Behavioral, cognitive, and adaptive development in infants with autism spectrum disorder in the first 2 years of life / Annette ESTES in Journal of Neurodevelopmental Disorders, 7-1 (December 2015)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.24 Titre : Behavioral, cognitive, and adaptive development in infants with autism spectrum disorder in the first 2 years of life Type de document : texte imprimé Auteurs : Annette ESTES, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Hongbin GU, Auteur ; Tanya ST JOHN, Auteur ; Sarah J. PATERSON, Auteur ; Jed T. ELISON, Auteur ; Heather C. HAZLETT, Auteur ; Kelly N. BOTTERON, Auteur ; Stephen R. DAGER, Auteur ; Robert T. SCHULTZ, Auteur ; Penelope KOSTOPOULOS, Auteur ; Alan EVANS, Auteur ; Geraldine DAWSON, Auteur ; Jordana ELIASON, Auteur ; Shanna ALVAREZ, Auteur ; Joseph PIVEN, Auteur Article en page(s) : p.24 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: To delineate the early progression of autism spectrum disorder (ASD) symptoms, this study investigated developmental characteristics of infants at high familial risk for ASD (HR), and infants at low risk (LR). METHODS: Participants included 210 HR and 98 LR infants across 4 sites with comparable behavioral data at age 6, 12, and 24 months assessed in the domains of cognitive development (Mullen Scales of Early Learning), adaptive skills (Vineland Adaptive Behavioral Scales), and early behavioral features of ASD (Autism Observation Scale for Infants). Participants evaluated according to the DSM-IV-TR criteria at 24 months and categorized as ASD-positive or ASD-negative were further stratified by empirically derived cutoff scores using the Autism Diagnostic Observation Schedule yielding four groups: HR-ASD-High, HR-ASD-Moderate (HR-ASD-Mod), HR-ASD-Negative (HR-Neg), and LR-ASD-Negative (LR-Neg). RESULTS: The four groups demonstrated different developmental trajectories that became increasingly distinct from 6 to 24 months across all domains. At 6 months, the HR-ASD-High group demonstrated less advanced Gross Motor and Visual Reception skills compared with the LR-Neg group. By 12 months, the HR-ASD-High group demonstrated increased behavioral features of ASD and decreased cognitive and adaptive functioning compared to the HR-Neg and LR-Neg groups. By 24 months, both the HR-ASD-High and HR-ASD-Moderate groups demonstrated differences from the LR- and HR-Neg groups in all domains. CONCLUSIONS: These findings reveal atypical sensorimotor development at 6 months of age which is associated with ASD at 24 months in the most severely affected group of infants. Sensorimotor differences precede the unfolding of cognitive and adaptive deficits and behavioral features of autism across the 6- to 24-month interval. The less severely affected group demonstrates later symptom onset, in the second year of life, with initial differences in the social-communication domain. En ligne : http://dx.doi.org/10.1186/s11689-015-9117-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347 [article] Behavioral, cognitive, and adaptive development in infants with autism spectrum disorder in the first 2 years of life [texte imprimé] / Annette ESTES, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Hongbin GU, Auteur ; Tanya ST JOHN, Auteur ; Sarah J. PATERSON, Auteur ; Jed T. ELISON, Auteur ; Heather C. HAZLETT, Auteur ; Kelly N. BOTTERON, Auteur ; Stephen R. DAGER, Auteur ; Robert T. SCHULTZ, Auteur ; Penelope KOSTOPOULOS, Auteur ; Alan EVANS, Auteur ; Geraldine DAWSON, Auteur ; Jordana ELIASON, Auteur ; Shanna ALVAREZ, Auteur ; Joseph PIVEN, Auteur . - p.24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.24 Index. décimale : PER Périodiques Résumé : BACKGROUND: To delineate the early progression of autism spectrum disorder (ASD) symptoms, this study investigated developmental characteristics of infants at high familial risk for ASD (HR), and infants at low risk (LR). METHODS: Participants included 210 HR and 98 LR infants across 4 sites with comparable behavioral data at age 6, 12, and 24 months assessed in the domains of cognitive development (Mullen Scales of Early Learning), adaptive skills (Vineland Adaptive