Dépouillements

Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics / Katherine CUMMINGS in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics Type de document : texte imprimé Auteurs : Katherine CUMMINGS, Auteur ; Alice WATKINS, Auteur ; Chris JONES, Auteur ; Renuka DIAS, Auteur ; Alice WELHAM, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/epidemiology/genetics  Germ-Line Mutation  Humans  Mutation  PTEN Phosphohydrolase/genetics  Prevalence  Retrospective Studies  Autism spectrum disorder  Behaviour  Cognition  Development  Emotional difficulties  Pten  PTEN hamartoma tumour syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocephaly, and research indicates possibly increased rates of developmental delay and autism spectrum disorder (ASD) for people with germline mutations affecting PTEN. METHOD: A systematic review of literature reporting behavioural and psychological variables for people with constitutional PTEN mutations/PHTS was conducted using four databases. Following in-depth screening, 25 articles met the inclusion criteria and were used in the review. Fourteen papers reported the proportion of people with PTEN mutations/PTHS meeting criteria for or having characteristics of ASD and were thus used in a pooled prevalence meta-analysis. RESULTS: Meta-analysis using a random effects model estimated pooled prevalence of ASD characteristics at 25% (95% CI 16-33%), although this should be interpreted cautiously due to possible biases in existing literature. Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. Emotional difficulties and impaired cognitive functioning in specific domains were noted but assessed/reported less frequently. Methods of assessment of psychological/behavioural factors varied widely (with retrospective examination of medical records common). CONCLUSIONS: Existing research suggests approximately 25% of people with constitutional PTEN mutations may meet criteria for or have characteristics of ASD. Studies have also begun to establish a range of possible cognitive impairments in affected individuals, especially when ASD is also reported. However, further large-scale studies are needed to elucidate psychological/behavioural corollaries of this mutation, and how they may relate to physiological/physical characteristics. En ligne : https://dx.doi.org/10.1186/s11689-021-09406-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics [texte imprimé] / Katherine CUMMINGS, Auteur ; Alice WATKINS, Auteur ; Chris JONES, Auteur ; Renuka DIAS, Auteur ; Alice WELHAM, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/epidemiology/genetics  Germ-Line Mutation  Humans  Mutation  PTEN Phosphohydrolase/genetics  Prevalence  Retrospective Studies  Autism spectrum disorder  Behaviour  Cognition  Development  Emotional difficulties  Pten  PTEN hamartoma tumour syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocephaly, and research indicates possibly increased rates of developmental delay and autism spectrum disorder (ASD) for people with germline mutations affecting PTEN. METHOD: A systematic review of literature reporting behavioural and psychological variables for people with constitutional PTEN mutations/PHTS was conducted using four databases. Following in-depth screening, 25 articles met the inclusion criteria and were used in the review. Fourteen papers reported the proportion of people with PTEN mutations/PTHS meeting criteria for or having characteristics of ASD and were thus used in a pooled prevalence meta-analysis. RESULTS: Meta-analysis using a random effects model estimated pooled prevalence of ASD characteristics at 25% (95% CI 16-33%), although this should be interpreted cautiously due to possible biases in existing literature. Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. Emotional difficulties and impaired cognitive functioning in specific domains were noted but assessed/reported less frequently. Methods of assessment of psychological/behavioural factors varied widely (with retrospective examination of medical records common). CONCLUSIONS: Existing research suggests approximately 25% of people with constitutional PTEN mutations may meet criteria for or have characteristics of ASD. Studies have also begun to establish a range of possible cognitive impairments in affected individuals, especially when ASD is also reported. However, further large-scale studies are needed to elucidate psychological/behavioural corollaries of this mutation, and how they may relate to physiological/physical characteristics. En ligne : https://dx.doi.org/10.1186/s11689-021-09406-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Trajectories of imitation skills in preschoolers with autism spectrum disorders / Irène PITTET in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Trajectories of imitation skills in preschoolers with autism spectrum disorders Type de document : texte imprimé Auteurs : Irène PITTET, Auteur ; Nada KOJOVIC, Auteur ; Martina FRANCHINI, Auteur ; Marie SCHAER, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/psychology  Child, Preschool  Humans  Imitative Behavior  Language  Autism spectrum disorders  Developmental trajectories  Heterogeneity  Imitation  role in the design of the study  in the collection, analysis, or interpretation  of data  in the writing of the manuscript  or in the decision to publish the  results. Index. décimale : PER Périodiques Résumé : BACKGROUND: Imitation skills play a crucial role in social cognitive development from early childhood. Many studies have shown a deficit in imitation skills in children with autism spectrum disorders (ASD). Little is known about the development of imitation behaviors in children with ASD. This study aims to measure the trajectories of early imitation skills in preschoolers with ASD and how these skills impact other areas of early development. METHODS: For this purpose, we assessed imitation, language, and cognition skills in 177 children with ASD and 43 typically developing children (TD) aged 2 to 5 years old, 126 of which were followed longitudinally, yielding a total of 396 time points. RESULTS: Our results confirmed the presence of an early imitation deficit in toddlers with ASD compared to TD children. The study of the trajectories showed that these difficulties were marked at the age of 2 years and gradually decreased until the age of 5 years old. Imitation skills were strongly linked with cognitive and language skills and level of symptoms in our ASD group at baseline. Moreover, the imitation skills at baseline were predictive of the language gains a year later in our ASD group. Using a data-driven clustering method, we delineated different developmental trajectories of imitation skills within the ASD group. CONCLUSIONS: The clinical implications of the findings are discussed, particularly the impact of an early imitation deficit on other areas of competence of the young child. En ligne : https://dx.doi.org/10.1186/s11689-021-09412-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Trajectories of imitation skills in preschoolers with autism spectrum disorders [texte imprimé] / Irène PITTET, Auteur ; Nada KOJOVIC, Auteur ; Martina FRANCHINI, Auteur ; Marie SCHAER, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/psychology  Child, Preschool  Humans  Imitative Behavior  Language  Autism spectrum disorders  Developmental trajectories  Heterogeneity  Imitation  role in the design of the study  in the collection, analysis, or interpretation  of data  in the writing of the manuscript  or in the decision to publish the  results. Index. décimale : PER Périodiques Résumé : BACKGROUND: Imitation skills play a crucial role in social cognitive development from early childhood. Many studies have shown a deficit in imitation skills in children with autism spectrum disorders (ASD). Little is known about the development of imitation behaviors in children with ASD. This study aims to measure the trajectories of early imitation skills in preschoolers with ASD and how these skills impact other areas of early development. METHODS: For this purpose, we assessed imitation, language, and cognition skills in 177 children with ASD and 43 typically developing children (TD) aged 2 to 5 years old, 126 of which were followed longitudinally, yielding a total of 396 time points. RESULTS: Our results confirmed the presence of an early imitation deficit in toddlers with ASD compared to TD children. The study of the trajectories showed that these difficulties were marked at the age of 2 years and gradually decreased until the age of 5 years old. Imitation skills were strongly linked with cognitive and language skills and level of symptoms in our ASD group at baseline. Moreover, the imitation skills at baseline were predictive of the language gains a year later in our ASD group. Using a data-driven clustering method, we delineated different developmental trajectories of imitation skills within the ASD group. CONCLUSIONS: The clinical implications of the findings are discussed, particularly the impact of an early imitation deficit on other areas of competence of the young child. En ligne : https://dx.doi.org/10.1186/s11689-021-09412-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Feasibility of delivering parent-implemented NDBI interventions in low-resource regions: a pilot randomized controlled study / Sally J. ROGERS in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Feasibility of delivering parent-implemented NDBI interventions in low-resource regions: a pilot randomized controlled study Type de document : texte imprimé Auteurs : Sally J. ROGERS, Auteur ; Aubyn STAHMER, Auteur ; Meagan TALBOTT, Auteur ; Gregory YOUNG, Auteur ; Elizabeth FULLER, Auteur ; Melanie PELLECCHIA, Auteur ; Angela BARBER, Auteur ; Elizabeth GRIFFITH, Auteur Langues : Anglais (eng) Mots-clés : Child  Child Development  Child, Preschool  Feasibility Studies  Humans  Parents/education  Pilot Projects  Research Design  Early intervention, ASD, Parent-implemented interventions, Parent coaching,  Implementation research, ESDM  in this study. AS, MT, GY, EF, MP, AB,& EG have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: This implementation feasibility study was conducted to determine whether an evidence-based parent-implemented distance-learning intervention model for young children at high likelihood of having ASD could be implemented at fidelity by Part C community providers and by parents in low-resource communities. METHODS: The study used a community-academic partnership model to adapt an evidence-based intervention tested in the current pilot trial involving randomization by agency in four states and enrollment of 35 coaches and 34 parent-family dyads. After baseline data were gathered, providers in the experimental group received 12-15 h of training while control providers received six webinars on early development. Providers delivered 6 months of intervention with children-families, concluding with data collection. Regression analyses were used to model outcomes of the coach behaviors, the parent fidelity ratings, and child outcomes. RESULTS: A block design model-building approach was used to test the null model followed by the inclusion of group as a predictor, and finally the inclusion of the planned covariates. Model fit was examined using changes in R(2) and F-statistic. As hypothesized, results demonstrated significant gains in (1) experimental provider fidelity of coaching implementation compared to the control group; and (2) experimental parent fidelity of implementation compared to the control group. There were no significant differences between groups on child developmental scores. CONCLUSIONS: Even though the experimental parent group averaged less than 30 min of intervention weekly with providers in the 6 months, both providers and parents demonstrated statistically significant gains on the fidelity of implementation scores with moderate effect sizes compared to control groups. Since child changes in parent-mediated models are dependent upon the parents' ability to deliver the intervention, and since parent delivery is dependent upon providers who are coaching the parents, these results demonstrated that two of these three links of the chain were positively affected by the experimental implementation model. However, a lack of significant differences in child group gains suggests that further work is needed on this model. Factors to consider include the amount of contact with the provider, the amount of practice children experience, the amount of contact both providers and parents spend on training materials, and motivational strategies for parents, among others. TRIAL REGISTRATION: Registry of Efficacy and Effectiveness Studies: #4360, registered 1xx, October, 2020 - Retrospectively registered, https://sreereg.icpsr.umich.edu/sreereg/. En ligne : https://dx.doi.org/10.1186/s11689-021-09410-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Feasibility of delivering parent-implemented NDBI interventions in low-resource regions: a pilot randomized controlled study [texte imprimé] / Sally J. ROGERS, Auteur ; Aubyn STAHMER, Auteur ; Meagan TALBOTT, Auteur ; Gregory YOUNG, Auteur ; Elizabeth FULLER, Auteur ; Melanie PELLECCHIA, Auteur ; Angela BARBER, Auteur ; Elizabeth GRIFFITH, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Child  Child Development  Child, Preschool  Feasibility Studies  Humans  Parents/education  Pilot Projects  Research Design  Early intervention, ASD, Parent-implemented interventions, Parent coaching,  Implementation research, ESDM  in this study. AS, MT, GY, EF, MP, AB,& EG have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: This implementation feasibility study was conducted to determine whether an evidence-based parent-implemented distance-learning intervention model for young children at high likelihood of having ASD could be implemented at fidelity by Part C community providers and by parents in low-resource communities. METHODS: The study used a community-academic partnership model to adapt an evidence-based intervention tested in the current pilot trial involving randomization by agency in four states and enrollment of 35 coaches and 34 parent-family dyads. After baseline data were gathered, providers in the experimental group received 12-15 h of training while control providers received six webinars on early development. Providers delivered 6 months of intervention with children-families, concluding with data collection. Regression analyses were used to model outcomes of the coach behaviors, the parent fidelity ratings, and child outcomes. RESULTS: A block design model-building approach was used to test the null model followed by the inclusion of group as a predictor, and finally the inclusion of the planned covariates. Model fit was examined using changes in R(2) and F-statistic. As hypothesized, results demonstrated significant gains in (1) experimental provider fidelity of coaching implementation compared to the control group; and (2) experimental parent fidelity of implementation compared to the control group. There were no significant differences between groups on child developmental scores. CONCLUSIONS: Even though the experimental parent group averaged less than 30 min of intervention weekly with providers in the 6 months, both providers and parents demonstrated statistically significant gains on the fidelity of implementation scores with moderate effect sizes compared to control groups. Since child changes in parent-mediated models are dependent upon the parents' ability to deliver the intervention, and since parent delivery is dependent upon providers who are coaching the parents, these results demonstrated that two of these three links of the chain were positively affected by the experimental implementation model. However, a lack of significant differences in child group gains suggests that further work is needed on this model. Factors to consider include the amount of contact with the provider, the amount of practice children experience, the amount of contact both providers and parents spend on training materials, and motivational strategies for parents, among others. TRIAL REGISTRATION: Registry of Efficacy and Effectiveness Studies: #4360, registered 1xx, October, 2020 - Retrospectively registered, https://sreereg.icpsr.umich.edu/sreereg/. En ligne : https://dx.doi.org/10.1186/s11689-021-09410-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Social behavior in RASopathies and idiopathic autism / Allison M.H. FOY in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Social behavior in RASopathies and idiopathic autism Type de document : texte imprimé Auteurs : Allison M.H. FOY, Auteur ; Rebekah L. HUDOCK, Auteur ; Ryan SHANLEY, Auteur ; Elizabeth I. PIERPONT, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications/psychology  Autistic Disorder/complications  Child  Child, Preschool  Cross-Sectional Studies  Failure to Thrive/complications/genetics  Humans  Social Behavior  Autism  Cardiofaciocutaneous syndrome  Costello syndrome  Neurofibromatosis type 1  Noonan syndrome  Prosocial  RASopathy  Social competence  Social function  Social skills Index. décimale : PER Périodiques Résumé : BACKGROUND: RASopathies are genetic syndromes that result from pathogenic variants in the RAS-MAPK cellular signaling pathway. These syndromes, which include neurofibromatosis type 1, Noonan syndrome, cardiofaciocutaneous syndrome, and Costello syndrome, are associated with a complex array of medical and behavioral health complications. Despite a heightened risk for social challenges and autism spectrum disorder (ASD), few studies have compared different aspects of social behavior across these conditions. It is also unknown whether the underlying neuropsychological characteristics that contribute to social competence and socially empathetic ("prosocial") behaviors differ in children with RASopathies as compared to children with nonsyndromic (i.e., idiopathic) ASD. METHODS: In this cross-sectional, survey-based investigation, caregivers of preschool and school-aged children with RASopathies (n = 202) or with idiopathic ASD (n = 109) provided demographic, medical, and developmental information about their child, including psychiatric comorbidities. For children who were able to communicate verbally, caregivers also completed standardized rating scales to assess social competence and empathetic behavior as well as symptoms of hyperactivity/inattention and emotional problems. RESULTS: As compared to children with idiopathic ASD, children with RASopathies were rated as demonstrating more resilience in the domain of empathy relative to their overall social competence. Similarities and differences emerged in the psychological factors that predicted social behavior in these two groups. Stronger communication skills and fewer hyperactive-impulsive behaviors were associated with increased empathy and social competence for both groups. Greater emotional challenges were associated with lower social competence for children with RASopathies and stronger empathy for children with idiopathic ASD. Among children with RASopathy and a co-occurring ASD diagnosis, socially empathetic behaviors were observed more often as compared to children with idiopathic ASD. CONCLUSIONS: Findings suggest that the development of social behavior among children with RASopathies involves a distinct pattern of strengths and weaknesses as compared to a behaviorally defined disorder (idiopathic ASD). Identification of areas of resilience as well as behavioral and social challenges will support more targeted intervention. En ligne : https://dx.doi.org/10.1186/s11689-021-09414-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Social behavior in RASopathies and idiopathic autism [texte imprimé] / Allison M.H. FOY, Auteur ; Rebekah L. HUDOCK, Auteur ; Ryan SHANLEY, Auteur ; Elizabeth I. PIERPONT, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/complications/psychology  Autistic Disorder/complications  Child  Child, Preschool  Cross-Sectional Studies  Failure to Thrive/complications/genetics  Humans  Social Behavior  Autism  Cardiofaciocutaneous syndrome  Costello syndrome  Neurofibromatosis type 1  Noonan syndrome  Prosocial  RASopathy  Social competence  Social function  Social skills Index. décimale : PER Périodiques Résumé : BACKGROUND: RASopathies are genetic syndromes that result from pathogenic variants in the RAS-MAPK cellular signaling pathway. These syndromes, which include neurofibromatosis type 1, Noonan syndrome, cardiofaciocutaneous syndrome, and Costello syndrome, are associated with a complex array of medical and behavioral health complications. Despite a heightened risk for social challenges and autism spectrum disorder (ASD), few studies have compared different aspects of social behavior across these conditions. It is also unknown whether the underlying neuropsychological characteristics that contribute to social competence and socially empathetic ("prosocial") behaviors differ in children with RASopathies as compared to children with nonsyndromic (i.e., idiopathic) ASD. METHODS: In this cross-sectional, survey-based investigation, caregivers of preschool and school-aged children with RASopathies (n = 202) or with idiopathic ASD (n = 109) provided demographic, medical, and developmental information about their child, including psychiatric comorbidities. For children who were able to communicate verbally, caregivers also completed standardized rating scales to assess social competence and empathetic behavior as well as symptoms of hyperactivity/inattention and emotional problems. RESULTS: As compared to children with idiopathic ASD, children with RASopathies were rated as demonstrating more resilience in the domain of empathy relative to their overall social competence. Similarities and differences emerged in the psychological factors that predicted social behavior in these two groups. Stronger communication skills and fewer hyperactive-impulsive behaviors were associated with increased empathy and social competence for both groups. Greater emotional challenges were associated with lower social competence for children with RASopathies and stronger empathy for children with idiopathic ASD. Among children with RASopathy and a co-occurring ASD diagnosis, socially empathetic behaviors were observed more often as compared to children with idiopathic ASD. CONCLUSIONS: Findings suggest that the development of social behavior among children with RASopathies involves a distinct pattern of strengths and weaknesses as compared to a behaviorally defined disorder (idiopathic ASD). Identification of areas of resilience as well as behavioral and social challenges will support more targeted intervention. En ligne : https://dx.doi.org/10.1186/s11689-021-09414-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Neural correlates of face processing associated with development of social communication in 12-month infants with familial risk of autism spectrum disorder / Joshua GLAUSER in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Neural correlates of face processing associated with development of social communication in 12-month infants with familial risk of autism spectrum disorder Type de document : texte imprimé Auteurs : Joshua GLAUSER, Auteur ; Carol L. WILKINSON, Auteur ; Laurel J. GABARD-DURNAM, Auteur ; Boin CHOI, Auteur ; Helen TAGER-FLUSBERG, Auteur ; Charles A. NELSON, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis  Communication  Evoked Potentials/physiology  Facial Recognition  Female  Genetic Predisposition to Disease  Humans  Infant  Autism  Eeg  Event-related potential  Face processing  Language development Index. décimale : PER Périodiques Résumé : BACKGROUND: Differences in face processing in individuals with ASD is hypothesized to impact the development of social communication skills. This study aimed to characterize the neural correlates of face processing in 12-month-old infants at familial risk of developing ASD by (1) comparing face-sensitive event-related potentials (ERP) (Nc, N290, P400) between high-familial-risk infants who develop ASD (HR-ASD), high-familial-risk infants without ASD (HR-NoASD), and low-familial-risk infants (LR), and (2) evaluating how face-sensitive ERP components are associated with development of social communication skills. METHODS: 12-month-old infants participated in a study in which they were presented with alternating images of their mother's face and the face of a stranger (LR = 45, HR-NoASD = 41, HR-ASD = 24) as EEG data were collected. Parent-reported and laboratory-observed social communication measures were obtained at 12 and 18 months. Group differences in ERP responses were evaluated using ANOVA, and multiple linear regressions were conducted with maternal education and outcome groups as covariates to assess relationships between ERP and behavioral measures. RESULTS: For each of the ERP components (Nc [negative-central], N290, and P400), the amplitude difference between mother and stranger (Mother-Stranger) trials was not statistically different between the three outcome groups (Nc p = 0.72, N290 p = 0.88, P400 p = 0.91). Marginal effects analyses found that within the LR group, a greater Nc Mother-Stranger response was associated with better expressive language skills on the Mullen Scales of Early Learning, controlling for maternal education and outcome group effects (marginal effects dy/dx = 1.15; p < 0.01). No significant associations were observed between the Nc and language or social measures in HR-NoASD or HR-ASD groups. In contrast, specific to the HR-ASD group, amplitude difference between the Mother versus Stranger P400 response was positively associated with expressive (dy/dx = 2.1, p < 0.001) and receptive language skills at 12 months (dy/dx = 1.68, p < 0.005), and negatively associated with social affect scores on the Autism Diagnostic Observation Schedule (dy/dx = - 1.22, p < 0.001) at 18 months. CONCLUSIONS: In 12-month-old infant siblings with subsequent ASD, increased P400 response to Mother over Stranger faces is positively associated with concurrent language and future social skills. En ligne : https://dx.doi.org/10.1186/s11689-021-09413-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Neural correlates of face processing associated with development of social communication in 12-month infants with familial risk of autism spectrum disorder [texte imprimé] / Joshua GLAUSER, Auteur ; Carol L. WILKINSON, Auteur ; Laurel J. GABARD-DURNAM, Auteur ; Boin CHOI, Auteur ; Helen TAGER-FLUSBERG, Auteur ; Charles A. NELSON, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/diagnosis  Communication  Evoked Potentials/physiology  Facial Recognition  Female  Genetic Predisposition to Disease  Humans  Infant  Autism  Eeg  Event-related potential  Face processing  Language development Index. décimale : PER Périodiques Résumé : BACKGROUND: Differences in face processing in individuals with ASD is hypothesized to impact the development of social communication skills. This study aimed to characterize the neural correlates of face processing in 12-month-old infants at familial risk of developing ASD by (1) comparing face-sensitive event-related potentials (ERP) (Nc, N290, P400) between high-familial-risk infants who develop ASD (HR-ASD), high-familial-risk infants without ASD (HR-NoASD), and low-familial-risk infants (LR), and (2) evaluating how face-sensitive ERP components are associated with development of social communication