Dépouillements

Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders / Gregory COSTAIN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p. Titre : Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders Type de document : texte imprimé Auteurs : Gregory COSTAIN, Auteur ; Susan WALKER, Auteur ; Bob ARGIROPOULOS, Auteur ; Danielle A. BARIBEAU, Auteur ; Anne S. BASSETT, Auteur ; Erik BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; Barbara KELLAM, Auteur ; Christian R. MARSHALL, Auteur ; Aparna PRASAD, Auteur ; Moises A. SERRANO, Auteur ; Dimitri J. STAVROPOULOS, Auteur ; Hope TWEDE, Auteur ; Joris R. VERMEESCH, Auteur ; Jacob A.S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur Article en page(s) : 3 p. Langues : Anglais (eng) Mots-clés : Adhd  Autism  Copy number variation  Dmxl2  Grik5  Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders [texte imprimé] / Gregory COSTAIN, Auteur ; Susan WALKER, Auteur ; Bob ARGIROPOULOS, Auteur ; Danielle A. BARIBEAU, Auteur ; Anne S. BASSETT, Auteur ; Erik BOOT, Auteur ; Koenraad DEVRIENDT, Auteur ; Barbara KELLAM, Auteur ; Christian R. MARSHALL, Auteur ; Aparna PRASAD, Auteur ; Moises A. SERRANO, Auteur ; Dimitri J. STAVROPOULOS, Auteur ; Hope TWEDE, Auteur ; Joris R. VERMEESCH, Auteur ; Jacob A.S. VORSTMAN, Auteur ; Stephen SCHERER, Auteur . - 3 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 3 p. Mots-clés : Adhd  Autism  Copy number variation  Dmxl2  Grik5  Genome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Ultra-rare genetic variants, including non-recurrent copy number variations (CNVs) affecting important dosage-sensitive genes, are important contributors to the etiology of neurodevelopmental disorders (NDDs). Pairing family-based whole-genome sequencing (WGS) with detailed phenotype data can enable novel gene associations in NDDs. METHODS: We performed WGS of six members from a three-generation family, where three individuals each had a spectrum of features suggestive of a NDD. CNVs and sequence-level variants were identified and further investigated in disease and control databases. RESULTS: We identified a novel 252-kb deletion at 15q21 that overlaps the synaptic gene DMXL2 and the gene GLDN. The microdeletion segregated in NDD-affected individuals. Additional rare inherited and de novo sequence-level variants were found that may also be involved, including a missense change in GRIK5. Multiple CNVs and loss-of-function sequence variants affecting DMXL2 were discovered in additional unrelated individuals with a range of NDDs. CONCLUSIONS: Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder. The robust interpretation of private variants requires a multifaceted approach that incorporates multigenerational pedigrees and genome-wide and population-scale data. En ligne : http://dx.doi.org/10.1186/s11689-019-9263-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study / Michael P. HONG in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 1 p. Titre : Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study Type de document : texte imprimé Auteurs : Michael P. HONG, Auteur ; Eleanor M. ECKERT, Auteur ; Ernest V. PEDAPATI, Auteur ; Rebecca C. SHAFFER, Auteur ; Kelli C. DOMINICK, Auteur ; Logan K. WINK, Auteur ; John A. SWEENEY, Auteur ; Craig ERICKSON, Auteur Article en page(s) : 1 p. Langues : Anglais (eng) Mots-clés : Autism  Eye tracking  Fragile X syndrome  Gaze aversion  Social anxiety  Social interest Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms. METHODS: Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively. Participants completed a battery of cognitive testing and caregiver-reported measures for neurobehavioral characterization. RESULTS: Individuals with FXS exhibited reduced eye and increased mouth gaze to emotional faces compared to TDC. Gaze aversive findings were found to correlate with measures of anxiety, social communication deficits, and behavioral problems. In the social interest task, while individuals with idiopathic ASD showed significantly less social preference, individuals with FXS displayed social preference similar to TDC. CONCLUSIONS: These findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments. En ligne : http://dx.doi.org/10.1186/s11689-019-9262-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study [texte imprimé] / Michael P. HONG, Auteur ; Eleanor M. ECKERT, Auteur ; Ernest V. PEDAPATI, Auteur ; Rebecca C. SHAFFER, Auteur ; Kelli C. DOMINICK, Auteur ; Logan K. WINK, Auteur ; John A. SWEENEY, Auteur ; Craig ERICKSON, Auteur . - 1 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 1 p. Mots-clés : Autism  Eye tracking  Fragile X syndrome  Gaze aversion  Social anxiety  Social interest Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms. METHODS: Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively. Participants completed a battery of cognitive testing and caregiver-reported measures for neurobehavioral characterization. RESULTS: Individuals with FXS exhibited reduced eye and increased mouth gaze to emotional faces compared to TDC. Gaze aversive findings were found to correlate with measures of anxiety, social communication deficits, and behavioral problems. In the social interest task, while individuals with idiopathic ASD showed significantly less social preference, individuals with FXS displayed social preference similar to TDC. CONCLUSIONS: These findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments. En ligne : http://dx.doi.org/10.1186/s11689-019-9262-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers / Ziqi WANG in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 2 p. Titre : Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers Type de document : texte imprimé Auteurs : Ziqi WANG, Auteur ; Pravin KHEMANI, Auteur ; Lauren M. SCHMITT, Auteur ; Su LUI, Auteur ; Matthew W. MOSCONI, Auteur Article en page(s) : 2 p. Langues : Anglais (eng) Mots-clés : Cerebellum  FMR1gene premutation allele  Fragile X mental retardation 1 (FMR1) gene  Fragile X-associated tremor/ataxia syndrome (FXTAS)  Postural control Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS. METHODS: We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG repeat length was measured for each premutation carrier, and MRI and neurological evaluations were conducted to identify carriers who currently met criteria for FXTAS. Of the 18 premutation carriers, seven met criteria for definite/probable FXTAS (FXTAS+), seven showed no MRI or neurological signs of FXTAS (FXTAS-), and four were inconclusive due to insufficient data. RESULTS: Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COPML) direction during static stance and reduced COP variability in the anterior-posterior (COPAP) direction during dynamic AP sway. They also showed reductions in COPML complexity during each postural condition. FXTAS+ individuals showed reduced COPAP variability compared to FXTAS- carriers and healthy controls during dynamic AP sway. Across all carriers, increased sway variability during static stance and decreased sway variability in target directions during dynamic sways were associated with greater CGG repeat length and more severe neurologically rated posture and gait abnormalities. CONCLUSION: Our findings indicate that aging FMR1 premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS+ and FXTAS- premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset. En ligne : http://dx.doi.org/10.1186/s11689-018-9261-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers [texte imprimé] / Ziqi WANG, Auteur ; Pravin KHEMANI, Auteur ; Lauren M. SCHMITT, Auteur ; Su LUI, Auteur ; Matthew W. MOSCONI, Auteur . - 2 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 2 p. Mots-clés : Cerebellum  FMR1gene premutation allele  Fragile X mental retardation 1 (FMR1) gene  Fragile X-associated tremor/ataxia syndrome (FXTAS)  Postural control Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS. METHODS: We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG repeat length was measured for each premutation carrier, and MRI and neurological evaluations were conducted to identify carriers who currently met criteria for FXTAS. Of the 18 premutation carriers, seven met criteria for definite/probable FXTAS (FXTAS+), seven showed no MRI or neurological signs of FXTAS (FXTAS-), and four were inconclusive due to insufficient data. RESULTS: Compared to controls, premutation carriers showed increased center of pressure (COP) variability in the mediolateral (COPML) direction during static stance and reduced COP variability in the anterior-posterior (COPAP) direction during dynamic AP sway. They also showed reductions in COPML complexity during each postural condition. FXTAS+ individuals showed reduced COPAP variability compared to FXTAS- carriers and healthy controls during dynamic AP sway. Across all carriers, increased sway variability during static stance and decreased sway variability in target directions during dynamic sways were associated with greater CGG repeat length and more severe neurologically rated posture and gait abnormalities. CONCLUSION: Our findings indicate that aging FMR1 premutation carriers show static and dynamic postural control deficits relative to healthy controls implicating degenerative processes of spinocerebellar and cerebellar-brainstem circuits that may be independent of or precede the onset of FXTAS. Our finding that FXTAS+ and FXTAS- premutation carriers differed on their level of intentional AP sway suggests that neural mechanisms of dynamic postural control may be differentially impacted in patients with FXTAS, and its measurement may be useful for rapidly and precisely identifying disease presence and onset. En ligne : http://dx.doi.org/10.1186/s11689-018-9261-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

Adaptation to different communicative contexts: an eye tracking study of autistic adults / Julia PARISH-MORRIS in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 5 p. Titre : Adaptation to different communicative contexts: an eye tracking study of autistic adults Type de document : texte imprimé Auteurs : Julia PARISH-MORRIS, Auteur ; Ashley A. PALLATHRA, Auteur ; Emily FERGUSON, Auteur ; Brenna B. MADDOX, Auteur ; Alison POMYKACZ, Auteur ; Leat PEREZ, Auteur ; Leila BATEMAN, Auteur ; Juhi PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Edward S. BRODKIN, Auteur Article en page(s) : 5 p. Langues : Anglais (eng) Mots-clés : Adults  Autism spectrum disorder  Eye gaze  Face processing/perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Learning through social observation (i.e., watching other people interact) lays the foundation for later social skills and social cognition. However, social situations are often complex, and humans are only capable of attending to one aspect of a scene at a time. How do people choose where to allocate their visual resources when viewing complex social scenarios? For typically developing (TD) individuals, faces are often given priority. Depending upon context, however, it may be more useful to attend to other aspects of the environment, such as hands, tools, or background objects. Previous studies reported reduced face looking in individuals with autism spectrum disorder (ASD), but modulation of visual attention in response to contextual differences (e.g., according to social richness, or the presence/absence of communicative behaviors between two people) has only briefly been explored. In this study, we used eye-tracking technology to test the extent to which ASD adults and TD adults use social context to guide their gaze behavior. METHODS: Fifty-five adults participated (28 with ASD). The location and duration of participants' gaze were recorded while they watched a series of naturalistic social videos. Half of the videos depicted two people engaging in non-verbal communication (rich social scenes) while playing with toys. The other half depicted two people playing with toys separately, not interacting with each other (lean social scenes). RESULTS: ASD and TD adults both increased their attention to faces in communicative contexts (rich social scenes) as compared to non-communicative contexts (lean social scenes). However, TD adults increased their attention to faces significantly more when watching two people communicate than did ASD adults, who increased their attention to a lesser degree. Further analysis revealed that ASD adults persisted in looking at hands and toys, even when observing two people communicate in a rich social scene. CONCLUSIONS: Diminished gaze to faces when observing two people communicating may lead to fewer opportunities for social learning and subsequent reductions in social knowledge. Naturalistic measures of contextual modulation could help identify areas of need for individuals learning about the social world and could become treatment targets to improve everyday social learning. En ligne : https://dx.doi.org/10.1186/s11689-019-9265-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Adaptation to different communicative contexts: an eye tracking study of autistic adults [texte imprimé] / Julia PARISH-MORRIS, Auteur ; Ashley A. PALLATHRA, Auteur ; Emily FERGUSON, Auteur ; Brenna B. MADDOX, Auteur ; Alison POMYKACZ, Auteur ; Leat PEREZ, Auteur ; Leila BATEMAN, Auteur ; Juhi PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Edward S. BRODKIN, Auteur . - 5 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 5 p. Mots-clés : Adults  Autism spectrum disorder  Eye gaze  Face processing/perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Learning through social observation (i.e., watching other people interact) lays the foundation for later social skills and social cognition. However, social situations are often complex, and humans are only capable of attending to one aspect of a scene at a time. How do people choose where to allocate their visual resources when viewing complex social scenarios? For typically developing (TD) individuals, faces are often given priority. Depending upon context, however, it may be more useful to attend to other aspects of the environment, such as hands, tools, or background objects. Previous studies reported reduced face looking in individuals with autism spectrum disorder (ASD), but modulation of visual attention in response to contextual differences (e.g., according to social richness, or the presence/absence of communicative behaviors between two people) has only briefly been explored. In this study, we used eye-tracking technology to test the extent to which ASD adults and TD adults use social context to guide their gaze behavior. METHODS: Fifty-five adults participated (28 with ASD). The location and duration of participants' gaze were recorded while they watched a series of naturalistic social videos. Half of the videos depicted two people engaging in non-verbal communication (rich social scenes) while playing with toys. The other half depicted two people playing with toys separately, not interacting with each other (lean social scenes). RESULTS: ASD and TD adults both increased their attention to faces in communicative contexts (rich social scenes) as compared to non-communicative contexts (lean social scenes). However, TD adults increased their attention to faces significantly more when watching two people communicate than did ASD adults, who increased their attention to a lesser degree. Further analysis revealed that ASD adults persisted in looking at hands and toys, even when observing two people communicate in a rich social scene. CONCLUSIONS: Diminished gaze to faces when observing two people communicating may lead to fewer opportunities for social learning and subsequent reductions in social knowledge. Naturalistic measures of contextual modulation could help identify areas of need for individuals learning about the social world and could become treatment targets to improve everyday social learning. En ligne : https://dx.doi.org/10.1186/s11689-019-9265-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed / David HESSL in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 4 p. Titre : Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed Type de document : texte imprimé Auteurs : David HESSL, Auteur ; Julie B. SCHWEITZER, Auteur ; Danh V. NGUYEN, Auteur ; Yingratana MCLENNAN, Auteur ; Cindy JOHNSTON, Auteur ; Ryan SHICKMAN, Auteur ; Yanjun CHEN, Auteur Année de publication : 2019 Article en page(s) : 4 p. Langues : Anglais (eng) Mots-clés : FMR1 gene  Fragile X mental retardation protein  Intellectual disability  Treatment  Working memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with fragile X syndrome (FXS) typically demonstrate profound executive function (EF) deficits that interfere with learning, socialization, and emotion regulation. We completed the first large, non-pharmacological controlled trial for FXS, designed to evaluate the efficacy of Cogmed, a computer/tablet-based working memory (WM) training program. METHODS: The study was a randomized, blinded, parallel two-arm controlled trial in 100 children and adolescents with FXS (63 male, 37 female; 15.28 +/- 3.36 yrs.). Participants were randomized equally to adaptive (difficulty level adjusted to performance) or non-adaptive (control) Cogmed training. Participants were assessed at home using objective measures of WM (primary outcome) and EF at baseline, following 20-25 caregiver-supported sessions over 5-6 weeks, and at follow-up 3 months after cessation of training. Parents and teachers provided ratings of WM, attention, and EF. RESULTS: The WM composite and selective domains of EF (distractibility, cognitive flexibility), as well as parent- and teacher-reported attention and EF, significantly improved across the full study sample, with many changes maintained at follow-up. However, comparisons of improvement between adaptive and non-adaptive control conditions did not differ, showing that progressively challenging the WM system by expanding span length did not provide added benefit overall. CONCLUSIONS: Further experimental comparisons are needed before Cogmed working memory training can be considered empirically validated for children with FXS, forming the basis of treatment recommendation. However, given that prior studies show no significant changes on these measures in FXS without treatment, that improvements were maintained for 3 months, and that blinded teachers reported improvements in the classroom, the modest benefits seen in both adaptive and non-adaptive groups overall are unlikely to be attributable to placebo or practice effects alone. Future analyses examining inter-individual differences (e.g., baseline capacity, training efficiency, co-morbidity, training environment, characteristics of training aide) may help to link this intervention to outcomes and potential transfer effects. TRIAL REGISTRATION: US National Institutes of Health (ClinicalTrials.gov), NCT02747394 . En ligne : https://dx.doi.org/10.1186/s11689-019-9264-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed [texte imprimé] / David HESSL, Auteur ; Julie B. SCHWEITZER, Auteur ; Danh V. NGUYEN, Auteur ; Yingratana MCLENNAN, Auteur ; Cindy JOHNSTON, Auteur ; Ryan SHICKMAN, Auteur ; Yanjun CHEN, Auteur . - 2019 . - 4 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 4 p. Mots-clés : FMR1 gene  Fragile X mental retardation protein  Intellectual disability  Treatment  Working memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with fragile X syndrome (FXS) typically demonstrate profound executive function (EF) deficits that interfere with learning, socialization, and emotion regulation. We completed the first large, non-pharmacological controlled trial for FXS, designed to evaluate the efficacy of Cogmed, a computer/tablet-based working memory (WM) training program. METHODS: The study was a randomized, blinded, parallel two-arm controlled trial in 100 children and adolescents with FXS (63 male, 37 female; 15.28 +/- 3.36 yrs.). Participants were randomized equally to adaptive (difficulty level adjusted to performance) or non-adaptive (control) Cogmed training. Participants were assessed at home using objective measures of WM (primary outcome) and EF at baseline, following 20-25 caregiver-supported sessions over 5-6 weeks, and at follow-up 3 months after cessation of training. Parents and teachers provided ratings of WM, attention, and EF. RESULTS: The WM composite and selective domains of EF (distractibility, cognitive flexibility), as well as parent- and teacher-reported attention and EF, significantly improved across the full study sample, with many changes maintained at follow-up. However, comparisons of improvement between adaptive and non-adaptive control conditions did not differ, showing that progressively challenging the WM system by expanding span length did not provide added benefit overall. CONCLUSIONS: Further experimental comparisons are needed before Cogmed working memory training can be considered empirically validated for children with FXS, forming the basis of treatment recommendation. However, given that prior studies show no significant changes on these measures in FXS without treatment, that improvements were maintained for 3 months, and that blinded teachers reported improvements in the classroom, the modest benefits seen in both adaptive and non-adaptive groups overall are unlikely to be attributable to placebo or practice effects alone. Future analyses examining inter-individual differences (e.g., baseline capacity, training efficiency, co-morbidity, training environment, characteristics of training aide) may help to link this intervention to outcomes and potential transfer effects. TRIAL REGISTRATION: US National Institutes of Health (ClinicalTrials.gov), NCT02747394 . En ligne : https://dx.doi.org/10.1186/s11689-019-9264-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis / Laura GROVES in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 6 p. Titre : Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis Type de document : texte imprimé Auteurs : Laura GROVES, Auteur ; Jo MOSS, Auteur ; Hayley CRAWFORD, Auteur ; Lisa NELSON, Auteur ; Chris STINTON, Auteur ; Gursharan SINGLA, Auteur ; Chris OLIVER, Auteur Article en page(s) : 6 p. Langues : Anglais (eng) Mots-clés : Affect  Cornelia de Lange syndrome  Fragile X syndrome  Mood  Trajectory Index. décimale : PER Périodiques Résumé : BACKGROUND: Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast. METHODS: A 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS (n = 44) and FXS (n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time 3 (7 years later). RESULTS: The CdLS group were lower in mood than the FXS group overall (p < .001). Interest and pleasure scores showed a significant decline over the lifespan for individuals with CdLS (p < .001) but not the FXS group. Lower level of ability at Time 1 was associated with lower mood at Time 1 and Time 3 in the FXS group only. Higher levels of ASD symptomology at Time 1 were associated with low mood and interest and pleasure in both syndrome groups at Time 1 and Time 3. Greater insistence on sameness at Time 1 was associated with lower mood at Time 1 in the FXS group and lower interest and pleasure at Time 1 and Time 3 in the CdLS group. CONCLUSIONS: Low affect in specific genetic syndromes may be associated with differing lifespan trajectories and behavioural profiles. Specifically, individuals with CdLS appear at risk for experiencing declines in levels of interest and pleasure whereas individuals with FXS show no significant change in the level of affect with age. En ligne : https://dx.doi.org/10.1186/s11689-019-9269-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis [texte imprimé] / Laura GROVES, Auteur ; Jo MOSS, Auteur ; Hayley CRAWFORD, Auteur ; Lisa NELSON, Auteur ; Chris STINTON, Auteur ; Gursharan SINGLA, Auteur ; Chris OLIVER, Auteur . - 6 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 