Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome / V. SARAVANAPANDIAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 54 p. Titre : Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome Type de document : Texte imprimé et/ou numérique Auteurs : V. SARAVANAPANDIAN, Auteur ; D. NADKARNI, Auteur ; S. H. HSU, Auteur ; S. A. HUSSAIN, Auteur ; K. MASKI, Auteur ; P. GOLSHANI, Auteur ; C. S. COLWELL, Auteur ; S. BALASUBRAMANIAN, Auteur ; A. DIXON, Auteur ; Daniel H. GESCHWIND, Auteur ; S. S. JESTE, Auteur Article en page(s) : 54 p. Langues : Anglais (eng) Mots-clés : Autism  Biomarkers  Dup15q syndrome  Eeg  Gabaar  Sleep  Slow wave sleep  Spindles  UBE3A  Hoffmann-La Roche Ltd. and Yamo Pharmaceuticals. All the other authors declare that  they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for neurodevelopmental disorders (NDDs) such as intellectual disability and ASD, as well as sleep disturbances. Genes in the 15q region, particularly UBE3A and a cluster of GABA(A) receptor genes, are critical for neural development, synaptic protein synthesis and degradation, and inhibitory neurotransmission. During awake electroencephalography (EEG), children with Dup15q syndrome demonstrate increased beta band oscillations (12-30 Hz) that likely reflect aberrant GABAergic neurotransmission. Healthy sleep rhythms, necessary for robust cognitive development, are also highly dependent on GABAergic neurotransmission. We therefore hypothesized that sleep physiology would be abnormal in children with Dup15q syndrome. METHODS: To test the hypothesis that elevated beta oscillations persist in sleep in Dup15q syndrome and that NREM sleep rhythms would be disrupted, we computed: (1) beta power, (2) spindle density, and (3) percentage of slow-wave sleep (SWS) in overnight sleep EEG recordings from a cohort of children with Dup15q syndrome (n?=?15) and compared them to age-matched neurotypical children (n?=?12). RESULTS: Children with Dup15q syndrome showed abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls. LIMITATIONS: This study relied on clinical EEG where sleep staging was not available. However, considering that clinical polysomnograms are challenging to collect in this population, the ability to quantify these biomarkers on clinical EEG-routinely ordered for epilepsy monitoring-opens the door for larger-scale studies. While comparable to other human studies in rare genetic disorders, a larger sample would allow for examination of the role of seizure severity, medications, and developmental age that may impact sleep physiology. CONCLUSIONS: We have identified three quantitative EEG biomarkers of sleep disruption in Dup15q syndrome, a genetic condition highly penetrant for ASD. Insights from this study not only promote a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome, but also lay the foundation for studies that investigate the association between sleep and cognition. Abnormal sleep physiology may undermine healthy cognitive development and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions. En ligne : http://dx.doi.org/10.1186/s13229-021-00460-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome [Texte imprimé et/ou numérique] / V. SARAVANAPANDIAN, Auteur ; D. NADKARNI, Auteur ; S. H. HSU, Auteur ; S. A. HUSSAIN, Auteur ; K. MASKI, Auteur ; P. GOLSHANI, Auteur ; C. S. COLWELL, Auteur ; S. BALASUBRAMANIAN, Auteur ; A. DIXON, Auteur ; Daniel H. GESCHWIND, Auteur ; S. S. JESTE, Auteur . - 54 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 54 p. Mots-clés : Autism  Biomarkers  Dup15q syndrome  Eeg  Gabaar  Sleep  Slow wave sleep  Spindles  UBE3A  Hoffmann-La Roche Ltd. and Yamo Pharmaceuticals. All the other authors declare that  they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for neurodevelopmental disorders (NDDs) such as intellectual disability and ASD, as well as sleep disturbances. Genes in the 15q region, particularly UBE3A and a cluster of GABA(A) receptor genes, are critical for neural development, synaptic protein synthesis and degradation, and inhibitory neurotransmission. During awake electroencephalography (EEG), children with Dup15q syndrome demonstrate increased beta band oscillations (12-30 Hz) that likely reflect aberrant GABAergic neurotransmission. Healthy sleep rhythms, necessary for robust cognitive development, are also highly dependent on GABAergic neurotransmission. We therefore hypothesized that sleep physiology would be abnormal in children with Dup15q syndrome. METHODS: To test the hypothesis that elevated beta oscillations persist in sleep in Dup15q syndrome and that NREM sleep rhythms would be disrupted, we computed: (1) beta power, (2) spindle density, and (3) percentage of slow-wave sleep (SWS) in overnight sleep EEG recordings from a cohort of children with Dup15q syndrome (n?=?15) and compared them to age-matched neurotypical children (n?