skills. METHODS: 12-month-old infants participated in a study in which they were presented with alternating images of their mother's face and the face of a stranger (LR = 45, HR-NoASD = 41, HR-ASD = 24) as EEG data were collected. Parent-reported and laboratory-observed social communication measures were obtained at 12 and 18 months. Group differences in ERP responses were evaluated using ANOVA, and multiple linear regressions were conducted with maternal education and outcome groups as covariates to assess relationships between ERP and behavioral measures. RESULTS: For each of the ERP components (Nc [negative-central], N290, and P400), the amplitude difference between mother and stranger (Mother-Stranger) trials was not statistically different between the three outcome groups (Nc p = 0.72, N290 p = 0.88, P400 p = 0.91). Marginal effects analyses found that within the LR group, a greater Nc Mother-Stranger response was associated with better expressive language skills on the Mullen Scales of Early Learning, controlling for maternal education and outcome group effects (marginal effects dy/dx = 1.15; p < 0.01). No significant associations were observed between the Nc and language or social measures in HR-NoASD or HR-ASD groups. In contrast, specific to the HR-ASD group, amplitude difference between the Mother versus Stranger P400 response was positively associated with expressive (dy/dx = 2.1, p < 0.001) and receptive language skills at 12 months (dy/dx = 1.68, p < 0.005), and negatively associated with social affect scores on the Autism Diagnostic Observation Schedule (dy/dx = - 1.22, p < 0.001) at 18 months. CONCLUSIONS: In 12-month-old infant siblings with subsequent ASD, increased P400 response to Mother over Stranger faces is positively associated with concurrent language and future social skills. En ligne : https://dx.doi.org/10.1186/s11689-021-09413-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation / Jessica KLUSEK in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation Type de document : texte imprimé Auteurs : Jessica KLUSEK, Auteur ; Amanda FAIRCHILD, Auteur ; Carly MOSER, Auteur ; Marsha R. MAILICK, Auteur ; Angela John THURMAN, Auteur ; Leonard ABBEDUTO, Auteur Langues : Anglais (eng) Mots-clés : Adult  Alleles  Ataxia/genetics  Child  Cognitive Dysfunction/complications/genetics  Female  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/complications/genetics  Humans  Language Disorders  Middle Aged  Mothers  Neurodegenerative Diseases/complications/genetics  Tremor/genetics  Aging  Fragile X premutation  Grammatical complexity  Language production  trials from F. Hoffman-LaRoche, Ltd., Roche TCRC, Inc., Neuren Pharmaceuticals  Limited, Inc, and the LuMind IDSC Foundation. AJT has received funding to develop  and implement outcome measures from Fulcrum Therapeutic. MM serves as the chair  of the Scientific Advisory Board of the John Merck Fund Developmental  Disabilities Program. The authors have no other relevant conflicts of interest to  disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Women who carry a premutation allele of the FMR1 gene are at increased vulnerability to an array of age-related symptoms and disorders, including age-related decline in select cognitive skills. However, the risk factors for age-related decline are poorly understood, including the potential role of family history and genetic factors. In other forms of pathological aging, early decline in syntactic complexity is observed and predicts the later onset of neurodegenerative disease. To shed light on the earliest signs of degeneration, the present study characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, and associations with family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length. METHODS: Forty-five women with the FMR1 premutation aged 35-64 years at study entry participated in 1-5 longitudinal assessments spaced approximately a year apart (130 observations total). All participants were mothers of children with confirmed fragile X syndrome. Language samples were analyzed for syntactic complexity and participants provided information on family history of FXTAS. CGG repeat length was determined via molecular genetic testing. RESULTS: Hierarchical linear models indicated that women who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than those without a family history, with that difference emerging as the women reached their mid-50 s. CGG repeat length was not a significant predictor of age-related change. CONCLUSIONS: Results suggest that women with the FMR1 premutation who have a family history of FXTAS may be at increased risk for neurodegenerative disease, as indicated by age-related loss of syntactic complexity. Thus, family history of FXTAS may represent a personalized risk factor for age-related disease. Follow-up study is needed to determine whether syntactic decline is an early indicator of FXTAS specifically, as opposed to being a more general age-related cognitive decline associated with the FMR1 premutation. En ligne : https://dx.doi.org/10.1186/s11689-022-09415-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation [texte imprimé] / Jessica KLUSEK, Auteur ; Amanda FAIRCHILD, Auteur ; Carly MOSER, Auteur ; Marsha R. MAILICK, Auteur ; Angela John THURMAN, Auteur ; Leonard ABBEDUTO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adult  Alleles  Ataxia/genetics  Child  Cognitive Dysfunction/complications/genetics  Female  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/complications/genetics  Humans  Language Disorders  Middle Aged  Mothers  Neurodegenerative Diseases/complications/genetics  Tremor/genetics  Aging  Fragile X premutation  Grammatical complexity  Language production  trials from F. Hoffman-LaRoche, Ltd., Roche TCRC, Inc., Neuren Pharmaceuticals  Limited, Inc, and the LuMind IDSC Foundation. AJT has received funding to develop  and implement outcome measures from Fulcrum Therapeutic. MM serves as the chair  of the Scientific Advisory Board of the John Merck Fund Developmental  Disabilities Program. The authors have no other relevant conflicts of interest to  disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Women who carry a premutation allele of the FMR1 gene are at increased vulnerability to an array of age-related symptoms and disorders, including age-related decline in select cognitive skills. However, the risk factors for age-related decline are poorly understood, including the potential role of family history and genetic factors. In other forms of pathological aging, early decline in syntactic complexity is observed and predicts the later onset of neurodegenerative disease. To shed light on the earliest signs of degeneration, the present study characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, and associations with family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length. METHODS: Forty-five women with the FMR1 premutation aged 35-64 years at study entry participated in 1-5 longitudinal assessments spaced approximately a year apart (130 observations total). All participants were mothers of children with confirmed fragile X syndrome. Language samples were analyzed for syntactic complexity and participants provided information on family history of FXTAS. CGG repeat length was determined via molecular genetic testing. RESULTS: Hierarchical linear models indicated that women who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than those without a family history, with that difference emerging as the women reached their mid-50 s. CGG repeat length was not a significant predictor of age-related change. CONCLUSIONS: Results suggest that women with the FMR1 premutation who have a family history of FXTAS may be at increased risk for neurodegenerative disease, as indicated by age-related loss of syntactic complexity. Thus, family history of FXTAS may represent a personalized risk factor for age-related disease. Follow-up study is needed to determine whether syntactic decline is an early indicator of FXTAS specifically, as opposed to being a more general age-related cognitive decline associated with the FMR1 premutation. En ligne : https://dx.doi.org/10.1186/s11689-022-09415-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period / Anatoly KOROTKOV in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period Type de document : texte imprimé Auteurs : Anatoly KOROTKOV, Auteur ; Mark J. LUINENBURG, Auteur ; Alessia ROMAGNOLO, Auteur ; Till S. ZIMMER, Auteur ; Jackelien VAN SCHEPPINGEN, Auteur ; Anika BONGAARTS, Auteur ; Diede W.M. BROEKAART, Auteur ; Jasper J. ANINK, Auteur ; Caroline MIJNSBERGEN, Auteur ; Floor E. JANSEN, Auteur ; Wim VAN HECKE, Auteur ; Wim G. SPLIET, Auteur ; Peter C. VAN RIJEN, Auteur ; Martha FEUCHT, Auteur ; Johannes A. HAINFELLNER, Auteur ; Pavel KRSEK, Auteur ; Josef ZAMECNIK, Auteur ; Peter B. CRINO, Auteur ; Katarzyna KOTULSKA, Auteur ; Lieven LAGAE, Auteur ; Anna C. JANSEN, Auteur ; David J.. KWIATKOWSKI, Auteur ; Sergiusz JOZWIAK, Auteur ; Paolo CURATOLO, Auteur ; Angelika MÃœHLEBNER, Auteur ; Erwin A. VAN VLIET, Auteur ; James D. MILLS, Auteur ; Eleonora ARONICA, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/complications/metabolism  Brain/metabolism  Child  Child, Preschool  Contactins/genetics/metabolism  Down-Regulation  Humans  Infant  Infant, Newborn  Middle Aged  Tuberous Sclerosis/complications/metabolism  Young Adult  Cell adhesion  Cerebral cortex development  Epilepsy  Neurodevelopmental disorders  mTORopathies Index. décimale : PER Périodiques Résumé : BACKGROUND: The genetic disorder tuberous sclerosis complex (TSC) is frequently accompanied by the development of neuropsychiatric disorders, including autism spectrum disorder and intellectual disability, with varying degrees of impairment. These co-morbidities in TSC have been linked to the structural brain abnormalities, such as cortical tubers, and recurrent epileptic seizures (in 70-80% cases). Previous transcriptomic analysis of cortical tubers revealed dysregulation of genes involved in cell adhesion in the brain, which may be associated with the neurodevelopmental deficits in TSC. In this study we aimed to investigate the expression of one of these genes - cell-adhesion molecule contactin-3. METHODS: Reverse transcription quantitative polymerase chain reaction for the contactin-3 gene (CNTN3) was performed in resected cortical tubers from TSC patients with drug-resistant epilepsy (n = 35, age range: 1-48 years) and compared to autopsy-derived cortical control tissue (n = 27, age range: 0-44 years), as well as by western blot analysis of contactin-3 (n = 7 vs n = 7, age range: 0-3 years for both TSC and controls) and immunohistochemistry (n = 5 TSC vs n = 4 controls). The expression of contactin-3 was further analyzed in fetal and postnatal control tissue by western blotting and in-situ hybridization, as well as in the SH-SY5Y neuroblastoma cell line differentiation model in vitro. RESULTS: CNTN3 gene expression was lower in cortical tubers from patients across a wide range of ages (fold change = - 0.5, p < 0.001) as compared to controls. Contactin-3 protein expression was lower in the age range of 0-3 years old (fold change = - 3.8, p < 0.001) as compared to the age-matched controls. In control brain tissue, contactin-3 gene and protein expression could be detected during fetal development, peaked around birth and during infancy and declined in the adult brain. CNTN3 expression was induced in the differentiated SH-SY5Y neuroblastoma cells in vitro (fold change = 6.2, p < 0.01). CONCLUSIONS: Our data show a lower expression of contactin-3 in cortical tubers of TSC patients during early postnatal period as compared to controls, which may affect normal brain development and might contribute to neuropsychiatric co-morbidities observed in patients with TSC. En ligne : https://dx.doi.org/10.1186/s11689-022-09416-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period [texte imprimé] / Anatoly KOROTKOV, Auteur ; Mark J. LUINENBURG, Auteur ; Alessia ROMAGNOLO, Auteur ; Till S. ZIMMER, Auteur ; Jackelien VAN SCHEPPINGEN, Auteur ; Anika BONGAARTS, Auteur ; Diede W.M. BROEKAART, Auteur ; Jasper J. ANINK, Auteur ; Caroline MIJNSBERGEN, Auteur ; Floor E. JANSEN, Auteur ; Wim VAN HECKE, Auteur ; Wim G. SPLIET, Auteur ; Peter C. VAN RIJEN, Auteur ; Martha FEUCHT, Auteur ; Johannes A. HAINFELLNER, Auteur ; Pavel KRSEK, Auteur ; Josef ZAMECNIK, Auteur ; Peter B. CRINO, Auteur ; Katarzyna KOTULSKA, Auteur ; Lieven LAGAE, Auteur ; Anna C. JANSEN, Auteur ; David J.. KWIATKOWSKI, Auteur ; Sergiusz JOZWIAK, Auteur ; Paolo CURATOLO, Auteur ; Angelika MÃœHLEBNER, Auteur ; Erwin A. VAN VLIET, Auteur ; James D. MILLS, Auteur ; Eleonora ARONICA, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/complications/metabolism  Brain/metabolism  Child  Child, Preschool  Contactins/genetics/metabolism  Down-Regulation  Humans  Infant  Infant, Newborn  Middle Aged  Tuberous Sclerosis/complications/metabolism  Young Adult  Cell adhesion  Cerebral cortex development  Epilepsy  Neurodevelopmental disorders  mTORopathies Index. décimale : PER Périodiques Résumé : BACKGROUND: The genetic disorder tuberous sclerosis complex (TSC) is frequently accompanied by the development of neuropsychiatric disorders, including autism spectrum disorder and intellectual disability, with varying degrees of impairment. These co-morbidities in TSC have been linked to the structural brain abnormalities, such as cortical tubers, and recurrent epileptic seizures (in 70-80% cases). Previous transcriptomic analysis of cortical tubers revealed dysregulation of genes involved in cell adhesion in the brain, which may be associated with the neurodevelopmental deficits in TSC. In this study we aimed to investigate the expression of one of these genes - cell-adhesion molecule contactin-3. METHODS: Reverse transcription quantitative polymerase chain reaction for the contactin-3 gene (CNTN3) was performed in resected cortical tubers from TSC patients with drug-resistant epilepsy (n = 35, age range: 1-48 years) and compared to autopsy-derived cortical control tissue (n = 27, age range: 0-44 years), as well as by western blot analysis of contactin-3 (n = 7 vs n = 7, age range: 0-3 years for both TSC and controls) and immunohistochemistry (n = 5 TSC vs n = 4 controls). The expression of contactin-3 was further analyzed in fetal and postnatal control tissue by western blotting and in-situ hybridization, as well as in the SH-SY5Y neuroblastoma cell line differentiation model in vitro. RESULTS: CNTN3 gene expression was lower in cortical tubers from patients across a wide range of ages (fold change = - 0.5, p < 0.001) as compared to controls. Contactin-3 protein expression was lower in the age range of 0-3 years old (fold change = - 3.8, p < 0.001) as compared to the age-matched controls. In control brain tissue, contactin-3 gene and protein expression could be detected during fetal development, peaked around birth and during infancy and declined in the adult brain. CNTN3 expression was induced in the differentiated SH-SY5Y neuroblastoma cells in vitro (fold change = 6.2, p < 0.01). CONCLUSIONS: Our data show a lower expression of contactin-3 in cortical tubers of TSC patients during early postnatal period as compared to controls, which may affect normal brain development and might contribute to neuropsychiatric co-morbidities observed in patients with TSC. En ligne : https://dx.doi.org/10.1186/s11689-022-09416-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Social communication in fragile X syndrome: pilot examination of the Brief Observation of Social Communication Change (BOSCC) / Rebecca SHAFFER in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Social communication in fragile X syndrome: pilot examination of the Brief Observation of Social Communication Change (BOSCC) Type de document : texte imprimé Auteurs : Rebecca SHAFFER, Auteur ; Angela John THURMAN, Auteur ; Lucienne RONCO, Auteur ; Diego CADAVID, Auteur ; Shane RAINES, Auteur ; So Hyun KIM, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis  Child  Child, Preschool  Communication  Fragile X Syndrome/diagnosis  Humans  Male  Reproducibility of Results  Social Communication Disorder/diagnosis  Boscc  Fragile X syndrome  Outcome measure  Repetitive behaviors  Social communication  Diego Cadavid and Lucienne Ronco were employees of Fulcrum Therapeutics at the  time of the study and they own stock in Fulcrum Therapeutics. Shane Raines was a  paid consultant to Fulcrum Therapeutics. The other authors have no conflicts to  report. Index. décimale : PER Périodiques Résumé : BACKGROUND: Social communication is a key area of difficulty in fragile X syndrome (FXS) and there are not yet adequate outcome measurement tools. Appropriate outcome measures for FXS have been identified as a key area of research interest in order to evaluate future therapeutic trials. The Brief Observation of Social Communication Change-Minimally Verbal (BOSCC-MV), an outcome measure with strong psychometrics developed for autism spectrum disorder, has promise as an outcome measure to assess social communication change with FXS participants. METHODS: We examined the BOSCC-MV via central coders in this multi-site-trial to assess its appropriateness for FXS. Eighteen minimally verbal males ages 3-12 years were enrolled and assessed on two consecutive days and 7 participants completed a third visit 6 months later. We examined test-retest reliability, inter-rater reliability, and both convergent and divergent validity with standard clinical measures including the Autism Diagnostic and Observation Schedule-2, Vineland 3, Social Responsiveness Scale, and the Aberrant Behavior Checklist. RESULTS: The BOSCC-MV in FXS demonstrated strong inter-rater and test-retest reliability, comparable to previous trials in idiopathic ASD. Strong convergent validity was found with Autism Diagnostic Observation Schedule-2 and Vineland-3. Divergent validity was demonstrated between BOSCC-MV and unrelated measures. CONCLUSIONS: The BOSCC-MV shows promise as a FXS social communication outcome measure, warranting further large-scale evaluation. En ligne : https://dx.doi.org/10.1186/s11689-021-09411-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Social communication in fragile X syndrome: pilot examination of the Brief Observation of Social Communication Change (BOSCC) [texte imprimé] / Rebecca SHAFFER, Auteur ; Angela John THURMAN, Auteur ; Lucienne RONCO, Auteur ; Diego CADAVID, Auteur ; Shane RAINES, Auteur ; So Hyun KIM, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/diagnosis  Child  Child, Preschool  Communication  Fragile X Syndrome/diagnosis  Humans  Male  Reproducibility of Results  Social Communication Disorder/diagnosis  Boscc  Fragile X syndrome  Outcome measure  Repetitive behaviors  Social communication  Diego Cadavid and Lucienne Ronco were employees of Fulcrum Therapeutics at the  time of the study and they own stock in Fulcrum Therapeutics. Shane Raines was a  paid consultant to Fulcrum Therapeutics. The other authors have no conflicts to  report. Index. décimale : PER Périodiques Résumé : BACKGROUND: Social communication is a key area of difficulty in fragile X syndrome (FXS) and there are not yet adequate outcome measurement tools. Appropriate outcome measures for FXS have been identified as a key area of research interest in order to evaluate future therapeutic trials. The Brief Observation of Social Communication Change-Minimally Verbal (BOSCC-MV), an outcome measure with strong psychometrics developed for autism spectrum disorder, has promise as an outcome measure to assess social communication change with FXS participants. METHODS: We examined the BOSCC-MV via central coders in this multi-site-trial to assess its appropriateness for FXS. Eighteen minimally verbal males ages 3-12 years were enrolled and assessed on two consecutive days and 7 participants completed a third visit 6 months later. We examined test-retest reliability, inter-rater reliability, and both convergent and divergent validity with standard clinical measures including the Autism Diagnostic and Observation Schedule-2, Vineland 3, Social Responsiveness Scale, and the Aberrant Behavior Checklist. RESULTS: The BOSCC-MV in FXS demonstrated strong inter-rater and test-retest reliability, comparable to previous trials in idiopathic ASD. Strong convergent validity was found with Autism Diagnostic Observation Schedule-2 and Vineland-3. Divergent validity was demonstrated between BOSCC-MV and unrelated measures. CONCLUSIONS: The BOSCC-MV shows promise as a FXS social communication outcome measure, warranting further large-scale evaluation. En ligne : https://dx.doi.org/10.1186/s11689-021-09411-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Parahippocampal deactivation and hyperactivation of central executive, saliency and social cognition networks in autism spectrum disorder / Susana MOUGA in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Parahippocampal deactivation and hyperactivation of central executive, saliency and social cognition networks in autism spectrum disorder Type de document : texte imprimé Auteurs : Susana MOUGA, Auteur ; Isabel Catarina DUARTE, Auteur ; Cátia CAFÉ, Auteur ; Daniela SOUSA, Auteur ; Frederico DUQUE, Auteur ; Guiomar OLIVEIRA, Auteur ; Miguel CASTELO-BRANCO, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/complications  Cognition  Humans  Magnetic Resonance Imaging  Neuroimaging  Social Cognition  Autism spectrum disorder  Central executive network  Ecological task  Saliency network  Social cognition network  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: The concomitant role of the Central Executive, the Saliency and the Social Cognition networks in autism spectrum disorder (ASD) in demanding ecological tasks remains unanswered. We addressed this question using a novel task-based fMRI virtual-reality task mimicking a challenging daily-life chore that may present some difficulties to individuals with ASD: the EcoSupermarketX. METHODS: Participants included 29 adolescents: 15 with ASD and 15 with typical neurodevelopment (TD). They performed the EcoSupermarketX (a shopping simulation with three goal-oriented sub-tasks including "no cue", "non-social" or "social" cues), during neuroimaging and eye-tracking. RESULTS: ASD differed from TD only in total time and distance to complete the "social cue" sub-task with matched eye-tracking measures. Neuroimaging revealed simultaneous hyperactivation across social, executive, and saliency circuits in ASD. In contrast, ASD showed reduced activation in the parahippocampal gyrus, involved in scene recognition. CONCLUSIONS: When performing a virtual shopping task matching the performance of controls, ASD adolescents hyperactivate three core networks: executive, saliency and social cognition. Parahippocampal hypoactivation is consistent with effortless eidetic scene processing, in line with the notion of peaks and valleys of neural recruitment in individuals with ASD. These hyperactivation/hypoactivation patterns in daily life tasks provide a circuit-level signature of neural diversity in ASD, a possible intervention target. En ligne : https://dx.doi.org/10.1186/s11689-022-09417-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Parahippocampal deactivation and hyperactivation of central executive, saliency and social cognition networks in autism spectrum disorder [texte imprimé] / Susana MOUGA, Auteur ; Isabel Catarina DUARTE, Auteur ; Cátia CAFÉ, Auteur ; Daniela SOUSA, Auteur ; Frederico DUQUE, Auteur ; Guiomar OLIVEIRA, Auteur ; Miguel CASTELO-BRANCO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Autism Spectrum Disorder/complications  Cognition  Humans  Magnetic Resonance Imaging  Neuroimaging  Social Cognition  Autism spectrum disorder  Central executive network  Ecological task  Saliency network  Social cognition network  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: The concomitant role of the Central Executive, the Saliency and the Social Cognition networks in autism spectrum disorder (ASD) in demanding ecological tasks remains unanswered. We addressed this question using a novel task-based fMRI virtual-reality task mimicking a challenging daily-life chore that may present some difficulties to individuals with ASD: the EcoSupermarketX. METHODS: Participants included 29 adolescents: 15 with ASD and 15 with typical neurodevelopment (TD). They performed the EcoSupermarketX (a shopping simulation with three goal-oriented sub-tasks including "no cue", "non-social" or "social" cues), during neuroimaging and eye-tracking. RESULTS: ASD differed from TD only in total time and distance to complete the "social cue" sub-task with matched eye-tracking measures. Neuroimaging revealed simultaneous hyperactivation across social, executive, and saliency circuits in ASD. In contrast, ASD showed reduced activation in the parahippocampal gyrus, involved in scene recognition. CONCLUSIONS: When performing a virtual shopping task matching the performance of controls, ASD adolescents hyperactivate three core networks: executive, saliency and social cognition. Parahippocampal hypoactivation is consistent with effortless eidetic scene processing, in line with the notion of peaks and valleys of neural recruitment in individuals with ASD. These hyperactivation/hypoactivation patterns in daily life tasks provide a circuit-level signature of neural diversity in ASD, a possible intervention target. En ligne : https://dx.doi.org/10.1186/s11689-022-09417-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

LiCl treatment leads to long-term restoration of spine maturation and synaptogenesis in adult Tbr1 mutants / Siavash FAZEL DARBANDI in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : LiCl treatment leads to long-term restoration of spine maturation and synaptogenesis in adult Tbr1 mutants Type de document : texte imprimé Auteurs : Siavash FAZEL DARBANDI, Auteur ; Andrew D. NELSON, Auteur ; Emily Ling-Lin PAI, Auteur ; Kevin J. BENDER, Auteur ; John L.R. RUBENSTEIN, Auteur Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/genetics  Humans  Mice  Neurogenesis/physiology  Neurons  Synaptic Transmission  T-Box Domain Proteins/genetics  Transcription Factors  Autism spectrum disorder  Cortex  Dendritic spine  Excitatory neuron  Synaptic rescue  Synaptogenesis  Tbr1  mPFCx  Neurona, a company studying the potential therapeutic use of interneuron  transplantation. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tbr1 encodes a T-box transcription factor and is considered a high confidence autism spectrum disorder (ASD) gene. Tbr1 is expressed in the postmitotic excitatory neurons of the deep neocortical layers 5 and 6. Postnatally and neonatally, Tbr1 conditional mutants (CKOs) have immature dendritic spines and reduced synaptic density. However, an understanding of Tbr1's function in the adult mouse brain remains elusive. METHODS: We used conditional mutagenesis to interrogate Tbr1's function in cortical layers 5 and 6 of the adult mouse cortex. RESULTS: Adult Tbr1 CKO mutants have dendritic spine and synaptic deficits as well as reduced frequency of mEPSCs and mIPSCs. LiCl, a WNT signaling agonist, robustly rescues the dendritic spine maturation, synaptic defects, and excitatory and inhibitory synaptic transmission deficits. CONCLUSIONS: LiCl treatment could be used as a therapeutic approach for some cases of ASD with deficits in synaptic transmission. En ligne : https://dx.doi.org/10.1186/s11689-022-09421-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] LiCl treatment leads to long-term restoration of spine maturation and synaptogenesis in adult Tbr1 mutants [texte imprimé] / Siavash FAZEL DARBANDI, Auteur ; Andrew D. NELSON, Auteur ; Emily Ling-Lin PAI, Auteur ; Kevin J. BENDER, Auteur ; John L.R. RUBENSTEIN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Animals  Autism Spectrum Disorder/genetics  Humans  Mice  Neurogenesis/physiology  Neurons  Synaptic Transmission  T-Box Domain Proteins/genetics  Transcription Factors  Autism spectrum disorder  Cortex  Dendritic spine  Excitatory neuron  Synaptic rescue  Synaptogenesis  Tbr1  mPFCx  Neurona, a company studying the potential therapeutic use of interneuron  transplantation. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tbr1 encodes a T-box transcription factor and is considered a high confidence autism spectrum disorder (ASD) gene. Tbr1 is expressed in the postmitotic excitatory neurons of the deep neocortical layers 5 and 6. Postnatally and neonatally, Tbr1 conditional mutants (CKOs) have immature dendritic spines and reduced synaptic density. However, an understanding of Tbr1's function in the adult mouse brain remains elusive. METHODS: We used conditional mutagenesis to interrogate Tbr1's function in cortical layers 5 and 6 of the adult mouse cortex. RESULTS: Adult Tbr1 CKO mutants have dendritic spine and synaptic deficits as well as reduced frequency of mEPSCs and mIPSCs. LiCl, a WNT signaling agonist, robustly rescues the dendritic spine maturation, synaptic defects, and excitatory and inhibitory synaptic transmission deficits. CONCLUSIONS: LiCl treatment could be used as a therapeutic approach for some cases of ASD with deficits in synaptic transmission. En ligne : https://dx.doi.org/10.1186/s11689-022-09421-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