6 p. Mots-clés : Affect  Cornelia de Lange syndrome  Fragile X syndrome  Mood  Trajectory Index. décimale : PER Périodiques Résumé : BACKGROUND: Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast. METHODS: A 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS (n = 44) and FXS (n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time 3 (7 years later). RESULTS: The CdLS group were lower in mood than the FXS group overall (p < .001). Interest and pleasure scores showed a significant decline over the lifespan for individuals with CdLS (p < .001) but not the FXS group. Lower level of ability at Time 1 was associated with lower mood at Time 1 and Time 3 in the FXS group only. Higher levels of ASD symptomology at Time 1 were associated with low mood and interest and pleasure in both syndrome groups at Time 1 and Time 3. Greater insistence on sameness at Time 1 was associated with lower mood at Time 1 in the FXS group and lower interest and pleasure at Time 1 and Time 3 in the CdLS group. CONCLUSIONS: Low affect in specific genetic syndromes may be associated with differing lifespan trajectories and behavioural profiles. Specifically, individuals with CdLS appear at risk for experiencing declines in levels of interest and pleasure whereas individuals with FXS show no significant change in the level of affect with age. En ligne : https://dx.doi.org/10.1186/s11689-019-9269-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? / Zahra MOTAHARI in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 7 p. Titre : In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? Type de document : texte imprimé Auteurs : Zahra MOTAHARI, Auteur ; Sally Ann MOODY, Auteur ; Thomas Michael MAYNARD, Auteur ; Anthony Samuel LAMANTIA, Auteur Article en page(s) : 7 p. Langues : Anglais (eng) Mots-clés : 22q11DS  Cardiovascular  Cognition  Copy number variants  Craniofacial  Neural development  Polygenic Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). RESULTS: The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive "line-up" of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene-a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus-versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. CONCLUSIONS: Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. En ligne : https://dx.doi.org/10.1186/s11689-019-9267-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? [texte imprimé] / Zahra MOTAHARI, Auteur ; Sally Ann MOODY, Auteur ; Thomas Michael MAYNARD, Auteur ; Anthony Samuel LAMANTIA, Auteur . - 7 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 7 p. Mots-clés : 22q11DS  Cardiovascular  Cognition  Copy number variants  Craniofacial  Neural development  Polygenic Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). RESULTS: The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive "line-up" of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene-a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus-versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. CONCLUSIONS: Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. En ligne : https://dx.doi.org/10.1186/s11689-019-9267-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Using kinematic analyses to explore sensorimotor control impairments in children with 22q11.2 deletion syndrome / Adam C. CUNNINGHAM in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 8 p. Titre : Using kinematic analyses to explore sensorimotor control impairments in children with 22q11.2 deletion syndrome Type de document : texte imprimé Auteurs : Adam C. CUNNINGHAM, Auteur ; Liam HILL, Auteur ; Mark MON-WILLIAMS, Auteur ; Kathryn J. PEALL, Auteur ; David E.J. LINDEN, Auteur ; Jeremy HALL, Auteur ; Michael J. OWEN, Auteur ; Marianne B.M. VAN DEN BREE, Auteur Article en page(s) : 8 p. Langues : Anglais (eng) Mots-clés : 22q11.2 deletion syndrome  Adhd  Asd  Anxiety  Coordination  Movement difficulties Index. décimale : PER Périodiques Résumé : BACKGROUND: The 22q11.2 deletion is associated with psychiatric and behavioural disorders, intellectual disability and multiple physical abnormalities. Recent research also indicates impaired coordination skills may be part of the clinical phenotype. This study aimed to characterise sensorimotor control abilities in children with 22q11.2 deletion syndrome (22q11.2DS) and investigate their relationships with co-occurring IQ impairments and psychopathology. METHODS: Fifty-four children with 22q11.2DS and 24 unaffected sibling controls, comparable in age and gender, underwent kinematic analysis of their hand movements, whilst performing a battery of three visuo-manual coordination tasks that measured their tracking, aiming and steering abilities. Additionally, standardised assessments of full-scale IQ (FSIQ), attention deficit hyperactivity disorder, indicative autism spectrum disorder (ASD) and anxiety disorder symptomatology were conducted. RESULTS: Children with 22q11.2DS showed deficits on seven of eight kinematic descriptors of movement quality across the three coordination tasks, compared to controls. Within 22q11.2DS cases, the extent of impairment on only three kinematic descriptors was significantly related to FSIQ after correction for multiple testing. Moreover, only error whilst visuo-manually tracking was nominally associated with ADHD symptom counts. CONCLUSIONS: Impairments in sensorimotor control are seen on a range of visuo-manual tasks in children with 22q11.2DS but the extent of these impairments are largely unrelated to the severity of other psychopathological and intellectual impairments commonly found in children with 22q11.2DS. En ligne : https://dx.doi.org/10.1186/s11689-019-9271-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Using kinematic analyses to explore sensorimotor control impairments in children with 22q11.2 deletion syndrome [texte imprimé] / Adam C. CUNNINGHAM, Auteur ; Liam HILL, Auteur ; Mark MON-WILLIAMS, Auteur ; Kathryn J. PEALL, Auteur ; David E.J. LINDEN, Auteur ; Jeremy HALL, Auteur ; Michael J. OWEN, Auteur ; Marianne B.M. VAN DEN BREE, Auteur . - 8 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 8 p. Mots-clés : 22q11.2 deletion syndrome  Adhd  Asd  Anxiety  Coordination  Movement difficulties Index. décimale : PER Périodiques Résumé : BACKGROUND: The 22q11.2 deletion is associated with psychiatric and behavioural disorders, intellectual disability and multiple physical abnormalities. Recent research also indicates impaired coordination skills may be part of the clinical phenotype. This study aimed to characterise sensorimotor control abilities in children with 22q11.2 deletion syndrome (22q11.2DS) and investigate their relationships with co-occurring IQ impairments and psychopathology. METHODS: Fifty-four children with 22q11.2DS and 24 unaffected sibling controls, comparable in age and gender, underwent kinematic analysis of their hand movements, whilst performing a battery of three visuo-manual coordination tasks that measured their tracking, aiming and steering abilities. Additionally, standardised assessments of full-scale IQ (FSIQ), attention deficit hyperactivity disorder, indicative autism spectrum disorder (ASD) and anxiety disorder symptomatology were conducted. RESULTS: Children with 22q11.2DS showed deficits on seven of eight kinematic descriptors of movement quality across the three coordination tasks, compared to controls. Within 22q11.2DS cases, the extent of impairment on only three kinematic descriptors was significantly related to FSIQ after correction for multiple testing. Moreover, only error whilst visuo-manually tracking was nominally associated with ADHD symptom counts. CONCLUSIONS: Impairments in sensorimotor control are seen on a range of visuo-manual tasks in children with 22q11.2DS but the extent of these impairments are largely unrelated to the severity of other psychopathological and intellectual impairments commonly found in children with 22q11.2DS. En ligne : https://dx.doi.org/10.1186/s11689-019-9271-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study / Shigeki AOKI in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 9 p. Titre : Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study Type de document : texte imprimé Auteurs : Shigeki AOKI, Auteur ; Kuriko KAGITANI-SHIMONO, Auteur ; Junko MATSUZAKI, Auteur ; Ryuzo HANAIE, Auteur ; Mariko NAKANISHI, Auteur ; Koji TOMINAGA, Auteur ; Yukie NAGAI, Auteur ; Ikuko MOHRI, Auteur ; Masako TANIIKE, Auteur Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders (ASD)  Bright visual stimuli  Magnetoencephalography (MEG)  Neural suppression  Supramarginal gyrus (SMG)  Visual abnormality Index. décimale : PER Périodiques Résumé : BACKGROUND: Visual abnormality is a common sensory impairment in autism spectrum disorder (ASD), which may cause behavioral problems. However, only a few studies exist on the neural features corresponding to the visual symptoms in ASD. The purpose of this study was to investigate the relationship between cortical responses to visual stimuli and visual abnormality to examine the neurophysiological mechanisms of the visual abnormality in ASD. METHODS: Twenty-two high-functioning children with ASD (10.95 +/- 2.01 years old) and 23 age-matched typically developing (TD) children (10.13 +/- 2.80 years old) participated in this study. We measured the cortical responses (i.e., activated intensity and attenuation ratio) elicited by the Original visual image and other two types of bright images (the Dot noise or Blind image, which includes overlapped particles onto the Original image or the enhanced-brightness version of the Original image, respectively) using magnetoencephalography. RESULTS: The severity of visual abnormalities was significantly associated with behavioral problems in children with ASD. In addition, we found the increased cortical activation in response to the Original image in the left supramarginal gyrus (SMG) and middle temporal gyrus in children with ASD. However, there were no inter-group differences in the primary visual and medial orbitofrontal cortices. Furthermore, when we compared cortical responses according to the type of images, children with ASD showed lesser attenuation of the activated intensities than children with TD in response to the bright images compared with the Original image in the right SMG. These attenuation ratios (Dot noise/Original and Blind/Original) were also associated with the severity of visual abnormalities. CONCLUSIONS: Our results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention. En ligne : https://dx.doi.org/10.1186/s11689-019-9266-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Lesser suppression of response to bright visual stimuli and visual abnormality in children with autism spectrum disorder: a magnetoencephalographic study [texte imprimé] / Shigeki AOKI, Auteur ; Kuriko KAGITANI-SHIMONO, Auteur ; Junko MATSUZAKI, Auteur ; Ryuzo HANAIE, Auteur ; Mariko NAKANISHI, Auteur ; Koji TOMINAGA, Auteur ; Yukie NAGAI, Auteur ; Ikuko MOHRI, Auteur ; Masako TANIIKE, Auteur . - 9 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 9 p. Mots-clés : Autism spectrum disorders (ASD)  Bright visual stimuli  Magnetoencephalography (MEG)  Neural suppression  Supramarginal gyrus (SMG)  Visual abnormality Index. décimale : PER Périodiques Résumé : BACKGROUND: Visual abnormality is a common sensory impairment in autism spectrum disorder (ASD), which may cause behavioral problems. However, only a few studies exist on the neural features corresponding to the visual symptoms in ASD. The purpose of this study was to investigate the relationship between cortical responses to visual stimuli and visual abnormality to examine the neurophysiological mechanisms of the visual abnormality in ASD. METHODS: Twenty-two high-functioning children with ASD (10.95 +/- 2.01 years old) and 23 age-matched typically developing (TD) children (10.13 +/- 2.80 years old) participated in this study. We measured the cortical responses (i.e., activated intensity and attenuation ratio) elicited by the Original visual image and other two types of bright images (the Dot noise or Blind image, which includes overlapped particles onto the Original image or the enhanced-brightness version of the Original image, respectively) using magnetoencephalography. RESULTS: The severity of visual abnormalities was significantly associated with behavioral problems in children with ASD. In addition, we found the increased cortical activation in response to the Original image in the left supramarginal gyrus (SMG) and middle temporal gyrus in children with ASD. However, there were no inter-group differences in the primary visual and medial orbitofrontal cortices. Furthermore, when we compared cortical responses according to the type of images, children with ASD showed lesser attenuation of the activated intensities than children with TD in response to the bright images compared with the Original image in the right SMG. These attenuation ratios (Dot noise/Original and Blind/Original) were also associated with the severity of visual abnormalities. CONCLUSIONS: Our results show that dysfunction of stimulus-driven neural suppression plays a crucial role in the neural mechanism of visual abnormality in children with ASD. To the best of our knowledge, this is the first magnetoencephalography study to demonstrate the association between the severity of visual abnormality and lower attenuation ratios in children with ASD. Our results contribute to the knowledge of the mechanisms underlying visual abnormality in children with ASD, and may therefore lead to more effective diagnosis and earlier intervention. En ligne : https://dx.doi.org/10.1186/s11689-019-9266-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk / Santosh KUMAR in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 10 p. Titre : Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk Type de document : texte imprimé Auteurs : Santosh KUMAR, Auteur ; Kurt REYNOLDS, Auteur ; Yuelong JI, Auteur ; Ran GU, Auteur ; Sunil RAI, Auteur ; Chengji J. ZHOU, Auteur Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  BMP/TGF-beta  Fgf  Neurodevelopmental disorders  Retinoic acid (RA)  Shh  Signaling crosstalk  Wnt Index. décimale : PER Périodiques Résumé : BACKGROUND: The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment. MAIN BODY: Recent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-beta signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-beta, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD. CONCLUSION: The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods. En ligne : https://dx.doi.org/10.1186/s11689-019-9268-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk [texte imprimé] / Santosh KUMAR, Auteur ; Kurt REYNOLDS, Auteur ; Yuelong JI, Auteur ; Ran GU, Auteur ; Sunil RAI, Auteur ; Chengji J. ZHOU, Auteur . - 10 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 10 p. Mots-clés : Autism spectrum disorder  BMP/TGF-beta  Fgf  Neurodevelopmental disorders  Retinoic acid (RA)  Shh  Signaling crosstalk  Wnt Index. décimale : PER Périodiques Résumé : BACKGROUND: The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment. MAIN BODY: Recent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-beta signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-beta, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD. CONCLUSION: The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods. En ligne : https://dx.doi.org/10.1186/s11689-019-9268-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders / Joanne TRINH in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 11 p. Titre : Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders Type de document : texte imprimé Auteurs : Joanne TRINH, Auteur ; Krishna Kumar KANDASWAMY, Auteur ; Martin WERBER, Auteur ; Maximilian E.R. WEISS, Auteur ; Gabriela OPREA, Auteur ; Shivendra KISHORE, Auteur ; Katja LOHMANN, Auteur ; Arndt ROLFS, Auteur Article en page(s) : 11 p. Langues : Anglais (eng) Mots-clés : De novo variants  Neurodevelopmental disorders  Trio exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Rare denovo variants represent a significant cause of neurodevelopmental delay and intellectual disability (ID). METHODS: Exome sequencing was performed on 4351 patients with global developmental delay, seizures, microcephaly, macrocephaly, motor delay, delayed speech and language development, or ID according to Human Phenotype Ontology (HPO) terms. All patients had previously undergone whole exome sequencing as part of diagnostic genetic testing with a focus on variants in genes implicated in neurodevelopmental disorders up to January 2017. This resulted in a genetic diagnosis in 1336 of the patients. In this study, we specifically searched for variants in 14 recently implicated novel neurodevelopmental disorder (NDD) genes. RESULTS: We identified 65 rare, protein-changing variants in 11 of these 14 novel candidate genes. Fourteen variants in CDK13, CHD4, KCNQ3, KMT5B, TCF20, and ZBTB18 were scored pathogenic or likely pathogenic. Of note, two of these patients had a previously identified cause of their disease, and thus, multiple molecular diagnoses were made including pathogenic/likely pathogenic variants in FOXG1 and CDK13 or in TMEM237 and KMT5B. CONCLUSIONS: Looking for pathogenic variants in newly identified NDD genes enabled us to provide a molecular diagnosis to 14 patients and their close relatives and caregivers. This underlines the relevance of re-evaluation of existing exome data on a regular basis to improve the diagnostic yield and serve the needs of our patients. En ligne : https://dx.doi.org/10.1186/s11689-019-9270-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders [texte imprimé] / Joanne TRINH, Auteur ; Krishna Kumar KANDASWAMY, Auteur ; Martin WERBER, Auteur ; Maximilian E.R. WEISS, Auteur ; Gabriela OPREA, Auteur ; Shivendra KISHORE, Auteur ; Katja LOHMANN, Auteur ; Arndt ROLFS, Auteur . - 11 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 11 p. Mots-clés : De novo variants  Neurodevelopmental disorders  Trio exome sequencing Index. décimale : PER Périodiques Résumé : BACKGROUND: Rare denovo variants represent a significant cause of neurodevelopmental delay and intellectual disability (ID). METHODS: Exome sequencing was performed on 4351 patients with global developmental delay, seizures, microcephaly, macrocephaly, motor delay, delayed speech and language development, or ID according to Human Phenotype Ontology (HPO) terms. All patients had previously undergone whole exome sequencing as part of diagnostic genetic testing with a focus on variants in genes implicated in neurodevelopmental disorders up to January 2017. This resulted in a genetic diagnosis in 1336 of the patients. In this study, we specifically searched for variants in 14 recently implicated novel neurodevelopmental disorder (NDD) genes. RESULTS: We identified 65 rare, protein-changing variants in 11 of these 14 novel candidate genes. Fourteen variants in CDK13, CHD4, KCNQ3, KMT5B, TCF20, and ZBTB18 were scored pathogenic or likely pathogenic. Of note, two of these patients had a previously identified cause of their disease, and thus, multiple molecular diagnoses were made including pathogenic/likely pathogenic variants in FOXG1 and CDK13 or in TMEM237 and KMT5B. CONCLUSIONS: Looking for pathogenic variants in newly identified NDD genes enabled us to provide a molecular diagnosis to 14 patients and their close relatives and caregivers. This underlines the relevance of re-evaluation of existing exome data on a regular basis to improve the diagnostic yield and serve the needs of our patients. En ligne : https://dx.doi.org/10.1186/s11689-019-9270-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Children with facial paralysis due to Moebius syndrome exhibit reduced autonomic modulation during emotion processing / Elisa DE STEFANI in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 12 p. Titre : Children with facial paralysis due to Moebius syndrome exhibit reduced autonomic modulation during emotion processing Type de document : texte imprimé Auteurs : Elisa DE STEFANI, Auteur ; Martina ARDIZZI, Auteur ; Ylenia NICOLINI, Auteur ; Mauro BELLUARDO, Auteur ; Anna BARBOT, Auteur ; Chiara BERTOLINI, Auteur ; Gioacchino GAROFALO, Auteur ; Bernardo BIANCHI, Auteur ; G. COUDE, Auteur ; Lynne MURRAY, Auteur ; Pier Francesco FERRARI, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autonomic nervous system  Emotion recognition  Facial expressions  Moebius children  Respiratory sinus arrhythmia  Thermal infrared imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Facial mimicry is crucial in the recognition of others' emotional state. Thus, the observation of others' facial expressions activates the same neural representation of that affective state in the observer, along with related autonomic and somatic responses. What happens, therefore, when someone cannot mimic others' facial expressions? METHODS: We investigated whether psychophysiological emotional responses to others' facial expressions were impaired in 13 children (9 years) with Moebius syndrome (MBS), an extremely rare neurological disorder (1/250,000 live births) characterized by congenital facial paralysis. We inspected autonomic responses and vagal regulation through facial cutaneous thermal variations and by the computation of respiratory sinus arrhythmia (RSA). These parameters provide measures of emotional arousal and show the autonomic adaptation to others' social cues. Physiological responses in children with MBS were recorded during dynamic facial expression observation and were compared to those of a control group (16 non-affected children, 9 years). RESULTS: There were significant group effects on thermal patterns and RSA, with lower values in children with MBS. We also observed a mild deficit in emotion recognition in these patients. CONCLUSION: Results support "embodied" theory, whereby the congenital inability to produce facial expressions induces alterations in the processing of facial expression of emotions. Such alterations may constitute a risk for emotion dysregulation. En ligne : https://dx.doi.org/10.1186/s11689-019-9272-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Children with facial paralysis due to Moebius syndrome exhibit reduced autonomic modulation during emotion processing [texte imprimé] / Elisa DE STEFANI, Auteur ; Martina ARDIZZI, Auteur ; Ylenia NICOLINI, Auteur ; Mauro BELLUARDO, Auteur ; Anna BARBOT, Auteur ; Chiara BERTOLINI, Auteur ; Gioacchino GAROFALO, Auteur ; Bernardo BIANCHI, Auteur ; G. COUDE, Auteur ; Lynne MURRAY, Auteur ; Pier Francesco FERRARI, Auteur . - 12 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 12 p. Mots-clés : Autonomic nervous system  Emotion recognition  Facial expressions  Moebius children  Respiratory sinus arrhythmia  Thermal infrared imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Facial mimicry is crucial in the recognition of others' emotional state. Thus, the observation of others' facial expressions activates the same neural representation of that affective state in the observer, along with related autonomic and somatic responses. What happens, therefore, when someone cannot mimic others' facial expressions? METHODS: We investigated whether psychophysiological emotional responses to others' facial expressions were impaired in 13 children (9 years) with Moebius syndrome (MBS), an extremely rare neurological disorder (1/250,000 live births) characterized by congenital facial paralysis. We inspected autonomic responses and vagal regulation through facial cutaneous thermal variations and by the computation of respiratory sinus arrhythmia (RSA). These parameters provide measures of emotional arousal and show the autonomic adaptation to others' social cues. Physiological responses in children with MBS were recorded