index. décimale : PER Périodiques Résumé : ABSTRACT Postural control deviations remain largely unexplored in middle aged and older autistic adults. With the increased prevalence of neurodegenerative conditions and heightened fall risk, precise quantification of postural variability and coordination may provide valuable insights into aging associated neuromotor deviations in autistic adults. Forty-seven autistic and 48 non-autistic individuals completed static stance, anterior?posterior (AP), and mediolateral (ML) postural sway on a force platform. Center of pressure (COP) metrics were derived and interpreted using ANCOVAs for between-group comparisons and multilinear regressions for group? ? ?age interaction. Correlations between clinical measures and COP variables that differentiated groups were explored. Compared to non-autistic individuals, autistic adults exhibited greater COP standard deviation (COPSD) and COP trajectory length during static stance and demonstrated significant COPSD-AP reductions in older age. Autistic adults also exhibited decreased COP range of motion (ROM) but increased ROM variability in the target direction during dynamic stance. Autistic adults' postural sway was jerkier during dynamic stance, and increased ROM variability during dynamic AP sway was moderately associated with lower verbal IQ in autistic adults. Our findings highlight persistent postural control deviations in middle aged and older autistic adults. Static and dynamic stance are differentially associated with unique profiles of postural control in ASD. Specifically, autistic adults demonstrated pronounced increases in postural sway variability during static stance, while reducing coordination during dynamic conditions. The extent to which postural control deviations found in autistic adults are predictive to the onset of neurodegenerative conditions and the severity of falls warrants future longitudinal research. En ligne : https://doi.org/10.1002/aur.70024 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=554 [article] Atypical Postural Control Variability and Coordination Persist Into Middle and Older Adulthood in Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Jingying WANG, Auteur ; Desirae J. SHIRLEY, Auteur ; Hanna M. GEMMELL, Auteur ; Danielle CHRISTENSEN, Auteur ; Ann-Marie ORLANDO, Auteur ; Regilda A. ROMERO, Auteur ; Brandon A. ZIELINSKI, Auteur ; Zheng WANG, Auteur . - p.752-764. Langues : Anglais (eng) in Autism Research > 18-4 (April 2025) . - p.752-764 Mots-clés : aging  autism spectrum disorder  dynamic postural sway  middle aged and older  postural control  static stance Index. décimale : PER Périodiques Résumé : ABSTRACT Postural control deviations remain largely unexplored in middle aged and older autistic adults. With the increased prevalence of neurodegenerative conditions and heightened fall risk, precise quantification of postural variability and coordination may provide valuable insights into aging associated neuromotor deviations in autistic adults. Forty-seven autistic and 48 non-autistic individuals completed static stance, anterior?posterior (AP), and mediolateral (ML) postural sway on a force platform. Center of pressure (COP) metrics were derived and interpreted using ANCOVAs for between-group comparisons and multilinear regressions for group? ? ?age interaction. Correlations between clinical measures and COP variables that differentiated groups were explored. Compared to non-autistic individuals, autistic adults exhibited greater COP standard deviation (COPSD) and COP trajectory length during static stance and demonstrated significant COPSD-AP reductions in older age. Autistic adults also exhibited decreased COP range of motion (ROM) but increased ROM variability in the target direction during dynamic stance. Autistic adults' postural sway was jerkier during dynamic stance, and increased ROM variability during dynamic AP sway was moderately associated with lower verbal IQ in autistic adults. Our findings highlight persistent postural control deviations in middle aged and older autistic adults. Static and dynamic stance are differentially associated with unique profiles of postural control in ASD. Specifically, autistic adults demonstrated pronounced increases in postural sway variability during static stance, while reducing coordination during dynamic conditions. The extent to which postural control deviations found in autistic adults are predictive to the onset of neurodegenerative conditions and the severity of falls warrants future longitudinal research. En ligne : https://doi.org/10.1002/aur.70024 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=554

Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder / Lin WANG in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 75 p. Titre : Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Lin WANG, Auteur ; Yi ZHANG, Auteur ; Kuokuo LI, Auteur ; Zheng WANG, Auteur ; Xiaomeng WANG, Auteur ; Bin LI, Auteur ; Guihu ZHAO, Auteur ; Zhenghuan FANG, Auteur ; Zhengbao LING, Auteur ; Tengfei LUO, Auteur ; Lu XIA, Auteur ; Yanping LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Jinchen LI, Auteur ; Zhongsheng SUN, Auteur ; Kun XIA, Auteur Article en page(s) : 75 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  De novo variant  Expression pattern  Functional network  Recessive inherited variant Index. décimale : PER Périodiques Résumé : BACKGROUND: Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). METHODS: We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. RESULTS: Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p?=?0.038) and X-linked inherited PTVs in males (p?=?0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. LIMITATIONS: The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. CONCLUSIONS: ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs. En ligne : http://dx.doi.org/10.1186/s13229-020-00382-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433 [article] Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder [Texte imprimé et/ou numérique] / Lin WANG, Auteur ; Yi ZHANG, Auteur ; Kuokuo LI, Auteur ; Zheng WANG, Auteur ; Xiaomeng WANG, Auteur ; Bin LI, Auteur ; Guihu ZHAO, Auteur ; Zhenghuan FANG, Auteur ; Zhengbao LING, Auteur ; Tengfei LUO, Auteur ; Lu XIA, Auteur ; Yanping LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Jinchen LI, Auteur ; Zhongsheng SUN, Auteur ; Kun XIA, Auteur . - 75 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 75 p. Mots-clés : Autism spectrum disorder  De novo variant  Expression pattern  Functional network  Recessive inherited variant Index. décimale : PER Périodiques Résumé : BACKGROUND: Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). METHODS: We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. RESULTS: Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p?=?0.038) and X-linked inherited PTVs in males (p?=?0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. LIMITATIONS: The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. CONCLUSIONS: ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs. En ligne : http://dx.doi.org/10.1186/s13229-020-00382-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433

Transcallosal white matter and cortical gray matter variations in autistic adults aged 30-73 years / Danielle CHRISTENSEN ; Jingying WANG ; Desirae J SHIRLEY ; Ann-Marie ORLANDO ; Regilda A ROMERO ; David E VAILLANCOURT ; Bradley J WILKES ; Stephen A COOMBES ; Zheng WANG in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 16 Titre : Transcallosal white matter and cortical gray matter variations in autistic adults aged 30-73 years Type de document : Texte imprimé et/ou numérique Auteurs : Danielle CHRISTENSEN, Auteur ; Jingying WANG, Auteur ; Desirae J SHIRLEY, Auteur ; Ann-Marie ORLANDO, Auteur ; Regilda A ROMERO, Auteur ; David E VAILLANCOURT, Auteur ; Bradley J WILKES, Auteur ; Stephen A COOMBES, Auteur ; Zheng WANG, Auteur Article en page(s) : 16 Langues : Anglais (eng) Mots-clés : Humans  Male  Gray Matter/diagnostic imaging/pathology  White Matter/diagnostic imaging/pathology  Female  Adult  Middle Aged  Aged  Case-Control Studies  Autistic Disorder/diagnostic imaging/pathology  Corpus Callosum/diagnostic imaging/pathology  Autism Spectrum Disorder/diagnostic imaging/pathology  Anisotropy  Diffusion Magnetic Resonance Imaging  Aging  Autism spectrum disorder  Autistic adults  Diffusion MRI  Free water  Free water corrected fractional anisotropy  Free water corrected mean diffusivity  Gray matter  Transcallosal tracts  White matter  in this study were approved by the Institutional Review Board (IRB) at the  University of Florida following the Declaration of Helsinki. The IRB number is  202100659, with an approval date of July 26, 2022. Consent for publication: All  authors have read and approved the submission. Competing interests: The authors  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a lifelong condition that profoundly impacts health, independence, and quality of life. However, research on brain aging in autistic adults is limited, and microstructural variations in white and gray matter remain poorly understood. To address this critical gap, we assessed novel diffusion MRI (dMRI) biomarkers, free water, and free water corrected fractional anisotropy (fwcFA), and mean diffusivity (fwcMD) across 32 transcallosal tracts and their corresponding homotopic grey matter origin/endpoint regions of interest (ROIs) in middle and old aged autistic adults. METHODS: Forty-three autistic adults aged 30-73 and 43 age-, sex-, and IQ-matched neurotypical controls underwent dMRI scans. We examined free water, fwcFA, fwcMD differences between the two groups and age-related pattern of each dMRI metric across the whole brain for each group. The relationships between clinical measures of ASD and free water in regions that significantly differentiated autistic adults from neurotypical controls were also explored. In supplementary analyses, we also assessed free water uncorrected FA and MD using conventional single tensor modeling. RESULTS: Autistic adults exhibited significantly elevated free water in seven frontal transcallosal tracts compared to controls. In controls, age-related increases in free water and decreases in fwcFA were observed across most transcallosal tracts. However, these age-associated patterns were entirely