A randomized, double-blind, placebo-controlled phase II trial to explore the effects of a GABA(A)-α5 NAM (basmisanil) on intellectual disability associated with Down syndrome / Celia GOELDNER in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : A randomized, double-blind, placebo-controlled phase II trial to explore the effects of a GABA(A)-α5 NAM (basmisanil) on intellectual disability associated with Down syndrome Type de document : texte imprimé Auteurs : Celia GOELDNER, Auteur ; Priya S. KISHNANI, Auteur ; Brian G. SKOTKO, Auteur ; Julian Lirio CASERO, Auteur ; Joerg F. HIPP, Auteur ; Michael DERKS, Auteur ; Maria-Clemencia HERNANDEZ, Auteur ; Omar KHWAJA, Auteur ; Sian LENNON-CHRIMES, Auteur ; Jana NOELDEKE, Auteur ; Sabine PELLICER, Auteur ; Lisa SQUASSANTE, Auteur ; Jeannie VISOOTSAK, Auteur ; Christoph WANDEL, Auteur ; Paulo FONTOURA, Auteur ; Xavier Liogier D'ARDHUY, Auteur ; CLEMATIS STUDY GROUP, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Child  Child, Preschool  Down Syndrome/complications/drug therapy  Humans  Intellectual Disability/complications/drug therapy  Morpholines  Oxazoles  Pyridines  Quality of Life  Treatment Outcome  Young Adult  gamma-Aminobutyric Acid/therapeutic use  Adaptive behavior  Cognition  Down syndrome  Eeg  GABAA-α5  Khwaja, X Liogier d’Ardhuy, J Noeldeke, S Pellicer, L Squassante, C Wandel were  employees of F.Hoffmann-La Roche AG Switzerland  M Derks and S Lennon-Chrimes  were employees of Roche Products Ltd. UK  J Visootsak was an employee of Roche  New York. All employees (former and current) may be eligible for stock and stock  options. P S Kishnani has no disclosures for Down syndrome-related research. J  Lirio Casero has no disclosures. B G Skotko occasionally consults on the topic of  Down syndrome through the Gerson Lehrman Group. He receives remuneration from  Down syndrome non-profit organizations for speaking engagements and associated  travel expenses. Dr. Skotko receives annual royalties from Woodbine House, Inc.,  for the publication of his book, Fasten Your Seatbelt: A Crash Course on Down  Syndrome for Brothers and Sisters. Within the past 2 years, he has also received  research funding from AC Immune and LuMind Research Down Syndrome Foundation to  conduct clinical trials for people with Down syndrome. Dr. Skotko is occasionally  asked to serve as an expert witness for legal cases where Down syndrome is  discussed. Dr. Skotko serves in a non-paid capacity on the Honorary Board of  Directors for the Massachusetts Down Syndrome Congress and the Professional  Advisory Committee for the National Center for Prenatal and Postnatal Down  Syndrome Resources. Dr. Skotko has a sister with Down syndrome. Index. décimale : PER Périodiques Résumé : BACKGROUND: There are currently no pharmacological therapies to address the intellectual disability associated with Down syndrome. Excitatory/inhibitory imbalance has been hypothesized to contribute to impairments in cognitive functioning in Down syndrome. Negative modulation of the GABA(A)-α5 receptor is proposed as a mechanism to attenuate GABAergic function and restore the excitatory/inhibitory balance. METHODS: Basmisanil, a selective GABA(A)-α5 negative allosteric modulator, was evaluated at 120 mg or 240 mg BID (80 or 160 mg for 12-13 years) in a 6-month, randomized, double-blind, placebo-controlled phase II trial (Clematis) for efficacy and safety in adolescents and young adults with Down syndrome. The primary endpoint was based on a composite analysis of working memory (Repeatable Battery for the Assessment of Neuropsychological Scale [RBANS]) and independent functioning and adaptive behavior (Vineland Adaptive Behavior Scales [VABS-II] or the Clinical Global Impression-Improvement [CGI-I]). Secondary measures included the Behavior Rating Inventory of Executive Functioning-Preschool (BRIEF-P), Clinical Evaluation of Language Fundamentals (CELF-4), and Pediatric Quality of Life Inventory (Peds-QL). EEG was conducted for safety monitoring and quantitatively analyzed in adolescents. RESULTS: Basmisanil was safe and well-tolerated; the frequency and nature of adverse events were similar in basmisanil and placebo arms. EEG revealed treatment-related changes in spectral power (increase in low ~ 4-Hz and decrease in high ~ 20-Hz frequencies) providing evidence of functional target engagement. All treatment arms had a similar proportion of participants showing above-threshold improvement on the primary composite endpoint, evaluating concomitant responses in cognition and independent functioning (29% in placebo, 20% in low dose, and 25% in high dose). Further analysis of the individual measures contributing to the primary endpoint revealed no difference between placebo and basmisanil-treated groups in either adolescents or adults. There were also no differences across the secondary endpoints assessing changes in executive function, language, or quality of life. CONCLUSIONS: Basmisanil did not meet the primary efficacy objective of concomitant improvement on cognition and adaptive functioning after 6 months of treatment, despite evidence for target engagement. This study provides key learnings for future clinical trials in Down syndrome. TRIAL REGISTRATION: The study was registered on December 31, 2013, at clinicaltrials.gov as NCT02024789. En ligne : https://dx.doi.org/10.1186/s11689-022-09418-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] A randomized, double-blind, placebo-controlled phase II trial to explore the effects of a GABA(A)-α5 NAM (basmisanil) on intellectual disability associated with Down syndrome [texte imprimé] / Celia GOELDNER, Auteur ; Priya S. KISHNANI, Auteur ; Brian G. SKOTKO, Auteur ; Julian Lirio CASERO, Auteur ; Joerg F. HIPP, Auteur ; Michael DERKS, Auteur ; Maria-Clemencia HERNANDEZ, Auteur ; Omar KHWAJA, Auteur ; Sian LENNON-CHRIMES, Auteur ; Jana NOELDEKE, Auteur ; Sabine PELLICER, Auteur ; Lisa SQUASSANTE, Auteur ; Jeannie VISOOTSAK, Auteur ; Christoph WANDEL, Auteur ; Paulo FONTOURA, Auteur ; Xavier Liogier D'ARDHUY, Auteur ; CLEMATIS STUDY GROUP, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Child  Child, Preschool  Down Syndrome/complications/drug therapy  Humans  Intellectual Disability/complications/drug therapy  Morpholines  Oxazoles  Pyridines  Quality of Life  Treatment Outcome  Young Adult  gamma-Aminobutyric Acid/therapeutic use  Adaptive behavior  Cognition  Down syndrome  Eeg  GABAA-α5  Khwaja, X Liogier d’Ardhuy, J Noeldeke, S Pellicer, L Squassante, C Wandel were  employees of F.Hoffmann-La Roche AG Switzerland  M Derks and S Lennon-Chrimes  were employees of Roche Products Ltd. UK  J Visootsak was an employee of Roche  New York. All employees (former and current) may be eligible for stock and stock  options. P S Kishnani has no disclosures for Down syndrome-related research. J  Lirio Casero has no disclosures. B G Skotko occasionally consults on the topic of  Down syndrome through the Gerson Lehrman Group. He receives remuneration from  Down syndrome non-profit organizations for speaking engagements and associated  travel expenses. Dr. Skotko receives annual royalties from Woodbine House, Inc.,  for the publication of his book, Fasten Your Seatbelt: A Crash Course on Down  Syndrome for Brothers and Sisters. Within the past 2 years, he has also received  research funding from AC Immune and LuMind Research Down Syndrome Foundation to  conduct clinical trials for people with Down syndrome. Dr. Skotko is occasionally  asked to serve as an expert witness for legal cases where Down syndrome is  discussed. Dr. Skotko serves in a non-paid capacity on the Honorary Board of  Directors for the Massachusetts Down Syndrome Congress and the Professional  Advisory Committee for the National Center for Prenatal and Postnatal Down  Syndrome Resources. Dr. Skotko has a sister with Down syndrome. Index. décimale : PER Périodiques Résumé : BACKGROUND: There are currently no pharmacological therapies to address the intellectual disability associated with Down syndrome. Excitatory/inhibitory imbalance has been hypothesized to contribute to impairments in cognitive functioning in Down syndrome. Negative modulation of the GABA(A)-α5 receptor is proposed as a mechanism to attenuate GABAergic function and restore the excitatory/inhibitory balance. METHODS: Basmisanil, a selective GABA(A)-α5 negative allosteric modulator, was evaluated at 120 mg or 240 mg BID (80 or 160 mg for 12-13 years) in a 6-month, randomized, double-blind, placebo-controlled phase II trial (Clematis) for efficacy and safety in adolescents and young adults with Down syndrome. The primary endpoint was based on a composite analysis of working memory (Repeatable Battery for the Assessment of Neuropsychological Scale [RBANS]) and independent functioning and adaptive behavior (Vineland Adaptive Behavior Scales [VABS-II] or the Clinical Global Impression-Improvement [CGI-I]). Secondary measures included the Behavior Rating Inventory of Executive Functioning-Preschool (BRIEF-P), Clinical Evaluation of Language Fundamentals (CELF-4), and Pediatric Quality of Life Inventory (Peds-QL). EEG was conducted for safety monitoring and quantitatively analyzed in adolescents. RESULTS: Basmisanil was safe and well-tolerated; the frequency and nature of adverse events were similar in basmisanil and placebo arms. EEG revealed treatment-related changes in spectral power (increase in low ~ 4-Hz and decrease in high ~ 20-Hz frequencies) providing evidence of functional target engagement. All treatment arms had a similar proportion of participants showing above-threshold improvement on the primary composite endpoint, evaluating concomitant responses in cognition and independent functioning (29% in placebo, 20% in low dose, and 25% in high dose). Further analysis of the individual measures contributing to the primary endpoint revealed no difference between placebo and basmisanil-treated groups in either adolescents or adults. There were also no differences across the secondary endpoints assessing changes in executive function, language, or quality of life. CONCLUSIONS: Basmisanil did not meet the primary efficacy objective of concomitant improvement on cognition and adaptive functioning after 6 months of treatment, despite evidence for target engagement. This study provides key learnings for future clinical trials in Down syndrome. TRIAL REGISTRATION: The study was registered on December 31, 2013, at clinicaltrials.gov as NCT02024789. En ligne : https://dx.doi.org/10.1186/s11689-022-09418-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Childhood infections and autism spectrum disorders and/or intellectual disability: a register-based cohort study / HÃ¥kan KARLSSON in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Childhood infections and autism spectrum disorders and/or intellectual disability: a register-based cohort study Type de document : texte imprimé Auteurs : HÃ¥kan KARLSSON, Auteur ; Hugo SJÖQVIST, Auteur ; Martin BRYNGE, Auteur ; Renee GARDNER, Auteur ; Christina DALMAN, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications/diagnosis/epidemiology  Child  Cohort Studies  Female  Humans  Intellectual Disability/complications/diagnosis/epidemiology  Pregnancy  Siblings  Autism spectrum disorders  Childhood  Infection  Intellectual disability  Risk Index. décimale : PER Périodiques Résumé : OBJECTIVE: To explore the associations between childhood infections and subsequent diagnoses of autism spectrum disorder (ASD), intellectual disability (ID), and their co-occurrence. METHODS: The association between specialized care for any infection, defined by ICD-codes, and later ASD or ID was investigated in a register-based cohort of 556,732 individuals born 1987-2010, resident in Stockholm County, followed from birth to their 18th birthday or December 31, 2016. We considered as potential confounders children's characteristics, family socioeconomic factors, obstetric complications, and parental histories of treatment for infection and psychiatric disorders in survival analyses with extended Cox regression models. Residual confounding by shared familial factors was addressed in sibling analyses using within-strata estimation in Cox regression models. Sensitivity analyses with the exclusion of congenital causes of ASD/ID and documented risk for infections were also performed. RESULTS: Crude estimates indicated that infections during childhood were associated with later ASD and ID with the largest risks observed for diagnoses involving ID. Inclusion of covariates, exclusion of congenital causes of ASD/ID from the population, and sibling comparisons highlighted the potential for confounding by both heritable and non-heritable factors, though risks remained in all adjusted models. In adjusted sibling comparisons, excluding congenital causes, infections were associated with later "ASD without ID" (HR 1.24, 95%CI 1.15-1.33), "ASD with ID" (1.57, 1.35-1.82), and "ID without ASD" (2.01, 1.76-2.28). Risks associated with infections varied by age at exposure and by age at diagnosis of ASD/ID. CONCLUSIONS: Infections during childhood may contribute to a later diagnosis of ID and ASD. En ligne : https://dx.doi.org/10.1186/s11689-022-09422-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Childhood infections and autism spectrum disorders and/or intellectual disability: a register-based cohort study [texte imprimé] / HÃ¥kan KARLSSON, Auteur ; Hugo SJÖQVIST, Auteur ; Martin BRYNGE, Auteur ; Renee GARDNER, Auteur ; Christina DALMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/complications/diagnosis/epidemiology  Child  Cohort Studies  Female  Humans  Intellectual Disability/complications/diagnosis/epidemiology  Pregnancy  Siblings  Autism spectrum disorders  Childhood  Infection  Intellectual disability  Risk Index. décimale : PER Périodiques Résumé : OBJECTIVE: To explore the associations between childhood infections and subsequent diagnoses of autism spectrum disorder (ASD), intellectual disability (ID), and their co-occurrence. METHODS: The association between specialized care for any infection, defined by ICD-codes, and later ASD or ID was investigated in a register-based cohort of 556,732 individuals born 1987-2010, resident in Stockholm County, followed from birth to their 18th birthday or December 31, 2016. We considered as potential confounders children's characteristics, family socioeconomic factors, obstetric complications, and parental histories of treatment for infection and psychiatric disorders in survival analyses with extended Cox regression models. Residual confounding by shared familial factors was addressed in sibling analyses using within-strata estimation in Cox regression models. Sensitivity analyses with the exclusion of congenital causes of ASD/ID and documented risk for infections were also performed. RESULTS: Crude estimates indicated that infections during childhood were associated with later ASD and ID with the largest risks observed for diagnoses involving ID. Inclusion of covariates, exclusion of congenital causes of ASD/ID from the population, and sibling comparisons highlighted the potential for confounding by both heritable and non-heritable factors, though risks remained in all adjusted models. In adjusted sibling comparisons, excluding congenital causes, infections were associated with later "ASD without ID" (HR 1.24, 95%CI 1.15-1.33), "ASD with ID" (1.57, 1.35-1.82), and "ID without ASD" (2.01, 1.76-2.28). Risks associated with infections varied by age at exposure and by age at diagnosis of ASD/ID. CONCLUSIONS: Infections during childhood may contribute to a later diagnosis of ID and ASD. En ligne : https://dx.doi.org/10.1186/s11689-022-09422-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

The research landscape of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)-a comprehensive scoping review / Stephanie VANCLOOSTER in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The research landscape of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)-a comprehensive scoping review Type de document : texte imprimé Auteurs : Stephanie VANCLOOSTER, Auteur ; Stacey BISSELL, Auteur ; Agnies M. VAN EEGHEN, Auteur ; Nola CHAMBERS, Auteur ; Liesbeth DE WAELE, Auteur ; Anna W. BYARS, Auteur ; Jamie K. CAPAL, Auteur ; Sebastián CUKIER, Auteur ; Peter DAVIS, Auteur ; Jennifer FLINN, Auteur ; Sugnet GARDNER-LUBBE, Auteur ; Tanjala GIPSON, Auteur ; Tosca-Marie HEUNIS, Auteur ; Dena HOOK, Auteur ; J. Christopher KINGSWOOD, Auteur ; Darcy A. KRUEGER, Auteur ; Aubrey J. KUMM, Auteur ; Mustafa SAHIN, Auteur ; Eva SCHOETERS, Auteur ; Catherine SMITH, Auteur ; Shoba SRIVASTAVA, Auteur ; Megumi TAKEI, Auteur ; Robert WALTEREIT, Auteur ; Anna C. JANSEN, Auteur ; Petrus J. DE VRIES, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Aged  Autism Spectrum Disorder  Cohort Studies  Humans  Tuberous Sclerosis/complications/psychology  Autism  Behaviour  Intellectual  Neuropsychological  Psychiatric  Psychosocial  Scholastic  Scoping review  TSC-associated neuropsychiatric disorders  Tuberous sclerosis complex  syndromes, including TSC. PD receives partial salary support from the NIH for  participation in studies related to TSC, as well as from Aucta Pharmaceuticals  for a study of topical sirolimus for facial angiofibromas in TSC and Marinus  Pharmaceuticals for a study of ganaxolone for TSC-related epilepsy. DAK reports  grants from National Institutes of Health (NINDS) during the conduct of the study  as well as the personal fees from Novartis Pharmaceuticals, personal fees from  Greenwich Bioscience, grants from Marinus Pharmaceuticals, personal fees from  Nobelpharma America, personal fees from REGENXBIO, and grants and non-financial  support from TSC Alliance outside the submitted work. CS receives salary support  from the TSC Alliance, a non-profit organisation which reports revenue from  individual donors and corporations including Greenwich Biosciences, GW Pharma,  Mallinckrodt, Nobelpharma, Novartis, Ovid, UCB and Upsher-Smith. PJdV was a study  steering committee member of three phase III trials sponsored by Novartis. He and  AJ were also on the scientific advisory group of the TOSCA international disease  registry sponsored by Novartis. MS reports grant support from Novartis, Biogen,  Astellas, Aeovian, Bridgebio and Aucta, and has served on Scientific Advisory  Boards for Novartis, Roche, Regenxbio, SpringWorks Therapeutics, Jaguar  Therapeutics and Alkermes. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) is an umbrella term for the behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations of TSC. Although TAND affects 90% of individuals with TSC during their lifetime, these manifestations are relatively under-assessed, under-treated and under-researched. We performed a comprehensive scoping review of all TAND research to date (a) to describe the existing TAND research landscape and (b) to identify knowledge gaps to guide future TAND research. METHODS: The study was conducted in accordance with stages outlined within the Arksey and O'Malley scoping review framework. Ten research questions relating to study characteristics, research design and research content of TAND levels and clusters were examined. RESULTS: Of the 2841 returned searches, 230 articles published between 1987 and 2020 were included (animal studies = 30, case studies = 47, cohort studies = 153), with more than half published since the term TAND was coined in 2012 (118/230; 51%). Cohort studies largely involved children and/or adolescents (63%) as opposed to older adults (16%). Studies were represented across 341 individual research sites from 45 countries, the majority from the USA (89/341; 26%) and the UK (50/341; 15%). Only 48 research sites (14%) were within low-middle income countries (LMICs). Animal studies and case studies were of relatively high/high quality, but cohort studies showed significant variability. Of the 153 cohort studies, only 16 (10%) included interventions. None of these were non-pharmacological, and only 13 employed remote methodologies (e.g. telephone interviews, online surveys). Of all TAND clusters, the autism spectrum disorder-like cluster was the most widely researched (138/230; 60%) and the scholastic cluster the least (53/200; 27%). CONCLUSIONS: Despite the recent increase in TAND research, studies that represent participants across the lifespan, LMIC research sites and non-pharmacological interventions were identified as future priorities. The quality of cohort studies requires improvement, to which the use of standardised direct behavioural assessments may contribute. In human studies, the academic level in particular warrants further investigation. Remote technologies could help to address many of the TAND knowledge gaps identified. En ligne : https://dx.doi.org/10.1186/s11689-022-09423-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] The research landscape of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)-a comprehensive scoping review [texte imprimé] / Stephanie VANCLOOSTER, Auteur ; Stacey BISSELL, Auteur ; Agnies M. VAN EEGHEN, Auteur ; Nola CHAMBERS, Auteur ; Liesbeth DE WAELE, Auteur ; Anna W. BYARS, Auteur ; Jamie K. CAPAL, Auteur ; Sebastián CUKIER, Auteur ; Peter DAVIS, Auteur ; Jennifer FLINN, Auteur ; Sugnet GARDNER-LUBBE, Auteur ; Tanjala GIPSON, Auteur ; Tosca-Marie HEUNIS, Auteur ; Dena HOOK, Auteur ; J. Christopher KINGSWOOD, Auteur ; Darcy A. KRUEGER, Auteur ; Aubrey J. KUMM, Auteur ; Mustafa SAHIN, Auteur ; Eva SCHOETERS, Auteur ; Catherine SMITH, Auteur ; Shoba SRIVASTAVA, Auteur ; Megumi TAKEI, Auteur ; Robert WALTEREIT, Auteur ; Anna C. JANSEN, Auteur ; Petrus J. DE VRIES, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Aged  Autism Spectrum Disorder  Cohort Studies  Humans  Tuberous Sclerosis/complications/psychology  Autism  Behaviour  Intellectual  Neuropsychological  Psychiatric  Psychosocial  Scholastic  Scoping review  TSC-associated neuropsychiatric disorders  Tuberous sclerosis complex  syndromes, including TSC. PD receives partial salary support from the NIH for  participation in studies related to TSC, as well as from Aucta Pharmaceuticals  for a study of topical sirolimus for facial angiofibromas in TSC and Marinus  Pharmaceuticals for a study of ganaxolone for TSC-related epilepsy. DAK reports  grants from National Institutes of Health (NINDS) during the conduct of the study  as well as the personal fees from Novartis Pharmaceuticals, personal fees from  Greenwich Bioscience, grants from Marinus Pharmaceuticals, personal fees from  Nobelpharma America, personal fees from REGENXBIO, and grants and non-financial  support from TSC Alliance outside the submitted work. CS receives salary support  from the TSC Alliance, a non-profit organisation which reports revenue from  individual donors and corporations including Greenwich Biosciences, GW Pharma,  Mallinckrodt, Nobelpharma, Novartis, Ovid, UCB and Upsher-Smith. PJdV was a study  steering committee member of three phase III trials sponsored by Novartis. He and  AJ were also on the scientific advisory group of the TOSCA international disease  registry sponsored by Novartis. MS reports grant support from Novartis, Biogen,  Astellas, Aeovian, Bridgebio and Aucta, and has served on Scientific Advisory  Boards for Novartis, Roche, Regenxbio, SpringWorks Therapeutics, Jaguar  Therapeutics and Alkermes. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) is an umbrella term for the behavioural, psychiatric, intellectual, academic, neuropsychological and psychosocial manifestations of TSC. Although TAND affects 90% of individuals with TSC during their lifetime, these manifestations are relatively under-assessed, under-treated and under-researched. We performed a comprehensive scoping review of all TAND research to date (a) to describe the existing TAND research landscape and (b) to identify knowledge gaps to guide future TAND research. METHODS: The study was conducted in accordance with stages outlined within the Arksey and O'Malley scoping review framework. Ten research questions relating to study characteristics, research design and research content of TAND levels and clusters were examined. RESULTS: Of the 2841 returned searches, 230 articles published between 1987 and 2020 were included (animal studies = 30, case studies = 47, cohort studies = 153), with more than half published since the term TAND was coined in 2012 (118/230; 51%). Cohort studies largely involved children and/or adolescents (63%) as opposed to older adults (16%). Studies were represented across 341 individual research sites from 45 countries, the majority from the USA (89/341; 26%) and the UK (50/341; 15%). Only 48 research sites (14%) were within low-middle income countries (LMICs). Animal studies and case studies were of relatively high/high quality, but cohort studies showed significant variability. Of the 153 cohort studies, only 16 (10%) included interventions. None of these were non-pharmacological, and only 13 employed remote methodologies (e.g. telephone interviews, online surveys). Of all TAND clusters, the autism spectrum disorder-like cluster was the most widely researched (138/230; 60%) and the scholastic cluster the least (53/200; 27%). CONCLUSIONS: Despite the recent increase in TAND research, studies that represent participants across the lifespan, LMIC research sites and non-pharmacological interventions were identified as future priorities. The quality of cohort studies requires improvement, to which the use of standardised direct behavioural assessments may contribute. In human studies, the academic level in particular warrants further investigation. Remote technologies could help to address many of the TAND knowledge gaps identified. En ligne : https://dx.doi.org/10.1186/s11689-022-09423-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Altered subcortical and cortical brain morphology in adult women with 47,XXX: a 7-Tesla magnetic resonance imaging study / Chaira SERRARENS in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Altered subcortical and cortical brain morphology in adult women with 47,XXX: a 7-Tesla magnetic resonance imaging study Type de document : texte imprimé Auteurs : Chaira SERRARENS, Auteur ; Maarten OTTER, Auteur ; Bea C.M. CAMPFORTS, Auteur ; Constance T.R.M. STUMPEL, Auteur ; Henk JANSMA, Auteur ; Therese A.M.J. VAN AMELSVOORT, Auteur ; Claudia VINGERHOETS, Auteur Langues : Anglais (eng) Mots-clés : Adult  Brain/pathology  Chromosomes, Human, X  Female  Humans  Magnetic Resonance Imaging/methods  Sex Chromosome Aberrations  Sex Chromosome Disorders of Sex Development/pathology  Trisomy  47,xxx  7t  Adults  Cortical folding  Cortical surface area  Cortical thickness  Social cognition  Social functioning  Subcortical volume Index. décimale : PER Périodiques Résumé : BACKGROUND: Triple X syndrome (47,XXX) is a relatively common sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome in females and has been associated with a variable cognitive, behavioural and psychiatric phenotype. 