during dynamic facial expression observation and were compared to those of a control group (16 non-affected children, 9 years). RESULTS: There were significant group effects on thermal patterns and RSA, with lower values in children with MBS. We also observed a mild deficit in emotion recognition in these patients. CONCLUSION: Results support "embodied" theory, whereby the congenital inability to produce facial expressions induces alterations in the processing of facial expression of emotions. Such alterations may constitute a risk for emotion dysregulation. En ligne : https://dx.doi.org/10.1186/s11689-019-9272-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case / Claudia Ismania SAMOGY-COSTA in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 13 p. Titre : A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case Type de document : texte imprimé Auteurs : Claudia Ismania SAMOGY-COSTA, Auteur ; Elisa VARELLA-BRANCO, Auteur ; Frederico MONFARDINI, Auteur ; Helen FERRAZ, Auteur ; Rodrigo Ambrósio FOCK, Auteur ; Ricardo Henrique Almeida BARBOSA, Auteur ; André Luiz Santos PESSOA, Auteur ; Ana Beatriz Alvarez PEREZ, Auteur ; N. LOURENCO, Auteur ; Maria VIBRANOVSKI, Auteur ; Ana KREPISCHI, Auteur ; Carla ROSENBERG, Auteur ; Maria Rita PASSOS-BUENO, Auteur Article en page(s) : 13 p. Langues : Anglais (eng) Mots-clés : 22q13.3 deletion syndrome  Autism spectrum disorder  Phelan-McDermid syndrome  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition. En ligne : https://dx.doi.org/10.1186/s11689-019-9273-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case [texte imprimé] / Claudia Ismania SAMOGY-COSTA, Auteur ; Elisa VARELLA-BRANCO, Auteur ; Frederico MONFARDINI, Auteur ; Helen FERRAZ, Auteur ; Rodrigo Ambrósio FOCK, Auteur ; Ricardo Henrique Almeida BARBOSA, Auteur ; André Luiz Santos PESSOA, Auteur ; Ana Beatriz Alvarez PEREZ, Auteur ; N. LOURENCO, Auteur ; Maria VIBRANOVSKI, Auteur ; Ana KREPISCHI, Auteur ; Carla ROSENBERG, Auteur ; Maria Rita PASSOS-BUENO, Auteur . - 13 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 13 p. Mots-clés : 22q13.3 deletion syndrome  Autism spectrum disorder  Phelan-McDermid syndrome  Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition. En ligne : https://dx.doi.org/10.1186/s11689-019-9273-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits / Rachael BEDFORD in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 14 p. Titre : Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits Type de document : texte imprimé Auteurs : Rachael BEDFORD, Auteur ; Teodora GLIGA, Auteur ; Alexandra HENDRY, Auteur ; Emily Jane Harrison JONES, Auteur ; Greg PASCO, Auteur ; Tony CHARMAN, Auteur ; Mark Henry JOHNSON, Auteur ; Andrew PICKLES, Auteur Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Attention deficit/hyperactivity disorder  Autism spectrum disorder  Callous unemotional traits  Executive function  Infants at risk  Regulatory function Index. décimale : PER Périodiques Résumé : BACKGROUND: Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. METHODS: Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). RESULTS: Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. CONCLUSIONS: Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms. En ligne : https://dx.doi.org/10.1186/s11689-019-9274-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits [texte imprimé] / Rachael BEDFORD, Auteur ; Teodora GLIGA, Auteur ; Alexandra HENDRY, Auteur ; Emily Jane Harrison JONES, Auteur ; Greg PASCO, Auteur ; Tony CHARMAN, Auteur ; Mark Henry JOHNSON, Auteur ; Andrew PICKLES, Auteur . - 14 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 14 p. Mots-clés : Attention deficit/hyperactivity disorder  Autism spectrum disorder  Callous unemotional traits  Executive function  Infants at risk  Regulatory function Index. décimale : PER Périodiques Résumé : BACKGROUND: Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. METHODS: Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). RESULTS: Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. CONCLUSIONS: Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms. En ligne : https://dx.doi.org/10.1186/s11689-019-9274-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Electroencephalographic spectral power as a marker of cortical function and disease severity in girls with Rett syndrome / Katherine J. ROCHE in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 15 p. Titre : Electroencephalographic spectral power as a marker of cortical function and disease severity in girls with Rett syndrome Type de document : texte imprimé Auteurs : Katherine J. ROCHE, Auteur ; Jocelyn J. LEBLANC, Auteur ; April R. LEVIN, Auteur ; Heather M. O'LEARY, Auteur ; Lauren M. BACZEWSKI, Auteur ; Charles A. NELSON, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : Biomarker  Eeg  Electroencephalography  Electrophysiology  Rett syndrome  Spectral power Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome is a neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene. Individuals with Rett syndrome typically develop normally until around 18 months of age before undergoing a developmental regression, and the disorder can lead to cognitive, motor, sensory, and autonomic dysfunction. Understanding the mechanism of developmental regression represents a unique challenge when viewed through a neuroscience lens. Are circuits that were previously established erased, and are new ones built to supplant old ones? One way to examine circuit-level changes is with the use of electroencephalography (EEG). Previous studies of the EEG in individuals with Rett syndrome have focused on morphological characteristics, but few have explored spectral power, including power as an index of brain function or disease severity. This study sought to determine if EEG power differs in girls with Rett syndrome and typically developing girls and among girls with Rett syndrome based on various clinical characteristics in order to better understand neural connectivity and cortical organization in individuals with this disorder. METHODS: Resting state EEG data were acquired from girls with Rett syndrome (n = 57) and typically developing children without Rett syndrome (n = 37). Clinical data were also collected for girls with Rett syndrome. EEG power across several brain regions in numerous frequency bands was then compared between girls with Rett syndrome and typically developing children and power in girls with Rett syndrome was compared based on these clinical measures. 1/f slope was also compared between groups. RESULTS: Girls with Rett syndrome demonstrate significantly lower power in the middle frequency bands across multiple brain regions. Additionally, girls with Rett syndrome that are postregression demonstrate significantly higher power in the lower frequency delta and theta bands and a significantly more negative slope of the power spectrum. Increased power in these bands, as well as a more negative 1/f slope, trended with lower cognitive assessment scores. CONCLUSIONS: Increased power in lower frequency bands is consistent with previous studies demonstrating a "slowing" of the background EEG in Rett syndrome. This increase, particularly in the delta band, could represent abnormal cortical inhibition due to dysfunctional GABAergic signaling and could potentially be used as a marker of severity due to associations with more severe Rett syndrome phenotypes. En ligne : https://dx.doi.org/10.1186/s11689-019-9275-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Electroencephalographic spectral power as a marker of cortical function and disease severity in girls with Rett syndrome [texte imprimé] / Katherine J. ROCHE, Auteur ; Jocelyn J. LEBLANC, Auteur ; April R. LEVIN, Auteur ; Heather M. O'LEARY, Auteur ; Lauren M. BACZEWSKI, Auteur ; Charles A. NELSON, Auteur . - 15 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 15 p. Mots-clés : Biomarker  Eeg  Electroencephalography  Electrophysiology  Rett syndrome  Spectral power Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome is a neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene. Individuals with Rett syndrome typically develop normally until around 18 months of age before undergoing a developmental regression, and the disorder can lead to cognitive, motor, sensory, and autonomic dysfunction. Understanding the mechanism of developmental regression represents a unique challenge when viewed through a neuroscience lens. Are circuits that were previously established erased, and are new ones built to supplant old ones? One way to examine circuit-level changes is with the use of electroencephalography (EEG). Previous studies of the EEG in individuals with Rett syndrome have focused on morphological characteristics, but few have explored spectral power, including power as an index of brain function or disease severity. This study sought to determine if EEG power differs in girls with Rett syndrome and typically developing girls and among girls with Rett syndrome based on various clinical characteristics in order to better understand neural connectivity and cortical organization in individuals with this disorder. METHODS: Resting state EEG data were acquired from girls with Rett syndrome (n = 57) and typically developing children without Rett syndrome (n = 37). Clinical data were also collected for girls with Rett syndrome. EEG power across several brain regions in numerous frequency bands was then compared between girls with Rett syndrome and typically developing children and power in girls with Rett syndrome was compared based on these clinical measures. 1/f slope was also compared between groups. RESULTS: Girls with Rett syndrome demonstrate significantly lower power in the middle frequency bands across multiple brain regions. Additionally, girls with Rett syndrome that are postregression demonstrate significantly higher power in the lower frequency delta and theta bands and a significantly more negative slope of the power spectrum. Increased power in these bands, as well as a more negative 1/f slope, trended with lower cognitive assessment scores. CONCLUSIONS: Increased power in lower frequency bands is consistent with previous studies demonstrating a "slowing" of the background EEG in Rett syndrome. This increase, particularly in the delta band, could represent abnormal cortical inhibition due to dysfunctional GABAergic signaling and could potentially be used as a marker of severity due to associations with more severe Rett syndrome phenotypes. En ligne : https://dx.doi.org/10.1186/s11689-019-9275-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome / Helen S. HEUSSLER in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 16 p. Titre : A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome Type de document : texte imprimé Auteurs : Helen S. HEUSSLER, Auteur ; Jonathan COHEN, Auteur ; Natalie SILOVE, Auteur ; Nancy TICH, Auteur ; Marcel O. BONN-MILLER, Auteur ; Wei DU, Auteur ; Carol O'NEILL, Auteur ; Terri SEBREE, Auteur Article en page(s) : 16 p. Langues : Anglais (eng) Mots-clés : Cannabidiol  Fragile X  Pediatric  Transdermal  Zyn002  Zynerba Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is characterized by a range of developmental, neuropsychiatric, and behavioral symptoms that cause significant impairment in those with the disorder. Cannabidiol (CBD) holds promise as a potential treatment for FXS symptoms due to its safety profile and positive effects on a number of emotional and behavioral symptoms associated with FXS. The aim of the current study was to evaluate the safety, tolerability, and initial efficacy of ZYN002, a transdermal CBD gel, in a pediatric population with FXS. METHODS: Twenty children and adolescents (aged 6-17 years) with a diagnosis of FXS (confirmed through molecular documentation of FMR1 full mutation) were enrolled in an open-label, multi-site, trial of ZYN002. Transdermal CBD gel was administered twice daily for 12 weeks, titrated from 50 mg to a maximum daily dose of 250 mg. The primary efficacy endpoint was change from screening to week 12 on the Anxiety, Depression, and Mood Scale (ADAMS). Secondary endpoint measures included the Aberrant Behavior Checklist-Community for FXS (ABC-CFXS), Pediatric Anxiety Rating Scale (PARS-R), Pediatric Quality of Life Inventory (PedsQL), three Visual Analogue Scales (VAS), and the Clinical Global Impression Scale-Severity (CGI-S) and Improvement (CGI-I). RESULTS: The majority of treatment-emergent AEs (reported by 85% of participants) were mild in severity (70%), and no serious adverse events were reported. There was a statistically significant reduction in ADAMS total score from screening to week 12 and significant reductions on nearly all other secondary endpoints, including all ADAMS subscales (except depressed mood), all ABC-CFXS subscale scores (e.g., social avoidance, irritability), PARS-R total severity score, and PedsQL total score. CONCLUSIONS: ZYN002 was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS. These findings support further study of ZYN002 in a randomized, well-controlled trial for the treatment of behavioral symptoms of FXS. TRIAL REGISTRATION: ANZCTR, ACTRN12617000150347 Registered 27 January 2017. En ligne : https://dx.doi.org/10.1186/s11689-019-9277-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome [texte imprimé] / Helen S. HEUSSLER, Auteur ; Jonathan COHEN, Auteur ; Natalie SILOVE, Auteur ; Nancy TICH, Auteur ; Marcel O. BONN-MILLER, Auteur ; Wei DU, Auteur ; Carol O'NEILL, Auteur ; Terri SEBREE, Auteur . - 16 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 16 p. Mots-clés : Cannabidiol  Fragile X  Pediatric  Transdermal  Zyn002  Zynerba Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is characterized by a range of developmental, neuropsychiatric, and behavioral symptoms that cause significant impairment in those with the disorder. Cannabidiol (CBD) holds promise as a potential treatment for FXS symptoms due to its safety profile and positive effects on a number of emotional and behavioral symptoms associated with FXS. The aim of the current study was to evaluate the safety, tolerability, and initial efficacy of ZYN002, a transdermal CBD gel, in a pediatric population with FXS. METHODS: Twenty children and adolescents (aged 6-17 years) with a diagnosis of FXS (confirmed through molecular documentation of FMR1 full mutation) were enrolled in an open-label, multi-site, trial of ZYN002. Transdermal CBD gel was administered twice daily for 12 weeks, titrated from 50 mg to a maximum daily dose of 250 mg. The primary efficacy endpoint was change from screening to week 12 on the Anxiety, Depression, and Mood Scale (ADAMS). Secondary endpoint measures included the Aberrant Behavior Checklist-Community for FXS (ABC-CFXS), Pediatric Anxiety Rating Scale (PARS-R), Pediatric Quality of Life Inventory (PedsQL), three Visual Analogue Scales (VAS), and the Clinical Global Impression Scale-Severity (CGI-S) and Improvement (CGI-I). RESULTS: The majority of treatment-emergent AEs (reported by 85% of participants) were mild in severity (70%), and no serious adverse events were reported. There was a statistically significant reduction in ADAMS total score from screening to week 12 and significant reductions on nearly all other secondary endpoints, including all ADAMS subscales (except depressed mood), all ABC-CFXS subscale scores (e.g., social avoidance, irritability), PARS-R total severity score, and PedsQL total score. CONCLUSIONS: ZYN002 was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS. These findings support further study of ZYN002 in a randomized, well-controlled trial for the treatment of behavioral symptoms of FXS. TRIAL REGISTRATION: ANZCTR, ACTRN12617000150347 Registered 27 January 2017. En ligne : https://dx.doi.org/10.1186/s11689-019-9277-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics / Sinéad O'BRIEN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 17 p. Titre : STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics Type de document : texte imprimé Auteurs : Sinéad O'BRIEN, Auteur ; Elise NG-CORDELL, Auteur ; Duncan E. ASTLE, Auteur ; Gaia SCERIF, Auteur ; Kate BAKER, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Epilepsy  Intellectual disability  Language  Stxbp1  Social Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). RESULTS: The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. CONCLUSIONS: De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families. En ligne : https://dx.doi.org/10.1186/s11689-019-9278-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] STXBP1-associated neurodevelopmental disorder: a comparative study of behavioural characteristics [texte imprimé] / Sinéad O'BRIEN, Auteur ; Elise NG-CORDELL, Auteur ; Duncan E. ASTLE, Auteur ; Gaia SCERIF, Auteur ; Kate BAKER, Auteur . - 17 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 17 p. Mots-clés : Epilepsy  Intellectual disability  Language  Stxbp1  Social Index. décimale : PER Périodiques Résumé : BACKGROUND: De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. METHODS: To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). RESULTS: The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. CONCLUSIONS: De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families. En ligne : https://dx.doi.org/10.1186/s11689-019-9278-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression / Andres JIMENEZ-GOMEZ in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 18 p. Titre : Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression Type de document : texte imprimé Auteurs : Andres JIMENEZ-GOMEZ, Auteur ; Sizhe NIU, Auteur ; Fabiola ANDUJAR-PEREZ, Auteur ; Elizabeth A. MCQUADE, Auteur ; Alfred BALASA, Auteur ; David HUSS, Auteur ; Rohini COORG, Auteur ; Michael QUACH, Auteur ; Sherry VINSON, Auteur ; Sarah RISEN, Auteur ; J. Lloyd HOLDER, Auteur Article en page(s) : 18 p. Langues : Anglais (eng) Mots-clés : Autism  Electroencephalogram  Neurodevelopment  Posterior dominant rhythm  Syngap1 Index. décimale : PER Périodiques Résumé : BACKGROUND: The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression. METHODS: A retrospective clinical data analysis of individuals with SYNGAP1 mutations was conducted. Data included genetic diagnosis, clinical history and examinations, neurophysiologic data, neuroimaging, and serial neurodevelopmental/behavioral assessments. All patients were seen longitudinally within a 6-year period; data analysis was completed on June 30, 2018. Records for all individuals diagnosed with deleterious SYNGAP1 variants (by clinical sequencing or exome sequencing panels) were reviewed. RESULTS: Fifteen individuals (53% male) with seventeen unique SYNGAP1 mutations are reported. Mean age at genetic diagnosis was 65.9 months (28-174 months). All individuals had epilepsy, with atypical absence seizures being the most common semiology (60%). EEG abnormalities included intermittent rhythmic delta activity (60%), slow or absent posterior dominant rhythm (87%), and epileptiform activity (93%), with generalized discharges being more common than focal. Neuroimaging revealed nonspecific abnormalities (53%). Neurodevelopmental evaluation revealed impairment in all individuals, with gross motor function being the least affected. Autism spectrum disorder was diagnosed in 73% and aggression in 60% of cases. Analysis of biomarkers revealed a trend toward a moderate positive correlation between visual-perceptual/fine motor/adaptive skills and language development, with posterior dominant rhythm on electroencephalogram (EEG), independent of age. No other neurophysiology-development associations or correlations were identified. CONCLUSIONS: A broad spectrum of neurologic and neurodevelopmental features are found with pathogenic variants of SYNGAP1. An abnormal posterior dominant rhythm on EEG correlated with abnormal developmental progression, providing a possible prognostic biomarker. En ligne : https://dx.doi.org/10.1186/s11689-019-9276-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression [texte imprimé] / Andres JIMENEZ-GOMEZ, Auteur ; Sizhe NIU, Auteur ; Fabiola ANDUJAR-PEREZ, Auteur ; Elizabeth A. MCQUADE, Auteur ; Alfred BALASA, Auteur ; David HUSS, Auteur ; Rohini COORG, Auteur ; Michael QUACH, Auteur ; Sherry VINSON, Auteur ; Sarah RISEN, Auteur ; J. Lloyd HOLDER, Auteur . - 18 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 18 p. Mots-clés : Autism  Electroencephalogram  Neurodevelopment  Posterior dominant rhythm  Syngap1 Index. décimale : PER Périodiques Résumé : BACKGROUND: The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression. METHODS: A retrospective clinical data analysis of individuals with SYNGAP1 mutations was conducted. Data included genetic diagnosis, clinical history and examinations, neurophysiologic data, neuroimaging, and serial neurodevelopmental/behavioral assessments. All patients were seen longitudinally within a 6-year period; data analysis was completed on June 30, 2018. Records for all individuals diagnosed with deleterious SYNGAP1 variants (by clinical sequencing or exome sequencing panels) were reviewed. RESULTS: Fifteen individuals (53% male) with seventeen unique SYNGAP1 mutations are reported. Mean age at genetic diagnosis was 65.9 months (28-174 months). All individuals had epilepsy, with atypical absence seizures being the most common semiology (60%). EEG abnormalities included intermittent rhythmic delta activity (60%), slow or absent posterior dominant rhythm (87%), and epileptiform activity (93%), with generalized discharges being more common than focal. Neuroimaging revealed nonspecific abnormalities (53%). Neurodevelopmental evaluation revealed impairment in all individuals, with gross motor function being the least affected. Autism spectrum disorder was diagnosed in 73% and aggression in 60% of cases. Analysis of biomarkers revealed a trend toward a moderate positive correlation between visual-perceptual/fine motor/adaptive skills and language development, with posterior dominant rhythm on electroencephalogram (EEG), independent of age. No other neurophysiology-development associations or correlations were identified. CONCLUSIONS: A broad spectrum of neurologic and neurodevelopmental features are found with pathogenic variants of SYNGAP1. An abnormal posterior dominant rhythm on EEG correlated with abnormal developmental progression, providing a possible prognostic biomarker. En ligne : https://dx.doi.org/10.1186/s11689-019-9276-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Magnetoencephalographic (MEG) brain activity during a mental flexibility task suggests some shared neurobiology in children with neurodevelopmental disorders / Alexandra MOGADAM in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 19 p. Titre : Magnetoencephalographic (MEG) brain activity during a mental flexibility task suggests some shared neurobiology in children with neurodevelopmental disorders Type de document : texte imprimé Auteurs : Alexandra MOGADAM, Auteur ; Alex E. KELLER, Auteur ; Paul D. ARNOLD, Auteur ; Russell SCHACHAR, Auteur ; Jason P. LERCH, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Elizabeth W. PANG, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Adhd  Asd  Corticostriatal projections  Executive function  Meg  Neurodevelopmental disorders  Ocd  Rbs-r  Set shifting  Tocs Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with neurodevelopmental disorders (NDDs) exhibit a shared phenotype that involves executive dysfunctions including impairments in mental flexibility (MF). It is of interest to understand if this phenotype stems from some shared neurobiology. METHODS: To investigate this possibility, we used magnetoencephalography (MEG) neuroimaging to compare brain activity in children (n = 88; 8-15 years) with autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as they completed a set-shifting/mental