Behavioral Scales), and early behavioral features of ASD (Autism Observation Scale for Infants). Participants evaluated according to the DSM-IV-TR criteria at 24 months and categorized as ASD-positive or ASD-negative were further stratified by empirically derived cutoff scores using the Autism Diagnostic Observation Schedule yielding four groups: HR-ASD-High, HR-ASD-Moderate (HR-ASD-Mod), HR-ASD-Negative (HR-Neg), and LR-ASD-Negative (LR-Neg). RESULTS: The four groups demonstrated different developmental trajectories that became increasingly distinct from 6 to 24 months across all domains. At 6 months, the HR-ASD-High group demonstrated less advanced Gross Motor and Visual Reception skills compared with the LR-Neg group. By 12 months, the HR-ASD-High group demonstrated increased behavioral features of ASD and decreased cognitive and adaptive functioning compared to the HR-Neg and LR-Neg groups. By 24 months, both the HR-ASD-High and HR-ASD-Moderate groups demonstrated differences from the LR- and HR-Neg groups in all domains. CONCLUSIONS: These findings reveal atypical sensorimotor development at 6 months of age which is associated with ASD at 24 months in the most severely affected group of infants. Sensorimotor differences precede the unfolding of cognitive and adaptive deficits and behavioral features of autism across the 6- to 24-month interval. The less severely affected group demonstrates later symptom onset, in the second year of life, with initial differences in the social-communication domain. En ligne : http://dx.doi.org/10.1186/s11689-015-9117-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347

Cataloguing and characterizing interests in typically developing toddlers and toddlers who develop ASD / Catherine A. BURROWS in Autism Research, 14-8 (August 2021)  

Public ISBD [article]  inAutism Research > 14-8 (August 2021) . - p.1710-1723 Titre : Cataloguing and characterizing interests in typically developing toddlers and toddlers who develop ASD Type de document : texte imprimé Auteurs : Catherine A. BURROWS, Auteur ; James W. BODFISH, Auteur ; Jason J. WOLFF, Auteur ; Elayne P. VOLLMAN, Auteur ; Melody R. ALTSCHULER, Auteur ; Kelly N. BOTTERON, Auteur ; Stephen R. DAGER, Auteur ; Annette M. ESTES, Auteur ; Heather C. HAZLETT, Auteur ; John R. PRUETT, Auteur ; Robert T. SCHULTZ, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Joseph PIVEN, Auteur ; Jed T. ELISON, Auteur Article en page(s) : p.1710-1723 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder  Child, Preschool  Family  Humans  Infant  Male  Phenotype  Risk  Siblings  attention  intense interests  problem behavior  restricted interests  toddlers Index. décimale : PER Périodiques Résumé : Intense interests are common in children with and without autism spectrum disorder (ASD), and little research has characterized aspects of interests that are unique to or shared among children with and without ASD. We aimed to characterize interests in a sample of infants at high-familial-risk (HR) and low-familial-risk (LR) for ASD using a novel interview. Participants included HR siblings who were diagnosed with ASD at 24 months (HR-ASD, n = 56), HR siblings who did not receive an ASD diagnosis at 24 months (HR-Neg, n = 187), and a LR comparison group (n = 109). We developed and collected data with the Intense Interests Inventory at 18- and 24-months of age, a semi-structured interview that measures intensity and peculiarity of interests in toddlers and preschool-aged children. Intensity of interests differed by familial risk at 24 months, with HR-ASD and HR-Neg groups demonstrating equivalent intensity of interests that were higher than the LR group. By contrast, peculiarity of interest differed by ASD diagnosis, with the HR-ASD group showing more peculiar interests than the HR-Neg and LR groups at 24 months. At 18 months the HR-ASD group had more peculiar interests than the LR group, though no differences emerged in intensity of interests. This measure may be useful in identifying clinically-relevant features of interests in young children with ASD. We also replicated previous findings of males showing more intense interests at 18 