47,XXX may serve as a suitable model for studying the effect of genetic architecture on brain morphology. Previous studies have shown alterations in brain structure in 47,XXX particularly in childhood and adolescence. In this study, we examined subcortical and cortical brain morphology in adult women with 47,XXX using ultra-high field 7T MRI. Given previous evidence of impaired social functioning and emotion recognition in adults with 47,XXX, we also investigated the relationship of these functions with brain morphology. METHODS: Twenty-one adult women with 47,XXX and 22 age- and sex-matched healthy controls were included. Structural T1-weighted images were acquired using a 7-Tesla magnetic resonance scanner. Measures of subcortical brain volumes, cortical surface area and thickness, and cortical folding were obtained and compared between the groups using general linear models. Additionally, we examined potential relationships between brain outcome measures and social functioning and social cognition in 47,XXX using correlation analyses. RESULTS: Adults with 47,XXX showed lower volumes of the thalamus, caudate, putamen, hippocampus, nucleus accumbens and pallidum, and larger lateral ventricle volumes. Lower surface area was found in the superior frontal gyrus and superior temporal gyrus in 47,XXX participants compared to healthy controls. Altered cortical thickness and cortical folding were not present in 47,XXX. Cortical thickness was associated with social cognition in 47,XXX. CONCLUSIONS: Results suggest that a supernumerary X chromosome in females affects subcortical and lateral ventricle volumes, and cortical surface area in adulthood. 47,XXX may serve as a suitable model for studying genetic influences on structural brain morphology across developmental stages in order to understand neurobiological mechanisms underlying cognitive and behavioural impairments. En ligne : https://dx.doi.org/10.1186/s11689-022-09425-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Altered subcortical and cortical brain morphology in adult women with 47,XXX: a 7-Tesla magnetic resonance imaging study [texte imprimé] / Chaira SERRARENS, Auteur ; Maarten OTTER, Auteur ; Bea C.M. CAMPFORTS, Auteur ; Constance T.R.M. STUMPEL, Auteur ; Henk JANSMA, Auteur ; Therese A.M.J. VAN AMELSVOORT, Auteur ; Claudia VINGERHOETS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adult  Brain/pathology  Chromosomes, Human, X  Female  Humans  Magnetic Resonance Imaging/methods  Sex Chromosome Aberrations  Sex Chromosome Disorders of Sex Development/pathology  Trisomy  47,xxx  7t  Adults  Cortical folding  Cortical surface area  Cortical thickness  Social cognition  Social functioning  Subcortical volume Index. décimale : PER Périodiques Résumé : BACKGROUND: Triple X syndrome (47,XXX) is a relatively common sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome in females and has been associated with a variable cognitive, behavioural and psychiatric phenotype. 47,XXX may serve as a suitable model for studying the effect of genetic architecture on brain morphology. Previous studies have shown alterations in brain structure in 47,XXX particularly in childhood and adolescence. In this study, we examined subcortical and cortical brain morphology in adult women with 47,XXX using ultra-high field 7T MRI. Given previous evidence of impaired social functioning and emotion recognition in adults with 47,XXX, we also investigated the relationship of these functions with brain morphology. METHODS: Twenty-one adult women with 47,XXX and 22 age- and sex-matched healthy controls were included. Structural T1-weighted images were acquired using a 7-Tesla magnetic resonance scanner. Measures of subcortical brain volumes, cortical surface area and thickness, and cortical folding were obtained and compared between the groups using general linear models. Additionally, we examined potential relationships between brain outcome measures and social functioning and social cognition in 47,XXX using correlation analyses. RESULTS: Adults with 47,XXX showed lower volumes of the thalamus, caudate, putamen, hippocampus, nucleus accumbens and pallidum, and larger lateral ventricle volumes. Lower surface area was found in the superior frontal gyrus and superior temporal gyrus in 47,XXX participants compared to healthy controls. Altered cortical thickness and cortical folding were not present in 47,XXX. Cortical thickness was associated with social cognition in 47,XXX. CONCLUSIONS: Results suggest that a supernumerary X chromosome in females affects subcortical and lateral ventricle volumes, and cortical surface area in adulthood. 47,XXX may serve as a suitable model for studying genetic influences on structural brain morphology across developmental stages in order to understand neurobiological mechanisms underlying cognitive and behavioural impairments. En ligne : https://dx.doi.org/10.1186/s11689-022-09425-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Atypical connectivity in the cortico-striatal network in NF1 children and its relationship with procedural perceptual-motor learning and motor skills / Eloïse BAUDOU in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Atypical connectivity in the cortico-striatal network in NF1 children and its relationship with procedural perceptual-motor learning and motor skills Type de document : texte imprimé Auteurs : Eloïse BAUDOU, Auteur ; Federico NEMMI, Auteur ; Patrice PERAN, Auteur ; Fabien CIGNETTI, Auteur ; Melody BLAIS, Auteur ; Stéphanie MAZIERO, Auteur ; Jessica TALLET, Auteur ; Yves CHAIX, Auteur Langues : Anglais (eng) Mots-clés : Child  Corpus Striatum  Humans  Learning  Magnetic Resonance Imaging  Motor Skills  Neurofibromatosis 1/complications  Cortico-striatal connectivity  Neurodevelopmental disorder  Neurofibromatosis type 1  Procedural memory  Resting-state MRI  Serial reaction time task Index. décimale : PER Périodiques Résumé : INTRODUCTION: Neurofibromatosis type 1 (NF1) is considered a model of neurodevelopmental disorder because of the high frequency of learning deficits, especially developmental coordination disorder. In neurodevelopmental disorder, Nicolson and Fawcett formulated the hypothesis of an impaired procedural learning system that has its origins in cortico-subcortical circuits. Our aim was to investigate the relationship between cortico-striatal connectivity and procedural perceptual-motor learning performance and motor skills in NF1 children. METHODS: Seventeen NF1 and 18 typically developing children aged between 8 and 12 years old participated in the study. All were right-handed and did not present intellectual or attention deficits. In all children, procedural perceptual-motor learning was assessed using a bimanual visuo-spatial serial reaction time task (SRTT) and motor skills using the Movement Assessment Battery for Children (M-ABC). All participants underwent a resting-state functional MRI session. We used a seed-based approach to explore cortico-striatal connectivity in somatomotor and frontoparietal networks. A comparison between the groups' striato-cortical connectivity and correlations between connectivity and learning (SRTT) and motor skills (M-ABC) were performed. RESULTS: At the behavioral level, SRTT scores are not significantly different in NF1 children compared to controls. However, M-ABC scores are significantly impaired within 9 patients (scores below the 15th percentile). At the cerebral level, NF1 children present a higher connectivity in the cortico-striatal regions mapping onto the right angular gyrus compared to controls. We found that the higher the connectivity values between these regions, differentiating NF1 and controls, the lower the M-ABC scores in the whole sample. No correlation was found for the SRTT scores. CONCLUSION: NF1 children present atypical hyperconnectivity in cortico-striatal connections. The relationship with motor skills could suggest a sensorimotor dysfunction already found in children with developmental coordination disorder. These abnormalities are not linked to procedural perceptual-motor learning assessed by SRTT. En ligne : https://dx.doi.org/10.1186/s11689-022-09428-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Atypical connectivity in the cortico-striatal network in NF1 children and its relationship with procedural perceptual-motor learning and motor skills [texte imprimé] / Eloïse BAUDOU, Auteur ; Federico NEMMI, Auteur ; Patrice PERAN, Auteur ; Fabien CIGNETTI, Auteur ; Melody BLAIS, Auteur ; Stéphanie MAZIERO, Auteur ; Jessica TALLET, Auteur ; Yves CHAIX, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Child  Corpus Striatum  Humans  Learning  Magnetic Resonance Imaging  Motor Skills  Neurofibromatosis 1/complications  Cortico-striatal connectivity  Neurodevelopmental disorder  Neurofibromatosis type 1  Procedural memory  Resting-state MRI  Serial reaction time task Index. décimale : PER Périodiques Résumé : INTRODUCTION: Neurofibromatosis type 1 (NF1) is considered a model of neurodevelopmental disorder because of the high frequency of learning deficits, especially developmental coordination disorder. In neurodevelopmental disorder, Nicolson and Fawcett formulated the hypothesis of an impaired procedural learning system that has its origins in cortico-subcortical circuits. Our aim was to investigate the relationship between cortico-striatal connectivity and procedural perceptual-motor learning performance and motor skills in NF1 children. METHODS: Seventeen NF1 and 18 typically developing children aged between 8 and 12 years old participated in the study. All were right-handed and did not present intellectual or attention deficits. In all children, procedural perceptual-motor learning was assessed using a bimanual visuo-spatial serial reaction time task (SRTT) and motor skills using the Movement Assessment Battery for Children (M-ABC). All participants underwent a resting-state functional MRI session. We used a seed-based approach to explore cortico-striatal connectivity in somatomotor and frontoparietal networks. A comparison between the groups' striato-cortical connectivity and correlations between connectivity and learning (SRTT) and motor skills (M-ABC) were performed. RESULTS: At the behavioral level, SRTT scores are not significantly different in NF1 children compared to controls. However, M-ABC scores are significantly impaired within 9 patients (scores below the 15th percentile). At the cerebral level, NF1 children present a higher connectivity in the cortico-striatal regions mapping onto the right angular gyrus compared to controls. We found that the higher the connectivity values between these regions, differentiating NF1 and controls, the lower the M-ABC scores in the whole sample. No correlation was found for the SRTT scores. CONCLUSION: NF1 children present atypical hyperconnectivity in cortico-striatal connections. The relationship with motor skills could suggest a sensorimotor dysfunction already found in children with developmental coordination disorder. These abnormalities are not linked to procedural perceptual-motor learning assessed by SRTT. En ligne : https://dx.doi.org/10.1186/s11689-022-09428-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Innovative computational approaches shed light on genetic mechanisms underlying cognitive impairment among children born extremely preterm / Weifang LIU in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Innovative computational approaches shed light on genetic mechanisms underlying cognitive impairment among children born extremely preterm Type de document : texte imprimé Auteurs : Weifang LIU, Auteur ; Quan SUN, Auteur ; Le HUANG, Auteur ; Arjun BHATTACHARYA, Auteur ; Geoffery W. WANG, Auteur ; Xianming TAN, Auteur ; Karl C.K. KUBAN, Auteur ; Robert M. JOSEPH, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur ; Yun LI, Auteur ; Hudson P. Jr SANTOS, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Brain  Child  Child, Preschool  Cognitive Dysfunction/genetics  DNA-Binding Proteins  Genome-Wide Association Study  Humans  Infant, Extremely Premature/psychology  Infant, Newborn  Muscle Proteins  Prospective Studies  TEA Domain Transcription Factors  Transcription Factors  Young Adult  Cognitive impairment  Genetic mechanisms  Genome-wide association study (GWAS)  Latent profile analysis (LPA)  Neurodevelopment  Preterm children Index. décimale : PER Périodiques Résumé : BACKGROUND: Although survival rates for infants born extremely preterm (gestation < 28 weeks) have improved significantly in recent decades, neurodevelopmental impairment remains a major concern. Children born extremely preterm remain at high risk for cognitive impairment from early childhood to adulthood. However, there is limited evidence on genetic factors associated with cognitive impairment in this population. METHODS: First, we used a latent profile analysis (LPA) approach to characterize neurocognitive function at age 10 for children born extremely preterm. Children were classified into two groups: (1) no or low cognitive impairment, and (2) moderate-to-severe cognitive impairment. Second, we performed TOPMed-based genotype imputation on samples with genotype array data (n = 528). Third, we then conducted a genome-wide association study (GWAS) for LPA-inferred cognitive impairment. Finally, computational analysis was conducted to explore potential mechanisms underlying the variant x LPA association. RESULTS: We identified two loci reaching genome-wide significance (p value < 5e-8): TEA domain transcription factor 4 (TEAD4 at rs11829294, p value = 2.40e-8) and syntaxin 18 (STX18 at rs79453226, p value = 1.91e-8). Integrative analysis with brain expression quantitative trait loci (eQTL), chromatin conformation, and epigenomic annotations suggests tetraspanin 9 (TSPAN9) and protein arginine methyltransferase 8 (PRMT8) as potential functional genes underlying the GWAS signal at the TEAD4 locus. CONCLUSIONS: We conducted a novel computational analysis by utilizing an LPA-inferred phenotype with genetics data for the first time. This study suggests that rs11829294 and its LD buddies have potential regulatory roles on genes that could impact neurocognitive impairment for extreme preterm born children. En ligne : https://dx.doi.org/10.1186/s11689-022-09429-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Innovative computational approaches shed light on genetic mechanisms underlying cognitive impairment among children born extremely preterm [texte imprimé] / Weifang LIU, Auteur ; Quan SUN, Auteur ; Le HUANG, Auteur ; Arjun BHATTACHARYA, Auteur ; Geoffery W. WANG, Auteur ; Xianming TAN, Auteur ; Karl C.K. KUBAN, Auteur ; Robert M. JOSEPH, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur ; Yun LI, Auteur ; Hudson P. Jr SANTOS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Brain  Child  Child, Preschool  Cognitive Dysfunction/genetics  DNA-Binding Proteins  Genome-Wide Association Study  Humans  Infant, Extremely Premature/psychology  Infant, Newborn  Muscle Proteins  Prospective Studies  TEA Domain Transcription Factors  Transcription Factors  Young Adult  Cognitive impairment  Genetic mechanisms  Genome-wide association study (GWAS)  Latent profile analysis (LPA)  Neurodevelopment  Preterm children Index. décimale : PER Périodiques Résumé : BACKGROUND: Although survival rates for infants born extremely preterm (gestation < 28 weeks) have improved significantly in recent decades, neurodevelopmental impairment remains a major concern. Children born extremely preterm remain at high risk for cognitive impairment from early childhood to adulthood. However, there is limited evidence on genetic factors associated with cognitive impairment in this population. METHODS: First, we used a latent profile analysis (LPA) approach to characterize neurocognitive function at age 10 for children born extremely preterm. Children were classified into two groups: (1) no or low cognitive impairment, and (2) moderate-to-severe cognitive impairment. Second, we performed TOPMed-based genotype imputation on samples with genotype array data (n = 528). Third, we then conducted a genome-wide association study (GWAS) for LPA-inferred cognitive impairment. Finally, computational analysis was conducted to explore potential mechanisms underlying the variant x LPA association. RESULTS: We identified two loci reaching genome-wide significance (p value < 5e-8): TEA domain transcription factor 4 (TEAD4 at rs11829294, p value = 2.40e-8) and syntaxin 18 (STX18 at rs79453226, p value = 1.91e-8). Integrative analysis with brain expression quantitative trait loci (eQTL), chromatin conformation, and epigenomic annotations suggests tetraspanin 9 (TSPAN9) and protein arginine methyltransferase 8 (PRMT8) as potential functional genes underlying the GWAS signal at the TEAD4 locus. CONCLUSIONS: We conducted a novel computational analysis by utilizing an LPA-inferred phenotype with genetics data for the first time. This study suggests that rs11829294 and its LD buddies have potential regulatory roles on genes that could impact neurocognitive impairment for extreme preterm born children. En ligne : https://dx.doi.org/10.1186/s11689-022-09429-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort / Maria M. LILJA in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort Type de document : texte imprimé Auteurs : Maria M. LILJA, Auteur ; Emil SANDBLOM, Auteur ; Paul LICHTENSTEIN, Auteur ; Eva SERLACHIUS, Auteur ; Clara HELLNER, Auteur ; Jyoti BHAGIA, Auteur ; Linda HALLDNER, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Attention Deficit Disorder with Hyperactivity/complications/drug therapy  Autism Spectrum Disorder/complications/drug therapy  Autistic Disorder/complications  Central Nervous System Stimulants/adverse effects  Child  Humans  Prospective Studies  Adhd  Asd  Adverse event  Effect  Pharmacological treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition that globally affects an average of around 5% of children and is associated with several adverse life outcomes. Comorbidity with autism spectrum disorder (ASD) is highly prevalent. Pharmacological treatment for ADHD symptoms has been shown to be effective. However, the prevailing perception is that children with ADHD and concomitant ASD symptoms report poorer efficacy and more side effects. This has been supported by studies on this population, but prospective studies directly comparing children with ADHD and different levels of ASD symptoms are lacking. We aimed to assess if children with ADHD and concomitant ASD symptoms differ regarding effects and side-effects of pharmacological ADHD treatment compared to children with ADHD without ASD traits. This is to our knowledge the second study to directly compare the effect of ADHD medication between ADHD patients with different levels of ASD symptoms. METHODS: In a non-randomized, observational, prospective cohort study, 323 patients aged 6 to 17 years who were diagnosed with ADHD and starting pharmacological treatment were divided into two groups: one with high level of ASD symptoms (ASD group, N=71) and one with low level of ASD symptoms (non-ASD group, N = 252). Treatment outcome was measured as ADHD symptoms, and evaluated using the Swanson, Nolan and Pelham Teacher and Parent ADHD rating scale-version IV (SNAP-IV). Side-effects were evaluated using the Pediatric Side Effects Checklist (P-SEC), at 3 months follow-up. RESULTS: From baseline to 3 months, there was no significant difference in neither treatment effect nor number of clinically significant adverse events experienced between the ASD group and the non-ASD group. CONCLUSIONS: Our results did not implicate that ADHD patients with concomitant ASD symptoms have decreased treatment effect of ADHD medication than patients with ADHD without concomitant ASD symptoms. Neither did the results support that ADHD patients with ASD symptoms experienced significantly more side-effects than ADHD patients without ASD symptoms. Although, we did not analyze different medications separately, this is in line with the only previous study directly comparing methylphenidate treatment in children with or without ASD. TRIAL REGISTRATION: NCT02136147 , May 12, 2014. En ligne : https://dx.doi.org/10.1186/s11689-022-09424-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] The effect of autistic traits on response to and side-effects of pharmacological ADHD treatment in children with ADHD: results from a prospective clinical cohort [texte imprimé] / Maria M. LILJA, Auteur ; Emil SANDBLOM, Auteur ; Paul LICHTENSTEIN, Auteur ; Eva SERLACHIUS, Auteur ; Clara HELLNER, Auteur ; Jyoti BHAGIA, Auteur ; Linda HALLDNER, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Attention Deficit Disorder with Hyperactivity/complications/drug therapy  Autism Spectrum Disorder/complications/drug therapy  Autistic Disorder/complications  Central Nervous System Stimulants/adverse effects  Child  Humans  Prospective Studies  Adhd  Asd  Adverse event  Effect  Pharmacological treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition that globally affects an average of around 5% of children and is associated with several adverse life outcomes. Comorbidity with autism spectrum disorder (ASD) is highly prevalent. Pharmacological treatment for ADHD symptoms has been shown to be effective. However, the prevailing perception is that children with ADHD and concomitant ASD symptoms report poorer efficacy and more side effects. This has been supported by studies on this population, but prospective studies directly comparing children with ADHD and different levels of ASD symptoms are lacking. We aimed to assess if children with ADHD and concomitant ASD symptoms differ regarding effects and side-effects of pharmacological ADHD treatment compared to children with ADHD without ASD traits. This is to our knowledge the second study to directly compare the effect of ADHD medication between ADHD patients with different levels of ASD symptoms. METHODS: In a non-randomized, observational, prospective cohort study, 323 patients aged 6 to 17 years who were diagnosed with ADHD and starting pharmacological treatment were divided into two groups: one with high level of ASD symptoms (ASD group, N=71) and one with low level of ASD symptoms (non-ASD group, N = 252). Treatment outcome was measured as ADHD symptoms, and evaluated using the Swanson, Nolan and Pelham Teacher and Parent ADHD rating scale-version IV (SNAP-IV). Side-effects were evaluated using the Pediatric Side Effects Checklist (P-SEC), at 3 months follow-up. RESULTS: From baseline to 3 months, there was no significant difference in neither treatment effect nor number of clinically significant adverse events experienced between the ASD group and the non-ASD group. CONCLUSIONS: Our results did not implicate that ADHD patients with concomitant ASD symptoms have decreased treatment effect of ADHD medication than patients with ADHD without concomitant ASD symptoms. Neither did the results support that ADHD patients with ASD symptoms experienced significantly more side-effects than ADHD patients without ASD symptoms. Although, we did not analyze different medications separately, this is in line with the only previous study directly comparing methylphenidate treatment in children with or without ASD. TRIAL REGISTRATION: NCT02136147 , May 12, 2014. En ligne : https://dx.doi.org/10.1186/s11689-022-09424-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Using causal methods to map symptoms to brain circuits in neurodevelopment disorders: moving from identifying correlates to developing treatments / Alexander Li COHEN in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Using causal methods to map symptoms to brain circuits in neurodevelopment disorders: moving from identifying correlates to developing treatments Type de document : texte imprimé Auteurs : Alexander Li COHEN, Auteur Langues : Anglais (eng) Mots-clés : Brain/diagnostic imaging  Neurodevelopmental Disorders/therapy  Neurofeedback/methods  Neuroimaging/methods  Transcranial Magnetic Stimulation/methods  Neurodevelopmental disorders  Real-time fMRI neurofeedback  Transcranial direct current stimulation  Transcranial magnetic Stimulation  Transdiagnostic symptoms  Translational neuroimaging Index. décimale : PER Périodiques Résumé : A wide variety of model systems and experimental techniques can provide insight into the structure and function of the human brain in typical development and in neurodevelopmental disorders. Unfortunately, this work, whether based on manipulation of animal models or observational and correlational methods in humans, has a high attrition rate in translating scientific discovery into practicable treatments and therapies for neurodevelopmental disorders.With new computational and neuromodulatory approaches to interrogating brain networks, opportunities exist for "bedside-to bedside-translation" with a potentially shorter path to therapeutic options. Specifically, methods like lesion network mapping can identify brain networks involved in the generation of complex symptomatology, both from acute onset lesion-related symptoms and from focal developmental anomalies. Traditional neuroimaging can examine the generalizability of these findings to idiopathic populations, while non-invasive neuromodulation techniques such as transcranial magnetic stimulation provide the ability to do targeted activation or inhibition of these specific brain regions and networks. In parallel, real-time functional MRI neurofeedback also allow for endogenous neuromodulation of specific targets that may be out of reach for transcranial exogenous methods.Discovery of novel neuroanatomical circuits for transdiagnostic symptoms and neuroimaging-based endophenotypes may now be feasible for neurodevelopmental disorders using data from cohorts with focal brain anomalies. These novel circuits, after validation in large-scale highly characterized research cohorts and tested prospectively using noninvasive neuromodulation and neurofeedback techniques, may represent a new pathway for symptom-based targeted therapy. En ligne : https://dx.doi.org/10.1186/s11689-022-09433-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Using causal methods to map symptoms to brain circuits in neurodevelopment disorders: moving from identifying correlates to developing treatments [texte imprimé] / Alexander Li COHEN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Brain/diagnostic imaging  Neurodevelopmental Disorders/therapy  Neurofeedback/methods  Neuroimaging/methods  Transcranial Magnetic Stimulation/methods  Neurodevelopmental disorders  Real-time fMRI neurofeedback  Transcranial direct current stimulation  Transcranial magnetic Stimulation  Transdiagnostic symptoms  Translational neuroimaging Index. décimale : PER Périodiques Résumé : A wide variety of model systems and experimental techniques can provide insight into the structure and function of the human brain in typical development and in neurodevelopmental disorders. Unfortunately, this work, whether based on manipulation of animal models or observational and correlational methods in humans, has a high attrition rate in translating scientific discovery into practicable treatments and therapies for neurodevelopmental disorders.With new computational and neuromodulatory approaches to interrogating brain networks, opportunities exist for "bedside-to bedside-translation" with a potentially shorter path to therapeutic options. Specifically, methods like lesion network mapping can identify brain networks involved in the generation of complex symptomatology, both from acute onset lesion-related symptoms and from focal developmental anomalies. Traditional neuroimaging can examine the generalizability of these findings to idiopathic populations, while non-invasive neuromodulation techniques such as transcranial magnetic stimulation provide the ability to do targeted activation or inhibition of these specific brain regions and networks. In parallel, real-time functional MRI neurofeedback also allow for endogenous neuromodulation of specific targets that may be out of reach for transcranial exogenous methods.Discovery of novel neuroanatomical circuits for transdiagnostic symptoms and neuroimaging-based endophenotypes may now be feasible for neurodevelopmental disorders using data from cohorts with focal brain anomalies. These novel circuits, after validation in large-scale highly characterized research cohorts and tested prospectively using noninvasive neuromodulation and neurofeedback techniques, may represent a new pathway for symptom-based targeted therapy. En ligne : https://dx.doi.org/10.1186/s11689-022-09433-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Patterns and predictors of adaptive skills in 2- to 7-year-old children with Down syndrome / Emily K. SCHWORER in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Patterns and predictors of adaptive skills in 2- to 7-year-old children with Down syndrome Type de document : texte imprimé Auteurs : Emily K. SCHWORER, Auteur ; Anna J. ESBENSEN, Auteur ; Vivian NGUYEN, Auteur ; Lauren BULLARD, Auteur ; Deborah J. FIDLER, Auteur ; Lisa A. DAUNHAUER, Auteur ; Carolyn B. MERVIS, Auteur ; Angela M. BECERRA, Auteur ; Leonard ABBEDUTO, Auteur ; Angela John THURMAN, Auteur Langues : Anglais (eng) Mots-clés : Adaptation, Psychological  Autism Spectrum Disorder/psychology  Child  Child, Preschool  Down Syndrome  Humans  Motor Skills  Socialization  ASD symptoms  Adaptive skills  Cognition  Down syndrome  Motor skills  Pharmaceuticals Ltd., Fulcrum Therapeutics, and Lumind to consult on and  implement outcome measures in clinical trials for FXS and DS. AJT has received  funding from Fulcrum Therapeutics to develop outcome measures for FXS. The other  authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: There is substantial variability in adaptive skills among individuals with Down syndrome. Few studies, however, have focused on the early developmental period or on the potential sources of variability in adaptive skills. This study characterizes adaptive skills in young children with Down syndrome and investigates child characteristics associated with adaptive skills. METHODS: Participants were 44 children with Down syndrome ranging in age from 2.50 to 7.99 years (M = 4.66 years, SD = 1.46). The Vineland Adaptive Behavior Scales-3 (VABS-3) Comprehensive Interview Form was used to assess adaptive behavior in the three core domains: socialization, daily living, and communication skills. Caregivers also reported on motor skills and autism spectrum disorder symptoms. Child cognitive abilities were assessed. RESULTS: Analyses comparing mean standard score performance across the three VABS-3 core domains demonstrated significant differences between all pairs of domains, resulting in a group-level pattern of socialization > daily living > communication skills. At the individual level, 10 different patterns of relative strength and weakness were identified, with only 18% of participants evidencing significant differences between adaptive skill domain standard scores corresponding to the group-level pattern of significant differences. Child characteristics (cognitive abilities, motor skills, and autism spectrum disorder symptoms) were significantly associated with VABS-3 adaptive domain standard scores. CONCLUSION: These findings underscore the importance of individualizing intervention programs focused on improving the adaptive skills of young children with Down syndrome based on consideration of the child's relative adaptive strengths and weaknesses. En ligne : https://dx.doi.org/10.1186/s11689-022-09430-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Patterns and predictors of adaptive skills in 2- to 7-year-old children with Down syndrome [texte imprimé] / Emily K. SCHWORER, Auteur ; Anna J. ESBENSEN, Auteur ; Vivian NGUYEN, Auteur ; Lauren BULLARD, Auteur ; Deborah J. FIDLER, Auteur ; Lisa A. DAUNHAUER, Auteur ; Carolyn B. MERVIS, Auteur ; Angela M. BECERRA, Auteur ; Leonard ABBEDUTO, Auteur ; Angela John THURMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adaptation, Psychological  Autism Spectrum Disorder/psychology  Child  Child, Preschool  Down Syndrome  Humans  Motor Skills  Socialization  ASD symptoms  Adaptive skills  Cognition  Down syndrome  Motor skills  Pharmaceuticals Ltd., Fulcrum Therapeutics, and Lumind to consult on and  implement outcome measures in clinical trials for FXS and DS. AJT has received  funding from Fulcrum Therapeutics to develop outcome measures for FXS. The other  authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: There is substantial variability in adaptive skills among individuals with Down syndrome. Few studies, however, have focused on the early developmental period or on the potential sources of variability in adaptive skills. This study characterizes adaptive skills in young children with Down syndrome and investigates child characteristics associated with adaptive skills. METHODS: Participants were 44 children with Down syndrome ranging in age from 2.50 to 7.99 years (M = 4.66 years, SD = 1.46). The Vineland Adaptive Behavior Scales-3 (VABS-3) Comprehensive Interview Form was used to assess adaptive behavior in the three core domains: socialization, daily living, and communication skills. Caregivers also reported on motor skills and autism spectrum disorder symptoms. Child cognitive abilities were assessed. RESULTS: Analyses comparing mean standard score performance across the three VABS-3 core domains demonstrated significant differences between all pairs of domains, resulting in a group-level pattern of socialization > daily living > communication skills. At the individual level, 10 different patterns of relative strength and weakness were identified, with only 18% of participants evidencing significant differences between adaptive skill domain standard scores corresponding to the group-level pattern of significant differences. Child characteristics (cognitive abilities, motor skills, and autism spectrum disorder symptoms) were significantly associated with VABS-3 adaptive domain standard scores. CONCLUSION: These findings underscore the importance of individualizing intervention programs focused on improving the adaptive skills of young children with Down syndrome based on consideration of the child's relative adaptive strengths and weaknesses. En ligne : https://dx.doi.org/10.1186/s11689-022-09430-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Neural patterns elicited by lexical processing in adolescents with specific language impairment: support for the procedural deficit hypothesis? / Julia L. EVANS in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Neural patterns elicited by lexical processing in adolescents with specific language impairment: support for the procedural deficit hypothesis? Type de document : texte imprimé Auteurs : Julia L. EVANS, Auteur ; Mandy J. MAGUIRE, Auteur ; Marisa L. SIZEMORE, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Electroencephalography  Evoked Potentials  Female  Humans  Language Development Disorders  Language Tests  Male  Specific Language Disorder  Developmental language disorder (DLD)  Event-related potentials  Imageability  N400  N700  Procedural deficit hypothesis  Procedural memory  Semantic processing  Specific language impairment (SLI)  Spoken word processing Index. décimale : PER Périodiques Résumé : BACKGROUND: Deficits in procedural memory have been proposed to account for the language deficits in specific language impairment (SLI). A key aspect of the procedural deficit hypothesis (PDH) account of SLI is that declarative memory is intact and functions as a compensatory mechanism in the acquisition of language in individuals with SLI. The current study examined the neural correlates of lexical-phonological and lexical-semantic processing with respect to these predictions in a group of adolescents with SLI with procedural memory impairment and a group of chronologically age-matched (CA) normal controls. METHODS: Participants completed tasks designed to measure procedural and declarative memory and two ERP tasks designed to assess lexical-semantic and lexical-phonological processing in the auditory modality. Procedural memory was assessed using a statistical learning task. Lexical-semantic processing was assessed using a sentence judgment task modulating semantic congruency and lexical-phonological processing was assessed using a word/nonword decision task modulating word frequency. Behavioral performance on the tasks, mean amplitude of the cortical response, and animated topographs were examined. RESULTS: Performance on the statistical word-learning task was at chance for the adolescents with SLI, whereas declarative memory was no different from the CA controls. Behavioral accuracy on the lexical-semantic task was the same for the adolescents with SLI and CA controls but accuracy on the lexical-phonological task was significantly poorer for the adolescents with SLI as compared to the CA controls. An N400 component was elicited in response to semantic congruency on the lexical-semantic task for both groups but differences were noted in both the location and time course of the cortical response for the SLI and CA groups. An N400 component was elicited by word frequency on the lexical-phonological task for the CA controls not for the adolescents with SLI. In contrast, post hoc analysis revealed a cortical response based on imageability for the adolescents with SLI, but not CA controls. Statistical word learning was significantly correlated with speed of processing on the lexical decision task for the CA controls but not for the adolescents with SLI. In contrast, statistical word learning ability was not correlated with the modulation of the N400 on either task for either group. CONCLUSION: The behavioral data suggests intact semantic conceptual knowledge, but impaired lexical phonological processing for the adolescents with SLI, consistent with the PDH. The pattern of cortical activation in response to semantic congruency and word frequency suggests, however, that the processing of lexical-semantic and lexical-phonological information by adolescents with a history of SLI may be supported by both overlapping and nonoverlapping neural generators to those of CA controls, and a greater reliance on declarative memory strategies. Taken together, the findings from this study suggest that the underlying representations of words in the lexicons of adolescents with a history of SLI may differ qualitatively from those of their typical peers, but these differences may only be evident when behavioral data and neural cortical patterns of activation are examined together. En ligne : https://dx.doi.org/10.1186/s11689-022-09419-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Neural patterns elicited by lexical processing in adolescents with specific language impairment: support for the procedural deficit hypothesis? [texte imprimé] / Julia L. EVANS, Auteur ; Mandy J. MAGUIRE, Auteur ; Marisa L. SIZEMORE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Electroencephalography  Evoked Potentials  Female  Humans  Language Development Disorders  Language Tests  Male  Specific Language Disorder  Developmental language disorder (DLD)  Event-related potentials  Imageability  N400  N700  Procedural deficit hypothesis  Procedural memory  Semantic processing  Specific language impairment (SLI)  Spoken word processing Index. décimale : PER Périodiques Résumé : BACKGROUND: Deficits in procedural memory have been proposed to account for the language deficits in specific language impairment (SLI). A key aspect of the procedural deficit hypothesis (PDH) account of SLI is that declarative memory is intact and functions as a compensatory mechanism in the acquisition of language in individuals with SLI. The current study examined the neural correlates of lexical-phonological and lexical-semantic processing with respect to these predictions in a group of adolescents with SLI with procedural memory impairment and a group of chronologically age-matched (CA) normal controls. METHODS: Participants completed tasks designed to measure procedural and declarative memory and two ERP tasks designed to assess lexical-semantic and lexical-phonological processing in the auditory modality. Procedural memory was assessed using a statistical learning task. Lexical-semantic processing was assessed using a sentence judgment task modulating semantic congruency and lexical-phonological processing was assessed using a word/nonword decision task modulating word frequency. Behavioral performance on the tasks, mean amplitude of the cortical response, and animated topographs were examined. RESULTS: Performance on the statistical word-learning task was at chance for the adolescents with SLI, whereas declarative memory was no different from the CA controls. Behavioral accuracy on the lexical-semantic task was the same for the adolescents with SLI and CA controls but accuracy on the lexical-phonological task was significantly poorer for the adolescents with SLI as compared to the CA controls. An N400 component was elicited in response to semantic congruency on the lexical-semantic task for both groups but differences were noted in both the location and time course of the cortical response for the SLI and CA groups. An N400 component was elicited by word frequency on the lexical-phonological task for the CA controls not for the adolescents with SLI. In contrast, post hoc analysis revealed a cortical response based on imageability for the adolescents with SLI, but not CA controls. Statistical word learning was significantly correlated with speed of processing on the lexical decision task for the CA controls but not for the adolescents with SLI. In contrast, statistical word learning ability was not correlated with the modulation of the N400 on either task for either group. CONCLUSION: The behavioral data suggests intact semantic conceptual knowledge, but impaired lexical phonological processing for the adolescents with SLI, consistent with the PDH. The pattern of cortical activation in response to semantic congruency and word frequency suggests, however, that the processing of lexical-semantic and lexical-phonological information by adolescents with a history of SLI may be supported by both overlapping and nonoverlapping neural generators to those of CA controls, and a greater reliance on declarative memory strategies. Taken together, the findings from this study suggest that the underlying representations of words in the lexicons of adolescents with a history of SLI may differ qualitatively from those of their typical peers, but these differences may only be evident when behavioral data and neural cortical patterns of activation are examined together. En ligne : https://dx.doi.org/10.1186/s11689-022-09419-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

mRNA expression analysis of the hippocampus in a vervet monkey model of fetal alcohol spectrum disorder / Rob F. GILLIS in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : mRNA expression analysis of the hippocampus in a vervet monkey model of fetal alcohol spectrum disorder Type de document : texte imprimé Auteurs : Rob F. GILLIS, Auteur ; Roberta M. PALMOUR, Auteur Langues : Anglais (eng) Mots-clés : Animals  Child, Preschool  Chlorocebus aethiops  Disease Models, Animal  Ephrin-B1/metabolism/pharmacology  Ethanol/metabolism  Female  Fetal Alcohol Spectrum Disorders/genetics/metabolism  Hippocampus/metabolism  Humans  Macaca mulatta/genetics/metabolism  Pregnancy  Prenatal Exposure Delayed Effects/genetics  RNA, Messenger/metabolism/pharmacology  Fetal alcohol spectrum disorders  Gene expression analysis  Neurodevelopment  Non-human primate model  that she is the scientific officer (unpaid) for the Behavioural Science  Foundation, a not-for-profit research foundation registered in the State of  Delaware (USA). Index. décimale : PER Périodiques Résumé : BACKGROUND: Fetal alcohol spectrum disorders (FASD) are common, yet preventable developmental disorders that stem from prenatal exposure to alcohol. This exposure leads to a wide array of behavioural and physical problems with a complex and poorly defined biological basis. Molecular investigations to date predominantly use rodent animal models, but because of genetic, developmental and social behavioral similarity, primate models are more relevant. We previously reported reduced cortical and hippocampal neuron levels in an Old World monkey (Chlorocebus sabaeus) model with ethanol exposure targeted to the period of rapid synaptogenesis and report here an initial molecular study of this model. The goal of this study was to evaluate mRNA expression of the hippocampus at two different behavioural stages (5 months, 2 years) corresponding to human infancy and early childhood. METHODS: Offspring of alcohol-preferring or control dams drank a maximum of 3.5 g ethanol per kg body weight or calorically matched sucrose solution 4 days per week during the last 2 months of gestation. Total mRNA expression was measured with the Affymetrix GeneChip Rhesus Macaque Genome Array in a 2 × 2 study design that interrogated two independent variables, age at sacrifice, and alcohol consumption during gestation. RESULTS AND DISCUSSION: Statistical analysis identified a preferential downregulation of expression when interrogating the factor 'alcohol' with a balanced effect of upregulation vs. downregulation for the independent variable 'age'. Functional exploration of both independent variables shows that the alcohol consumption factor generates broad functional annotation clusters that likely implicate a role for epigenetics in the observed differential expression, while the variable age reliably produced functional annotation clusters predominantly related to development. Furthermore, our data reveals a novel connection between EFNB1 and the FASDs; this is highly plausible both due to the role of EFNB1 in neuronal development as well as its central role in craniofrontal nasal syndrome (CFNS). Fold changes for key genes were subsequently confirmed via qRT-PCR. CONCLUSION: Prenatal alcohol exposure leads to global downregulation in mRNA expression. The cellular interference model of EFNB1 provides a potential clue regarding how genetically susceptible individuals may develop the phenotypic triad generally associated with classic fetal alcohol syndrome. En ligne : https://dx.doi.org/10.1186/s11689-022-09427-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] mRNA expression analysis of the hippocampus in a vervet monkey model of fetal alcohol spectrum disorder [texte imprimé] / Rob F. GILLIS, Auteur ; Roberta M. PALMOUR, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Animals  Child, Preschool  Chlorocebus aethiops  Disease Models, Animal  Ephrin-B1/metabolism/pharmacology  Ethanol/metabolism  Female  Fetal Alcohol Spectrum Disorders/genetics/metabolism  Hippocampus/metabolism  Humans  Macaca mulatta/genetics/metabolism  Pregnancy  Prenatal Exposure Delayed Effects/genetics  RNA, Messenger/metabolism/pharmacology  Fetal alcohol spectrum disorders  Gene expression analysis  Neurodevelopment  Non-human primate model  that she is the scientific officer (unpaid) for the Behavioural Science  Foundation, a not-for-profit research foundation registered in the State of  Delaware (USA). Index. décimale : PER Périodiques Résumé : BACKGROUND: Fetal alcohol spectrum disorders (FASD) are common, yet preventable developmental disorders that stem from prenatal exposure to alcohol. This exposure leads to a wide array of behavioural and physical problems with a complex and poorly defined biological basis. Molecular investigations to date predominantly use rodent animal models, but because of genetic, developmental and social behavioral similarity, primate models are more relevant. We previously reported reduced cortical and hippocampal neuron levels in an Old World monkey (Chlorocebus sabaeus) model with ethanol exposure targeted to the period of rapid synaptogenesis and report here an initial molecular study of this model. The goal of this study was to evaluate mRNA expression of the hippocampus at two different behavioural stages (5 months, 2 years) corresponding to human infancy and early childhood. METHODS: Offspring of alcohol-preferring or control dams drank a maximum of 3.5 g ethanol per kg body weight or calorically matched sucrose solution 4 days per week during the last 2 months of gestation. Total mRNA expression was measured with the Affymetrix GeneChip Rhesus Macaque Genome Array in a 2 × 2 study design that interrogated two independent variables, age at sacrifice, and alcohol consumption during gestation. RESULTS AND DISCUSSION: Statistical analysis identified a preferential downregulation of expression when interrogating the factor 'alcohol' with a balanced effect of upregulation vs. downregulation for the independent variable 'age'. Functional exploration of both independent variables shows that the alcohol consumption factor generates broad functional annotation clusters that likely implicate a role for epigenetics in the observed differential expression, while the variable age reliably produced functional annotation clusters predominantly related to development. Furthermore, our data reveals a novel connection between EFNB1 and the FASDs; this is highly plausible both due to the role of EFNB1 in neuronal development as well as its central role in craniofrontal nasal syndrome (CFNS). Fold changes for key genes were subsequently confirmed via qRT-PCR. CONCLUSION: Prenatal alcohol exposure leads to global downregulation in mRNA expression. The cellular interference model of EFNB1 provides a potential clue regarding how genetically susceptible individuals may develop the phenotypic triad generally associated with classic fetal alcohol syndrome. En ligne : https://dx.doi.org/10.1186/s11689-022-09427-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Conducting clinical trials in persons with Down syndrome: summary from the NIH INCLUDE Down syndrome clinical trials readiness working group / Nicole T. BAUMER in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Conducting clinical trials in persons with Down syndrome: summary from the NIH INCLUDE Down syndrome clinical trials readiness working group Type de document : texte imprimé Auteurs : Nicole T. BAUMER, Auteur ; Mara L. BECKER, Auteur ; George T. CAPONE, Auteur ; Kathleen EGAN, Auteur ; Juan FORTEA, Auteur ; Benjamin L. HANDEN, Auteur ; Elizabeth HEAD, Auteur ; James E. HENDRIX, Auteur ; Ruth Y. LITOVSKY, Auteur ; Andre STRYDOM, Auteur ; Ignacio E. TAPIA, Auteur ; Michael S. RAFII, Auteur Langues : Anglais (eng) Mots-clés : Cohort Studies  Down Syndrome/complications/therapy  Humans  Clinical research  Clinical trials  Down syndrome  Intellectual disability  Recruitment  Research engagement Index. décimale : PER Périodiques Résumé : The recent National Institute of Health (NIH) INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) initiative has bolstered capacity for the current increase in clinical trials involving individuals with Down syndrome (DS). This new NIH funding mechanism offers new opportunities to expand and develop novel approaches in engaging and effectively enrolling a broader representation of clinical trials participants addressing current medical issues faced by individuals with DS. To address this opportunity, the NIH assembled leading clinicians, scientists, and representatives of advocacy groups to review existing methods and to identify those areas where new approaches are needed to engage and prepare DS populations for participation in clinical trial research. This paper summarizes the results of the Clinical Trial Readiness Working Group that was part of the INCLUDE Project Workshop: Planning a Virtual Down Syndrome Cohort Across the Lifespan Workshop held virtually September 23 and 24, 2019. En ligne : https://dx.doi.org/10.1186/s11689-022-09435-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Conducting clinical trials in persons with Down syndrome: summary from the NIH INCLUDE Down syndrome clinical trials readiness working group [texte imprimé] / Nicole T. BAUMER, Auteur ; Mara L. BECKER, Auteur ; George T. CAPONE, Auteur ; Kathleen EGAN, Auteur ; Juan FORTEA, Auteur ; Benjamin L. HANDEN, Auteur ; Elizabeth HEAD, Auteur ; James E. HENDRIX, Auteur ; Ruth Y. LITOVSKY, Auteur ; Andre STRYDOM, Auteur ; Ignacio E. TAPIA, Auteur ; Michael S. RAFII, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Cohort Studies  Down Syndrome/complications/therapy  Humans  Clinical research  Clinical trials  Down syndrome  Intellectual disability  Recruitment  Research engagement Index. décimale : PER Périodiques Résumé : The recent National Institute of Health (NIH) INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) initiative has bolstered capacity for the current increase in clinical trials involving individuals with Down syndrome (DS). This new NIH funding mechanism offers new opportunities to expand and develop novel approaches in engaging and effectively enrolling a broader representation of clinical trials participants addressing current medical issues faced by individuals with DS. To address this opportunity, the NIH assembled leading clinicians, scientists, and representatives of advocacy groups to review existing methods and to identify those areas where new approaches are needed to engage and prepare DS populations for participation in clinical trial research. This paper summarizes the results of the Clinical Trial Readiness Working Group