flexibility task. RESULTS: Neuroimaging results revealed a similar parietal activation profile across the NDD, groups suggesting a link to their shared phenotype. Differences in frontal activity differentiated the three clinical groups. Brain-behaviour analyses showed a link with repetitive behaviours suggesting shared dysfunction in the associative loop of the corticostriatal system. CONCLUSION: Our study supports the notion that NDDs may exist along a complex phenotypic/biological continuum. All NDD groups showed a sustained parietal activity profile suggesting that they share a strong reliance on the posterior parietal cortices to complete the mental flexibility task; future studies could elucidate whether this is due to delayed brain development or compensatory functioning. The differences in frontal activity may play a role in differentiating the NDDs. The OCD group showed sustained prefrontal activity that may be reflective of hyperfrontality. The ASD group showed reduced frontal activation suggestive of frontal dysfunction and the ADHD group showed an extensive hypoactivity that included frontal and parietal regions. Brain-behaviour analyses showed a significant correlation with repetitive behaviours which may reflect dysfunction in the associative loop of the corticostriatal system, linked to inflexible behaviours. En ligne : https://dx.doi.org/10.1186/s11689-019-9280-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Magnetoencephalographic (MEG) brain activity during a mental flexibility task suggests some shared neurobiology in children with neurodevelopmental disorders [texte imprimé] / Alexandra MOGADAM, Auteur ; Alex E. KELLER, Auteur ; Paul D. ARNOLD, Auteur ; Russell SCHACHAR, Auteur ; Jason P. LERCH, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Elizabeth W. PANG, Auteur . - 19 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 19 p. Mots-clés : Adhd  Asd  Corticostriatal projections  Executive function  Meg  Neurodevelopmental disorders  Ocd  Rbs-r  Set shifting  Tocs Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with neurodevelopmental disorders (NDDs) exhibit a shared phenotype that involves executive dysfunctions including impairments in mental flexibility (MF). It is of interest to understand if this phenotype stems from some shared neurobiology. METHODS: To investigate this possibility, we used magnetoencephalography (MEG) neuroimaging to compare brain activity in children (n = 88; 8-15 years) with autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as they completed a set-shifting/mental flexibility task. RESULTS: Neuroimaging results revealed a similar parietal activation profile across the NDD, groups suggesting a link to their shared phenotype. Differences in frontal activity differentiated the three clinical groups. Brain-behaviour analyses showed a link with repetitive behaviours suggesting shared dysfunction in the associative loop of the corticostriatal system. CONCLUSION: Our study supports the notion that NDDs may exist along a complex phenotypic/biological continuum. All NDD groups showed a sustained parietal activity profile suggesting that they share a strong reliance on the posterior parietal cortices to complete the mental flexibility task; future studies could elucidate whether this is due to delayed brain development or compensatory functioning. The differences in frontal activity may play a role in differentiating the NDDs. The OCD group showed sustained prefrontal activity that may be reflective of hyperfrontality. The ASD group showed reduced frontal activation suggestive of frontal dysfunction and the ADHD group showed an extensive hypoactivity that included frontal and parietal regions. Brain-behaviour analyses showed a significant correlation with repetitive behaviours which may reflect dysfunction in the associative loop of the corticostriatal system, linked to inflexible behaviours. En ligne : https://dx.doi.org/10.1186/s11689-019-9280-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Assessing general cognitive and adaptive abilities in adults with Down syndrome: a systematic review / Sarah HAMBURG in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 20 p. Titre : Assessing general cognitive and adaptive abilities in adults with Down syndrome: a systematic review Type de document : texte imprimé Auteurs : Sarah HAMBURG, Auteur ; Bryony LOWE, Auteur ; Carla Marie STARTIN, Auteur ; Concepcion PADILLA, Auteur ; Antonia COPPUS, Auteur ; Wendy SILVERMAN, Auteur ; Juan FORTEA, Auteur ; Shahid ZAMAN, Auteur ; Elizabeth HEAD, Auteur ; Benjamin L. HANDEN, Auteur ; Ira LOTT, Auteur ; Weihong SONG, Auteur ; Andre STRYDOM, Auteur Article en page(s) : 20 p. Langues : Anglais (eng) Mots-clés : Ab  Adaptive ability  Adaptive behaviour  Cognition  Down syndrome  General ability  Iq  Intelligence Index. décimale : PER Périodiques Résumé : BACKGROUND: Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community. RESULTS: Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while five were used in two different studies. Eleven studies reporting AB test data met inclusion for this review, with seven different AB tests used. The only AB scales to be used by more than one study were the Vineland Adaptive Behaviour Scale (VABS; used by three studies) and the Vineland Adaptive Behavior Scale 2nd Edition (VABS-II; used by two studies). A variety of additional factors were identified which make comparison of test scores between studies problematic, including different score types provided between studies (e.g. raw scores compared to age-equivalent scores) and different participant inclusion criteria (e.g. whether individuals with cognitive decline were excluded). Floor effects were common for IQ tests (particularly for standardised test scores). Data exists to suggest that floor effects may be minimised by the use of raw test scores rather than standardised test scores. Raw scores may, therefore, be particularly useful in longitudinal studies to track change in cognitive ability over time. CONCLUSIONS: Studies assessing general ability in adults with DS are likely to benefit from the use of both IQ and AB scales. The DS research community may benefit from the development of reporting standards for IQ and AB data, and from the sharing of raw study data enabling further in-depth investigation of issues highlighted by this review. En ligne : https://dx.doi.org/10.1186/s11689-019-9279-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Assessing general cognitive and adaptive abilities in adults with Down syndrome: a systematic review [texte imprimé] / Sarah HAMBURG, Auteur ; Bryony LOWE, Auteur ; Carla Marie STARTIN, Auteur ; Concepcion PADILLA, Auteur ; Antonia COPPUS, Auteur ; Wendy SILVERMAN, Auteur ; Juan FORTEA, Auteur ; Shahid ZAMAN, Auteur ; Elizabeth HEAD, Auteur ; Benjamin L. HANDEN, Auteur ; Ira LOTT, Auteur ; Weihong SONG, Auteur ; Andre STRYDOM, Auteur . - 20 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 20 p. Mots-clés : Ab  Adaptive ability  Adaptive behaviour  Cognition  Down syndrome  General ability  Iq  Intelligence Index. décimale : PER Périodiques Résumé : BACKGROUND: Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community. RESULTS: Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while five were used in two different studies. Eleven studies reporting AB test data met inclusion for this review, with seven different AB tests used. The only AB scales to be used by more than one study were the Vineland Adaptive Behaviour Scale (VABS; used by three studies) and the Vineland Adaptive Behavior Scale 2nd Edition (VABS-II; used by two studies). A variety of additional factors were identified which make comparison of test scores between studies problematic, including different score types provided between studies (e.g. raw scores compared to age-equivalent scores) and different participant inclusion criteria (e.g. whether individuals with cognitive decline were excluded). Floor effects were common for IQ tests (particularly for standardised test scores). Data exists to suggest that floor effects may be minimised by the use of raw test scores rather than standardised test scores. Raw scores may, therefore, be particularly useful in longitudinal studies to track change in cognitive ability over time. CONCLUSIONS: Studies assessing general ability in adults with DS are likely to benefit from the use of both IQ and AB scales. The DS research community may benefit from the development of reporting standards for IQ and AB data, and from the sharing of raw study data enabling further in-depth investigation of issues highlighted by this review. En ligne : https://dx.doi.org/10.1186/s11689-019-9279-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Within-task variability on standardized language tests predicts autism spectrum disorder: a pilot study of the Response Dispersion Index / Abby E. HARE-HARRIS in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 21 p. Titre : Within-task variability on standardized language tests predicts autism spectrum disorder: a pilot study of the Response Dispersion Index Type de document : texte imprimé Auteurs : Abby E. HARE-HARRIS, Auteur ; Marissa W. MITCHEL, Auteur ; Scott M. MYERS, Auteur ; Aaron D. MITCHEL, Auteur ; Brian R. KING, Auteur ; Brittany G. RUOCCO, Auteur ; Christa Lese MARTIN, Auteur ; Judy F. FLAX, Auteur ; Linda M. BRZUSTOWICZ, Auteur Article en page(s) : 21 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Developmental difference  Intra-subtest scatter  Language impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Qualitatively atypical language development characterized by non-sequential skill acquisition within a developmental domain, which has been called developmental deviance or difference, is a common characteristic of autism spectrum disorder (ASD). We developed the Response Dispersion Index (RDI), a measure of this phenomenon based on intra-subtest scatter of item responses on standardized psychometric assessments, to assess the within-task variability among individuals with language impairment (LI) and/or ASD. METHODS: Standard clinical assessments of language were administered to 502 individuals from the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Participants were divided into four diagnostic groups: unaffected, ASD-only, LI-only, and ASD + LI. For each language measure, RDI was defined as the product of the total number of test items and the sum of the weight (based on item difficulty) of test items missed. Group differences in RDI were assessed, and the relationship between RDI and ASD diagnosis among individuals with LI was investigated for each language assessment. RESULTS: Although standard scores were unable to distinguish the LI-only and ASD/ASD + LI groups, the ASD/ASD + LI groups had higher RDI scores compared to LI-only group across all measures of expressive, pragmatic, and metalinguistic language. RDI was positively correlated with quantitative ASD traits across all subgroups and was an effective predictor of ASD diagnosis among individuals with LI. CONCLUSIONS: The RDI is an effective quantitative metric of developmental deviance/difference that correlates with ASD traits, supporting previous associations between ASD and non-sequential skill acquisition. The RDI can be adapted to other clinical measures to investigate the degree of difference that is not captured by standard performance summary scores. En ligne : https://dx.doi.org/10.1186/s11689-019-9283-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Within-task variability on standardized language tests predicts autism spectrum disorder: a pilot study of the Response Dispersion Index [texte imprimé] / Abby E. HARE-HARRIS, Auteur ; Marissa W. MITCHEL, Auteur ; Scott M. MYERS, Auteur ; Aaron D. MITCHEL, Auteur ; Brian R. KING, Auteur ; Brittany G. RUOCCO, Auteur ; Christa Lese MARTIN, Auteur ; Judy F. FLAX, Auteur ; Linda M. BRZUSTOWICZ, Auteur . - 21 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 21 p. Mots-clés : Autism spectrum disorder  Developmental difference  Intra-subtest scatter  Language impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Qualitatively atypical language development characterized by non-sequential skill acquisition within a developmental domain, which has been called developmental deviance or difference, is a common characteristic of autism spectrum disorder (ASD). We developed the Response Dispersion Index (RDI), a measure of this phenomenon based on intra-subtest scatter of item responses on standardized psychometric assessments, to assess the within-task variability among individuals with language impairment (LI) and/or ASD. METHODS: Standard clinical assessments of language were administered to 502 individuals from the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Participants were divided into four diagnostic groups: unaffected, ASD-only, LI-only, and ASD + LI. For each language measure, RDI was defined as the product of the total number of test items and the sum of the weight (based on item difficulty) of test items missed. Group differences in RDI were assessed, and the relationship between RDI and ASD diagnosis among individuals with LI was investigated for each language assessment. RESULTS: Although standard scores were unable to distinguish the LI-only and ASD/ASD + LI groups, the ASD/ASD + LI groups had higher RDI scores compared to LI-only group across all measures of expressive, pragmatic, and metalinguistic language. RDI was positively correlated with quantitative ASD traits across all subgroups and was an effective predictor of ASD diagnosis among individuals with LI. CONCLUSIONS: The RDI is an effective quantitative metric of developmental deviance/difference that correlates with ASD traits, supporting previous associations between ASD and non-sequential skill acquisition. The RDI can be adapted to other clinical measures to investigate the degree of difference that is not captured by standard performance summary scores. En ligne : https://dx.doi.org/10.1186/s11689-019-9283-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism / Carla A. WALL in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 22 p. Titre : Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism Type de document : texte imprimé Auteurs : Carla A. WALL, Auteur ; Abigail L. HOGAN-BROWN, Auteur ; Elizabeth A. WILL, Auteur ; Samuel MCQUILLIN, Auteur ; Bridgette L. KELLEHER, Auteur ; Jane E. ROBERTS, Auteur Article en page(s) : 22 p. Langues : Anglais (eng) Mots-clés : Anxiety  Autism spectrum disorder  Fragile X syndrome  Negative affect  Sex differences Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a genetic disorder that is highly comorbid with anxiety and autism spectrum disorder (ASD). Elevated negative affect in young children has been associated with increased risk for both anxiety and ASD; however, these relations remain poorly understood in FXS. METHODS: The present prospective longitudinal study examined the trajectory of negative affect from infancy through preschool in males and females with FXS and typical development and its relation to anxiety and ASD. RESULTS: Results indicate a complex association reflecting group, developmental, and sex effects. Specifically, the group with FXS displayed a trajectory of increasing negative affect across age that was distinct from the typical controls. This atypical trajectory of negative affect in FXS was driven by sex effects in that males showed lower negative affect during infancy followed by steep increases across the toddler and preschool years whereas the females displayed a flatter trajectory. Finally, elevated negative affect predicted anxiety symptoms in males, but not females, with no relationship to ASD in males or females with FXS. CONCLUSIONS: The current work addresses the importance of studying the development of psychopathology in a specific neurogenetic population. Temperamental negative affect was shown to be an important early marker for anxiety in young children with FXS, with subtle differences observed between males and females. En ligne : https://dx.doi.org/10.1186/s11689-019-9284-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism [texte imprimé] / Carla A. WALL, Auteur ; Abigail L. HOGAN-BROWN, Auteur ; Elizabeth A. WILL, Auteur ; Samuel MCQUILLIN, Auteur ; Bridgette L. KELLEHER, Auteur ; Jane E. ROBERTS, Auteur . - 22 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 22 p. Mots-clés : Anxiety  Autism spectrum disorder  Fragile X syndrome  Negative affect  Sex differences Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a genetic disorder that is highly comorbid with anxiety and autism spectrum disorder (ASD). Elevated negative affect in young children has been associated with increased risk for both anxiety and ASD; however, these relations remain poorly understood in FXS. METHODS: The present prospective longitudinal study examined the trajectory of negative affect from infancy through preschool in males and females with FXS and typical development and its relation to anxiety and ASD. RESULTS: Results indicate a complex association reflecting group, developmental, and sex effects. Specifically, the group with FXS displayed a trajectory of increasing negative affect across age that was distinct from the typical controls. This atypical trajectory of negative affect in FXS was driven by sex effects in that males showed lower negative affect during infancy followed by steep increases across the toddler and preschool years whereas the females displayed a flatter trajectory. Finally, elevated negative affect predicted anxiety symptoms in males, but not females, with no relationship to ASD in males or females with FXS. CONCLUSIONS: The current work addresses the importance of studying the development of psychopathology in a specific neurogenetic population. Temperamental negative affect was shown to be an important early marker for anxiety in young children with FXS, with subtle differences observed between males and females. En ligne : https://dx.doi.org/10.1186/s11689-019-9284-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes / Alice WATKINS in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 24 p. Titre : Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes Type de document : texte imprimé Auteurs : Alice WATKINS, Auteur ; Stacey BISSELL, Auteur ; Jo MOSS, Auteur ; Chris OLIVER, Auteur ; Jill CLAYTON-SMITH, Auteur ; Lorraine HAYE, Auteur ; Mary HEALD, Auteur ; Alice WELHAM, Auteur Article en page(s) : 24 p. Langues : Anglais (eng) Mots-clés : Angelman syndrome  Autism spectrum disorder  Behavioural phenotype  Cornelia de Lange syndrome  Pitt-Hopkins syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS). METHODS: Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex. RESULTS: Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS. CONCLUSIONS: Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research. En ligne : https://dx.doi.org/10.1186/s11689-019-9282-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes [texte imprimé] / Alice WATKINS, Auteur ; Stacey BISSELL, Auteur ; Jo MOSS, Auteur ; Chris OLIVER, Auteur ; Jill CLAYTON-SMITH, Auteur ; Lorraine HAYE, Auteur ; Mary HEALD, Auteur ; Alice WELHAM, Auteur . - 24 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 24 p. Mots-clés : Angelman syndrome  Autism spectrum disorder  Behavioural phenotype  Cornelia de Lange syndrome  Pitt-Hopkins syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS). METHODS: Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex. RESULTS: Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS. CONCLUSIONS: Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research. En ligne : https://dx.doi.org/10.1186/s11689-019-9282-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism / Elizabeth A. WILL in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 23 p. Titre : Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism Type de document : texte imprimé Auteurs : Elizabeth A. WILL, Auteur ; Somer L. BISHOP, Auteur ; Jane E. ROBERTS, Auteur Article en page(s) : 23 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Developmental trajectories  Fragile X syndrome  Motor development Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is highly prevalent in fragile X syndrome (FXS), affecting 50-70% of males. Motor impairments are a shared feature across autism and FXS that may help to better characterize autism in FXS. As motor skills provide a critical foundation for various language, cognitive, and social outcomes, they may serve an important mechanistic role for autism in FXS. As such, this study aimed to identify differences in motor trajectories across direct assessment and parent-report measures of fine and gross motor development between FXS with and without autism, and typical development, while controlling for cognitive functioning. METHODS: This prospective longitudinal study included 42 children with FXS, 24 of whom also had ASD (FXS + ASD), as well as 40 typically developing children. The Mullen Scales of Early Learning provided a direct measure of fine and gross motor skills, and the Vineland Adaptive Behavior Scales provided a measure of parent-reported fine and gross motor skills. Random slopes and random intercepts multilevel models were tested to determine divergence in developmental motor trajectories between groups when controlling for cognitive level. RESULTS: Model results indicated the children with FXS + ASD diverged from TD children by 9-months on all measures of gross and fine motor skills, even when controlling for cognitive level. Results also indicated an early divergence in motor trajectories of fine and gross motor skills between the FXS + ASD and FXS groups when controlling for cognitive level. This divergence was statistically significant by 18 months, with the FXS + ASD showing decelerated growth in motor skills across direct observation and parent-report measures. CONCLUSIONS: This study is the first to examine longitudinal trends in motor development in children with FXS with and without comorbid ASD using both direct assessment and parent-report measures of fine and gross motor. Furthermore, it is among the first to account for nonverbal cognitive delays, a step towards elucidating the isolated role of motor impairments in FXS with and without ASD. Findings underscore the role of motor impairments as a possible signal representing greater underlying genetic liability, or as a potential catalyst or consequence, of co-occurring autism in FXS. En ligne : https://dx.doi.org/10.1186/s11689-019-9281-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism [texte imprimé] / Elizabeth A. WILL, Auteur ; Somer L. BISHOP, Auteur ; Jane E. ROBERTS, Auteur . - 23 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 23 p. Mots-clés : Autism spectrum disorder  Developmental trajectories  Fragile X syndrome  Motor development Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is highly prevalent in fragile X syndrome (FXS), affecting 50-70% of males. Motor impairments are a shared feature across autism and FXS that may help to better characterize autism in FXS. As motor skills provide a critical foundation for various language, cognitive, and social outcomes, they may serve an important mechanistic role for autism in FXS. As such, this study aimed to identify differences in motor trajectories across direct assessment and parent-report measures of fine and gross motor development between FXS with and without autism, and typical development, while controlling for cognitive functioning. METHODS: This prospective longitudinal study included 42 children with FXS, 24 of whom also had ASD (FXS + ASD), as well as 40 typically developing children. The Mullen Scales of Early Learning provided a direct measure of fine and gross motor skills, and the Vineland Adaptive Behavior Scales provided a measure