months in our non-ASD sample. These results reveal new information about the nature of interests and preoccupations in the early autism phenotype. LAY SUMMARY: Intense interests are common in young children with autism and their family members. Intense interests are also prevalent among typically-developing children, and especially boys. Here we catalog interests and features of these interests in a large sample of toddlers enriched for autism risk. Children who had family members with autism had more intense interests, and those who developed autism themselves had more unusual interests at 24 months. These results highlight the importance of different aspects of interest in autism. En ligne : http://dx.doi.org/10.1002/aur.2543 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 [article] Cataloguing and characterizing interests in typically developing toddlers and toddlers who develop ASD [texte imprimé] / Catherine A. BURROWS, Auteur ; James W. BODFISH, Auteur ; Jason J. WOLFF, Auteur ; Elayne P. VOLLMAN, Auteur ; Melody R. ALTSCHULER, Auteur ; Kelly N. BOTTERON, Auteur ; Stephen R. DAGER, Auteur ; Annette M. ESTES, Auteur ; Heather C. HAZLETT, Auteur ; John R. PRUETT, Auteur ; Robert T. SCHULTZ, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Joseph PIVEN, Auteur ; Jed T. ELISON, Auteur . - p.1710-1723. Langues : Anglais (eng) in Autism Research > 14-8 (August 2021) . - p.1710-1723 Mots-clés : Autism Spectrum Disorder  Child, Preschool  Family  Humans  Infant  Male  Phenotype  Risk  Siblings  attention  intense interests  problem behavior  restricted interests  toddlers Index. décimale : PER Périodiques Résumé : Intense interests are common in children with and without autism spectrum disorder (ASD), and little research has characterized aspects of interests that are unique to or shared among children with and without ASD. We aimed to characterize interests in a sample of infants at high-familial-risk (HR) and low-familial-risk (LR) for ASD using a novel interview. Participants included HR siblings who were diagnosed with ASD at 24 months (HR-ASD, n = 56), HR siblings who did not receive an ASD diagnosis at 24 months (HR-Neg, n = 187), and a LR comparison group (n = 109). We developed and collected data with the Intense Interests Inventory at 18- and 24-months of age, a semi-structured interview that measures intensity and peculiarity of interests in toddlers and preschool-aged children. Intensity of interests differed by familial risk at 24 months, with HR-ASD and HR-Neg groups demonstrating equivalent intensity of interests that were higher than the LR group. By contrast, peculiarity of interest differed by ASD diagnosis, with the HR-ASD group showing more peculiar interests than the HR-Neg and LR groups at 24 months. At 18 months the HR-ASD group had more peculiar interests than the LR group, though no differences emerged in intensity of interests. This measure may be useful in identifying clinically-relevant features of interests in young children with ASD. We also replicated previous findings of males showing more intense interests at 18 months in our non-ASD sample. These results reveal new information about the nature of interests and preoccupations in the early autism phenotype. LAY SUMMARY: Intense interests are common in young children with autism and their family members. Intense interests are also prevalent among typically-developing children, and especially boys. Here we catalog interests and features of these interests in a large sample of toddlers enriched for autism risk. Children who had family members with autism had more intense interests, and those who developed autism themselves had more unusual interests at 24 months. These results highlight the importance of different aspects of interest in autism. En ligne : http://dx.doi.org/10.1002/aur.2543 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449