that was part of the INCLUDE Project Workshop: Planning a Virtual Down Syndrome Cohort Across the Lifespan Workshop held virtually September 23 and 24, 2019. En ligne : https://dx.doi.org/10.1186/s11689-022-09435-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Neuropsychological changes in FMR1 premutation carriers and onset of fragile X-associated tremor/ataxia syndrome / Jessica FAMULA in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Neuropsychological changes in FMR1 premutation carriers and onset of fragile X-associated tremor/ataxia syndrome Type de document : texte imprimé Auteurs : Jessica FAMULA, Auteur ; Emilio FERRER, Auteur ; Randi J. HAGERMAN, Auteur ; Flora TASSONE, Auteur ; Andrea SCHNEIDER, Auteur ; Susan M. RIVERA, Auteur ; David HESSL, Auteur Langues : Anglais (eng) Mots-clés : Adult  Aged  Aged, 80 and over  Ataxia/complications/genetics  Cross-Sectional Studies  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome  Humans  Longitudinal Studies  Male  Memory, Short-Term/physiology  Middle Aged  Neurodegenerative Diseases/complications  Tremor/genetics  Ataxia  Cantab  Executive function  Fxtas  Fragile X premutation  Tremor  Davis, in support of fragile X syndrome treatment programs, and he receives no  personal funds and has no relevant financial interest in any of the commercial  entities listed: Autifony, Ovid, Tetra, Healx, and Zynerba pharmaceutical  companies to consult on outcome measures and clinical trial design. RJH has  received funding from Zynerba and the Azrieli foundation for treatment studies in  Fragile X syndrome and unrelated to this study. Index. décimale : PER Périodiques Résumé : BACKGROUND: Carriers of the FMR1 premutation are at increased risk of developing a late-onset progressive neurodegenerative disease, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by intention tremor, gait ataxia, and cognitive decline. Cross-sectional studies to date have provided evidence that neuropsychological changes, such as executive function alterations, or subtle motor changes, may precede the onset of formal FXTAS, perhaps characterizing a prodromal state. However, the lack of longitudinal data has prevented the field from forming a clear picture of progression over time within individuals, and we lack consensus regarding early markers of risk and measures that may be used to track response to intervention. METHODS: This was a longitudinal study of 64 male FMR1 premutation carriers (Pm) without FXTAS at study entry and 30 normal controls (Nc), aged 40 to 80 years (Pm M = 60.0 years; Nc M = 57.4 years). Fifty of the Pm and 22 of the Nc were re-assessed after an average of 2.33 years, and 37 Pm and 20 Nc were re-assessed a third time after an average of another 2.15 years. Eighteen of 64 carriers (28%) converted to FXTAS during the study to date. Neuropsychological assessments at each time point, including components of the Cambridge Neuropsychological Test Automated Battery (CANTAB), tapped domains of episodic and working memory, inhibitory control, visual attention, planning, executive control of movement, and manual speed and dexterity. Age-based mixed models were used to examine group differences in change over time on the outcomes in the full sample, and differences were further evaluated in 15 trios (n = 45; 15 Pm "converters," 15 Pm "nonconverters," 15 Nc) that were one-one matched on age, education, and socioeconomic status. RESULTS: Compared to Nc, Pm showed significantly greater rates of change over time in visual working memory, motor dexterity, inhibitory control, and manual movement speed. After multiple comparison correction, significant effects remained for motor dexterity. Worsening inhibitory control and slower manual movements were related to progression in FXTAS stage, but these effects became statistically non-significant after correcting for multiple comparisons. Higher FMR1 mRNA correlated with worsening manual reaction time but did not survive multiple comparisons and no other molecular measures correlated with neuropsychological changes. Finally, trio comparisons revealed greater rate of decline in planning and manual movement speed in Pm converters compared to Pm nonconverters. CONCLUSIONS: Accelerated decline in executive function and subtle motor changes, likely mediated by frontocerebellar circuits, may precede, and then track with the emergence of formal FXTAS symptoms. Further research to develop and harmonize clinical assessment of FMR1 carriers across centers is needed to prepare for future prophylactic and treatment trials for this disorder. En ligne : https://dx.doi.org/10.1186/s11689-022-09436-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Neuropsychological changes in FMR1 premutation carriers and onset of fragile X-associated tremor/ataxia syndrome [texte imprimé] / Jessica FAMULA, Auteur ; Emilio FERRER, Auteur ; Randi J. HAGERMAN, Auteur ; Flora TASSONE, Auteur ; Andrea SCHNEIDER, Auteur ; Susan M. RIVERA, Auteur ; David HESSL, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adult  Aged  Aged, 80 and over  Ataxia/complications/genetics  Cross-Sectional Studies  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome  Humans  Longitudinal Studies  Male  Memory, Short-Term/physiology  Middle Aged  Neurodegenerative Diseases/complications  Tremor/genetics  Ataxia  Cantab  Executive function  Fxtas  Fragile X premutation  Tremor  Davis, in support of fragile X syndrome treatment programs, and he receives no  personal funds and has no relevant financial interest in any of the commercial  entities listed: Autifony, Ovid, Tetra, Healx, and Zynerba pharmaceutical  companies to consult on outcome measures and clinical trial design. RJH has  received funding from Zynerba and the Azrieli foundation for treatment studies in  Fragile X syndrome and unrelated to this study. Index. décimale : PER Périodiques Résumé : BACKGROUND: Carriers of the FMR1 premutation are at increased risk of developing a late-onset progressive neurodegenerative disease, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by intention tremor, gait ataxia, and cognitive decline. Cross-sectional studies to date have provided evidence that neuropsychological changes, such as executive function alterations, or subtle motor changes, may precede the onset of formal FXTAS, perhaps characterizing a prodromal state. However, the lack of longitudinal data has prevented the field from forming a clear picture of progression over time within individuals, and we lack consensus regarding early markers of risk and measures that may be used to track response to intervention. METHODS: This was a longitudinal study of 64 male FMR1 premutation carriers (Pm) without FXTAS at study entry and 30 normal controls (Nc), aged 40 to 80 years (Pm M = 60.0 years; Nc M = 57.4 years). Fifty of the Pm and 22 of the Nc were re-assessed after an average of 2.33 years, and 37 Pm and 20 Nc were re-assessed a third time after an average of another 2.15 years. Eighteen of 64 carriers (28%) converted to FXTAS during the study to date. Neuropsychological assessments at each time point, including components of the Cambridge Neuropsychological Test Automated Battery (CANTAB), tapped domains of episodic and working memory, inhibitory control, visual attention, planning, executive control of movement, and manual speed and dexterity. Age-based mixed models were used to examine group differences in change over time on the outcomes in the full sample, and differences were further evaluated in 15 trios (n = 45; 15 Pm "converters," 15 Pm "nonconverters," 15 Nc) that were one-one matched on age, education, and socioeconomic status. RESULTS: Compared to Nc, Pm showed significantly greater rates of change over time in visual working memory, motor dexterity, inhibitory control, and manual movement speed. After multiple comparison correction, significant effects remained for motor dexterity. Worsening inhibitory control and slower manual movements were related to progression in FXTAS stage, but these effects became statistically non-significant after correcting for multiple comparisons. Higher FMR1 mRNA correlated with worsening manual reaction time but did not survive multiple comparisons and no other molecular measures correlated with neuropsychological changes. Finally, trio comparisons revealed greater rate of decline in planning and manual movement speed in Pm converters compared to Pm nonconverters. CONCLUSIONS: Accelerated decline in executive function and subtle motor changes, likely mediated by frontocerebellar circuits, may precede, and then track with the emergence of formal FXTAS symptoms. Further research to develop and harmonize clinical assessment of FMR1 carriers across centers is needed to prepare for future prophylactic and treatment trials for this disorder. En ligne : https://dx.doi.org/10.1186/s11689-022-09436-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Validation of a computational phenotype for finding patients eligible for genetic testing for pathogenic PTEN variants across three centers / Cartik KOTHARI in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Validation of a computational phenotype for finding patients eligible for genetic testing for pathogenic PTEN variants across three centers Type de document : texte imprimé Auteurs : Cartik KOTHARI, Auteur ; Siddharth SRIVASTAVA, Auteur ; Youssef KOUSA, Auteur ; Rima IZEM, Auteur ; Marcin GIERDALSKI, Auteur ; Dongkyu KIM, Auteur ; Amy GOOD, Auteur ; Kira A. DIES, Auteur ; Gregory GEISEL, Auteur ; Hiroki MORIZONO, Auteur ; Vittorio GALLO, Auteur ; Scott L. POMEROY, Auteur ; Gwenn A. GARDEN, Auteur ; Lisa GUAY-WOODFORD, Auteur ; Mustafa SAHIN, Auteur ; Paul AVILLACH, Auteur Langues : Anglais (eng) Mots-clés : Electronic Health Records  Genetic Testing  Hamartoma Syndrome, Multiple/diagnosis/genetics/pathology  Humans  PTEN Phosphohydrolase/genetics  Phenotype  Autism  Computational phenotype  Genetic disease  Rare disease  from GLG, Guidepoint (which connected to a client, Fortress Biotech), and  Novartis. 3. YK has no competing interests to declare. 4. RI has no competing  interests to declare. 5. MG has no competing interests to declare. 6. DK has no  competing interests to declare. 7. AG has no competing interests to declare. 8.  KAD has no competing interests to declare. 9. GG has no competing interests to  declare. 10. HM has no competing interests to declare. 11. VG has no competing  interests to declare. 12. SP has no competing interests to declare. 13. GAG has  no competing interests to declare. 14. LGW has no competing interests to declare.  15. MS reports grant support from Novartis, Roche, Biogen, Astellas, Aeovian,  Bridgebio, Aucta, and Quadrant Biosciences. He has served on Scientific Advisory  Boards for PTEN Research, Novartis, Roche, Celgene, Regenxbio, Alkermes, and  Takeda. 16. PA has no competing interests to declare Index. décimale : PER Périodiques Résumé : BACKGROUND: Computational phenotypes are most often combinations of patient billing codes that are highly predictive of disease using electronic health records (EHR). In the case of rare diseases that can only be diagnosed by genetic testing, computational phenotypes identify patient cohorts for genetic testing and possible diagnosis. This article details the validation of a computational phenotype for PTEN hamartoma tumor syndrome (PHTS) against the EHR of patients at three collaborating clinical research centers: Boston Children's Hospital, Children's National Hospital, and the University of Washington. METHODS: A combination of billing codes from the International Classification of Diseases versions 9 and 10 (ICD-9 and ICD-10) for diagnostic criteria postulated by a research team at Cleveland Clinic was used to identify patient cohorts for genetic testing from the clinical data warehouses at the three research centers. Subsequently, the EHR-including billing codes, clinical notes, and genetic reports-of these patients were reviewed by clinical experts to identify patients with PHTS. RESULTS: The PTEN genetic testing yield of the computational phenotype, the number of patients who needed to be genetically tested for incidence of pathogenic PTEN gene variants, ranged from 82 to 94% at the three centers. CONCLUSIONS: Computational phenotypes have the potential to enable the timely and accurate diagnosis of rare genetic diseases such as PHTS by identifying patient cohorts for genetic sequencing and testing. En ligne : https://dx.doi.org/10.1186/s11689-022-09434-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Validation of a computational phenotype for finding patients eligible for genetic testing for pathogenic PTEN variants across three centers [texte imprimé] / Cartik KOTHARI, Auteur ; Siddharth SRIVASTAVA, Auteur ; Youssef KOUSA, Auteur ; Rima IZEM, Auteur ; Marcin GIERDALSKI, Auteur ; Dongkyu KIM, Auteur ; Amy GOOD, Auteur ; Kira A. DIES, Auteur ; Gregory GEISEL, Auteur ; Hiroki MORIZONO, Auteur ; Vittorio GALLO, Auteur ; Scott L. POMEROY, Auteur ; Gwenn A. GARDEN, Auteur ; Lisa GUAY-WOODFORD, Auteur ; Mustafa SAHIN, Auteur ; Paul AVILLACH, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Electronic Health Records  Genetic Testing  Hamartoma Syndrome, Multiple/diagnosis/genetics/pathology  Humans  PTEN Phosphohydrolase/genetics  Phenotype  Autism  Computational phenotype  Genetic disease  Rare disease  from GLG, Guidepoint (which connected to a client, Fortress Biotech), and  Novartis. 3. YK has no competing interests to declare. 4. RI has no competing  interests to declare. 5. MG has no competing interests to declare. 6. DK has no  competing interests to declare. 7. AG has no competing interests to declare. 8.  KAD has no competing interests to declare. 9. GG has no competing interests to  declare. 10. HM has no competing interests to declare. 11. VG has no competing  interests to declare. 12. SP has no competing interests to declare. 13. GAG has  no competing interests to declare. 14. LGW has no competing interests to declare.  15. MS reports grant support from Novartis, Roche, Biogen, Astellas, Aeovian,  Bridgebio, Aucta, and Quadrant Biosciences. He has served on Scientific Advisory  Boards for PTEN Research, Novartis, Roche, Celgene, Regenxbio, Alkermes, and  Takeda. 16. PA has no competing interests to declare Index. décimale : PER Périodiques Résumé : BACKGROUND: Computational phenotypes are most often combinations of patient billing codes that are highly predictive of disease using electronic health records (EHR). In the case of rare diseases that can only be diagnosed by genetic testing, computational phenotypes identify patient cohorts for genetic testing and possible diagnosis. This article details the validation of a computational phenotype for PTEN hamartoma tumor syndrome (PHTS) against the EHR of patients at three collaborating clinical research centers: Boston Children's Hospital, Children's National Hospital, and the University of Washington. METHODS: A combination of billing codes from the International Classification of Diseases versions 9 and 10 (ICD-9 and ICD-10) for diagnostic criteria postulated by a research team at Cleveland Clinic was used to identify patient cohorts for genetic testing from the clinical data warehouses at the three research centers. Subsequently, the EHR-including billing codes, clinical notes, and genetic reports-of these patients were reviewed by clinical experts to identify patients with PHTS. RESULTS: The PTEN genetic testing yield of the computational phenotype, the number of patients who needed to be genetically tested for incidence of pathogenic PTEN gene variants, ranged from 82 to 94% at the three centers. CONCLUSIONS: Computational phenotypes have the potential to enable the timely and accurate diagnosis of rare genetic diseases such as PHTS by identifying patient cohorts for genetic sequencing and testing. En ligne : https://dx.doi.org/10.1186/s11689-022-09434-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

The behavioural phenotype of SATB2-associated syndrome: a within-group and cross-syndrome analysis / Stacey BISSELL in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The behavioural phenotype of SATB2-associated syndrome: a within-group and cross-syndrome analysis Type de document : texte imprimé Auteurs : Stacey BISSELL, Auteur ; Chris OLIVER, Auteur ; Joanna MOSS, Auteur ; Mary HEALD, Auteur ; Jane WAITE, Auteur ; Hayley CRAWFORD, Auteur ; Vishakha KOTHARI, Auteur ; Lauren RUMBELLOW, Auteur ; Grace WALTERS, Auteur ; Caroline RICHARDS, Auteur Langues : Anglais (eng) Mots-clés : Abnormalities, Multiple  Adolescent  Adult  Child  Child, Preschool  Craniofacial Abnormalities  Cross-Sectional Studies  Female  Humans  Infant  Intellectual Disability/complications/psychology  Male  Matrix Attachment Region Binding Proteins/genetics  Phenotype  Transcription Factors/genetics  Young Adult  Angelman syndrome  Autism  Behavioural phenotype  Challenging behaviour  Compulsive behaviour  Emotional characteristics  Repetitive behaviour  SATB2-associated syndrome  Stereotyped behaviour Index. décimale : PER Périodiques Résumé : BACKGROUND: SATB2-associated syndrome (SAS) is a multisystem neurodevelopmental disorder characterised by intellectual disability, speech delay, and craniofacial anomalies. Although the clinical presentation of SAS is well-delineated, behaviours associated with SAS are less well-defined. Given the varied social profile reported in SAS of a 'jovial' predisposition and autistic behaviours, there may be phenotypic overlap with both Angelman syndrome (AS) and non-syndromal autism. This study aimed to describe behaviours in SAS in relation to chronological age and level of ability and contrast aspects of the behavioural phenotype with AS and non-syndromal autism. METHODS: Informant report questionnaire measures of behaviour, emotion, and autism characteristics were completed for 81 individuals with SAS (aged 1-36 years; 43 male). Within-group associations were analysed, and categorical data were compared between pre-school (1-5 years), school-age (6-15 years), and adolescent and adult SAS sub-groups (16 years and over). Cross-syndrome subscale and item-level analyses were conducted for 63 individuals with SAS (aged 1-27 years; 31 male), who were matched according to age and level of ability to 63 individuals with AS (aged 2-25 years; 32 male) and 63 individuals with non-syndromal autism (aged 3-26 years; 53 male). RESULTS: In SAS, higher rates of overactivity were moderately associated with lower self-help ability, and higher general anxiety scores were reported for males compared with females. Cross-syndrome subscale analyses uncovered several significant differences (p < .01), with comparatively low rates of stereotyped behaviour, overactivity, insistence on sameness and positive affect, and comparatively greater interest and pleasure and compulsive behaviour in individuals with SAS. Item-level analyses revealed a distinct profile of repetitive and autistic behaviours. LIMITATIONS: Developmental analysis was based on a cross-sectional rather than a longitudinal research design, the contribution of pain and sleep to behaviour was not explored, and molecular genetic testing to determine genotype-phenotype behavioural relationships was not possible. CONCLUSIONS: This study highlights the importance of behavioural comparisons to well-delineated groups and the utility of fine-grained item-level analyses to elucidate aspects of behaviour that might be syndrome related or shared across neurodevelopmental disorders. Future research is needed to further describe the distinctive repetitive and autistic behavioural phenotype in SAS. En ligne : https://dx.doi.org/10.1186/s11689-022-09426-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] The behavioural phenotype of SATB2-associated syndrome: a within-group and cross-syndrome analysis [texte imprimé] / Stacey BISSELL, Auteur ; Chris OLIVER, Auteur ; Joanna MOSS, Auteur ; Mary HEALD, Auteur ; Jane WAITE, Auteur ; Hayley CRAWFORD, Auteur ; Vishakha KOTHARI, Auteur ; Lauren RUMBELLOW, Auteur ; Grace WALTERS, Auteur ; Caroline RICHARDS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Abnormalities, Multiple  Adolescent  Adult  Child  Child, Preschool  Craniofacial Abnormalities  Cross-Sectional Studies  Female  Humans  Infant  Intellectual Disability/complications/psychology  Male  Matrix Attachment Region Binding Proteins/genetics  Phenotype  Transcription Factors/genetics  Young Adult  Angelman syndrome  Autism  Behavioural phenotype  Challenging behaviour  Compulsive behaviour  Emotional characteristics  Repetitive behaviour  SATB2-associated syndrome  Stereotyped behaviour Index. décimale : PER Périodiques Résumé : BACKGROUND: SATB2-associated syndrome (SAS) is a multisystem neurodevelopmental disorder characterised by intellectual disability, speech delay, and craniofacial anomalies. Although the clinical presentation of SAS is well-delineated, behaviours associated with SAS are less well-defined. Given the varied social profile reported in SAS of a 'jovial' predisposition and autistic behaviours, there may be phenotypic overlap with both Angelman syndrome (AS) and non-syndromal autism. This study aimed to describe behaviours in SAS in relation to chronological age and level of ability and contrast aspects of the behavioural phenotype with AS and non-syndromal autism. METHODS: Informant report questionnaire measures of behaviour, emotion, and autism characteristics were completed for 81 individuals with SAS (aged 1-36 years; 43 male). Within-group associations were analysed, and categorical data were compared between pre-school (1-5 years), school-age (6-15 years), and adolescent and adult SAS sub-groups (16 years and over). Cross-syndrome subscale and item-level analyses were conducted for 63 individuals with SAS (aged 1-27 years; 31 male), who were matched according to age and level of ability to 63 individuals with AS (aged 2-25 years; 32 male) and 63 individuals with non-syndromal autism (aged 3-26 years; 53 male). RESULTS: In SAS, higher rates of overactivity were moderately associated with lower self-help ability, and higher general anxiety scores were reported for males compared with females. Cross-syndrome subscale analyses uncovered several significant differences (p < .01), with comparatively low rates of stereotyped behaviour, overactivity, insistence on sameness and positive affect, and comparatively greater interest and pleasure and compulsive behaviour in individuals with SAS. Item-level analyses revealed a distinct profile of repetitive and autistic behaviours. LIMITATIONS: Developmental analysis was based on a cross-sectional rather than a longitudinal research design, the contribution of pain and sleep to behaviour was not explored, and molecular genetic testing to determine genotype-phenotype behavioural relationships was not possible. CONCLUSIONS: This study highlights the importance of behavioural comparisons to well-delineated groups and the utility of fine-grained item-level analyses to elucidate aspects of behaviour that might be syndrome related or shared across neurodevelopmental disorders. Future research is needed to further describe the distinctive repetitive and autistic behavioural phenotype in SAS. En ligne : https://dx.doi.org/10.1186/s11689-022-09426-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Computational analysis of cortical neuronal excitotoxicity in a large animal model of neonatal brain injury / Panagiotis KRATIMENOS in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Computational analysis of cortical neuronal excitotoxicity in a large animal model of neonatal brain injury Type de document : texte imprimé Auteurs : Panagiotis KRATIMENOS, Auteur ; Abhya VIJ, Auteur ; Robinson VIDVA, Auteur ; Ioannis KOUTROULIS, Auteur ; Maria DELIVORIA-PAPADOPOULOS, Auteur ; Vittorio GALLO, Auteur ; Aaron SATHYANESAN, Auteur Langues : Anglais (eng) Mots-clés : Animals  Animals, Newborn  Brain Injuries/metabolism  Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism  Cerebral Cortex/metabolism  Disease Models, Animal  Humans  Neurons/metabolism  Swine  Calcium/calmodulin  Computational modeling  Excitotoxicity  Neonatal brain injury  Nuclear calcium  SimBiology  Src kinase Index. décimale : PER Périodiques Résumé : BACKGROUND: Neonatal hypoxic brain injury is a major cause of intellectual and developmental disability. Hypoxia causes neuronal dysfunction and death in the developing cerebral cortex due to excitotoxic Ca(2+)-influx. In the translational piglet model of hypoxic encephalopathy, we have previously shown that hypoxia overactivates Ca(2+)/Calmodulin (CaM) signaling via Sarcoma (Src) kinase in cortical neurons, resulting in overexpression of proapoptotic genes. However, identifying the exact relationship between alterations in neuronal Ca(2+)-influx, molecular determinants of cell death, and the degree of hypoxia in a dynamic system represents a significant challenge. METHODS: We used experimental and computational methods to identify molecular events critical to the onset of excitotoxicity-induced apoptosis in the cerebral cortex of newborn piglets. We used 2-3-day-old piglets (normoxic [Nx], hypoxic [Hx], and hypoxic + Src-inhibitor-treatment [Hx+PP2] groups) for biochemical analysis of ATP production, Ca(2+)-influx, and Ca(2+)/CaM-dependent protein kinase kinase 2 (CaMKK2) expression. We then used SimBiology to build a computational model of the Ca(2+)/CaM-Src-kinase signaling cascade, simulating Nx, Hx, and Hx+PP2 conditions. To evaluate our model, we used Sobol variance decomposition, multiparametric global sensitivity analysis, and parameter scanning. RESULTS: Our model captures important molecular trends caused by hypoxia in the piglet brain. Incorporating the action of Src kinase inhibitor PP2 further validated our model and enabled predictive analysis of the effect of hypoxia on CaMKK2. We determined the impact of a feedback loop related to Src phosphorylation of NMDA receptors and activation kinetics of CaMKII. We also identified distinct modes of signaling wherein Ca(2+) level alterations following Src kinase inhibition may not be a linear predictor of changes in Bax expression. Importantly, our model indicates that while pharmacological pre-treatment significantly reduces the onset of abnormal Ca(2+)-influx, there exists a window of intervention after hypoxia during which targeted modulation of Src-NMDAR interaction kinetics in combination with PP2 administration can reduce Ca(2+)-influx and Bax expression to similar levels as pre-treatment. CONCLUSIONS: Our model identifies new dynamics of critical components in the Ca(2+)/CaM-Src signaling pathway leading to neuronal injury and provides a feasible framework for drug efficacy studies in translational models of neonatal brain injury for the prevention of intellectual and developmental disabilities. En ligne : https://dx.doi.org/10.1186/s11689-022-09431-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Computational analysis of cortical neuronal excitotoxicity in a large animal model of neonatal brain injury [texte imprimé] / Panagiotis KRATIMENOS, Auteur ; Abhya VIJ, Auteur ; Robinson VIDVA, Auteur ; Ioannis KOUTROULIS, Auteur ; Maria DELIVORIA-PAPADOPOULOS, Auteur ; Vittorio GALLO, Auteur ; Aaron SATHYANESAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Animals  Animals, Newborn  Brain Injuries/metabolism  Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism  Cerebral Cortex/metabolism  Disease Models, Animal  