of parent-reported fine and gross motor skills. Random slopes and random intercepts multilevel models were tested to determine divergence in developmental motor trajectories between groups when controlling for cognitive level. RESULTS: Model results indicated the children with FXS + ASD diverged from TD children by 9-months on all measures of gross and fine motor skills, even when controlling for cognitive level. Results also indicated an early divergence in motor trajectories of fine and gross motor skills between the FXS + ASD and FXS groups when controlling for cognitive level. This divergence was statistically significant by 18 months, with the FXS + ASD showing decelerated growth in motor skills across direct observation and parent-report measures. CONCLUSIONS: This study is the first to examine longitudinal trends in motor development in children with FXS with and without comorbid ASD using both direct assessment and parent-report measures of fine and gross motor. Furthermore, it is among the first to account for nonverbal cognitive delays, a step towards elucidating the isolated role of motor impairments in FXS with and without ASD. Findings underscore the role of motor impairments as a possible signal representing greater underlying genetic liability, or as a potential catalyst or consequence, of co-occurring autism in FXS. En ligne : https://dx.doi.org/10.1186/s11689-019-9281-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Vocabulary comprehension in adults with fragile X syndrome (FXS) / Anne HOFFMANN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 25 p. Titre : Vocabulary comprehension in adults with fragile X syndrome (FXS) Type de document : texte imprimé Auteurs : Anne HOFFMANN, Auteur ; Sue Ellen KRAUSE, Auteur ; Joanne WUU, Auteur ; Sue LEURGANS, Auteur ; Stephen GUTER, Auteur ; Sandra S. BLOCK, Auteur ; Jeff SALT, Auteur ; Edwin COOK, Auteur ; Dominick M. MAINO, Auteur ; Elizabeth BERRY-KRAVIS, Auteur Article en page(s) : 25 p. Langues : Anglais (eng) Mots-clés : Adults  Cognition  Comprehension  Fragile X syndrome  Language  Vocabulary Index. décimale : PER Périodiques Résumé : BACKGROUND: Receptive and expressive vocabulary in adult and adolescent males with fragile X syndrome (FXS) have been shown as significantly lower than their chronological age; however, receptive vocabulary has been considered a strength relative to mental age. This has not been formally examined, however, and data are needed to compare receptive vocabulary with other language skills and with mental age in individuals with FXS. This is especially important as vocabulary measures are sometimes used as a proxy to estimate language ability. METHODS: This preliminary study examined receptive vocabulary, global language, and cognitive skills in 42 adults (33 males and 9 females) with FXS as a portion of the baseline evaluation prior to randomization in a clinical trial of ampakine CX516. The battery of standardized tests addressed receptive vocabulary with the Peabody Picture Vocabulary Test, Third Edition (PPVT-III), receptive and expressive language (termed henceforth as global language) via the Preschool Language Scale, Fourth Edition or the Clinical Evaluation of Language Fundamentals, Third Edition, and non-verbal cognition via the Stanford-Binet Intelligence Scales, Fourth Edition (SB-IV). RESULTS: Results showed (1) significantly higher receptive vocabulary than global language, (2) significantly better receptive vocabulary than non-verbal cognition, (3) equivalent non-verbal cognition and global language, and (4) severity of autism symptomatology was not correlated to receptive vocabulary or global language once non-verbal cognition was removed as factor. The scores from the PPVT-III did not represent the global language skills in our sample of adults with FXS. CONCLUSIONS: Findings from this investigation strongly suggest that the PPVT-III should not be used as a screening tool for language levels or cognitive function in clinical studies since the scores from the PPVT-III were not representative of global language or non-verbal cognitive skills in adults with intellectual disabilities. This finding is critical in order to understand how to evaluate, as well as to treat, language in individuals with FXS. Development of efficient and appropriate tools to measure language, cognition, and behavior in individuals with FXS is essential. En ligne : https://dx.doi.org/10.1186/s11689-019-9285-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Vocabulary comprehension in adults with fragile X syndrome (FXS) [texte imprimé] / Anne HOFFMANN, Auteur ; Sue Ellen KRAUSE, Auteur ; Joanne WUU, Auteur ; Sue LEURGANS, Auteur ; Stephen GUTER, Auteur ; Sandra S. BLOCK, Auteur ; Jeff SALT, Auteur ; Edwin COOK, Auteur ; Dominick M. MAINO, Auteur ; Elizabeth BERRY-KRAVIS, Auteur . - 25 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 25 p. Mots-clés : Adults  Cognition  Comprehension  Fragile X syndrome  Language  Vocabulary Index. décimale : PER Périodiques Résumé : BACKGROUND: Receptive and expressive vocabulary in adult and adolescent males with fragile X syndrome (FXS) have been shown as significantly lower than their chronological age; however, receptive vocabulary has been considered a strength relative to mental age. This has not been formally examined, however, and data are needed to compare receptive vocabulary with other language skills and with mental age in individuals with FXS. This is especially important as vocabulary measures are sometimes used as a proxy to estimate language ability. METHODS: This preliminary study examined receptive vocabulary, global language, and cognitive skills in 42 adults (33 males and 9 females) with FXS as a portion of the baseline evaluation prior to randomization in a clinical trial of ampakine CX516. The battery of standardized tests addressed receptive vocabulary with the Peabody Picture Vocabulary Test, Third Edition (PPVT-III), receptive and expressive language (termed henceforth as global language) via the Preschool Language Scale, Fourth Edition or the Clinical Evaluation of Language Fundamentals, Third Edition, and non-verbal cognition via the Stanford-Binet Intelligence Scales, Fourth Edition (SB-IV). RESULTS: Results showed (1) significantly higher receptive vocabulary than global language, (2) significantly better receptive vocabulary than non-verbal cognition, (3) equivalent non-verbal cognition and global language, and (4) severity of autism symptomatology was not correlated to receptive vocabulary or global language once non-verbal cognition was removed as factor. The scores from the PPVT-III did not represent the global language skills in our sample of adults with FXS. CONCLUSIONS: Findings from this investigation strongly suggest that the PPVT-III should not be used as a screening tool for language levels or cognitive function in clinical studies since the scores from the PPVT-III were not representative of global language or non-verbal cognitive skills in adults with intellectual disabilities. This finding is critical in order to understand how to evaluate, as well as to treat, language in individuals with FXS. Development of efficient and appropriate tools to measure language, cognition, and behavior in individuals with FXS is essential. En ligne : https://dx.doi.org/10.1186/s11689-019-9285-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Quantitative gait assessment in children with 16p11.2 syndrome / Sylvie GOLDMAN in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 26 p. Titre : Quantitative gait assessment in children with 16p11.2 syndrome Type de document : texte imprimé Auteurs : Sylvie GOLDMAN, Auteur ; Aston K. MCCULLOUGH, Auteur ; Sally Dunaway YOUNG, Auteur ; Carly MUELLER, Auteur ; Adrianna STAHL, Auteur ; Audrey ZOELLER, Auteur ; Laurel Daniels ABBRUZZESE, Auteur ; Ashwini K. RAO, Auteur ; Jacqueline MONTES, Auteur Article en page(s) : 26 p. Langues : Anglais (eng) Mots-clés : 16p11.2  Autism spectrum disorder  Children  Gait  Motor function  Neurodevelopment disorder Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as 16p11.2 syndrome are frequently associated with motor impairments including locomotion. The lack of precise measures of gait, combined with the challenges inherent in studying children with neurodevelopmental disorders, hinders quantitative motor assessments. Gait and balance are quantifiable measures that may help to refine the motor phenotype in 16p11.2. The characterization of motor profile is useful to study the trajectories of locomotion performance of children with genetic variants and may provide insights into neural pathway dysfunction based on genotype/phenotype model. METHODS: Thirty-six children (21 probands with 16p11.2 deletion and duplication mutation and 15 unaffected siblings), with a mean age of 8.5 years (range 3.2-15.4) and 55% male, were enrolled. Of the probands, 23% (n = 6) had a confirmed diagnosis of autism spectrum disorder (ASD) and were all male. Gait assessments included 6-min walk test (6MWT), 10-m walk/run test (10MWR), timed-up-and-go test (TUG), and spatio-temporal measurements of preferred- and fast-paced walking. The Pediatric Evaluation of Disability Inventory-Computer Adaptive Tests (PEDI-CAT), a caregiver-reported functional assessment, was administered. Measures of balance were calculated using percent time in double support and base of support. Analyses of the six children with ASD were described separately. RESULTS: Thirty-six participants completed the protocol. Compared with sibling controls, probands had significantly lower scores on the 6MWT (p = 0.04), 10MWR (p = 0.01), and TUG (p = 0.005). Group differences were also identified in base of support (p = 0.003). Probands had significantly lower PEDI-CAT scores in all domains including the mobility scale (p < 0.001). Using age-matched subsamples, the ASD and non-ASD genetic variant groups had larger base of support compared to the controls. In the fast-paced condition, all participants increased their velocity, and there was a corresponding decrease in percent time in double support compared to the preferred-pace condition in all participants. Only the ASD group presented with upper limb arm/hand stereotypies. CONCLUSIONS: Children with 16p11.2, with and without ASD, present with balance impairment during locomotion activities. Probands performed worse on functional assessments, and quantitative measures revealed differences in base of support. These results highlight the importance of using precise measures to differentiate motor dysfunction in children with neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-019-9286-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Quantitative gait assessment in children with 16p11.2 syndrome [texte imprimé] / Sylvie GOLDMAN, Auteur ; Aston K. MCCULLOUGH, Auteur ; Sally Dunaway YOUNG, Auteur ; Carly MUELLER, Auteur ; Adrianna STAHL, Auteur ; Audrey ZOELLER, Auteur ; Laurel Daniels ABBRUZZESE, Auteur ; Ashwini K. RAO, Auteur ; Jacqueline MONTES, Auteur . - 26 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 26 p. Mots-clés : 16p11.2  Autism spectrum disorder  Children  Gait  Motor function  Neurodevelopment disorder Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as 16p11.2 syndrome are frequently associated with motor impairments including locomotion. The lack of precise measures of gait, combined with the challenges inherent in studying children with neurodevelopmental disorders, hinders quantitative motor assessments. Gait and balance are quantifiable measures that may help to refine the motor phenotype in 16p11.2. The characterization of motor profile is useful to study the trajectories of locomotion performance of children with genetic variants and may provide insights into neural pathway dysfunction based on genotype/phenotype model. METHODS: Thirty-six children (21 probands with 16p11.2 deletion and duplication mutation and 15 unaffected siblings), with a mean age of 8.5 years (range 3.2-15.4) and 55% male, were enrolled. Of the probands, 23% (n = 6) had a confirmed diagnosis of autism spectrum disorder (ASD) and were all male. Gait assessments included 6-min walk test (6MWT), 10-m walk/run test (10MWR), timed-up-and-go test (TUG), and spatio-temporal measurements of preferred- and fast-paced walking. The Pediatric Evaluation of Disability Inventory-Computer Adaptive Tests (PEDI-CAT), a caregiver-reported functional assessment, was administered. Measures of balance were calculated using percent time in double support and base of support. Analyses of the six children with ASD were described separately. RESULTS: Thirty-six participants completed the protocol. Compared with sibling controls, probands had significantly lower scores on the 6MWT (p = 0.04), 10MWR (p = 0.01), and TUG (p = 0.005). Group differences were also identified in base of support (p = 0.003). Probands had significantly lower PEDI-CAT scores in all domains including the mobility scale (p < 0.001). Using age-matched subsamples, the ASD and non-ASD genetic variant groups had larger base of support compared to the controls. In the fast-paced condition, all participants increased their velocity, and there was a corresponding decrease in percent time in double support compared to the preferred-pace condition in all participants. Only the ASD group presented with upper limb arm/hand stereotypies. CONCLUSIONS: Children with 16p11.2, with and without ASD, present with balance impairment during locomotion activities. Probands performed worse on functional assessments, and quantitative measures revealed differences in base of support. These results highlight the importance of using precise measures to differentiate motor dysfunction in children with neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-019-9286-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Are there shared neural correlates between dyslexia and ADHD? A meta-analysis of voxel-based morphometry studies / Lauren M. MCGRATH in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 31 Titre : Are there shared neural correlates between dyslexia and ADHD? A meta-analysis of voxel-based morphometry studies Type de document : texte imprimé Auteurs : Lauren M. MCGRATH, Auteur ; Catherine J. STOODLEY, Auteur Article en page(s) : 31 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/diagnostic imaging/epidemiology  Caudate Nucleus/diagnostic imaging  Comorbidity  Dyslexia/diagnostic imaging/epidemiology  Gray Matter/diagnostic imaging  Humans  Neuroimaging  Attention-deficit/hyperactivity disorder  Caudate  Dyslexia  Meta-analysis  Voxel-based morphometry Index. décimale : PER Périodiques Résumé : BACKGROUND: Dyslexia and Attention-deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders (estimates of 25-40% bidirectional comorbidity). Previous work has identified strong genetic and cognitive overlap between the disorders, but neural overlap is relatively unexplored. This study is a systematic meta-analysis of existing voxel-based morphometry studies to determine whether there is any overlap in the gray matter correlates of both disorders. METHODS: We conducted anatomic likelihood estimate (ALE) meta-analyses of voxel-based morphometry studies in which individuals with dyslexia (15 studies; 417 cases, 416 controls) or ADHD (22 studies; 898 cases, 763 controls) were compared to typically developing controls. We generated ALE maps for dyslexia vs. controls and ADHD vs. controls using more conservative (p < .001, k = 50) and more lenient (p < .005, k = 50) thresholds. To determine the overlap of gray matter correlates of dyslexia and ADHD, we examined the statistical conjunction between the ALE maps for dyslexia vs. controls and ADHD vs. controls (false discovery rate [FDR] p < .05, k = 50, 5000 permutations). RESULTS: Results showed largely distinct gray matter differences associated with dyslexia and ADHD. There was no evidence of statistically significant gray matter overlap at our conservative threshold, and only one region of overlap in the right caudate at our more lenient threshold. Reduced gray matter in the right caudate may be relevant to shared cognitive correlates in executive functioning and/or procedural learning. The more general finding of largely distinct regional differences in gray matter between dyslexia and ADHD suggests that other neuroimaging modalities may be more sensitive to overlapping neural correlates, and that current neuroimaging recruitment approaches may be hindering progress toward uncovering neural systems associated with comorbidity. CONCLUSIONS: The current study is the first to meta-analyze overlap between gray matter differences in dyslexia and ADHD, which is a critical step toward constructing a multi-level understanding of this comorbidity that spans the genetic, neural, and cognitive levels of analysis. En ligne : https://dx.doi.org/10.1186/s11689-019-9287-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Are there shared neural correlates between dyslexia and ADHD? A meta-analysis of voxel-based morphometry studies [texte imprimé] / Lauren M. MCGRATH, Auteur ; Catherine J. STOODLEY, Auteur . - 31. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 31 Mots-clés : Attention Deficit Disorder with Hyperactivity/diagnostic imaging/epidemiology  Caudate Nucleus/diagnostic imaging  Comorbidity  Dyslexia/diagnostic imaging/epidemiology  Gray Matter/diagnostic imaging  Humans  Neuroimaging  Attention-deficit/hyperactivity disorder  Caudate  Dyslexia  Meta-analysis  Voxel-based morphometry Index. décimale : PER Périodiques Résumé : BACKGROUND: Dyslexia and Attention-deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders (estimates of 25-40% bidirectional comorbidity). Previous work has identified strong genetic and cognitive overlap between the disorders, but neural overlap is relatively unexplored. This study is a systematic meta-analysis of existing voxel-based morphometry studies to determine whether there is any overlap in the gray matter correlates of both disorders. METHODS: We conducted anatomic likelihood estimate (ALE) meta-analyses of voxel-based morphometry studies in which individuals with dyslexia (15 studies; 417 cases, 416 controls) or ADHD (22 studies; 898 cases, 763 controls) were compared to typically developing controls. We generated ALE maps for dyslexia vs. controls and ADHD vs. controls using more conservative (p < .001, k = 50) and more lenient (p < .005, k = 50) thresholds. To determine the overlap of gray matter correlates of dyslexia and ADHD, we examined the statistical conjunction between the ALE maps for dyslexia vs. controls and ADHD vs. controls (false discovery rate [FDR] p < .05, k = 50, 5000 permutations). RESULTS: Results showed largely distinct gray matter differences associated with dyslexia and ADHD. There was no evidence of statistically significant gray matter overlap at our conservative threshold, and only one region of overlap in the right caudate at our more lenient threshold. Reduced gray matter in the right caudate may be relevant to shared cognitive correlates in executive functioning and/or procedural learning. The more general finding of largely distinct regional differences in gray matter between dyslexia and ADHD suggests that other neuroimaging modalities may be more sensitive to overlapping neural correlates, and that current neuroimaging recruitment approaches may be hindering progress toward uncovering neural systems associated with comorbidity. CONCLUSIONS: The current study is the first to meta-analyze overlap between gray matter differences in dyslexia and ADHD, which is a critical step toward constructing a multi-level understanding of this comorbidity that spans the genetic, neural, and cognitive levels of analysis. En ligne : https://dx.doi.org/10.1186/s11689-019-9287-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children / Derek Sayre ANDREWS in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 32 Titre : A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children Type de document : texte imprimé Auteurs : Derek Sayre ANDREWS, Auteur ; Joshua K. LEE, Auteur ; Marjorie SOLOMON, Auteur ; Sally J. ROGERS, Auteur ; David G. AMARAL, Auteur ; Christine Wu NORDAHL, Auteur Article en page(s) : 32 Langues : Anglais (eng) Mots-clés : Anisotropy  Autism Spectrum Disorder/diagnostic imaging/pathology  Brain/diagnostic imaging/pathology  Child, Preschool  Cross-Sectional Studies  Diffusion Magnetic Resonance Imaging  Female  Humans  Image Processing, Computer-Assisted  Male  Sex Characteristics  White Matter/diagnostic imaging/pathology Index. décimale : PER Périodiques Résumé : BACKGROUND: The core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e., < 30-40 months) suggest individuals with ASD have increased measures of WM FA earlier in development. METHODS: We analyzed 127 individuals with ASD (85♂, 42♀) and 54 typically developing (TD) controls (42♂, 26♀), aged 25.1-49.6 months. Voxel-wise effects of ASD diagnosis, sex, age, and their interaction on DWI measures of FA, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were investigated using tract-based spatial statistics (TBSS) while controlling mean absolute and relative motion. RESULTS: Compared to TD controls, males and females with ASD had significantly increased measures of FA in eight clusters (threshold-free cluster enhancement p < 0.05) that incorporated several WM tracts including regions of the genu, body, and splenium of the corpus callosum, inferior frontal-occipital fasciculi, inferior and superior longitudinal fasciculi, middle and superior cerebellar peduncles, and corticospinal tract. A diagnosis by sex interaction was observed in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of the corpus collosum. In these tracts, females with ASD showed increased AD compared to TD females, while males with ASD showed decreased AD compared to TD males. CONCLUSIONS: The current findings support growing evidence that preschool-aged children with ASD have atypical measures of WM microstructure that appear to differ in directionality from alterations observed in older individuals with the condition. To our knowledge, this study represents the largest sample of preschool-aged females with ASD to be evaluated using DWI. Microstructural differences associated with ASD largely overlapped between sexes. However, differential relationships of AD measures indicate that sex likely modulates ASD neuroanatomical phenotypes. Further longitudinal study is needed to confirm and quantify the developmental relationship of WM structure in ASD. En ligne : https://dx.doi.org/10.1186/s11689-019-9291-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children [texte imprimé] / Derek Sayre ANDREWS, Auteur ; Joshua K. LEE, Auteur ; Marjorie SOLOMON, Auteur ; Sally J. ROGERS, Auteur ; David G. AMARAL, Auteur ; Christine Wu NORDAHL, Auteur . - 32. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 32 Mots-clés : Anisotropy  Autism Spectrum Disorder/diagnostic imaging/pathology  Brain/diagnostic imaging/pathology  Child, Preschool  Cross-Sectional Studies  Diffusion Magnetic Resonance Imaging  Female  Humans  Image Processing, Computer-Assisted  Male  Sex Characteristics  White Matter/diagnostic imaging/pathology Index. décimale : PER Périodiques Résumé : BACKGROUND: The core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e., < 30-40 months) suggest individuals with ASD have increased measures of WM FA earlier in development. METHODS: We analyzed 127 individuals with ASD (85♂, 42♀) and 54 typically developing (TD) controls (42♂, 26♀), aged 25.1-49.6 months. Voxel-wise effects of ASD diagnosis, sex, age, and their interaction on DWI measures of FA, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were investigated using tract-based spatial statistics (TBSS) while controlling mean absolute and relative motion. RESULTS: Compared to TD controls, males and females with ASD had significantly increased measures of FA in eight clusters (threshold-free cluster enhancement p < 0.05) that incorporated several WM tracts including regions of the genu, body, and splenium of the corpus callosum, inferior frontal-occipital fasciculi, inferior and superior longitudinal fasciculi, middle and superior cerebellar peduncles, and corticospinal tract. A diagnosis by sex interaction was observed in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of the corpus collosum. In these tracts, females with ASD showed increased AD compared to TD females, while males with ASD showed decreased AD compared to TD males. CONCLUSIONS: The current findings support growing evidence that preschool-aged children with ASD have atypical measures of WM microstructure that appear to differ in directionality from alterations observed in older individuals with the condition. To our knowledge, this study represents the largest sample of preschool-aged females with ASD to be evaluated using DWI. Microstructural differences associated with ASD largely overlapped between sexes. However, differential relationships of AD measures indicate that sex likely modulates ASD neuroanatomical phenotypes. Further longitudinal study is needed to confirm and quantify the developmental relationship of WM structure in ASD. En ligne : https://dx.doi.org/10.1186/s11689-019-9291-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Spatiotemporal development of spinal neuronal and glial populations in the Ts65Dn mouse model of Down syndrome / Nadine M. AZIZ in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 35 Titre : Spatiotemporal development of spinal neuronal and glial populations in the Ts65Dn mouse model of Down syndrome Type de document : texte imprimé Auteurs : Nadine M. AZIZ, Auteur ; Jenny A. KLEIN, Auteur ; Morgan R. BRADY, Auteur ; Jose Luis OLMOS-SERRANO, Auteur ; Vittorio GALLO, Auteur ; Tarik F. HAYDAR, Auteur Article en page(s) : 35 Langues : Anglais (eng) Mots-clés : Animals  Disease Models, Animal  Down Syndrome/physiopathology  Female  Gene Expression Regulation, Developmental  Homeobox Protein Nkx-2.2  Homeodomain Proteins  Male  Mice, Transgenic  Neuroglia/physiology  Neurons/physiology  Nuclear Proteins  Spinal Cord/growth & development  Transcription Factors  White Matter/growth & development Index. décimale : PER Périodiques Résumé : BACKGROUND: Down syndrome (DS), caused by the triplication of chromosome 21, results in a constellation of clinical features including changes in intellectual and motor function. Although altered neural development and function have been well described in people with DS, few studies have investigated the etiology underlying the observed motor phenotypes. Here, we examine the development, patterning, and organization of the spinal cord throughout life in the Ts65Dn mouse, a model that recapitulates many of the motor changes observed in people with DS. METHODS: Spinal cords from embryonic to adult animals were processed for gene and protein expression (immunofluorescence) to track the spatiotemporal development of excitatory and inhibitory neurons and oligodendroglia. Postnatal analyses were focused on the lumbar region due to the reflex and gait abnormalities found in Ts65Dn mice and locomotive alterations seen in people with DS. RESULTS: Between embryonic days E10.5 and E14.5, we found a larger motor neuron progenitor domain in Ts65Dn animals containing more OLIG2-expressing progenitor cells. These disturbed progenitors are delayed in motor neuron production but eventually generate a large number of ISL1+ migrating motor neurons. We found that higher numbers of PAX6+ and NKX2.2+ interneurons (INs) are also produced during this time frame. In the adult lumbar spinal cord, we found an increased level of Hb9 and a decreased level of Irx3 gene expression in trisomic animals. This was accompanied by an increase in Calretinin+ INs, but no changes in other neuronal populations. In aged Ts65Dn animals, both Calbindin+ and ChAT+ neurons were decreased compared to euploid controls. Additionally, in the dorsal corticospinal white matter tract, there were significantly fewer CC1+ mature OLs in 30- and 60-day old trisomic animals and this normalized to euploid levels at 10-11 months. In contrast, the mature OL population was increased in the lateral funiculus, an ascending white matter tract carrying sensory information. In 30-day old animals, we also found a decrease in the number of nodes of Ranvier in both tracts. This decrease normalized both in 60-day old and aged animals. CONCLUSIONS: We show marked changes in both spinal white matter and neuronal composition that change regionally over the life span. In the embryonic Ts65Dn spinal cord, we observe alterations in motor neuron production and migration. In the adult spinal cord, we observe changes in oligodendrocyte maturation and motor neuron loss, the latter of which has also been observed in human spinal cord tissue samples. This work uncovers multiple cellular perturbations during Ts65Dn development and aging, many of which may underlie the motor deficits found in DS. En ligne : https://dx.doi.org/10.1186/s11689-019-9294-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Spatiotemporal development of spinal neuronal and glial populations in the Ts65Dn mouse model of Down syndrome [texte imprimé] / Nadine M. AZIZ, Auteur ; Jenny A. KLEIN, Auteur ; Morgan R. BRADY, Auteur ; Jose Luis OLMOS-SERRANO, Auteur ; Vittorio GALLO, Auteur ; Tarik F. HAYDAR, Auteur . - 35. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 35 Mots-clés : Animals  Disease Models, Animal  Down Syndrome/physiopathology  Female  Gene Expression Regulation, Developmental  Homeobox Protein Nkx-2.2  Homeodomain Proteins  Male  Mice, Transgenic  Neuroglia/physiology  Neurons/physiology  Nuclear Proteins  Spinal Cord/growth & development  Transcription Factors  White Matter/growth & development Index. décimale : PER Périodiques Résumé : BACKGROUND: Down syndrome (DS), caused by the triplication of chromosome 21, results in a constellation of clinical features including changes in intellectual and motor function. Although altered neural development and function have been well described in people with DS, few studies have investigated the etiology underlying the observed motor phenotypes. Here, we examine the development, patterning, and organization of the spinal cord throughout life in the Ts65Dn mouse, a model that recapitulates many of the motor changes observed in people with DS. METHODS: Spinal cords from embryonic to adult animals were processed for gene and protein expression (immunofluorescence) to track the spatiotemporal development of excitatory and inhibitory neurons and oligodendroglia. Postnatal analyses were focused on the lumbar region due to the reflex and gait abnormalities found in Ts65Dn mice and locomotive alterations seen in people with DS. RESULTS: Between embryonic days E10.5 and E14.5, we found a larger motor neuron progenitor domain in Ts65Dn animals containing more OLIG2-expressing progenitor cells. These disturbed progenitors are delayed in motor neuron production but eventually generate a large number of ISL1+ migrating motor neurons. We found that higher numbers of PAX6+ and NKX2.2+ interneurons (INs) are also produced during this time frame. In the adult lumbar spinal cord, we found an increased level of Hb9 and a decreased level of Irx3 gene expression in trisomic animals. This was accompanied by an increase in Calretinin+ INs, but no changes in other neuronal populations. In aged Ts65Dn animals, both Calbindin+ and ChAT+ neurons were decreased compared to euploid controls. Additionally, in the dorsal corticospinal white matter tract, there were significantly fewer CC1+ mature OLs in 30- and 60-day old trisomic animals and this normalized to euploid levels at 10-11 months. In contrast, the mature OL population was increased in the lateral funiculus, an ascending white matter tract carrying sensory information. In 30-day old animals, we also found a decrease in the number of nodes of Ranvier in both tracts. This decrease normalized both in 60-day old and aged animals. CONCLUSIONS: We show marked changes in both spinal white matter and neuronal composition that change regionally over the life span. In the embryonic Ts65Dn spinal cord, we observe alterations in motor neuron production and migration. In the adult spinal cord, we observe changes in oligodendrocyte maturation and motor neuron loss, the latter of which has also been observed in human spinal cord tissue samples. This work uncovers multiple cellular perturbations during Ts65Dn development and aging, many of which may underlie the motor deficits found in DS. En ligne : https://dx.doi.org/10.1186/s11689-019-9294-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

In memory of Jean de Vellis (1935-2018) / Susan Y. BOOKHEIMER in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 28 Titre : In memory of Jean de Vellis (1935-2018) Type de document : texte imprimé Auteurs : Susan Y. BOOKHEIMER, Auteur ; Harley I. KORNBLUM, Auteur Article en page(s) : 28 Langues : Anglais (eng) Mots-clés : History, 20th Century  History, 21st Century  Neurodevelopmental Disorders/history  Neurosciences/history Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-019-9298-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] In memory of Jean de Vellis (1935-2018) [texte imprimé] / Susan Y. BOOKHEIMER, Auteur ; Harley I. KORNBLUM, Auteur . - 28. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 28 Mots-clés : History, 20th Century  History, 21st Century  Neurodevelopmental Disorders/history  Neurosciences/history Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-019-9298-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

The impact of expressive language development and the left inferior longitudinal fasciculus on listening and reading comprehension / Stephanie N. DEL TUFO in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 37 Titre : The impact of expressive language development and the left inferior longitudinal fasciculus on listening and reading comprehension Type de document : texte imprimé Auteurs : Stephanie N. DEL TUFO, Auteur ; F. Sayako EARLE, Auteur ; Laurie E. CUTTING, Auteur Article en page(s) : 37 Langues : Anglais (eng) Mots-clés : Child  Comprehension/physiology  Diffusion Magnetic Resonance Imaging  Female  Humans  Language Development  Language Development Disorders/diagnosis/pathology  Male  Neural Pathways  Prefrontal Cortex/pathology/physiopathology  Reading  Speech Perception/physiology  Temporal Lobe/pathology/physiopathology  Developmental disorder  Expressive language development  Genre  Inferior longitudinal fasciculus  Intervention  Longitudinal  Modality  Passage comprehension  Socioeconomic  Survival analysis Index. décimale : PER Périodiques Résumé : BACKGROUND: During the first 3-years of life, as the brain undergoes dramatic growth, children begin to develop speech and language. Hallmarks of this progression are seen when children reach developmental milestones, forming the foundation of language. Expressive language milestones, such as the production of a child's first word, are delayed in 5-8% of children. While for some children delays in reaching these milestones are harbingers of developmental disorders, for others expressive language delays appear to resolve. Regardless of whether or not early language skills appear resolved, difficulty with later comprehension is a likely outcome. Whether this heightened risk for poor comprehension differs based on text features, individual characteristics, or receipt of intervention remains unknown. Moreover, this relationship between expressive language development and comprehension is not yet linked to neurobiology, though the inferior longitudinal fasciculus (ILF) is a potential neurobiological correlate. Therefore, we investigated the impact of, and interactions between, expressive language development, early intervention, and the ILF on comprehension. METHODS: Longitudinal recurrent survival analyses predicted the risk of answering a comprehension question incorrectly. Predictors of comprehension included expressive language development, passage features, participant characteristics, fractional anisotropy, receipt of early intervention, and later diagnosis of speech or language disorders. RESULTS: Children with later expressive language milestones had poorer comprehension. When comprehension text features were examined, children with later milestones had poorer listening and reading comprehension, and poorer narrative and expository comprehension. The left ILF acted as a neurodevelopmental correlate, one that moderated the relationship between expressive language milestones and comprehension. Specifically, the left ILF exacerbated the relationship for those who did not receive early intervention and buffered the relationship for those who received intervention services. Early intervention decreased the risk of poor comprehension by 39% for children later diagnosed with a speech or language disorder. CONCLUSIONS: Early intervention should be provided for children with delayed expressive language milestones, particularly those who are at risk for speech or language disorders. The ILF plays a critical role in the relationship between expressive language development and comprehension, which may be that of a protective factor for children with the most severe early issues with speech and language. En ligne : https://dx.doi.org/10.1186/s11689-019-9296-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] The impact of expressive language development and the left inferior longitudinal fasciculus on listening and reading comprehension [texte imprimé] / Stephanie N. DEL TUFO, Auteur ; F. Sayako EARLE, Auteur ; Laurie E. CUTTING, Auteur . - 37. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 37 Mots-clés : Child  Comprehension/physiology  Diffusion Magnetic Resonance Imaging  Female  Humans  Language Development  Language Development Disorders/diagnosis/pathology  Male  Neural Pathways  Prefrontal Cortex/pathology/physiopathology  Reading  Speech Perception/physiology  Temporal Lobe/pathology/physiopathology  Developmental disorder  Expressive language development  Genre  Inferior longitudinal fasciculus  Intervention  Longitudinal  Modality  Passage comprehension  Socioeconomic  Survival analysis Index. décimale : PER Périodiques Résumé : BACKGROUND: During the first 3-years of life, as the brain undergoes dramatic growth, children begin to develop speech and language. Hallmarks of this progression are seen when children reach developmental milestones, forming the foundation of language. Expressive language milestones, such as the production of a child's first word, are delayed in 5-8% of children. While for some children delays in reaching these milestones are harbingers of developmental disorders, for others expressive language delays appear to resolve. Regardless of whether or not early language skills appear resolved, difficulty with later comprehension is a likely outcome. Whether this heightened risk for poor comprehension differs based on text features, individual characteristics, or receipt of intervention remains unknown. Moreover, this relationship between expressive language development and comprehension is not yet linked to neurobiology, though the inferior longitudinal fasciculus (ILF) is a potential neurobiological correlate. Therefore, we investigated the impact of, and interactions between, expressive language development, early intervention, and the ILF on comprehension. METHODS: Longitudinal recurrent survival analyses predicted the risk of answering a comprehension question incorrectly. Predictors of comprehension included expressive language development, passage features, participant characteristics, fractional anisotropy, receipt of early intervention, and later diagnosis of speech or language disorders. RESULTS: Children with later expressive language milestones had poorer comprehension. When comprehension text features were examined, children with later milestones had poorer listening and reading comprehension, and poorer narrative and expository comprehension. The left ILF acted as a neurodevelopmental correlate, one that moderated the relationship between expressive language milestones and comprehension. Specifically, the left ILF exacerbated the relationship for those who did not receive early intervention and buffered the relationship for those who received intervention services. Early intervention decreased the risk of poor comprehension by 39% for children later diagnosed with a speech or language disorder. CONCLUSIONS: Early intervention should be provided for children with delayed expressive language milestones, particularly those who are at risk for speech or language disorders. The ILF plays a critical role in the relationship between expressive language development and comprehension, which may be that of a protective factor for children with the most severe early issues with speech and language. En ligne : https://dx.doi.org/10.1186/s11689-019-9296-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Mitochondrial aminoacyl-tRNA synthetase disorders: an emerging group of developmental disorders of myelination / Amena Smith FINE in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 29 Titre : Mitochondrial aminoacyl-tRNA synthetase disorders: an emerging group of developmental disorders of myelination Type de document : texte imprimé Auteurs : Amena Smith FINE, Auteur ; Christina L. NEMETH, Auteur ; Miriam L. KAUFMAN, Auteur Article en page(s) : 29 Langues : Anglais (eng) Mots-clés : Amino Acyl-tRNA Synthetases/metabolism  Animals  Brain/enzymology/pathology  Demyelinating Diseases/complications/enzymology  Humans  Mitochondria/metabolism  Mitochondrial Diseases/complications/enzymology  Mitochondrial Proteins/metabolism  Neurodevelopmental Disorders/enzymology  Dars2  Ears2  Lbsl  Ltbl aars2  Leukodystrophy  Mitochondrial aminoacyl-tRNA synthetases  Ovario-leukodystropy Index. décimale : PER Périodiques Résumé : BACKGROUND: The mitochondrial aminoacyl-tRNA synthetase proteins (mt-aaRSs) are a group of nuclear-encoded enzymes that facilitate conjugation of each of the 20 amino acids to its cognate tRNA molecule. Mitochondrial diseases are a large, clinically heterogeneous group of disorders with diverse etiologies, ages of onset, and involved organ systems. Diseases related to mt-aaRS mutations are associated with specific syndromes that affect the central nervous system and produce highly characteristic MRI patterns, prototypically the DARS2, EARS, and AARS2 leukodystrophies, which are caused by mutations in mitochondrial aspartyl-tRNA synthetase, mitochondria glutamate tRNA synthetase, and mitochondrial alanyl-tRNA synthetase, respectively. BODY: The disease patterns emerging for these leukodystrophies are distinct in terms of the age of onset, nature of disease progression, and predominance of involved white matter tracts. In DARS2 and EARS2 disorders, earlier disease onset is typically correlated with more significant brain abnormalities, rapid neurological decline, and greater disability. In AARS2 leukodystrophy cases reported thus far, there is nearly invariable progression to severe disability and atrophy of involved brain regions, often within a decade. Although most mutations are compound heterozygous inherited in an autosomal recessive fashion, homozygous variants are found in each disorder and demonstrate high phenotypic variability. Affected siblings manifest disease on a wide spectrum. CONCLUSION: The syndromic nature and selective vulnerability of white matter tracts in these disorders suggests there may be a shared mechanism of mitochondrial dysfunction to target for study. There is evidence that the clinical variability and white matter tract specificity of each mt-aaRS leukodystrophy depend on both canonical and non-canonical effects of the mutations on the process of mitochondrial translation. Furthermore, different sensitivities to the mt-aaRS mutations have been observed based on cell type. Most mutations result in at least partial retention of mt-aaRS enzyme function with varied effects on the mitochondrial respiratory chain complexes. In EARS2 and AARS2 cells, this appears to result in cumulative impairment of respiration. Mt-aaRS mutations may also affect alternative biochemical pathways such as the integrated stress response, a homeostatic program in eukaryotic cells that typically confers cytoprotection, but can lead to cell death when abnormally activated in response to pathologic states. Systematic review of this group of disorders and further exploration of disease mechanisms in disease models and neural cells are warranted. En ligne : https://dx.doi.org/10.1186/s11689-019-9292-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Mitochondrial aminoacyl-tRNA synthetase disorders: an emerging group of developmental disorders of myelination [texte imprimé] / Amena Smith FINE, Auteur ; Christina L. NEMETH, Auteur ; Miriam L. KAUFMAN, Auteur . - 29. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 29 Mots-clés : Amino Acyl-tRNA Synthetases/metabolism  Animals  Brain/enzymology/pathology  Demyelinating Diseases/complications/enzymology  Humans  Mitochondria/metabolism  Mitochondrial Diseases/complications/enzymology  Mitochondrial Proteins/metabolism  Neurodevelopmental Disorders/enzymology  Dars2  Ears2  Lbsl  Ltbl aars2  Leukodystrophy  Mitochondrial aminoacyl-tRNA synthetases  Ovario-leukodystropy Index. décimale : PER Périodiques Résumé : BACKGROUND: The mitochondrial aminoacyl-tRNA synthetase proteins (mt-aaRSs) are a group of nuclear-encoded enzymes that facilitate conjugation of each of the 20 amino acids to its cognate tRNA molecule. Mitochondrial diseases are a large, clinically heterogeneous group of disorders with diverse etiologies, ages of onset, and involved organ systems. Diseases related to mt-aaRS mutations are associated with specific syndromes that affect the central nervous system and produce highly characteristic MRI patterns, prototypically the DARS2, EARS, and AARS2 leukodystrophies, which are caused by mutations in mitochondrial aspartyl-tRNA synthetase, mitochondria glutamate tRNA synthetase, and mitochondrial alanyl-tRNA synthetase, respectively. BODY: The disease patterns emerging for these leukodystrophies are distinct in terms of the age of onset, nature of disease progression, and predominance of involved white matter tracts. In DARS2 and EARS2 disorders, earlier disease onset is typically correlated with more significant brain abnormalities, rapid neurological decline, and greater disability. In AARS2 leukodystrophy cases reported thus far, there is nearly invariable progression to severe disability and atrophy of involved brain regions, often within a decade. Although most mutations are compound heterozygous inherited in an autosomal recessive fashion, homozygous variants are found in each disorder and demonstrate high phenotypic variability. Affected siblings manifest disease on a wide spectrum. CONCLUSION: The syndromic nature and selective vulnerability of white matter tracts in these disorders suggests there may be a shared mechanism of mitochondrial dysfunction to target for study. There is evidence that the clinical variability and white matter tract specificity of each mt-aaRS leukodystrophy depend on both canonical and non-canonical effects of the mutations on the process of mitochondrial translation. Furthermore, different sensitivities to the mt-aaRS mutations have been observed based on cell type. Most mutations result in at least partial retention of mt-aaRS enzyme function with varied effects on the mitochondrial respiratory chain complexes. In EARS2 and AARS2 cells, this appears to result in cumulative impairment of respiration. Mt-aaRS mutations may also affect alternative biochemical pathways such as the integrated stress response, a homeostatic program in eukaryotic cells that typically confers cytoprotection, but can lead to cell death when abnormally activated in response to pathologic states. Systematic review of this group of disorders and further exploration of disease mechanisms in disease models and neural cells are warranted. En ligne : https://dx.doi.org/10.1186/s11689-019-9292-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