Commonly used genomic arrays may lose information due to imperfect coverage of discovered variants for autism spectrum disorder / Michael YAO in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Commonly used genomic arrays may lose information due to imperfect coverage of discovered variants for autism spectrum disorder Type de document : texte imprimé Auteurs : Michael YAO, Auteur ; Jason DANIELS, Auteur ; Luke GROSVENOR, Auteur ; Valerie MORRILL, Auteur ; Jason I. FEINBERG, Auteur ; Kelly M. BAKULSKI, Auteur ; Joseph PIVEN, Auteur ; Heather C. HAZLETT, Auteur ; Mark D. SHEN, Auteur ; Craig NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur ; Rebecca J. SCHMIDT, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Lisa A. CROEN, Auteur ; M. Daniele FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur ; Heather VOLK, Auteur ; Kelly BENKE, Auteur Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics  Genome-Wide Association Study  Multifactorial Inheritance  Genetic Predisposition to Disease  Male  Female  Genotype  Polymorphism, Single Nucleotide  Autism spectrum disorder (ASD)  Information Loss  Polygenic scores (PGS) Index. décimale : PER Périodiques Résumé : BACKGROUND: Common genetic variation has been shown to account for a large proportion of ASD heritability. Polygenic scores generated for autism spectrum disorder (ASD-PGS) using the most recent discovery data, however, explain less variance than expected, despite reporting significant associations with ASD and other ASD-related traits. Here, we investigate the extent to which information loss on the target study genome-wide microarray weakens the predictive power of the ASD-PGS. METHODS: We studied genotype data from three cohorts of individuals with high familial liability for ASD: The Early Autism Risk Longitudinal Investigation (EARLI), Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), and the Infant Brain Imaging Study (IBIS), and one population-based sample, Study to Explore Early Development Phase I (SEED I). Individuals were genotyped on different microarrays ranging from 1 to 5 million sites. Coverage of the top 88 genome-wide suggestive variants implicated in the discovery was evaluated in all four studies before quality control (QC), after QC, and after imputation. We then created a novel method to assess coverage on the resulting ASD-PGS by correlating a PGS informed by a comprehensive list of variants to a PGS informed with only the available variants. RESULTS: Prior to imputations, None of the four cohorts directly or indirectly covered all 88 variants among the measured genotype data. After imputation, the two cohorts genotyped on 5-million arrays reached full coverage. Analysis of our novel metric showed generally high genome-wide coverage across all four studies, but a greater number of SNPs informing the ASD-PGS did not result in improved coverage according to our metric. LIMITATIONS: The studies we analyzed contained modest sample sizes. Our analyses included microarrays with more than 1-million sites, so smaller arrays such as Global Diversity and the PsychArray were not included. Our PGS metric for ASD is only generalizable to samples of European ancestries, though the coverage metric can be computed for traits that have sufficiently large-sized discovery findings in other ancestries. CONCLUSIONS: We show that commonly used genotyping microarrays have incomplete coverage for common ASD variants, and imputation cannot always recover lost information. Our novel metric provides an intuitive approach to reporting information loss in PGS and an alternative to reporting the total number of SNPs included in the PGS. While applied only to ASD here, this metric can easily be used with other traits. En ligne : https://dx.doi.org/10.1186/s11689-024-09571-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Commonly used genomic arrays may lose information due to imperfect coverage of discovered variants for autism spectrum disorder [texte imprimé] / Michael YAO, Auteur ; Jason DANIELS, Auteur ; Luke GROSVENOR, Auteur ; Valerie MORRILL, Auteur ; Jason I. FEINBERG, Auteur ; Kelly M. BAKULSKI, Auteur ; Joseph PIVEN, Auteur ; Heather C. HAZLETT, Auteur ; Mark D. SHEN, Auteur ; Craig NEWSCHAFFER, Auteur ; Kristen LYALL, Auteur ; Rebecca J. SCHMIDT, Auteur ; Irva HERTZ-PICCIOTTO, Auteur ; Lisa A. CROEN, Auteur ; M. Daniele FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur ; Heather