=?12). RESULTS: Children with Dup15q syndrome showed abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls. LIMITATIONS: This study relied on clinical EEG where sleep staging was not available. However, considering that clinical polysomnograms are challenging to collect in this population, the ability to quantify these biomarkers on clinical EEG-routinely ordered for epilepsy monitoring-opens the door for larger-scale studies. While comparable to other human studies in rare genetic disorders, a larger sample would allow for examination of the role of seizure severity, medications, and developmental age that may impact sleep physiology. CONCLUSIONS: We have identified three quantitative EEG biomarkers of sleep disruption in Dup15q syndrome, a genetic condition highly penetrant for ASD. Insights from this study not only promote a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome, but also lay the foundation for studies that investigate the association between sleep and cognition. Abnormal sleep physiology may undermine healthy cognitive development and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions. En ligne : http://dx.doi.org/10.1186/s13229-021-00460-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome / J. FROHLICH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 37 p. Titre : Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. FROHLICH, Auteur ; L. T. REITER, Auteur ; V. SARAVANAPANDIAN, Auteur ; C. DISTEFANO, Auteur ; S. HUBERTY, Auteur ; C. HYDE, Auteur ; S. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; P. GOLSHANI, Auteur ; A. IRIMIA, Auteur ; R. W. OLSEN, Auteur ; J. F. HIPP, Auteur ; S. S. JESTE, Auteur Article en page(s) : 37 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-019-0280-6.]. En ligne : http://dx.doi.org/10.1186/s13229-019-0288-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome [Texte imprimé et/ou numérique] / J. FROHLICH, Auteur ; L. T. REITER, Auteur ; V. SARAVANAPANDIAN, Auteur ; C. DISTEFANO, Auteur ; S. HUBERTY, Auteur ; C. HYDE, Auteur ; S. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; P. GOLSHANI, Auteur ; A. IRIMIA, Auteur ; R. W. OLSEN, Auteur ; J. F. HIPP, Auteur ; S. S. JESTE, Auteur . - 37 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 37 p. Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-019-0280-6.]. En ligne : http://dx.doi.org/10.1186/s13229-019-0288-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex / A. DICKINSON in Autism Research, 12-12 (December)  

Public ISBD [article]  inAutism Research > 12-12 (December) . - p.1758-1773 Titre : Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex Type de document : Texte imprimé et/ou numérique Auteurs : A. DICKINSON, Auteur ; Kandice J. VARCIN, Auteur ; M. SAHIN, Auteur ; C. A. NELSON, Auteur ; S. S. JESTE, Auteur Année de publication : 2019 Article en page(s) : p.1758-1773 Langues : Anglais (eng) Mots-clés : alpha oscillations  autism spectrum disorder  cognitive function  electroencephalography  functional connectivity  infancy  tuberous sclerosis complex Index. décimale : PER Périodiques Résumé : Tuberous sclerosis complex (TSC) is a rare genetic disorder that confers a high risk for autism spectrum disorders (ASD), with behavioral predictors of ASD emerging early in life. Deviations in structural and functional neural connectivity are highly implicated in both TSC and ASD. For the first time, we explore whether electroencephalographic (EEG) measures of neural network function precede or predict the emergence of ASD in TSC. We determine whether altered brain function (a) is present in infancy in TSC, (b) differentiates infants with TSC based on ASD diagnostic status, and (c) is associated with later cognitive function. We studied 35 infants with TSC (N = 35), and a group of typically developing infants (N = 20) at 12 and 24 months of age. Infants with TSC were later subdivided into ASD and non-ASD groups based on clinical evaluation. We measured features of spontaneous alpha oscillations (6-12 Hz) that are closely associated with neural network development: alpha power, alpha phase coherence (APC), and peak alpha frequency (PAF). Infants with TSC demonstrated reduced interhemispheric APC compared to controls at 12 months of age, and these differences were found to be most pronounced at 24 months in the infants who later developed ASD. Across all infants, PAF at 24 months was associated with verbal and nonverbal cognition at 36 months. Associations between early network function and later neurodevelopmental and cognitive outcomes highlight the potential utility of early scalable EEG markers to identify infants with TSC requiring additional targeted intervention initiated very early in life. Autism Res 2019, 12: 1758-1773. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Approximately half of infants with tuberous sclerosis complex (TSC) develop autism. Here, using EEG, we find that there is a reduction in communication between brain regions during infancy in TSC, and that the infants who show the largest reductions are those who later develop autism. Being able to identify infants who show early signs of disrupted brain development may improve the timing of early prediction and interventions in TSC, and also help us to understand how early brain changes lead to autism. En ligne : http://dx.doi.org/10.1002/aur.2193 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=413 [article] Early patterns of functional brain development associated with autism spectrum disorder in tuberous sclerosis complex [Texte imprimé et/ou numérique] / A. DICKINSON, Auteur ; Kandice J. VARCIN, Auteur ; M. SAHIN, Auteur ; C. A. NELSON, Auteur ; S. S. JESTE, Auteur . - 2019 . - p.1758-1773. Langues : Anglais (eng) in Autism Research > 12-12 (December) . - p.1758-1773 Mots-clés : alpha oscillations  autism spectrum disorder  cognitive function  electroencephalography  functional connectivity  infancy  tuberous sclerosis complex Index. décimale : PER Périodiques Résumé : Tuberous sclerosis complex (TSC) is a rare genetic disorder that confers a high risk for autism spectrum disorders (ASD), with behavioral predictors of ASD emerging early in life. Deviations in structural and functional neural connectivity are highly implicated in both TSC and ASD. For the first time, we explore whether electroencephalographic (EEG) measures of neural network function precede or predict the emergence of ASD in TSC. We determine whether altered brain function (a) is present in infancy in TSC, (b) differentiates infants with TSC based on ASD diagnostic status, and (c) is associated with later cognitive function. We studied 35 infants with TSC (N = 35), and a group of typically developing infants (N = 20) at 12 and 24 months of age. Infants with TSC were later subdivided into ASD and non-ASD groups based on clinical evaluation. We measured features of spontaneous alpha oscillations (6-12 Hz) that are closely associated with neural network development: alpha power, alpha phase coherence (APC), and peak alpha frequency (PAF). Infants with TSC demonstrated reduced interhemispheric APC compared to controls at 12 months of age, and these differences were found to be most pronounced at 24 months in the infants who later developed ASD. Across all infants, PAF at 24 months was associated with verbal and nonverbal cognition at 36 months. Associations between early network function and later neurodevelopmental and cognitive outcomes highlight the potential utility of early scalable EEG markers to identify infants with TSC requiring additional targeted intervention initiated very early in life. Autism Res 2019, 12: 1758-1773. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Approximately half of infants with tuberous sclerosis complex (TSC) develop autism. Here, using EEG, we find that there is a reduction in communication between brain regions during infancy in TSC, and that the infants who show the largest reductions are those who later develop autism. Being able to identify infants who show early signs of disrupted brain development may improve the timing of early prediction and interventions in TSC, and also help us to understand how early brain changes lead to autism. En ligne : http://dx.doi.org/10.1002/aur.2193 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=413

Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome / C. DISTEFANO in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.19 Titre : Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome Type de document : Texte imprimé et/ou numérique Auteurs : C. DISTEFANO, Auteur ; A. GULSRUD, Auteur ; S. HUBERTY, Auteur ; Connie KASARI, Auteur ; E. COOK, Auteur ; L. T. REITER, Auteur ; R. THIBERT, Auteur ; S. S. JESTE, Auteur Article en page(s) : p.19 Langues : Anglais (eng) Mots-clés : Adaptive functioning  Autism spectrum disorder  Duplication 15q syndrome  Intellectual disability  Social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: One of the most common genetic variants associated with autism spectrum disorder (ASD) are duplications of chromosome 15q11.2-q13.1 (Dup15q syndrome). To identify distinctive developmental and behavioral features in Dup15q syndrome, we examined the social communication, adaptive, and cognitive skills in clinic-referred subjects and compared the characteristics of children with Dup15q syndrome to age/IQ-matched children with non-syndromic ASD. Behavior and development were also analyzed within the Dup15q group for differences related to copy number or epilepsy. METHODS: Participants included 13 children with Dup15q syndrome and 13 children with non-syndromic ASD, matched on chronological and mental age, ages 22 months-12 years. In the Dup15q group, ten participants had isodicentric and three had interstitial duplications. Four children had active epilepsy (all isodicentric). Participants were assessed for verbal and non-verbal cognition, ASD characteristics based on the Autism Diagnostic Observation Schedule (ADOS), and adaptive function based on the Vineland Adaptive Behavior Scales (VABS). Group comparisons were performed between Dup15q and ASD participants, as well as within the Dup15q group based on duplication type and epilepsy status. RESULTS: All children with Dup15q syndrome met the criteria for ASD; ASD severity scores were significantly lower than children in the non-syndromic ASD group. ADOS profiles demonstrated a relative strength in items related to social interest. Children with Dup15q syndrome also demonstrated significantly more impairment in motor and daily living skills. Within the Dup15q group, children with epilepsy demonstrated significantly lower cognitive and adaptive function than those without