White matter and neurodevelopmental disorders: honoring Jean De Vellis through the work of the NICHD-funded intellectual and developmental disabilities research centers / Heather Cody HAZLETT in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 38 Titre : White matter and neurodevelopmental disorders: honoring Jean De Vellis through the work of the NICHD-funded intellectual and developmental disabilities research centers Type de document : texte imprimé Auteurs : Heather Cody HAZLETT, Auteur ; Vittorio GALLO, Auteur Article en page(s) : 38 Langues : Anglais (eng) Mots-clés : Brain/physiopathology  Humans  Intellectual Disability/complications/physiopathology  National Institute of Child Health and Human Development (U.S.)  Neurodevelopmental Disorders/complications/physiopathology  United States  White Matter/physiopathology Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-019-9299-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] White matter and neurodevelopmental disorders: honoring Jean De Vellis through the work of the NICHD-funded intellectual and developmental disabilities research centers [texte imprimé] / Heather Cody HAZLETT, Auteur ; Vittorio GALLO, Auteur . - 38. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 38 Mots-clés : Brain/physiopathology  Humans  Intellectual Disability/complications/physiopathology  National Institute of Child Health and Human Development (U.S.)  Neurodevelopmental Disorders/complications/physiopathology  United States  White Matter/physiopathology Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-019-9299-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Refining the concept of GFAP toxicity in Alexander disease / Albee MESSING in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 27 Titre : Refining the concept of GFAP toxicity in Alexander disease Type de document : texte imprimé Auteurs : Albee MESSING, Auteur Article en page(s) : 27 Langues : Anglais (eng) Mots-clés : Alexander Disease/genetics  Animals  Astrocytes/metabolism  Glial Fibrillary Acidic Protein/genetics/metabolism  Humans  Mutation  Antisense oligonucleotides  Astrocyte  Gfap Index. décimale : PER Périodiques Résumé : BACKGROUND: Alexander disease is caused by dominantly acting mutations in glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes in the central nervous system. MAIN BODY: In addition to the sequence variants that represent the origin of disease, GFAP accumulation also takes place, together leading to a gain-of-function that has sometimes been referred to as "GFAP toxicity." Whether the nature of GFAP toxicity in patients, who have mixtures of both mutant and normal protein, is the same as that produced by simple GFAP excess, is not yet clear. CONCLUSION: The implications of these questions for the design of effective treatments are discussed. En ligne : https://dx.doi.org/10.1186/s11689-019-9290-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Refining the concept of GFAP toxicity in Alexander disease [texte imprimé] / Albee MESSING, Auteur . - 27. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 27 Mots-clés : Alexander Disease/genetics  Animals  Astrocytes/metabolism  Glial Fibrillary Acidic Protein/genetics/metabolism  Humans  Mutation  Antisense oligonucleotides  Astrocyte  Gfap Index. décimale : PER Périodiques Résumé : BACKGROUND: Alexander disease is caused by dominantly acting mutations in glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes in the central nervous system. MAIN BODY: In addition to the sequence variants that represent the origin of disease, GFAP accumulation also takes place, together leading to a gain-of-function that has sometimes been referred to as "GFAP toxicity." Whether the nature of GFAP toxicity in patients, who have mixtures of both mutant and normal protein, is the same as that produced by simple GFAP excess, is not yet clear. CONCLUSION: The implications of these questions for the design of effective treatments are discussed. En ligne : https://dx.doi.org/10.1186/s11689-019-9290-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder / Anna K. PROHL in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 36 Titre : Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder Type de document : texte imprimé Auteurs : Anna K. PROHL, Auteur ; Benoit SCHERRER, Auteur ; Xavier TOMAS-FERNANDEZ, Auteur ; Peter E. DAVIS, Auteur ; Rajna FILIP-DHIMA, Auteur ; Sanjay P. PRABHU, Auteur ; Jurriaan M. PETERS, Auteur ; E. Martina BEBIN, Auteur ; Darcy A. KRUEGER, Auteur ; Hope NORTHRUP, Auteur ; Joyce Y. WU, Auteur ; Mustafa SAHIN, Auteur ; Simon K. WARFIELD, Auteur Article en page(s) : 36 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications/pathology  Brain/growth & development/pathology  Child, Preschool  Diffusion Tensor Imaging  Female  Humans  Infant  Longitudinal Studies  Male  Prospective Studies  Tuberous Sclerosis/complications/pathology  White Matter/growth & development/pathology  Autism spectrum disorder  Infant brain development  Tuberous sclerosis complex  White matter Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants. METHODS: TSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD. RESULTS: Subjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups. CONCLUSIONS: Underconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms. En ligne : https://dx.doi.org/10.1186/s11689-019-9293-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder [texte imprimé] / Anna K. PROHL, Auteur ; Benoit SCHERRER, Auteur ; Xavier TOMAS-FERNANDEZ, Auteur ; Peter E. DAVIS, Auteur ; Rajna FILIP-DHIMA, Auteur ; Sanjay P. PRABHU, Auteur ; Jurriaan M. PETERS, Auteur ; E. Martina BEBIN, Auteur ; Darcy A. KRUEGER, Auteur ; Hope NORTHRUP, Auteur ; Joyce Y. WU, Auteur ; Mustafa SAHIN, Auteur ; Simon K. WARFIELD, Auteur . - 36. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 36 Mots-clés : Autism Spectrum Disorder/complications/pathology  Brain/growth & development/pathology  Child, Preschool  Diffusion Tensor Imaging  Female  Humans  Infant  Longitudinal Studies  Male  Prospective Studies  Tuberous Sclerosis/complications/pathology  White Matter/growth & development/pathology  Autism spectrum disorder  Infant brain development  Tuberous sclerosis complex  White matter Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants. METHODS: TSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD. RESULTS: Subjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups. CONCLUSIONS: Underconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms. En ligne : https://dx.doi.org/10.1186/s11689-019-9293-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

White matter as a monitoring biomarker for neurodevelopmental disorder intervention studies / Meghan R. SWANSON in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 33 Titre : White matter as a monitoring biomarker for neurodevelopmental disorder intervention studies Type de document : texte imprimé Auteurs : Meghan R. SWANSON, Auteur ; Heather C. HAZLETT, Auteur Article en page(s) : 33 Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/diagnostic imaging/pathology/therapy  Biomarkers  Brain/diagnostic imaging/growth & development/pathology  Early Medical Intervention  Fragile X Syndrome/diagnostic imaging/pathology/therapy  Humans  Neurodevelopmental Disorders/diagnostic imaging/pathology/therapy  White Matter/diagnostic imaging/growth & development/pathology  Autism spectrum disorder  Brain  Clinical trial  Fragile X syndrome  Intervention  Myelin  Neurodevelopment  Treatment  White matter Index. décimale : PER Périodiques Résumé : BACKGROUND: Early intervention is a valuable tool to support the development of toddlers with neurodevelopmental disorders. With recent research advances in early identification that allow for pre-symptomatic detection of autism in infancy, scientists are looking forward to intervention during infancy. These advances may be supported by the identification of biologically based treatment and outcome measures that are sensitive and dimensional. The purpose of this review is to evaluate white matter neurodevelopment as a monitoring biomarker for early treatment of neurodevelopmental disorders. Fragile X syndrome (FXS) and autism spectrum disorder (ASD) as used as exemplars. White matter has unique neurobiology, including a prolonged period of dynamic development. This developmental pattern may make white matter especially responsive to treatment. White matter develops aberrantly in children with ASD and FXS. Histologic studies in rodents have provided targets for FXS pharmacological intervention. However, pharmaceutical clinical trials in humans failed to garner positive clinical results. In this article, we argue that the use of neurobiological monitoring biomarkers may overcome some of these limitations, as they are objective, not susceptible to placebo effects, and are dimensional in nature. SHORT CONCLUSION: As the field moves towards earlier detection and early intervention for neurodevelopmental disorders, we encourage scientists to consider the advantages of using neurobiological features as monitoring biomarkers. En ligne : https://dx.doi.org/10.1186/s11689-019-9295-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] White matter as a monitoring biomarker for neurodevelopmental disorder intervention studies [texte imprimé] / Meghan R. SWANSON, Auteur ; Heather C. HAZLETT, Auteur . - 33. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 33 Mots-clés : Animals  Autism Spectrum Disorder/diagnostic imaging/pathology/therapy  Biomarkers  Brain/diagnostic imaging/growth & development/pathology  Early Medical Intervention  Fragile X Syndrome/diagnostic imaging/pathology/therapy  Humans  Neurodevelopmental Disorders/diagnostic imaging/pathology/therapy  White Matter/diagnostic imaging/growth & development/pathology  Autism spectrum disorder  Brain  Clinical trial  Fragile X syndrome  Intervention  Myelin  Neurodevelopment  Treatment  White matter Index. décimale : PER Périodiques Résumé : BACKGROUND: Early intervention is a valuable tool to support the development of toddlers with neurodevelopmental disorders. With recent research advances in early identification that allow for pre-symptomatic detection of autism in infancy, scientists are looking forward to intervention during infancy. These advances may be supported by the identification of biologically based treatment and outcome measures that are sensitive and dimensional. The purpose of this review is to evaluate white matter neurodevelopment as a monitoring biomarker for early treatment of neurodevelopmental disorders. Fragile X syndrome (FXS) and autism spectrum disorder (ASD) as used as exemplars. White matter has unique neurobiology, including a prolonged period of dynamic development. This developmental pattern may make white matter especially responsive to treatment. White matter develops aberrantly in children with ASD and FXS. Histologic studies in rodents have provided targets for FXS pharmacological intervention. However, pharmaceutical clinical trials in humans failed to garner positive clinical results. In this article, we argue that the use of neurobiological monitoring biomarkers may overcome some of these limitations, as they are objective, not susceptible to placebo effects, and are dimensional in nature. SHORT CONCLUSION: As the field moves towards earlier detection and early intervention for neurodevelopmental disorders, we encourage scientists to consider the advantages of using neurobiological features as monitoring biomarkers. En ligne : https://dx.doi.org/10.1186/s11689-019-9295-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex / Michael WONG in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 30 Titre : The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex Type de document : texte imprimé Auteurs : Michael WONG, Auteur Article en page(s) : 30 Langues : Anglais (eng) Mots-clés : Animals  Brain/physiopathology  Epilepsy/complications/physiopathology  Humans  Intellectual Disability/complications/physiopathology  Neurodevelopmental Disorders/complications/physiopathology  Neuroglia/physiology  Neurons/physiology  Tuberous Sclerosis/complications/physiopathology  Astrocyte  Autism spectrum disorder  Epilepsy  Glia  Intellectual disability  Microglia  Oligodendrocyte  Tand  Tuberous sclerosis  White matter Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by severe neurological manifestations, including epilepsy, intellectual disability, autism, and a range of other behavioral and psychiatric symptoms, collectively referred to as TSC-associated neuropsychiatric disorders (TAND). Various tumors and hamartomas affecting different organs are the pathological hallmarks of the disease, especially cortical tubers of the brain, but specific cellular and molecular abnormalities, such as involving the mechanistic target of rapamycin (mTOR) pathway, have been identified that also cause or contribute to neurological manifestations of TSC independent of gross structural lesions. In particular, while neurons are immediate mediators of neurological symptoms, different types of glial cells have been increasingly recognized to play important roles in the phenotypes of TSC. MAIN BODY: This review summarizes the literature supporting glial dysfunction from both mouse models and clinical studies of TSC. In particular, evidence for the role of astrocytes, microglia, and oligodendrocytes in the pathophysiology of epilepsy and TAND in TSC is analyzed. Therapeutic implications of targeting glia cells in developing novel treatments for the neurological manifestations of TSC are also considered. CONCLUSIONS: Different types of glial cells have both cell autonomous effects and interactions with neurons and other cells that are involved in the pathophysiology of the neurological phenotype of TSC. Targeting glial-mediated mechanisms may represent a novel therapeutic approach for epilepsy and TAND in TSC patients. En ligne : https://dx.doi.org/10.1186/s11689-019-9289-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex [texte imprimé] / Michael WONG, Auteur . - 30. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 30 Mots-clés : Animals  Brain/physiopathology  Epilepsy/complications/physiopathology  Humans  Intellectual Disability/complications/physiopathology  Neurodevelopmental Disorders/complications/physiopathology  Neuroglia/physiology  Neurons/physiology  Tuberous Sclerosis/complications/physiopathology  Astrocyte  Autism spectrum disorder  Epilepsy  Glia  Intellectual disability  Microglia  Oligodendrocyte  Tand  Tuberous sclerosis  White matter Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by severe neurological manifestations, including epilepsy, intellectual disability, autism, and a range of other behavioral and psychiatric symptoms, collectively referred to as TSC-associated neuropsychiatric disorders (TAND). Various tumors and hamartomas affecting different organs are the pathological hallmarks of the disease, especially cortical tubers of the brain, but specific cellular and molecular abnormalities, such as involving the mechanistic target of rapamycin (mTOR) pathway, have been identified that also cause or contribute to neurological manifestations of TSC independent of gross structural lesions. In particular, while neurons are immediate mediators of neurological symptoms, different types of glial cells have been increasingly recognized to play important roles in the phenotypes of TSC. MAIN BODY: This review summarizes the literature supporting glial dysfunction from both mouse models and clinical studies of TSC. In particular, evidence for the role of astrocytes, microglia, and oligodendrocytes in the pathophysiology of epilepsy and TAND in TSC is analyzed. Therapeutic implications of targeting glia cells in developing novel treatments for the neurological manifestations of TSC are also considered. CONCLUSIONS: Different types of glial cells have both cell autonomous effects and interactions with neurons and other cells that are involved in the pathophysiology of the neurological phenotype of TSC. Targeting glial-mediated mechanisms may represent a novel therapeutic approach for epilepsy and TAND in TSC patients. En ligne : https://dx.doi.org/10.1186/s11689-019-9289-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Reducing Th2 inflammation through neutralizing IL-4 antibody rescues myelination in IUGR rat brain / Allison E. ZANNO in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 34 Titre : Reducing Th2 inflammation through neutralizing IL-4 antibody rescues myelination in IUGR rat brain Type de document : texte imprimé Auteurs : Allison E. ZANNO, Auteur ; Micah A. ROMER, Auteur ; Lauren FOX, Auteur ; Thea GOLDEN, Auteur ; Lane JAECKLE-SANTOS, Auteur ; Rebecca A. SIMMONS, Auteur ; Judith B. GRINSPAN, Auteur Article en page(s) : 34 Langues : Anglais (eng) Mots-clés : Animals  Brain/immunology  Disease Models, Animal  Encephalitis/complications/immunology  Female  Fetal Growth Retardation/immunology  Interleukin-4/immunology  Macrophages/immunology  Male  Microglia/immunology  Myelin Sheath/immunology  Rats, Sprague-Dawley  Th2 Cells/immunology  White Matter/immunology  Il-4  Inflammation  Myelin  Oligodendrocyte Index. décimale : PER Périodiques Résumé : BACKGROUND: Intrauterine growth restriction (IUGR) is a common complication of pregnancy and is associated with significant neurological deficits in infants, including white matter damage. Previous work using an animal model of IUGR has demonstrated that IUGR rats exhibit neurobehavioral deficits and developmental delays in oligodendrocyte maturation and myelination, but the mechanisms which cause this delay are unknown. Inflammation may be an important etiological factor in IUGR and has been recognized as playing a fundamental role in the pathogenesis of myelin disorders, including cerebral palsy. METHODS: To create the model, the uterine arteries of pregnant rats were ligated at embryonic day 15. Rats delivered spontaneously. Cytokine and chemokine expression was evaluated at one prenatal and three postnatal time points, and myelin protein expression and oligodendrocyte cell numbers were evaluated by several methods at postnatal day 14. IL-4 was identified as a potential inhibitor of myelination, and rat pups were injected with IL-4 function blocking antibody from postnatal days 1-5 and myelination was assessed. RESULTS: Here, we show a novel mechanism of white matter injury. IUGR induces an exaggerated Th2 response in the developing rat brain, including upregulation of several Th2 cytokines. Of these, IL-4 is significantly increased during the period corresponding to robust developmental myelination. We show that neutralizing IL-4 antibody therapy given in the newborn period ameliorates inflammation and restores myelin protein expression and oligodendrocyte cell number in the IUGR brain to control levels, demonstrating a novel role for Th2 responses and IL-4 in IUGR and white matter injury. In addition, IL-4 directly affects oligodendrocytes in vitro decreasing differentiation. CONCLUSIONS: In this study, we have identified inflammation as a factor in the decrease in myelin seen in an animal model of IUGR. IL-4, an inflammatory protein often thought to be protective in the adult, is specifically increased, and treatment of these animals to prevent this increase ameliorates white matter damage. Our results suggest that the immune system plays a role in IUGR that is different in the perinatal period than in the adult and preventing this exaggerated Th2 response may be a potential therapeutic target. En ligne : https://dx.doi.org/10.1186/s11689-019-9297-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Reducing Th2 inflammation through neutralizing IL-4 antibody rescues myelination in IUGR rat brain [texte imprimé] / Allison E. ZANNO, Auteur ; Micah A. ROMER, Auteur ; Lauren FOX, Auteur ; Thea GOLDEN, Auteur ; Lane JAECKLE-SANTOS, Auteur ; Rebecca A. SIMMONS, Auteur ; Judith B. GRINSPAN, Auteur . - 34. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 34 Mots-clés : Animals  Brain/immunology  Disease Models, Animal  Encephalitis/complications/immunology  Female  Fetal Growth Retardation/immunology  Interleukin-4/immunology  Macrophages/immunology  Male  Microglia/immunology  Myelin Sheath/immunology  Rats, Sprague-Dawley  Th2 Cells/immunology  White Matter/immunology  Il-4  Inflammation  Myelin  Oligodendrocyte Index. décimale : PER Périodiques Résumé : BACKGROUND: Intrauterine growth restriction (IUGR) is a common complication of pregnancy and is associated with significant neurological deficits in infants, including white matter damage. Previous work using an animal model of IUGR has demonstrated that IUGR rats exhibit neurobehavioral deficits and developmental delays in oligodendrocyte maturation and myelination, but the mechanisms which cause this delay are unknown. Inflammation may be an important etiological factor in IUGR and has been recognized as playing a fundamental role in the pathogenesis of myelin disorders, including cerebral palsy. METHODS: To create the model, the uterine arteries of pregnant rats were ligated at embryonic day 15. Rats delivered spontaneously. Cytokine and chemokine expression was evaluated at one prenatal and three postnatal time points, and myelin protein expression and oligodendrocyte cell numbers were evaluated by several methods at postnatal day 14. IL-4 was identified as a potential inhibitor of myelination, and rat pups were injected with IL-4 function blocking antibody from postnatal days 1-5 and myelination was assessed. RESULTS: Here, we show a novel mechanism of white matter injury. IUGR induces an exaggerated Th2 response in the developing rat brain, including upregulation of several Th2 cytokines. Of these, IL-4 is significantly increased during the period corresponding to robust developmental myelination. We show that neutralizing IL-4 antibody therapy given in the newborn period ameliorates inflammation and restores myelin protein expression and oligodendrocyte cell number in the IUGR brain to control levels, demonstrating a novel role for Th2 responses and IL-4 in IUGR and white matter injury. In addition, IL-4 directly affects oligodendrocytes in vitro decreasing differentiation. CONCLUSIONS: In this study, we have identified inflammation as a factor in the decrease in myelin seen in an animal model of IUGR. IL-4, an inflammatory protein often thought to be protective in the adult, is specifically increased, and treatment of these animals to prevent this increase ameliorates white matter damage. Our results suggest that the immune system plays a role in IUGR that is different in the perinatal period than in the adult and preventing this exaggerated Th2 response may be a potential therapeutic target. En ligne : https://dx.doi.org/10.1186/s11689-019-9297-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome / Christina N. LESSOV-SCHLAGGAR in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 39 Titre : Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome Type de document : texte imprimé Auteurs : Christina N. LESSOV-SCHLAGGAR, Auteur ; Olga L. DEL ROSARIO, Auteur ; John C. MORRIS, Auteur ; Beau M. ANCES, Auteur ; Bradley L. SCHLAGGAR, Auteur ; John N. CONSTANTINO, Auteur Article en page(s) : 39 Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Down Syndrome/diagnosis/psychology  Female  Humans  Male  Mental Status and Dementia Tests/standards  Middle Aged  Young Adult  Cognitive decline  Cognitive impairment  Dementia  Down syndrome  Premorbid ability Index. décimale : PER Périodiques Résumé : BACKGROUND: Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients. METHODS: We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR-a caregiver questionnaire and an in-person interview involving both the caregiver and the DS adult. Assessment also included the Dementia Scale for Down Syndrome (DSDS) and the Raven's Progressive Matrices to estimate IQ. RESULTS: Both modified questionnaire and interview instruments captured a range of cognitive impairments, a majority of which were found to be chronic when accounting for premorbid function. Two individuals in the sample were strongly suspected to have early dementia, both of whom had elevated scores on the modified CDR instruments. Among individuals rated as having no dementia based on the DSDS, about half showed subthreshold impairments on the modified CDR instruments; there was substantial agreement between caregiver questionnaire screening and in-person interview of caregivers and DS adults. CONCLUSIONS: The modified questionnaire and interview instruments capture a range of impairment in DS adults, including subthreshold symptomatology, and the instruments provide complementary information relevant to the ascertainment of dementia in DS. Decline was seen across all cognitive domains and was generally positively related to age and negatively related to IQ. Most importantly, adjusting instrument scores for chronic, premorbid impairment drastically shifted the distribution toward lower (no impairment) scores. En ligne : https://dx.doi.org/10.1186/s11689-019-9300-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome [texte imprimé] / Christina N. LESSOV-SCHLAGGAR, Auteur ; Olga L. DEL ROSARIO, Auteur ; John C. MORRIS, Auteur ; Beau M. ANCES, Auteur ; Bradley L. SCHLAGGAR, Auteur ; John N. CONSTANTINO, Auteur . - 39. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 39 Mots-clés : Adolescent  Adult  Down Syndrome/diagnosis/psychology  Female  Humans  Male  Mental Status and Dementia Tests/standards  Middle Aged  Young Adult  Cognitive decline  Cognitive impairment  Dementia  Down syndrome  Premorbid ability Index. décimale : PER Périodiques Résumé : BACKGROUND: Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients. METHODS: We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR-a caregiver questionnaire and an in-person interview involving both the caregiver and the DS adult. Assessment also included the Dementia Scale for Down Syndrome (DSDS) and the Raven's Progressive Matrices to estimate IQ. RESULTS: Both modified questionnaire and interview instruments captured a range of cognitive impairments, a majority of which were found to be chronic when accounting for premorbid function. Two individuals in the sample were strongly suspected to have early dementia, both of whom had elevated scores on the modified CDR instruments. Among individuals rated as having no dementia based on the DSDS, about half showed subthreshold impairments on the modified CDR instruments; there was substantial agreement between caregiver questionnaire screening and in-person interview of caregivers and DS adults. CONCLUSIONS: The modified questionnaire and interview instruments capture a range of impairment in DS adults, including subthreshold symptomatology, and the instruments provide complementary information relevant to the ascertainment of dementia in DS. Decline was seen across all cognitive domains and was generally positively related to age and negatively related to IQ. Most importantly, adjusting instrument scores for chronic, premorbid impairment drastically shifted the distribution toward lower (no impairment) scores. En ligne : https://dx.doi.org/10.1186/s11689-019-9300-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Quantifying the resolution of spatial and temporal representation in children with 22q11.2 deletion syndrome / Kathryn L. MCCABE in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 40 Titre : Quantifying the resolution of spatial and temporal representation in children with 22q11.2 deletion syndrome Type de document : texte imprimé Auteurs : Kathryn L. MCCABE, Auteur ; Abbie M. POPA, Auteur ; Courtney DURDLE, Auteur ; Michele AMATO, Auteur ; Margarita H. CABARAL, Auteur ; Joshua CRUZ, Auteur ; Ling M. WONG, Auteur ; Danielle HARVEY, Auteur ; Nicole TARTAGLIA, Auteur ; Tony J. SIMON, Auteur Article en page(s) : 40 Langues : Anglais (eng) Mots-clés : Adolescent  Attention/physiology  Auditory Perception/physiology  Child  DiGeorge Syndrome/complications/physiopathology  Female  Humans  Male  Mathematical Concepts  Perceptual Disorders/etiology/physiopathology  Sex Chromosome Aberrations  Space Perception/physiology  Time Perception/physiology  Visual Perception/physiology  22q11.2 deletion syndrome (22q11DS)  Attention  Children  Magnitude processing  Spatiotemporal attention Index. décimale : PER Périodiques Résumé : OBJECTIVES: Our ability to generate mental representation of magnitude from sensory information affects how we perceive and experience the world. Reduced resolution of the mental representations formed from sensory inputs may generate impairment in the proximal and distal information processes that utilize these representations. Impairment of spatial and temporal information processing likely underpins the non-verbal cognitive impairments observed in 22q11.2 deletion syndrome (22q11DS). The present study builds on prior research by seeking to quantify the resolution of spatial and temporal representation in children with 22q11DS, sex chromosome aneuploidy (SCA), and a typically developing (TD) control group. PARTICIPANTS AND METHODS: Children (22q11DS = 70, SCA = 49, TD = 46) responded to visual or auditory stimuli with varying difference ratios. The participant's task was to identify which of two sequentially presented stimuli was of larger magnitude in terms of, size, duration, or auditory frequency. Detection threshold was calculated as the minimum difference ratio between the "standard" and the "target" stimuli required to achieve 75% accuracy in detecting that the two stimuli were different. RESULTS: Children with 22q11DS required larger magnitude difference between spatial stimuli for accurate identification compared with both the SCA and TD groups (% difference from standard: 22q11DS = 14; SCA = 8; TD: 7; F = 8.42, p < 0.001). Temporal detection threshold was also higher for the 22q11DS group to both visual (% difference from standard: 22q11DS = 14; SCA = 8; TD = 7; F = 8.33, p < 0.001) and auditory (% difference from standard: 22q11DS = 23; SCA = 12; TD: 8; F = 8.99, p < 0.001) stimuli compared with both the SCA and TD groups, while the SCA and TD groups displayed equivalent performance on these measures (p's > 0.05). Pitch detection threshold did not differ among the groups (p's > 0.05). CONCLUSIONS: The observation of higher detection thresholds to spatial and temporal stimuli indicates further evidence for reduced resolution in both spatial and temporal magnitude representation in 22q11DS, that does not extend to frequency magnitude representation (pitch detection), and which is not explained by generalized cognitive impairment alone. These findings generate further support for the hypothesis that spatiotemporal hypergranularity of mental representations contributes to the non-verbal cognitive impairment seen in 22q11DS. En ligne : https://dx.doi.org/10.1186/s11689-019-9301-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Quantifying the resolution of spatial and temporal representation in children with 22q11.2 deletion syndrome [texte imprimé] / Kathryn L. MCCABE, Auteur ; Abbie M. POPA, Auteur ; Courtney DURDLE, Auteur ; Michele AMATO, Auteur ; Margarita H. CABARAL, Auteur ; Joshua CRUZ, Auteur ; Ling M. WONG, Auteur ; Danielle HARVEY, Auteur ; Nicole TARTAGLIA, Auteur ; Tony J. SIMON, Auteur . - 40. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 40 Mots-clés : Adolescent  Attention/physiology  Auditory Perception/physiology  Child  DiGeorge Syndrome/complications/physiopathology  Female  Humans  Male  Mathematical Concepts  Perceptual Disorders/etiology/physiopathology  Sex Chromosome Aberrations  Space Perception/physiology  Time Perception/physiology  Visual Perception/physiology  22q11.2 deletion syndrome (22q11DS)  Attention  Children  Magnitude processing  Spatiotemporal attention Index. décimale : PER Périodiques Résumé : OBJECTIVES: Our ability to generate mental representation of magnitude from sensory information affects how we perceive and experience the world. Reduced resolution of the mental representations formed from sensory inputs may generate impairment in the proximal and distal information processes that utilize these representations. Impairment of spatial and temporal information processing likely underpins the non-verbal cognitive impairments observed in 22q11.2 deletion syndrome (22q11DS). The present study builds on prior research by seeking to quantify the resolution of spatial and temporal representation in children with 22q11DS, sex chromosome aneuploidy (SCA), and a typically developing (TD) control group. PARTICIPANTS AND METHODS: Children (22q11DS = 70, SCA = 49, TD = 46) responded to visual or auditory stimuli with varying difference ratios. The participant's task was to identify which of two sequentially presented stimuli was of larger magnitude in terms of, size, duration, or auditory frequency. Detection threshold was calculated as the minimum difference ratio between the "standard" and the "target" stimuli required to achieve 75% accuracy in detecting that the two stimuli were different. RESULTS: Children with 22q11DS required larger magnitude difference between spatial stimuli for accurate identification compared with both the SCA and TD groups (% difference from standard: 22q11DS = 14; SCA = 8; TD: 7; F = 8.42, p < 0.001). Temporal detection threshold was also higher for the 22q11DS group to both visual (% difference from standard: 22q11DS = 14; SCA = 8; TD = 7; F = 8.33, p < 0.001) and auditory (% difference from standard: 22q11DS = 23; SCA = 12; TD: 8; F = 8.99, p < 0.001) stimuli compared with both the SCA and TD groups, while the SCA and TD groups displayed equivalent performance on these measures (p's > 0.05). Pitch detection threshold did not differ among the groups (p's > 0.05). CONCLUSIONS: The observation of higher detection thresholds to spatial and temporal stimuli indicates further evidence for reduced resolution in both spatial and temporal magnitude representation in 22q11DS, that does not extend to frequency magnitude representation (pitch detection), and which is not explained by generalized cognitive impairment alone. These findings generate further support for the hypothesis that spatiotemporal hypergranularity of mental representations contributes to the non-verbal cognitive impairment seen in 22q11DS. En ligne : https://dx.doi.org/10.1186/s11689-019-9301-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome / Emma K. BAKER in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 41 Titre : Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome Type de document : texte imprimé Auteurs : Emma K. BAKER, Auteur ; Marta ARPONE, Auteur ; Solange Aliaga VERA, Auteur ; Lesley BRETHERTON, Auteur ; Alexandra URE, Auteur ; Claudine M. KRAAN, Auteur ; Minh BUI, Auteur ; Ling LING, Auteur ; David FRANCIS, Auteur ; Matthew F. HUNTER, Auteur ; Justine ELLIOTT, Auteur ; Carolyn ROGERS, Auteur ; Michael J. FIELD, Auteur ; Jonathan COHEN, Auteur ; Lorena Santa MARIA, Auteur ; Victor FAUNDES, Auteur ; Bianca CUROTTO, Auteur ; Paulina MORALES, Auteur ; Cesar TRIGO, Auteur ; Isabel SALAS, Auteur ; Angelica M. ALLIENDE, Auteur ; David J. AMOR, Auteur ; David E. GODLER, Auteur Article en page(s) : 41 Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/etiology/genetics/physiopathology  Behavioral Symptoms/etiology/genetics/physiopathology  Child  Child, Preschool  Cohort Studies  Female  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/complications/genetics/physiopathology  Humans  Infant  Intellectual Disability/etiology/genetics/physiopathology  Male  Mosaicism  Mutation  Phenotype  Sex Factors  Young Adult  Autism spectrum disorder  Behaviour  Fragile X syndrome  Intellectual functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with a CGG expansion, termed full mutation (FM: CGG ≥ 200), increased DNA methylation of the FMR1 promoter and silencing of the gene. Mosaicism for presence of cells with either methylated FM or smaller unmethylated pre-mutation (PM: CGG 55-199) alleles in the same individual have been associated with better cognitive functioning. This study compares age- and sex-matched FM-only and PM/FM mosaic individuals on intellectual functioning, ASD features and maladaptive behaviours. METHODS: This study comprised a large international cohort of 126 male and female participants with FXS (aged 1.15 to 43.17 years) separated into FM-only and PM/FM mosaic groups (90 males, 77.8% FM-only; 36 females, 77.8% FM-only). Intellectual functioning was assessed with age appropriate developmental or intelligence tests. The Autism Diagnostic Observation Schedule-2nd Edition was used to examine ASD features while the Aberrant Behavior Checklist-Community assessed maladaptive behaviours. RESULTS: Comparing males and females (FM-only + PM/FM mosaic), males had poorer intellectual functioning on all domains (p < 0.0001). Although females had less ASD features and less parent-reported maladaptive behaviours, these differences were no longer significant after controlling for intellectual functioning. Participants with PM/FM mosaicism, regardless of sex, presented with better intellectual functioning and less maladaptive behaviours compared with their age- and sex-matched FM-only counterparts (p < 0.05). ASD features were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning. CONCLUSIONS: Males with FXS had significantly lower intellectual functioning than females with FXS. However, there were no significant differences in ASD features and maladaptive behaviours, after controlling for intellectual functioning, independent of the presence or absence of mosaicism. This suggests that interventions that primarily target cognitive abilities may in turn reduce the severity of maladaptive behaviours including ASD features in FXS. En ligne : https://dx.doi.org/10.1186/s11689-019-9288-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome [texte imprimé] / Emma K. BAKER, Auteur ; Marta ARPONE, Auteur ; Solange Aliaga VERA, Auteur ; Lesley BRETHERTON, Auteur ; Alexandra URE, Auteur ; Claudine M. KRAAN, Auteur ; Minh BUI, Auteur ; Ling LING, Auteur ; David FRANCIS, Auteur ; Matthew F. HUNTER, Auteur ; Justine ELLIOTT, Auteur ; Carolyn ROGERS, Auteur ; Michael J. FIELD, Auteur ; Jonathan COHEN, Auteur ; Lorena Santa MARIA, Auteur ; Victor FAUNDES, Auteur ; Bianca CUROTTO, Auteur ; Paulina MORALES, Auteur ; Cesar TRIGO, Auteur ; Isabel SALAS, Auteur ; Angelica M. ALLIENDE, Auteur ; David J. AMOR, Auteur ; David E. GODLER, Auteur . - 41. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 41 Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/etiology/genetics/physiopathology  Behavioral Symptoms/etiology/genetics/physiopathology  Child  Child, Preschool  Cohort Studies  Female  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/complications/genetics/physiopathology  Humans  Infant  Intellectual Disability/etiology/genetics/physiopathology  Male  Mosaicism  Mutation  Phenotype  Sex Factors  Young Adult  Autism spectrum disorder  Behaviour  Fragile X syndrome  Intellectual functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with a CGG expansion, termed full mutation (FM: CGG ≥ 200), increased DNA methylation of the FMR1 promoter and silencing of the gene. Mosaicism for presence of cells with either methylated FM or smaller unmethylated pre-mutation (PM: CGG 55-199) alleles in the same individual have been associated with better cognitive functioning. This study compares age- and sex-matched FM-only and PM/FM mosaic individuals on intellectual functioning, ASD features and maladaptive behaviours. METHODS: This study comprised a large international cohort of 126 male and female participants with FXS (aged 1.15 to 43.17 years) separated into FM-only and PM/FM mosaic groups (90 males, 77.8% FM-only; 36 females, 77.8% FM-only). Intellectual functioning was assessed with age appropriate developmental or intelligence tests. The Autism Diagnostic Observation Schedule-2nd Edition was used to examine ASD features while the Aberrant Behavior Checklist-Community assessed maladaptive behaviours. RESULTS: Comparing males and females (FM-only + PM/FM mosaic), males had poorer intellectual functioning on all domains (p < 0.0001). Although females had less ASD features and less parent-reported maladaptive behaviours, these differences were no longer significant after controlling for intellectual functioning. Participants with PM/FM mosaicism, regardless of sex, presented with better intellectual functioning and less maladaptive behaviours compared with their age- and sex-matched FM-only counterparts (p < 0.05). ASD features were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning. CONCLUSIONS: Males with FXS had significantly lower intellectual functioning than females with FXS. However, there were no significant differences in ASD features and maladaptive behaviours, after controlling for intellectual functioning, independent of the presence or absence of mosaicism. This suggests that interventions that primarily target cognitive abilities may in turn reduce the severity of maladaptive behaviours including ASD features in FXS. En ligne : https://dx.doi.org/10.1186/s11689-019-9288-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Initial eye gaze to faces and its functional consequence on face identification abilities in autism spectrum disorder / Kimberly B. SCHAUDER in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 42 Titre : Initial eye gaze to faces and its functional consequence on face identification abilities in autism spectrum disorder Type de document : texte imprimé Auteurs : Kimberly B. SCHAUDER, Auteur ; Woon Ju PARK, Auteur ; Yuliy TSANK, Auteur ; Miguel P. ECKSTEIN, Auteur ; Duje TADIN, Auteur ; Loisa BENNETTO, Auteur Article en page(s) : 42 Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/physiopathology  Child  Eye Movement Measurements  Facial Recognition/physiology  Female  Fixation, Ocular/physiology  Humans  Male  Social Perception  Autism spectrum disorder  Eye gaze  Face identification Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined and diagnosed by core deficits in social communication and the presence of restricted and repetitive behaviors. Research on face processing suggests deficits in this domain in ASD but includes many mixed findings regarding the nature and extent of these differences. The first eye movement to a face has been shown to be highly informative and sufficient to achieve high performance in face identification in neurotypical adults. The current study focused on this critical moment shown to be essential in the process of face identification. METHODS: We applied an established eye-tracking and face identification paradigm to comprehensively characterize the initial eye movement to a face and test its functional consequence on face identification performance in adolescents with and without ASD (n = 21 per group), and in neurotypical adults. Specifically, we presented a series of faces and measured the landing location of the first saccade to each face, while simultaneously measuring their face identification abilities. Then, individuals were guided to look at specific locations on the face, and we measured how face identification performance varied as a function of that location. Adolescent participants also completed a more traditional measure of face identification which allowed us to more fully characterize face identification abilities in ASD. RESULTS: Our results indicate that the location of the initial look to faces and face identification performance for briefly presented faces are intact in ASD, ruling out the possibility that deficits in face perception, at least in adolescents with ASD, begin with the initial eye movement to the face. However, individuals with ASD showed impairments on the more traditional measure of face identification. CONCLUSION: Together, the observed dissociation between initial, rapid face perception processes, and other measures of face perception offers new insights and hypotheses related to the timing and perceptual complexity of face processing and how these specific aspects of face identification may be disrupted in ASD. En ligne : https://dx.doi.org/10.1186/s11689-019-9303-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Initial eye gaze to faces and its functional consequence on face identification abilities in autism spectrum disorder [texte imprimé] / Kimberly B. SCHAUDER, Auteur ; Woon Ju PARK, Auteur ; Yuliy TSANK, Auteur ; Miguel P. ECKSTEIN, Auteur ; Duje TADIN, Auteur ; Loisa BENNETTO, Auteur . - 42. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 42 Mots-clés : Adolescent  Autism Spectrum Disorder/physiopathology  Child  Eye Movement Measurements  Facial Recognition/physiology  Female  Fixation, Ocular/physiology  Humans  Male  Social Perception  Autism spectrum disorder  Eye gaze  Face identification Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined and diagnosed by core deficits in social communication and the presence of restricted and repetitive behaviors. Research on face processing suggests deficits in this domain in ASD but includes many mixed findings regarding the nature and extent of these differences. The first eye movement to a face has been shown to be highly informative and sufficient to achieve high performance in face identification in neurotypical adults. The current study focused on this critical moment shown to be essential in the process of face identification. METHODS: We applied an established eye-tracking and face identification paradigm to comprehensively characterize the initial eye movement to a face and test its functional consequence on face identification performance in adolescents with and without ASD (n = 21 per group), and in neurotypical adults. Specifically, we presented a series of faces and measured the landing location of the first saccade to each face, while simultaneously measuring their face identification abilities. Then, individuals were guided to look at specific locations on the face, and we measured how face identification performance varied as a function of that location. Adolescent participants also completed a more traditional measure of face identification which allowed us to more fully characterize face identification abilities in ASD. RESULTS: Our results indicate that the location of the initial look to faces and face identification performance for briefly presented faces are intact in ASD, ruling out the possibility that deficits in face perception, at least in adolescents with ASD, begin with the initial eye movement to the face. However, individuals with ASD showed impairments on the more traditional measure of face identification. CONCLUSION: Together, the observed dissociation between initial, rapid face perception processes, and other measures of face perception offers new insights and hypotheses related to the timing and perceptual complexity of face processing and how these specific aspects of face identification may be disrupted in ASD. En ligne : https://dx.doi.org/10.1186/s11689-019-9303-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573