VOLK, Auteur ; Kelly BENKE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Autism Spectrum Disorder/genetics  Genome-Wide Association Study  Multifactorial Inheritance  Genetic Predisposition to Disease  Male  Female  Genotype  Polymorphism, Single Nucleotide  Autism spectrum disorder (ASD)  Information Loss  Polygenic scores (PGS) Index. décimale : PER Périodiques Résumé : BACKGROUND: Common genetic variation has been shown to account for a large proportion of ASD heritability. Polygenic scores generated for autism spectrum disorder (ASD-PGS) using the most recent discovery data, however, explain less variance than expected, despite reporting significant associations with ASD and other ASD-related traits. Here, we investigate the extent to which information loss on the target study genome-wide microarray weakens the predictive power of the ASD-PGS. METHODS: We studied genotype data from three cohorts of individuals with high familial liability for ASD: The Early Autism Risk Longitudinal Investigation (EARLI), Markers of Autism Risk in Babies-Learning Early Signs (MARBLES), and the Infant Brain Imaging Study (IBIS), and one population-based sample, Study to Explore Early Development Phase I (SEED I). Individuals were genotyped on different microarrays ranging from 1 to 5 million sites. Coverage of the top 88 genome-wide suggestive variants implicated in the discovery was evaluated in all four studies before quality control (QC), after QC, and after imputation. We then created a novel method to assess coverage on the resulting ASD-PGS by correlating a PGS informed by a comprehensive list of variants to a PGS informed with only the available variants. RESULTS: Prior to imputations, None of the four cohorts directly or indirectly covered all 88 variants among the measured genotype data. After imputation, the two cohorts genotyped on 5-million arrays reached full coverage. Analysis of our novel metric showed generally high genome-wide coverage across all four studies, but a greater number of SNPs informing the ASD-PGS did not result in improved coverage according to our metric. LIMITATIONS: The studies we analyzed contained modest sample sizes. Our analyses included microarrays with more than 1-million sites, so smaller arrays such as Global Diversity and the PsychArray were not included. Our PGS metric for ASD is only generalizable to samples of European ancestries, though the coverage metric can be computed for traits that have sufficiently large-sized discovery findings in other ancestries. CONCLUSIONS: We show that commonly used genotyping microarrays have incomplete coverage for common ASD variants, and imputation cannot always recover lost information. Our novel metric provides an intuitive approach to reporting information loss in PGS and an alternative to reporting the total number of SNPs included in the PGS. While applied only to ASD here, this metric can easily be used with other traits. En ligne : https://dx.doi.org/10.1186/s11689-024-09571-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome / Ridthi K-R PATEL ; Tasmai VULLI ; Audrey L SMITH ; Martin A. STYNER ; Li-Ming HSU ; Sung-Ho LEE ; Yen-Yu Ian SHIH ; Heather C. HAZLETT ; Mark D. SHEN ; Alain C BURETTE ; Benjamin D. PHILPOT in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 54 Titre : Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome Type de document : texte imprimé Auteurs : Ridthi K-R PATEL, Auteur ; Tasmai VULLI, Auteur ; Audrey L SMITH, Auteur ; Martin A. STYNER, Auteur ; Li-Ming HSU, Auteur ; Sung-Ho LEE, Auteur ; Yen-Yu Ian SHIH, Auteur ; Heather C. HAZLETT, Auteur ; Mark D. SHEN, Auteur ; Alain C BURETTE, Auteur ; Benjamin D. PHILPOT, Auteur Article en page(s) : 54 Langues : Anglais (eng) Mots-clés : Animals  *Angelman Syndrome/genetics/pathology/diagnostic imaging  *White Matter/diagnostic imaging/pathology  Humans  Female  Male  Child, Preschool  *Myelin Sheath/metabolism/pathology  Infant  Child  Mice  *Ubiquitin-Protein Ligases/genetics/metabolism  Magnetic Resonance Imaging  Brain/diagnostic imaging/pathology/metabolism  Disease Models, Animal  Organ Size  Mice, Knockout  Microcephaly  Myelin basic protein  Myelination  Ube3a  White matter  and treatment of animals followed institutional and NIH guidelines, and all  animal use protocols were reviewed and approved by the UNC Institutional Animal  Care and Use Committee. Parents of AS and NT individuals provided informed  consent, and the institutional review board approved the research protocol.  Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS), a severe neurodevelopmental disorder resulting from the loss of the maternal UBE3A gene, is marked by changes in the brain's white matter (WM). The extent of WM abnormalities seems to correlate with the severity of clinical symptoms, but these deficits are still poorly characterized or understood. This study provides the first large-scale measurement of WM volume reduction in children with AS. Furthermore, we probed the possibility of underlying WM neuropathology by examining the progression of myelination in an AS mouse model. METHODS: We conducted magnetic resonance imaging (MRI) on children with AS (n = 32) and neurotypical controls (n = 99) aged 0.5-12 years. In parallel, we examined myelination in postnatal Ube3a maternal-null mice (Ube3a(m-/p+); AS model), Ube3a paternal-null mice (Ube3a(m+/p-)), and wildtype controls (Ube3a(m+/p+)) using MRI, immunohistochemistry, western blotting, and electron microscopy. RESULTS: Our data revealed that AS individuals exhibit significant reductions in brain volume by ~ 1 year of age, and by 6-12 years of age WM is reduced by 26% and gray matter by 21%-approximately twice the reductions observed in the adult AS mouse model. Our AS mouse model saw a global delay in the onset of myelination, which normalized within days (likely corresponding to months or years in human development). This myelination delay is caused by the loss of UBE3A in neurons rather than UBE3A haploinsufficiency in oligodendrocytes. Interestingly, ultrastructural analyses did not reveal abnormalities in myelinated or unmyelinated axons. LIMITATIONS: It is difficult to extrapolate the timing and duration of the myelination delay observed in AS model mice to individuals with AS. CONCLUSIONS: This study reveals WM deficits as a hallmark in children with AS, demonstrating for the first time that these deficits are already apparent at 1 year of age. Parallel studies in a mouse model of AS show these deficits occur alongside the delayed onset of myelination, which results from the loss of neuronal (but not glial) UBE3A, though the causal relationship between these phenotypes remains to be determined. These findings emphasize the potential of WM as both a therapeutic target for interventions and a valuable biomarker for tracking the progression of AS and the effectiveness of potential treatments. En ligne : https://dx.doi.org/10.1186/s13229-024-00636-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Comparative profiling of white matter development in the human and mouse brain reveals volumetric deficits and delayed myelination in Angelman syndrome [texte imprimé] / Ridthi K-R PATEL, Auteur ; Tasmai VULLI, Auteur ; Audrey L SMITH, Auteur ; Martin A. STYNER, Auteur ; Li-Ming HSU, Auteur ; Sung-Ho LEE, Auteur ; Yen-Yu Ian SHIH, Auteur ; Heather C. HAZLETT, Auteur ; Mark D. SHEN, Auteur ; Alain C BURETTE, Auteur ; Benjamin D. PHILPOT, Auteur . - 54. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 54 Mots-clés : Animals  *Angelman Syndrome/genetics/pathology/diagnostic imaging  *White Matter/diagnostic imaging/pathology  Humans  Female  Male  Child, Preschool  *Myelin Sheath/metabolism/pathology  Infant  Child  Mice  *Ubiquitin-Protein Ligases/genetics/metabolism  Magnetic Resonance Imaging  Brain/diagnostic imaging/pathology/metabolism  Disease Models, Animal  Organ Size  Mice, Knockout  Microcephaly  Myelin basic protein  Myelination  Ube3a  White matter  and treatment of animals followed institutional and NIH guidelines, and all  animal use protocols were reviewed and approved by the UNC Institutional Animal  Care and Use Committee. Parents of AS and NT individuals provided informed  consent, and the institutional review board approved the research protocol.  Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS), a severe neurodevelopmental disorder resulting from the loss of the maternal UBE3A gene, is marked by changes in the brain's white matter (WM). The extent of WM abnormalities seems to correlate with the severity of clinical symptoms, but these deficits are still poorly characterized or understood. This study provides the first large-scale measurement of WM volume reduction in children with AS. Furthermore, we probed the possibility of underlying WM neuropathology by examining the progression of myelination in an AS mouse model. METHODS: We conducted magnetic resonance imaging (MRI) on children with AS (n = 32) and neurotypical controls (n = 99) aged 0.5-12 years. In parallel, we examined myelination in postnatal Ube3a maternal-null mice (Ube3a(m-/p+); AS model), Ube3a paternal-null mice (Ube3a(m+/p-)), and wildtype controls (Ube3a(m+/p+)) using MRI, immunohistochemistry, western blotting, and electron microscopy. RESULTS: Our data revealed that AS individuals exhibit significant reductions in brain volume by ~ 1 year of age, and by 6-12 years of age WM is reduced by 26% and gray matter by 21%-approximately twice the reductions observed in the adult AS mouse model. Our AS mouse model saw a global delay in the onset of myelination, which normalized within days (likely corresponding to months or years in human development). This myelination delay is caused by the loss of UBE3A in neurons rather than UBE3A haploinsufficiency in oligodendrocytes. Interestingly, ultrastructural analyses did not reveal abnormalities in myelinated or unmyelinated axons. LIMITATIONS: It is difficult to extrapolate the timing and duration of the myelination delay observed in AS model mice to individuals with AS. CONCLUSIONS: This study reveals WM deficits as a hallmark in children with AS, demonstrating for the first time that these deficits are already apparent at 1 year of age. Parallel studies in a mouse model of AS show these deficits occur alongside the delayed onset of myelination, which results from the loss of neuronal (but not glial) UBE3A, though the causal relationship between these phenotypes remains to be determined. These findings emphasize the potential of WM as both a therapeutic target for interventions and a valuable biomarker for tracking the progression of AS and the effectiveness of potential treatments. En ligne : https://dx.doi.org/10.1186/s13229-024-00636-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach / B. TUNC in Journal of Child Psychology and Psychiatry, 62-10 (October 2021)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 62-10 (October 2021) . - p.1236-1245 Titre : Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach Type de document : texte imprimé Auteurs : B. TUNC, Auteur ; Juhi PANDEY, Auteur ; Tanya ST JOHN, Auteur ; Shoba S. MEERA, Auteur ; Jennifer E. MALDARELLI, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Heather C. HAZLETT, Auteur ; Stephen R. DAGER, Auteur ; Kelly N. BOTTERON, Auteur ; Jessica B. GIRAULT, Auteur ; Robert C. MCKINSTRY, Auteur ; Ragini VERMA, Auteur ; Jed T. ELISON, Auteur ; John R. PRUETT, Auteur ; Joseph PIVEN, Auteur ; Annette M. ESTES, Auteur ; Robert T. SCHULTZ, Auteur Article en page(s) : p.1236-1245 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis  Child, Preschool  Cohort Studies  Early Diagnosis  Humans  Phenotype  Siblings  Autism spectrum disorders  diagnosis  infancy  machine learning  stability  interest Index. décimale : PER Périodiques Résumé : BACKGROUND: Diagnostic shifts at early ages may provide invaluable insights into the nature of separation between autism spectrum disorder (ASD) and typical development. Recent conceptualizations of ASD suggest the condition is only fuzzily separated from non-ASD, with intermediate cases between the two. These intermediate cases may shift along a transition region over time, leading to apparent instability of diagnosis. METHODS: We used a cohort of children with high ASD risk, by virtue of having an older sibling with ASD, assessed at 24 months (N = 212) and 36 months (N = 191). We applied machine learning to empirically characterize the classification boundary between ASD and