Humans  Neurons/metabolism  Swine  Calcium/calmodulin  Computational modeling  Excitotoxicity  Neonatal brain injury  Nuclear calcium  SimBiology  Src kinase Index. décimale : PER Périodiques Résumé : BACKGROUND: Neonatal hypoxic brain injury is a major cause of intellectual and developmental disability. Hypoxia causes neuronal dysfunction and death in the developing cerebral cortex due to excitotoxic Ca(2+)-influx. In the translational piglet model of hypoxic encephalopathy, we have previously shown that hypoxia overactivates Ca(2+)/Calmodulin (CaM) signaling via Sarcoma (Src) kinase in cortical neurons, resulting in overexpression of proapoptotic genes. However, identifying the exact relationship between alterations in neuronal Ca(2+)-influx, molecular determinants of cell death, and the degree of hypoxia in a dynamic system represents a significant challenge. METHODS: We used experimental and computational methods to identify molecular events critical to the onset of excitotoxicity-induced apoptosis in the cerebral cortex of newborn piglets. We used 2-3-day-old piglets (normoxic [Nx], hypoxic [Hx], and hypoxic + Src-inhibitor-treatment [Hx+PP2] groups) for biochemical analysis of ATP production, Ca(2+)-influx, and Ca(2+)/CaM-dependent protein kinase kinase 2 (CaMKK2) expression. We then used SimBiology to build a computational model of the Ca(2+)/CaM-Src-kinase signaling cascade, simulating Nx, Hx, and Hx+PP2 conditions. To evaluate our model, we used Sobol variance decomposition, multiparametric global sensitivity analysis, and parameter scanning. RESULTS: Our model captures important molecular trends caused by hypoxia in the piglet brain. Incorporating the action of Src kinase inhibitor PP2 further validated our model and enabled predictive analysis of the effect of hypoxia on CaMKK2. We determined the impact of a feedback loop related to Src phosphorylation of NMDA receptors and activation kinetics of CaMKII. We also identified distinct modes of signaling wherein Ca(2+) level alterations following Src kinase inhibition may not be a linear predictor of changes in Bax expression. Importantly, our model indicates that while pharmacological pre-treatment significantly reduces the onset of abnormal Ca(2+)-influx, there exists a window of intervention after hypoxia during which targeted modulation of Src-NMDAR interaction kinetics in combination with PP2 administration can reduce Ca(2+)-influx and Bax expression to similar levels as pre-treatment. CONCLUSIONS: Our model identifies new dynamics of critical components in the Ca(2+)/CaM-Src signaling pathway leading to neuronal injury and provides a feasible framework for drug efficacy studies in translational models of neonatal brain injury for the prevention of intellectual and developmental disabilities. En ligne : https://dx.doi.org/10.1186/s11689-022-09431-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Characterization of cell-cell communication in autistic brains with single-cell transcriptomes / Maider ASTORKIA in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Characterization of cell-cell communication in autistic brains with single-cell transcriptomes Type de document : texte imprimé Auteurs : Maider ASTORKIA, Auteur ; Herbert M. LACHMAN, Auteur ; Deyou ZHENG, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/pathology  Autistic Disorder/genetics  Brain/pathology  Cell Communication  Child  Humans  Transcriptome  Autism  Brain  Cell-cell communication  Ligand-receptor  Network  Single-cell RNA-seq Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder is a neurodevelopmental disorder, affecting 1-2% of children. Studies have revealed genetic and cellular abnormalities in the brains of affected individuals, leading to both regional and distal cell communication deficits. METHODS: Recent application of single-cell technologies, especially single-cell transcriptomics, has significantly expanded our understanding of brain cell heterogeneity and further demonstrated that multiple cell types and brain layers or regions are perturbed in autism. The underlying high-dimensional single-cell data provides opportunities for multilevel computational analysis that collectively can better deconvolute the molecular and cellular events altered in autism. Here, we apply advanced computation and pattern recognition approaches on single-cell RNA-seq data to infer and compare inter-cell-type signaling communications in autism brains and controls. RESULTS: Our results indicate that at a global level, there are cell-cell communication differences in autism in comparison with controls, largely involving neurons as both signaling senders and receivers, but glia also contribute to the communication disruption. Although the magnitude of changes is moderate, we find that excitatory and inhibitor neurons are involved in multiple intercellular signaling that exhibits increased strengths in autism, such as NRXN and CNTN signaling. Not all genes in the intercellular signaling pathways show differential expression, but genes in the affected pathways are enriched for axon guidance, synapse organization, neuron migration, and other critical cellular functions. Furthermore, those genes are highly connected to and enriched for genes previously associated with autism risks. CONCLUSIONS: Overall, our proof-of-principle computational study using single-cell data uncovers key intercellular signaling pathways that are potentially disrupted in the autism brains, suggesting that more studies examining cross-cell type effects can be valuable for understanding autism pathogenesis. En ligne : https://dx.doi.org/10.1186/s11689-022-09441-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Characterization of cell-cell communication in autistic brains with single-cell transcriptomes [texte imprimé] / Maider ASTORKIA, Auteur ; Herbert M. LACHMAN, Auteur ; Deyou ZHENG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/pathology  Autistic Disorder/genetics  Brain/pathology  Cell Communication  Child  Humans  Transcriptome  Autism  Brain  Cell-cell communication  Ligand-receptor  Network  Single-cell RNA-seq Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder is a neurodevelopmental disorder, affecting 1-2% of children. Studies have revealed genetic and cellular abnormalities in the brains of affected individuals, leading to both regional and distal cell communication deficits. METHODS: Recent application of single-cell technologies, especially single-cell transcriptomics, has significantly expanded our understanding of brain cell heterogeneity and further demonstrated that multiple cell types and brain layers or regions are perturbed in autism. The underlying high-dimensional single-cell data provides opportunities for multilevel computational analysis that collectively can better deconvolute the molecular and cellular events altered in autism. Here, we apply advanced computation and pattern recognition approaches on single-cell RNA-seq data to infer and compare inter-cell-type signaling communications in autism brains and controls. RESULTS: Our results indicate that at a global level, there are cell-cell communication differences in autism in comparison with controls, largely involving neurons as both signaling senders and receivers, but glia also contribute to the communication disruption. Although the magnitude of changes is moderate, we find that excitatory and inhibitor neurons are involved in multiple intercellular signaling that exhibits increased strengths in autism, such as NRXN and CNTN signaling. Not all genes in the intercellular signaling pathways show differential expression, but genes in the affected pathways are enriched for axon guidance, synapse organization, neuron migration, and other critical cellular functions. Furthermore, those genes are highly connected to and enriched for genes previously associated with autism risks. CONCLUSIONS: Overall, our proof-of-principle computational study using single-cell data uncovers key intercellular signaling pathways that are potentially disrupted in the autism brains, suggesting that more studies examining cross-cell type effects can be valuable for understanding autism pathogenesis. En ligne : https://dx.doi.org/10.1186/s11689-022-09441-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Bringing machine learning to research on intellectual and developmental disabilities: taking inspiration from neurological diseases / Chirag GUPTA in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Bringing machine learning to research on intellectual and developmental disabilities: taking inspiration from neurological diseases Type de document : texte imprimé Auteurs : Chirag GUPTA, Auteur ; Pramod CHANDRASHEKAR, Auteur ; Ting JIN, Auteur ; Chenfeng HE, Auteur ; Saniya KHULLAR, Auteur ; Qiang CHANG, Auteur ; Daifeng WANG, Auteur Langues : Anglais (eng) Mots-clés : Artificial Intelligence  Autism Spectrum Disorder/diagnosis  Child  Child, Preschool  Developmental Disabilities/diagnosis  Humans  Infant, Newborn  Intellectual Disability/diagnosis  Machine Learning  Brain  Genomics  Intellectual and developmental disabilities  Multi-omics Index. décimale : PER Périodiques Résumé : Intellectual and Developmental Disabilities (IDDs), such as Down syndrome, Fragile X syndrome, Rett syndrome, and autism spectrum disorder, usually manifest at birth or early childhood. IDDs are characterized by significant impairment in intellectual and adaptive functioning, and both genetic and environmental factors underpin IDD biology. Molecular and genetic stratification of IDDs remain challenging mainly due to overlapping factors and comorbidity. Advances in high throughput sequencing, imaging, and tools to record behavioral data at scale have greatly enhanced our understanding of the molecular, cellular, structural, and environmental basis of some IDDs. Fueled by the "big data" revolution, artificial intelligence (AI) and machine learning (ML) technologies have brought a whole new paradigm shift in computational biology. Evidently, the ML-driven approach to clinical diagnoses has the potential to augment classical methods that use symptoms and external observations, hoping to push the personalized treatment plan forward. Therefore, integrative analyses and applications of ML technology have a direct bearing on discoveries in IDDs. The application of ML to IDDs can potentially improve screening and early diagnosis, advance our understanding of the complexity of comorbidity, and accelerate the identification of biomarkers for clinical research and drug development. For more than five decades, the IDDRC network has supported a nexus of investigators at centers across the USA, all striving to understand the interplay between various factors underlying IDDs. In this review, we introduced fast-increasing multi-modal data types, highlighted example studies that employed ML technologies to illuminate factors and biological mechanisms underlying IDDs, as well as recent advances in ML technologies and their applications to IDDs and other neurological diseases. We discussed various molecular, clinical, and environmental data collection modes, including genetic, imaging, phenotypical, and behavioral data types, along with multiple repositories that store and share such data. Furthermore, we outlined some fundamental concepts of machine learning algorithms and presented our opinion on specific gaps that will need to be filled to accomplish, for example, reliable implementation of ML-based diagnosis technology in IDD clinics. We anticipate that this review will guide researchers to formulate AI and ML-based approaches to investigate IDDs and related conditions. En ligne : https://dx.doi.org/10.1186/s11689-022-09438-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Bringing machine learning to research on intellectual and developmental disabilities: taking inspiration from neurological diseases [texte imprimé] / Chirag GUPTA, Auteur ; Pramod CHANDRASHEKAR, Auteur ; Ting JIN, Auteur ; Chenfeng HE, Auteur ; Saniya KHULLAR, Auteur ; Qiang CHANG, Auteur ; Daifeng WANG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Artificial Intelligence  Autism Spectrum Disorder/diagnosis  Child  Child, Preschool  Developmental Disabilities/diagnosis  Humans  Infant, Newborn  Intellectual Disability/diagnosis  Machine Learning  Brain  Genomics  Intellectual and developmental disabilities  Multi-omics Index. décimale : PER Périodiques Résumé : Intellectual and Developmental Disabilities (IDDs), such as Down syndrome, Fragile X syndrome, Rett syndrome, and autism spectrum disorder, usually manifest at birth or early childhood. IDDs are characterized by significant impairment in intellectual and adaptive functioning, and both genetic and environmental factors underpin IDD biology. Molecular and genetic stratification of IDDs remain challenging mainly due to overlapping factors and comorbidity. Advances in high throughput sequencing, imaging, and tools to record behavioral data at scale have greatly enhanced our understanding of the molecular, cellular, structural, and environmental basis of some IDDs. Fueled by the "big data" revolution, artificial intelligence (AI) and machine learning (ML) technologies have brought a whole new paradigm shift in computational biology. Evidently, the ML-driven approach to clinical diagnoses has the potential to augment classical methods that use symptoms and external observations, hoping to push the personalized treatment plan forward. Therefore, integrative analyses and applications of ML technology have a direct bearing on discoveries in IDDs. The application of ML to IDDs can potentially improve screening and early diagnosis, advance our understanding of the complexity of comorbidity, and accelerate the identification of biomarkers for clinical research and drug development. For more than five decades, the IDDRC network has supported a nexus of investigators at centers across the USA, all striving to understand the interplay between various factors underlying IDDs. In this review, we introduced fast-increasing multi-modal data types, highlighted example studies that employed ML technologies to illuminate factors and biological mechanisms underlying IDDs, as well as recent advances in ML technologies and their applications to IDDs and other neurological diseases. We discussed various molecular, clinical, and environmental data collection modes, including genetic, imaging, phenotypical, and behavioral data types, along with multiple repositories that store and share such data. Furthermore, we outlined some fundamental concepts of machine learning algorithms and presented our opinion on specific gaps that will need to be filled to accomplish, for example, reliable implementation of ML-based diagnosis technology in IDD clinics. We anticipate that this review will guide researchers to formulate AI and ML-based approaches to investigate IDDs and related conditions. En ligne : https://dx.doi.org/10.1186/s11689-022-09438-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

The diagnostic journey of genetically defined neurodevelopmental disorders / Juliana SIMON in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The diagnostic journey of genetically defined neurodevelopmental disorders Type de document : texte imprimé Auteurs : Juliana SIMON, Auteur ; Carly HYDE, Auteur ; Vidya SARAVANAPANDIAN, Auteur ; Rujuta WILSON, Auteur ; Charlotte DISTEFANO, Auteur ; Aaron BESTERMAN, Auteur ; Shafali JESTE, Auteur Langues : Anglais (eng) Mots-clés : Adult  Caregivers/psychology  Child  Family  Humans  Infant  Neurodevelopmental Disorders/diagnosis/genetics  Parents/psychology  Diagnostic journey  Genetic testing  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: The development of advanced genetic technologies has resulted in rapid identification of genetic etiologies of neurodevelopmental disorders (NDDs) and has transformed the classification and diagnosis of various NDDs. However, diagnostic genetics has far outpaced our ability to provide timely medical counseling, guidance, and care for patients with genetically defined NDDs. These patients and their caregivers present with an unmet need for care coordination across multiple domains including medical, developmental, and psychiatric care and for educational resources and guidance from care professionals. After a genetic diagnosis is made, families also face several barriers in access to informed diagnostic evaluations and medical support. METHODS: As part of Care and Research in Neurogenetics (CARING), a multidisciplinary clinical program for children and adults with neurogenetic disorders, we conducted qualitative clinical interviews about the diagnostic journey of families. This included the overall timeline to receiving diagnoses, experiences before and after diagnosis, barriers to care, and resources that helped them to navigate the diagnostic process. RESULTS: A total of 37 interviews were conducted with parents of children ages 16 months to 33 years. Several key themes were identified: (1) delays between initial caregiver observations and formal developmental or genetic diagnoses; (2) practical barriers to clinical evaluation and care, including long wait times for an appointment, lack of insurance coverage, availability of local evaluations, transportation difficulties, and native language differences; (3) the importance of being part of a patient advocacy group to help navigate the diagnostic journey; and (4) unique challenges faced by adults (18 years or older). CONCLUSIONS: Families of children with complex neurodevelopmental and genetic disabilities face numerous challenges in finding adequate medical care and services for their child. They experience considerable delays in receiving timely diagnoses and face significant barriers that further delay the process of receiving access to services needed for the child's continued care. The gaps indicated in this study speak to the need for more comprehensive coordination of care for patients with intellectual and developmental disabilities, as well as the development of systematic, disorder-specific resources both for providers and families in order to improve patient outcomes. En ligne : https://dx.doi.org/10.1186/s11689-022-09439-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] The diagnostic journey of genetically defined neurodevelopmental disorders [texte imprimé] / Juliana SIMON, Auteur ; Carly HYDE, Auteur ; Vidya SARAVANAPANDIAN, Auteur ; Rujuta WILSON, Auteur ; Charlotte DISTEFANO, Auteur ; Aaron BESTERMAN, Auteur ; Shafali JESTE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adult  Caregivers/psychology  Child  Family  Humans  Infant  Neurodevelopmental Disorders/diagnosis/genetics  Parents/psychology  Diagnostic journey  Genetic testing  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: The development of advanced genetic technologies has resulted in rapid identification of genetic etiologies of neurodevelopmental disorders (NDDs) and has transformed the classification and diagnosis of various NDDs. However, diagnostic genetics has far outpaced our ability to provide timely medical counseling, guidance, and care for patients with genetically defined NDDs. These patients and their caregivers present with an unmet need for care coordination across multiple domains including medical, developmental, and psychiatric care and for educational resources and guidance from care professionals. After a genetic diagnosis is made, families also face several barriers in access to informed diagnostic evaluations and medical support. METHODS: As part of Care and Research in Neurogenetics (CARING), a multidisciplinary clinical program for children and adults with neurogenetic disorders, we conducted qualitative clinical interviews about the diagnostic journey of families. This included the overall timeline to receiving diagnoses, experiences before and after diagnosis, barriers to care, and resources that helped them to navigate the diagnostic process. RESULTS: A total of 37 interviews were conducted with parents of children ages 16 months to 33 years. Several key themes were identified: (1) delays between initial caregiver observations and formal developmental or genetic diagnoses; (2) practical barriers to clinical evaluation and care, including long wait times for an appointment, lack of insurance coverage, availability of local evaluations, transportation difficulties, and native language differences; (3) the importance of being part of a patient advocacy group to help navigate the diagnostic journey; and (4) unique challenges faced by adults (18 years or older). CONCLUSIONS: Families of children with complex neurodevelopmental and genetic disabilities face numerous challenges in finding adequate medical care and services for their child. They experience considerable delays in receiving timely diagnoses and face significant barriers that further delay the process of receiving access to services needed for the child's continued care. The gaps indicated in this study speak to the need for more comprehensive coordination of care for patients with intellectual and developmental disabilities, as well as the development of systematic, disorder-specific resources both for providers and families in order to improve patient outcomes. En ligne : https://dx.doi.org/10.1186/s11689-022-09439-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

The electroretinogram b-wave amplitude: a differential physiological measure for Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder / Irene O. LEE in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The electroretinogram b-wave amplitude: a differential physiological measure for Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Irene O. LEE, Auteur ; David H. SKUSE, Auteur ; Paul A. CONSTABLE, Auteur ; Fernando MARMOLEJO-RAMOS, Auteur ; Ludvig R. OLSEN, Auteur ; Dorothy A. THOMPSON, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Attention Deficit Disorder with Hyperactivity  Autism Spectrum Disorder/complications  Child  Child, Preschool  Glutamates  Humans  Photic Stimulation/methods  Young Adult  gamma-Aminobutyric Acid  Adhd  Asd  Differentiation  Electroretinogram  Gaba  Glutamate  Neurotransmission Imbalance  Physiological Marker Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent childhood neurodevelopmental disorder. It shares some genetic risk with Autism Spectrum Disorder (ASD), and the conditions often occur together. Both are potentially associated with abnormal glutamate and GABA neurotransmission, which can be modelled by measuring the synaptic activity in the retina with an electroretinogram (ERG). Reduction of retinal responses in ASD has been reported, but little is known about retinal activity in ADHD. In this study, we compared the light-adapted ERGs of individuals with ADHD, ASD and controls to investigate whether retinal responses differ between these neurodevelopmental conditions. METHODS: Full field light-adapted ERGs were recorded from 15 ADHD, 57 ASD (without ADHD) and 59 control participants, aged from 5.4 to 27.3 years old. A Troland protocol was used with a random series of nine flash strengths from -0.367 to 1.204 log photopic cd.s.m(-2). The time-to-peak and amplitude of the a- and b-waves and the parameters of the Photopic Negative Response (PhNR) were compared amongst the three groups of participants, using generalised estimating equations. RESULTS: Statistically significant elevations of the ERG b-wave amplitudes, PhNR responses and faster timings of the b-wave time-to-peak were found in those with ADHD compared with both the control and ASD groups. The greatest elevation in the b-wave amplitudes associated with ADHD were observed at 1.204 log phot cd.s.m(-2) flash strength (p < .0001), at which the b-wave amplitude in ASD was significantly lower than that in the controls. Using this measure, ADHD could be distinguished from ASD with an area under the curve of 0.88. CONCLUSIONS: The ERG b-wave amplitude appears to be a distinctive differential feature for both ADHD and ASD, which produced a reversed pattern of b-wave responses. These findings imply imbalances between glutamate and GABA neurotransmission which primarily regulate the b-wave formation. Abnormalities in the b-wave amplitude could provisionally serve as a biomarker for both neurodevelopmental conditions. En ligne : https://dx.doi.org/10.1186/s11689-022-09440-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] The electroretinogram b-wave amplitude: a differential physiological measure for Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder [texte imprimé] / Irene O. LEE, Auteur ; David H. SKUSE, Auteur ; Paul A. CONSTABLE, Auteur ; Fernando MARMOLEJO-RAMOS, Auteur ; Ludvig R. OLSEN, Auteur ; Dorothy A. THOMPSON, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Adult  Attention Deficit Disorder with Hyperactivity  Autism Spectrum Disorder/complications  Child  Child, Preschool  Glutamates  Humans  Photic Stimulation/methods  Young Adult  gamma-Aminobutyric Acid  Adhd  Asd  Differentiation  Electroretinogram  Gaba  Glutamate  Neurotransmission Imbalance  Physiological Marker Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent childhood neurodevelopmental disorder. It shares some genetic risk with Autism Spectrum Disorder (ASD), and the conditions often occur together. Both are potentially associated with abnormal glutamate and GABA neurotransmission, which can be modelled by measuring the synaptic activity in the retina with an electroretinogram (ERG). Reduction of retinal responses in ASD has been reported, but little is known about retinal activity in ADHD. In this study, we compared the light-adapted ERGs of individuals with ADHD, ASD and controls to investigate whether retinal responses differ between these neurodevelopmental conditions. METHODS: Full field light-adapted ERGs were recorded from 15 ADHD, 57 ASD (without ADHD) and 59 control participants, aged from 5.4 to 27.3 years old. A Troland protocol was used with a random series of nine flash strengths from -0.367 to 1.204 log photopic cd.s.m(-2). The time-to-peak and amplitude of the a- and b-waves and the parameters of the Photopic Negative Response (PhNR) were compared amongst the three groups of participants, using generalised estimating equations. RESULTS: Statistically significant elevations of the ERG b-wave amplitudes, PhNR responses and faster timings of the b-wave time-to-peak were found in those with ADHD compared with both the control and ASD groups. The greatest elevation in the b-wave amplitudes associated with ADHD were observed at 1.204 log phot cd.s.m(-2) flash strength (p < .0001), at which the b-wave amplitude in ASD was significantly lower than that in the controls. Using this measure, ADHD could be distinguished from ASD with an area under the curve of 0.88. CONCLUSIONS: The ERG b-wave amplitude appears to be a distinctive differential feature for both ADHD and ASD, which produced a reversed pattern of b-wave responses. These findings imply imbalances between glutamate and GABA neurotransmission which primarily regulate the b-wave formation. Abnormalities in the b-wave amplitude could provisionally serve as a biomarker for both neurodevelopmental conditions. En ligne : https://dx.doi.org/10.1186/s11689-022-09440-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Anxiety-like behavior and anxiolytic treatment in the Rett syndrome natural history study / Caroline B. BUCHANAN in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Anxiety-like behavior and anxiolytic treatment in the Rett syndrome natural history study Type de document : texte imprimé Auteurs : Caroline B. BUCHANAN, Auteur ; Jennifer L. STALLWORTH, Auteur ; Aubin E. JOY, Auteur ; Rebekah E. DIXON, Auteur ; Alexandra E. SCOTT, Auteur ; Arthur A. BEISANG, Auteur ; Timothy A. BENKE, Auteur ; Daniel G. GLAZE, Auteur ; Richard H. HAAS, Auteur ; Peter T. HEYDEMANN, Auteur ; Mary D. JONES, Auteur ; Jane B. LANE, Auteur ; David N. LIEBERMAN, Auteur ; Eric D. MARSH, Auteur ; Jeffrey L. NEUL, Auteur ; Sarika U. PETERS, Auteur ; Robin C. RYTHER, Auteur ; Steve A. SKINNER, Auteur ; Shannon M. STANDRIDGE, Auteur ; Walter E. KAUFMANN, Auteur ; Alan K. PERCY, Auteur Langues : Anglais (eng) Mots-clés : Anti-Anxiety Agents/therapeutic use  Anxiety/drug therapy/epidemiology  Female  Humans  Rett Syndrome/complications/drug therapy/epidemiology  Anti-anxiety agents  Anxiety  Methyl-CpG-binding protein 2  Natural history studies  Rett syndrome  Fellowship under U54 HD 061222 grant) and has done clinical trials with Acadia,  Anavex, GW Pharmaceuticals, and Zynerba. Timothy A. Benke received funding from  the NIH (U54 HD061222, R21 NS101288, R01 NS081248), International Foundation for  CDKL5 Research, Loulou Foundation, and Children’s Hospital Colorado Foundation  Ponzio Family Chair in Neurology Research. He is also a consultant for AveXis,  Ovid, GW Pharmaceuticals, International Rett Syndrome Foundation, Takeda, and  Marinus and has done clinical trials with Acadia, Ovid, GW Pharmaceuticals,  Marinus, and Rett Syndrome Research Trust  all remuneration has been made to his  department. Daniel G Glaze received funding from the NIH, Rettsyndrome.org, and  the Blue Bird Circle. He has done clinical trials with Acadia, Neuren, and  GW Pharmaceuticals. Richard H. Haas received funding from the NIH 5U54HD061222  grant and has done clinical trials sponsored by Acadia, GW Pharmaceuticals, and  Newron Pharmaceuticals. Jane B. Lane received funding from the NIH and is a  consultant for International Rett Syndrome Foundation and GW Pharmaceuticals.  