epilepsy. CONCLUSIONS: The relative strength observed in social interest and responsiveness in the context of impaired motor skills represents an important avenue for intervention, including aggressive treatment of epilepsy, early and consistent focus on motor skills, and intervention targeting joint attention and language within a play context, in order to build on social interest to further develop social communication abilities. Longitudinal research beginning in early development will elucidate the temporal relationships between developmental domains and neurological comorbidities in these children at high risk for neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/s11689-016-9152-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome [Texte imprimé et/ou numérique] / C. DISTEFANO, Auteur ; A. GULSRUD, Auteur ; S. HUBERTY, Auteur ; Connie KASARI, Auteur ; E. COOK, Auteur ; L. T. REITER, Auteur ; R. THIBERT, Auteur ; S. S. JESTE, Auteur . - p.19. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.19 Mots-clés : Adaptive functioning  Autism spectrum disorder  Duplication 15q syndrome  Intellectual disability  Social communication Index. décimale : PER Périodiques Résumé : BACKGROUND: One of the most common genetic variants associated with autism spectrum disorder (ASD) are duplications of chromosome 15q11.2-q13.1 (Dup15q syndrome). To identify distinctive developmental and behavioral features in Dup15q syndrome, we examined the social communication, adaptive, and cognitive skills in clinic-referred subjects and compared the characteristics of children with Dup15q syndrome to age/IQ-matched children with non-syndromic ASD. Behavior and development were also analyzed within the Dup15q group for differences related to copy number or epilepsy. METHODS: Participants included 13 children with Dup15q syndrome and 13 children with non-syndromic ASD, matched on chronological and mental age, ages 22 months-12 years. In the Dup15q group, ten participants had isodicentric and three had interstitial duplications. Four children had active epilepsy (all isodicentric). Participants were assessed for verbal and non-verbal cognition, ASD characteristics based on the Autism Diagnostic Observation Schedule (ADOS), and adaptive function based on the Vineland Adaptive Behavior Scales (VABS). Group comparisons were performed between Dup15q and ASD participants, as well as within the Dup15q group based on duplication type and epilepsy status. RESULTS: All children with Dup15q syndrome met the criteria for ASD; ASD severity scores were significantly lower than children in the non-syndromic ASD group. ADOS profiles demonstrated a relative strength in items related to social interest. Children with Dup15q syndrome also demonstrated significantly more impairment in motor and daily living skills. Within the Dup15q group, children with epilepsy demonstrated significantly lower cognitive and adaptive function than those without epilepsy. CONCLUSIONS: The relative strength observed in social interest and responsiveness in the context of impaired motor skills represents an important avenue for intervention, including aggressive treatment of epilepsy, early and consistent focus on motor skills, and intervention targeting joint attention and language within a play context, in order to build on social interest to further develop social communication abilities. Longitudinal research beginning in early development will elucidate the temporal relationships between developmental domains and neurological comorbidities in these children at high risk for neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/s11689-016-9152-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Inaugural annual special section of the intellectual and developmental disabilities research centers: developmental cognitive neuroscience and neurodevelopmental disorders / S. S. JESTE in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 36 p. Titre : Inaugural annual special section of the intellectual and developmental disabilities research centers: developmental cognitive neuroscience and neurodevelopmental disorders Type de document : Texte imprimé et/ou numérique Auteurs : S. S. JESTE, Auteur ; C. A. NELSON, Auteur Année de publication : 2018 Article en page(s) : 36 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s11689-018-9258-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Inaugural annual special section of the intellectual and developmental disabilities research centers: developmental cognitive neuroscience and neurodevelopmental disorders [Texte imprimé et/ou numérique] / S. S. JESTE, Auteur ; C. A. NELSON, Auteur . - 2018 . - 36 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 36 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s11689-018-9258-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Mechanisms underlying the EEG biomarker in Dup15q syndrome / J. FROHLICH in Molecular Autism, 10 (2019)  

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What's missing in autism spectrum disorder motor assessments? / R. B. WILSON in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

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