non-ASD, using variables quantifying developmental and adaptive skills. We computed the distance of children to the classification boundary. RESULTS: Children who switched diagnostic labels from 24 to 36 months, in both directions, (dynamic group) had intermediate phenotypic profiles. They were closer to the classification boundary compared to children who had stable diagnoses, both at 24 months (Cohen's d = .52) and at 36 months (d = .75). The magnitude of change in distance between the two time points was similar for the dynamic and stable groups (Cohen's d = .06), and diagnostic shifts were not associated with a large change. At the individual level, a few children in the dynamic group showed substantial change. CONCLUSIONS: Our results suggested that a diagnostic shift was largely due to a slight movement within a transition region between ASD and non-ASD. This fact highlights the need for more vigilant surveillance and intervention strategies. Young children with intermediate phenotypes may have an increased susceptibility to gain or lose their diagnosis at later ages, calling attention to the inherently dynamic nature of early ASD diagnoses. En ligne : http://dx.doi.org/10.1111/jcpp.13406 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456 [article] Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach [texte imprimé] / B. TUNC, Auteur ; Juhi PANDEY, Auteur ; Tanya ST JOHN, Auteur ; Shoba S. MEERA, Auteur ; Jennifer E. MALDARELLI, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Heather C. HAZLETT, Auteur ; Stephen R. DAGER, Auteur ; Kelly N. BOTTERON, Auteur ; Jessica B. GIRAULT, Auteur ; Robert C. MCKINSTRY, Auteur ; Ragini VERMA, Auteur ; Jed T. ELISON, Auteur ; John R. PRUETT, Auteur ; Joseph PIVEN, Auteur ; Annette M. ESTES, Auteur ; Robert T. SCHULTZ, Auteur . - p.1236-1245. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 62-10 (October 2021) . - p.1236-1245 Mots-clés : Autism Spectrum Disorder/diagnosis  Child, Preschool  Cohort Studies  Early Diagnosis  Humans  Phenotype  Siblings  Autism spectrum disorders  diagnosis  infancy  machine learning  stability  interest Index. décimale : PER Périodiques Résumé : BACKGROUND: Diagnostic shifts at early ages may provide invaluable insights into the nature of separation between autism spectrum disorder (ASD) and typical development. Recent conceptualizations of ASD suggest the condition is only fuzzily separated from non-ASD, with intermediate cases between the two. These intermediate cases may shift along a transition region over time, leading to apparent instability of diagnosis. METHODS: We used a cohort of children with high ASD risk, by virtue of having an older sibling with ASD, assessed at 24 months (N = 212) and 36 months (N = 191). We applied machine learning to empirically characterize the classification boundary between ASD and non-ASD, using variables quantifying developmental and adaptive skills. We computed the distance of children to the classification boundary. RESULTS: Children who switched diagnostic labels from 24 to 36 months, in both directions, (dynamic group) had intermediate phenotypic profiles. They were closer to the classification boundary compared to children who had stable diagnoses, both at 24 months (Cohen's d = .52) and at 36 months (d = .75). The magnitude of change in distance between the two time points was similar for the dynamic and stable groups (Cohen's d = .06), and diagnostic shifts were not associated with a large change. At the individual level, a few children in the dynamic group showed substantial change. CONCLUSIONS: Our results suggested that a diagnostic shift was largely due to a slight movement within a transition region between ASD and non-ASD. This fact highlights the need for more vigilant surveillance and intervention strategies. Young children with intermediate phenotypes may have an increased susceptibility to gain or lose their diagnosis at later ages, calling attention to the inherently dynamic nature of early ASD diagnoses. En ligne : http://dx.doi.org/10.1111/jcpp.13406 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=456

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