absent in autistic adults. In gray matter, autistic adults showed elevated free water in the calcarine cortices and lower fwcMD in the dorsal premotor cortices compared to controls. Lastly, age-related increases in free water were found across all white matter and gray matter ROIs in neurotypical controls, whereas no age-related associations were detected in any dMRI metrics for autistic adults. LIMITATIONS: We only recruited cognitively capable autistic adults, which limits the generalizability of our findings across the full autism spectrum. The cross-sectional design precludes inferences about microstructural changes over time in middle and old aged autistic adults. CONCLUSIONS: Our findings revealed increased free water load in frontal white matter in autistic adults and identified distinct age-associated microstructural variations between the two groups. These findings highlight more heterogeneous brain aging profiles in autistic adults. Our study also demonstrated the importance of quantifying free water in dMRI studies of ASD. En ligne : https://dx.doi.org/10.1186/s13229-025-00652-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Transcallosal white matter and cortical gray matter variations in autistic adults aged 30-73 years [Texte imprimé et/ou numérique] / Danielle CHRISTENSEN, Auteur ; Jingying WANG, Auteur ; Desirae J SHIRLEY, Auteur ; Ann-Marie ORLANDO, Auteur ; Regilda A ROMERO, Auteur ; David E VAILLANCOURT, Auteur ; Bradley J WILKES, Auteur ; Stephen A COOMBES, Auteur ; Zheng WANG, Auteur . - 16. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 16 Mots-clés : Humans  Male  Gray Matter/diagnostic imaging/pathology  White Matter/diagnostic imaging/pathology  Female  Adult  Middle Aged  Aged  Case-Control Studies  Autistic Disorder/diagnostic imaging/pathology  Corpus Callosum/diagnostic imaging/pathology  Autism Spectrum Disorder/diagnostic imaging/pathology  Anisotropy  Diffusion Magnetic Resonance Imaging  Aging  Autism spectrum disorder  Autistic adults  Diffusion MRI  Free water  Free water corrected fractional anisotropy  Free water corrected mean diffusivity  Gray matter  Transcallosal tracts  White matter  in this study were approved by the Institutional Review Board (IRB) at the  University of Florida following the Declaration of Helsinki. The IRB number is  202100659, with an approval date of July 26, 2022. Consent for publication: All  authors have read and approved the submission. Competing interests: The authors  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a lifelong condition that profoundly impacts health, independence, and quality of life. However, research on brain aging in autistic adults is limited, and microstructural variations in white and gray matter remain poorly understood. To address this critical gap, we assessed novel diffusion MRI (dMRI) biomarkers, free water, and free water corrected fractional anisotropy (fwcFA), and mean diffusivity (fwcMD) across 32 transcallosal tracts and their corresponding homotopic grey matter origin/endpoint regions of interest (ROIs) in middle and old aged autistic adults. METHODS: Forty-three autistic adults aged 30-73 and 43 age-, sex-, and IQ-matched neurotypical controls underwent dMRI scans. We examined free water, fwcFA, fwcMD differences between the two groups and age-related pattern of each dMRI metric across the whole brain for each group. The relationships between clinical measures of ASD and free water in regions that significantly differentiated autistic adults from neurotypical controls were also explored. In supplementary analyses, we also assessed free water uncorrected FA and MD using conventional single tensor modeling. RESULTS: Autistic adults exhibited significantly elevated free water in seven frontal transcallosal tracts compared to controls. In controls, age-related increases in free water and decreases in fwcFA were observed across most transcallosal tracts. However, these age-associated patterns were entirely absent in autistic adults. In gray matter, autistic adults showed elevated free water in the calcarine cortices and lower fwcMD in the dorsal premotor cortices compared to controls. Lastly, age-related increases in free water were found across all white matter and gray matter ROIs in neurotypical controls, whereas no age-related associations were detected in any dMRI metrics for autistic adults. LIMITATIONS: We only recruited cognitively capable autistic adults, which limits the generalizability of our findings across the full autism spectrum. The cross-sectional design precludes inferences about microstructural changes over time in middle and old aged autistic adults. CONCLUSIONS: Our findings revealed increased free water load in frontal white matter in autistic adults and identified distinct age-associated microstructural variations between the two groups. These findings highlight more heterogeneous brain aging profiles in autistic adults. Our study also demonstrated the importance of quantifying free water in dMRI studies of ASD. En ligne : https://dx.doi.org/10.1186/s13229-025-00652-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

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