David N. Lieberman has done clinical trials with Anavex, Acadia, GW  Pharmaceuticals, and Rett Syndrome Research Trust. Eric D. Marsh received funding  from Rett Syndrome Research Trust, NIH, State of Pennsylvania, Penn Orphan  Disease Center, International Rett Syndrome Foundation, LouLou Foundation, and  Eagles Autism Foundation. He is a consultant for Cilpa Therapeutics and Stoke  Therapeutics. He has done clinical trials with Zogenix, GW Pharmaceuticals,  Acadia, Marinus, Stoke Therapeutics, and Rett Syndrome Research Trust. Jeffrey L.  Neul received funding from the NIH and is a consultant for AveXis, Biohaven,  Eloxx Pharmaceuticals, Ovid, Takeda, and Teva Pharmaceuticals. He has done  clinical trials with Acadia and Newron Pharmaceuticals. Sarika U. Peters received  funding from NIH, Rettsyndrome.org and is a consultant for Acadia  Pharmaceuticals. Steve A. Skinner has done clinical trials with Acadia, Anavex,  and GW Pharmaceuticals. Shannon M. Standridge is a speaker for Greenwich  Biosciences and Scientific Advisory Board of Acadia. Walter E. Kaufmann received  funding from the NIH and CDC, and is a consultant for Anavex, AveXis, Acadia,  EryDel, Newron, GW Pharmaceuticals, Marinus, Biohaven, Zynerba, Ovid  Therapeutics, and Stalicla. Currently, he is Chief Medical Officer of Anavex Life  Sciences Corp. Alan K. Percy received funding from the NIH and is a consultant  for Anavex, AveXis, Acadia, and GW Pharmaceuticals. He has done clinical trials  with Anavex, Acadia, GW Pharmaceuticals, and Rett Syndrome Research Trust. The  rest of the authors, Jennifer L. Stallworth, Aubin E. Joy, Rebekah E. Dixon,  Alexandra E. Scott, Arthur A. Beisang, Peter T. Heydemann, Mary D. Jones, and  Robin C. Ryther, declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder most often related to a pathogenic variant in the X-linked MECP2 gene. Internalizing behaviors appear to be common, but standard methods of diagnosing anxiety are not readily applied in this population which typically has cognitive impairment and limited expressive language. This study aims to describe the frequency of anxiety-like behavior and anxiolytic treatments along with associated clinical features in individuals with RTT. METHODS: Parental reports and medication logs provided data from 1380 females with RTT participating in two iterations of the multicenter U.S. RTT Natural History Study (RNHS) from 2006 to 2019. RESULTS: Most participants with RTT (77.5%) had at least occasional anxious or nervous behavior. Anxiety was reported to be the most troublesome concern for 2.6%, and within the top 3 concerns for 10.0%, of participants in the second iteration. Parents directly reported treatment for anxious or nervous behavior in 16.6% of participants in the second iteration with most reporting good control of the behavior (71.6%). In the medication logs of both RNHS iterations, the indication of anxiety was listed for a similar number of participants (15% and 14.5%, respectively). Increased use of anxiolytics and selective serotonin reuptake inhibitors (SSRIs) was related to more frequent anxiety-like behaviors (P < 0.001), older age (P < 0.001), and mild MECP2 variants (P = 0.002). CONCLUSION: Anxiety-like behavior is frequent at all ages and is a significant parental concern in RTT. Older individuals and those with mild MECP2 variants are more likely to be treated with medications. Better diagnosis and treatment of anxiety in RTT should be a goal of both future studies and clinical care. TRIAL REGISTRATION: NCT00299312 and NCT02738281. En ligne : https://dx.doi.org/10.1186/s11689-022-09432-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Anxiety-like behavior and anxiolytic treatment in the Rett syndrome natural history study [texte imprimé] / Caroline B. BUCHANAN, Auteur ; Jennifer L. STALLWORTH, Auteur ; Aubin E. JOY, Auteur ; Rebekah E. DIXON, Auteur ; Alexandra E. SCOTT, Auteur ; Arthur A. BEISANG, Auteur ; Timothy A. BENKE, Auteur ; Daniel G. GLAZE, Auteur ; Richard H. HAAS, Auteur ; Peter T. HEYDEMANN, Auteur ; Mary D. JONES, Auteur ; Jane B. LANE, Auteur ; David N. LIEBERMAN, Auteur ; Eric D. MARSH, Auteur ; Jeffrey L. NEUL, Auteur ; Sarika U. PETERS, Auteur ; Robin C. RYTHER, Auteur ; Steve A. SKINNER, Auteur ; Shannon M. STANDRIDGE, Auteur ; Walter E. KAUFMANN, Auteur ; Alan K. PERCY, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Anti-Anxiety Agents/therapeutic use  Anxiety/drug therapy/epidemiology  Female  Humans  Rett Syndrome/complications/drug therapy/epidemiology  Anti-anxiety agents  Anxiety  Methyl-CpG-binding protein 2  Natural history studies  Rett syndrome  Fellowship under U54 HD 061222 grant) and has done clinical trials with Acadia,  Anavex, GW Pharmaceuticals, and Zynerba. Timothy A. Benke received funding from  the NIH (U54 HD061222, R21 NS101288, R01 NS081248), International Foundation for  CDKL5 Research, Loulou Foundation, and Children’s Hospital Colorado Foundation  Ponzio Family Chair in Neurology Research. He is also a consultant for AveXis,  Ovid, GW Pharmaceuticals, International Rett Syndrome Foundation, Takeda, and  Marinus and has done clinical trials with Acadia, Ovid, GW Pharmaceuticals,  Marinus, and Rett Syndrome Research Trust  all remuneration has been made to his  department. Daniel G Glaze received funding from the NIH, Rettsyndrome.org, and  the Blue Bird Circle. He has done clinical trials with Acadia, Neuren, and  GW Pharmaceuticals. Richard H. Haas received funding from the NIH 5U54HD061222  grant and has done clinical trials sponsored by Acadia, GW Pharmaceuticals, and  Newron Pharmaceuticals. Jane B. Lane received funding from the NIH and is a  consultant for International Rett Syndrome Foundation and GW Pharmaceuticals.  David N. Lieberman has done clinical trials with Anavex, Acadia, GW  Pharmaceuticals, and Rett Syndrome Research Trust. Eric D. Marsh received funding  from Rett Syndrome Research Trust, NIH, State of Pennsylvania, Penn Orphan  Disease Center, International Rett Syndrome Foundation, LouLou Foundation, and  Eagles Autism Foundation. He is a consultant for Cilpa Therapeutics and Stoke  Therapeutics. He has done clinical trials with Zogenix, GW Pharmaceuticals,  Acadia, Marinus, Stoke Therapeutics, and Rett Syndrome Research Trust. Jeffrey L.  Neul received funding from the NIH and is a consultant for AveXis, Biohaven,  Eloxx Pharmaceuticals, Ovid, Takeda, and Teva Pharmaceuticals. He has done  clinical trials with Acadia and Newron Pharmaceuticals. Sarika U. Peters received  funding from NIH, Rettsyndrome.org and is a consultant for Acadia  Pharmaceuticals. Steve A. Skinner has done clinical trials with Acadia, Anavex,  and GW Pharmaceuticals. Shannon M. Standridge is a speaker for Greenwich  Biosciences and Scientific Advisory Board of Acadia. Walter E. Kaufmann received  funding from the NIH and CDC, and is a consultant for Anavex, AveXis, Acadia,  EryDel, Newron, GW Pharmaceuticals, Marinus, Biohaven, Zynerba, Ovid  Therapeutics, and Stalicla. Currently, he is Chief Medical Officer of Anavex Life  Sciences Corp. Alan K. Percy received funding from the NIH and is a consultant  for Anavex, AveXis, Acadia, and GW Pharmaceuticals. He has done clinical trials  with Anavex, Acadia, GW Pharmaceuticals, and Rett Syndrome Research Trust. The  rest of the authors, Jennifer L. Stallworth, Aubin E. Joy, Rebekah E. Dixon,  Alexandra E. Scott, Arthur A. Beisang, Peter T. Heydemann, Mary D. Jones, and  Robin C. Ryther, declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder most often related to a pathogenic variant in the X-linked MECP2 gene. Internalizing behaviors appear to be common, but standard methods of diagnosing anxiety are not readily applied in this population which typically has cognitive impairment and limited expressive language. This study aims to describe the frequency of anxiety-like behavior and anxiolytic treatments along with associated clinical features in individuals with RTT. METHODS: Parental reports and medication logs provided data from 1380 females with RTT participating in two iterations of the multicenter U.S. RTT Natural History Study (RNHS) from 2006 to 2019. RESULTS: Most participants with RTT (77.5%) had at least occasional anxious or nervous behavior. Anxiety was reported to be the most troublesome concern for 2.6%, and within the top 3 concerns for 10.0%, of participants in the second iteration. Parents directly reported treatment for anxious or nervous behavior in 16.6% of participants in the second iteration with most reporting good control of the behavior (71.6%). In the medication logs of both RNHS iterations, the indication of anxiety was listed for a similar number of participants (15% and 14.5%, respectively). Increased use of anxiolytics and selective serotonin reuptake inhibitors (SSRIs) was related to more frequent anxiety-like behaviors (P < 0.001), older age (P < 0.001), and mild MECP2 variants (P = 0.002). CONCLUSION: Anxiety-like behavior is frequent at all ages and is a significant parental concern in RTT. Older individuals and those with mild MECP2 variants are more likely to be treated with medications. Better diagnosis and treatment of anxiety in RTT should be a goal of both future studies and clinical care. TRIAL REGISTRATION: NCT00299312 and NCT02738281. En ligne : https://dx.doi.org/10.1186/s11689-022-09432-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Development of a phenotype ontology for autism spectrum disorder by natural language processing on electronic health records / Mengge ZHAO in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Development of a phenotype ontology for autism spectrum disorder by natural language processing on electronic health records Type de document : texte imprimé Auteurs : Mengge ZHAO, Auteur ; James HAVRILLA, Auteur ; Jacqueline PENG, Auteur ; Madison DRYE, Auteur ; Maddie FECHER, Auteur ; Whitney GUTHRIE, Auteur ; Birkan TUNC, Auteur ; Robert SCHULTZ, Auteur ; Kai WANG, Auteur ; Yunyun ZHOU, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis/genetics  Electronic Health Records  Humans  Natural Language Processing  Phenotype  Vocabulary  Autism  Autism spectrum disorder  Electronic health record  Natural language processing  Phenotype ontology  Terminology set Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by restricted, repetitive behavior, and impaired social communication and interactions. However, significant challenges remain in diagnosing and subtyping ASD due in part to the lack of a validated, standardized vocabulary to characterize clinical phenotypic presentation of ASD. Although the human phenotype ontology (HPO) plays an important role in delineating nuanced phenotypes for rare genetic diseases, it is inadequate to capture characteristic of behavioral and psychiatric phenotypes for individuals with ASD. There is a clear need, therefore, for a well-established phenotype terminology set that can assist in characterization of ASD phenotypes from patients' clinical narratives. METHODS: To address this challenge, we used natural language processing (NLP) techniques to identify and curate ASD phenotypic terms from high-quality unstructured clinical notes in the electronic health record (EHR) on 8499 individuals with ASD, 8177 individuals with non-ASD psychiatric disorders, and 8482 individuals without a documented psychiatric disorder. We further performed dimensional reduction clustering analysis to subgroup individuals with ASD, using nonnegative matrix factorization method. RESULTS: Through a note-processing pipeline that includes several steps of state-of-the-art NLP approaches, we identified 3336 ASD terms linking to 1943 unique medical concepts, which represents among the largest ASD terminology set to date. The extracted ASD terms were further organized in a formal ontology structure similar to the HPO. Clustering analysis showed that these terms could be used in a diagnostic pipeline to differentiate individuals with ASD from individuals with other psychiatric disorders. CONCLUSION: Our ASD phenotype ontology can assist clinicians and researchers in characterizing individuals with ASD, facilitating automated diagnosis, and subtyping individuals with ASD to facilitate personalized therapeutic decision-making. En ligne : https://dx.doi.org/10.1186/s11689-022-09442-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Development of a phenotype ontology for autism spectrum disorder by natural language processing on electronic health records [texte imprimé] / Mengge ZHAO, Auteur ; James HAVRILLA, Auteur ; Jacqueline PENG, Auteur ; Madison DRYE, Auteur ; Maddie FECHER, Auteur ; Whitney GUTHRIE, Auteur ; Birkan TUNC, Auteur ; Robert SCHULTZ, Auteur ; Kai WANG, Auteur ; Yunyun ZHOU, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/diagnosis/genetics  Electronic Health Records  Humans  Natural Language Processing  Phenotype  Vocabulary  Autism  Autism spectrum disorder  Electronic health record  Natural language processing  Phenotype ontology  Terminology set Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by restricted, repetitive behavior, and impaired social communication and interactions. However, significant challenges remain in diagnosing and subtyping ASD due in part to the lack of a validated, standardized vocabulary to characterize clinical phenotypic presentation of ASD. Although the human phenotype ontology (HPO) plays an important role in delineating nuanced phenotypes for rare genetic diseases, it is inadequate to capture characteristic of behavioral and psychiatric phenotypes for individuals with ASD. There is a clear need, therefore, for a well-established phenotype terminology set that can assist in characterization of ASD phenotypes from patients' clinical narratives. METHODS: To address this challenge, we used natural language processing (NLP) techniques to identify and curate ASD phenotypic terms from high-quality unstructured clinical notes in the electronic health record (EHR) on 8499 individuals with ASD, 8177 individuals with non-ASD psychiatric disorders, and 8482 individuals without a documented psychiatric disorder. We further performed dimensional reduction clustering analysis to subgroup individuals with ASD, using nonnegative matrix factorization method. RESULTS: Through a note-processing pipeline that includes several steps of state-of-the-art NLP approaches, we identified 3336 ASD terms linking to 1943 unique medical concepts, which represents among the largest ASD terminology set to date. The extracted ASD terms were further organized in a formal ontology structure similar to the HPO. Clustering analysis showed that these terms could be used in a diagnostic pipeline to differentiate individuals with ASD from individuals with other psychiatric disorders. CONCLUSION: Our ASD phenotype ontology can assist clinicians and researchers in characterizing individuals with ASD, facilitating automated diagnosis, and subtyping individuals with ASD to facilitate personalized therapeutic decision-making. En ligne : https://dx.doi.org/10.1186/s11689-022-09442-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer's disease, and normative aging / Helen WONG in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer's disease, and normative aging Type de document : texte imprimé Auteurs : Helen WONG, Auteur ; Jordan M. BUCK, Auteur ; Curtis BORSKI, Auteur ; Jessica T. PAFFORD, Auteur ; Bailey N. KELLER, Auteur ; Ryan A. MILSTEAD, Auteur ; Jessica L. HANSON, Auteur ; Jerry A. STITZEL, Auteur ; Charles A. HOEFFER, Auteur Langues : Anglais (eng) Mots-clés : Aging/physiology  Alzheimer Disease/genetics/metabolism  Animals  Calcium-Binding Proteins/genetics/metabolism  Chronobiology Disorders/genetics/metabolism  DNA-Binding Proteins/genetics/metabolism  Disease Models, Animal  Down Syndrome/genetics/metabolism  Female  Male  Mice  Motor Activity/physiology  Muscle Proteins/genetics/metabolism  Suprachiasmatic Nucleus/metabolism  Transcription Factors/genetics/metabolism  Aging  Alzheimer’s  Calcineurin  Circadian rhythms  Dscr1  Down syndrome  Free-running  Light-entrained Index. décimale : PER Périodiques Résumé : BACKGROUND: Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer's disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. METHODS: The present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3-6 months old) and aged (9-14 months old) mice of both sexes. RESULTS: We found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and RCAN1-overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN. CONCLUSIONS: Collectively, this study's findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and possibly aging. En ligne : https://dx.doi.org/10.1186/s11689-022-09444-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer's disease, and normative aging [texte imprimé] / Helen WONG, Auteur ; Jordan M. BUCK, Auteur ; Curtis BORSKI, Auteur ; Jessica T. PAFFORD, Auteur ; Bailey N. KELLER, Auteur ; Ryan A. MILSTEAD, Auteur ; Jessica L. HANSON, Auteur ; Jerry A. STITZEL, Auteur ; Charles A. HOEFFER, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Aging/physiology  Alzheimer Disease/genetics/metabolism  Animals  Calcium-Binding Proteins/genetics/metabolism  Chronobiology Disorders/genetics/metabolism  DNA-Binding Proteins/genetics/metabolism  Disease Models, Animal  Down Syndrome/genetics/metabolism  Female  Male  Mice  Motor Activity/physiology  Muscle Proteins/genetics/metabolism  Suprachiasmatic Nucleus/metabolism  Transcription Factors/genetics/metabolism  Aging  Alzheimer’s  Calcineurin  Circadian rhythms  Dscr1  Down syndrome  Free-running  Light-entrained Index. décimale : PER Périodiques Résumé : BACKGROUND: Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer's disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. METHODS: The present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3-6 months old) and aged (9-14 months old) mice of both sexes. RESULTS: We found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and RCAN1-overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN. CONCLUSIONS: Collectively, this study's findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and possibly aging. En ligne : https://dx.doi.org/10.1186/s11689-022-09444-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description / Damien WRIGHT in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description Type de document : texte imprimé Auteurs : Damien WRIGHT, Auteur ; Aisling KENNY, Auteur ; Sarah ELEY, Auteur ; Andrew G. MCKECHANIE, Auteur ; Andrew C. STANFIELD, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/epidemiology  Caregivers  Child  Epilepsy/complications/genetics  Humans  Intellectual Disability/genetics  Parents  ras GTPase-Activating Proteins/genetics  Behavioural phenotype  Intellectual disability, Autism  SYNGAP1-related ID  received consultancy fees from GW Pharma. ACS has previously received grants and  consultancy fees from Novartis and Roche. Index. décimale : PER Périodiques Résumé : BACKGROUND: SYNGAP1-related intellectual disability (ID) is a recently described neurodevelopmental disorder that is caused by pathogenic variation in the SYNGAP1 gene. To date, the behavioural characteristics of this disorder have mainly been highlighted via the prevalence of existing diagnoses in case series. We set out to detail the behavioural features of this disorder by undertaking interviews with those who have a child with SYNGAP1-related ID to allow them to describe their child's behaviour. METHODS: We conducted 27 semi-structured interviews with parents and caregivers which covered basic information (e.g., age, gender), family history, perinatal history, past medical history, developmental history, epilepsy, behavioural history, and a general description of their child's behaviour. RESULTS: Using a mixed quantitative and qualitative approach, the responses from the parents indicated that those with SYNGAP1-related ID showed high rates of autism spectrum disorder (52%), difficulties with fine and gross motor skills, delays in language development, and a high prevalence of epilepsy (70%). A qualitative analysis highlighted their general behaviour affected the themes of daily living skills, distress-related behaviours, emotional regulation, difficulties with change, a lack of danger awareness, and sensory differences. Sensory features described involved auditory, visual, tactile, gustatory, and proprioceptive themes. CONCLUSIONS: Our findings and behavioural descriptions provide important insights as well as implications for the diagnosis and care of those with SYNGAP1-related ID. En ligne : https://dx.doi.org/10.1186/s11689-022-09437-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description [texte imprimé] / Damien WRIGHT, Auteur ; Aisling KENNY, Auteur ; Sarah ELEY, Auteur ; Andrew G. MCKECHANIE, Auteur ; Andrew C. STANFIELD, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/epidemiology  Caregivers  Child  Epilepsy/complications/genetics  Humans  Intellectual Disability/genetics  Parents  ras GTPase-Activating Proteins/genetics  Behavioural phenotype  Intellectual disability, Autism  SYNGAP1-related ID  received consultancy fees from GW Pharma. ACS has previously received grants and  consultancy fees from Novartis and Roche. Index. décimale : PER Périodiques Résumé : BACKGROUND: SYNGAP1-related intellectual disability (ID) is a recently described neurodevelopmental disorder that is caused by pathogenic variation in the SYNGAP1 gene. To date, the behavioural characteristics of this disorder have mainly been highlighted via the prevalence of existing diagnoses in case series. We set out to detail the behavioural features of this disorder by undertaking interviews with those who have a child with SYNGAP1-related ID to allow them to describe their child's behaviour. METHODS: We conducted 27 semi-structured interviews with parents and caregivers which covered basic information (e.g., age, gender), family history, perinatal history, past medical history, developmental history, epilepsy, behavioural history, and a general description of their child's behaviour. RESULTS: Using a mixed quantitative and qualitative approach, the responses from the parents indicated that those with SYNGAP1-related ID showed high rates of autism spectrum disorder (52%), difficulties with fine and gross motor skills, delays in language development, and a high prevalence of epilepsy (70%). A qualitative analysis highlighted their general behaviour affected the themes of daily living skills, distress-related behaviours, emotional regulation, difficulties with change, a lack of danger awareness, and sensory differences. Sensory features described involved auditory, visual, tactile, gustatory, and proprioceptive themes. CONCLUSIONS: Our findings and behavioural descriptions provide important insights as well as implications for the diagnosis and care of those with SYNGAP1-related ID. En ligne : https://dx.doi.org/10.1186/s11689-022-09437-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder / Jonathan D. SANTORO in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder Type de document : texte imprimé Auteurs : Jonathan D. SANTORO, Auteur ; Rebecca PARTRIDGE, Auteur ; Runi TANNA, Auteur ; Dania PAGARKAR, Auteur ; Mellad KHOSHNOOD, Auteur ; Mustafa REHMANI, Auteur ; Ryan M. KAMMEYER, Auteur ; Grace Y. GOMBOLAY, Auteur ; Kristen FISHER, Auteur ; Allison CONRAVEY, Auteur ; Jane EL-DAHR, Auteur ; Alison L. CHRISTY, Auteur ; Lina PATEL, Auteur ; Melanie A. MANNING, Auteur ; Heather VAN MATER, Auteur ; Michael S. RAFII, Auteur ; Eileen A. QUINN, Auteur Langues : Anglais (eng) Mots-clés : Activities of Daily Living  Case-Control Studies  Down Syndrome/complications/therapy  Humans  Immunotherapy/methods  Neuroinflammatory Diseases  Retrospective Studies  Cerebrospinal fluid  Down syndrome  Encephalopathy  Immunotherapy  Regression Index. décimale : PER Périodiques Résumé : BACKGROUND: Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention. METHODS: A retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms. RESULTS: Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04-1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64-37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88-9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective. CONCLUSIONS: This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology. En ligne : https://dx.doi.org/10.1186/s11689-022-09446-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder [texte imprimé] / Jonathan D. SANTORO, Auteur ; Rebecca PARTRIDGE, Auteur ; Runi TANNA, Auteur ; Dania PAGARKAR, Auteur ; Mellad KHOSHNOOD, Auteur ; Mustafa REHMANI, Auteur ; Ryan M. KAMMEYER, Auteur ; Grace Y. GOMBOLAY, Auteur ; Kristen FISHER, Auteur ; Allison CONRAVEY, Auteur ; Jane EL-DAHR, Auteur ; Alison L. CHRISTY, Auteur ; Lina PATEL, Auteur ; Melanie A. MANNING, Auteur ; Heather VAN MATER, Auteur ; Michael S. RAFII, Auteur ; Eileen A. QUINN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Activities of Daily Living  Case-Control Studies  Down Syndrome/complications/therapy  Humans  Immunotherapy/methods  Neuroinflammatory Diseases  Retrospective Studies  Cerebrospinal fluid  Down syndrome  Encephalopathy  Immunotherapy  Regression Index. décimale : PER Périodiques Résumé : BACKGROUND: Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention. METHODS: A retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms. RESULTS: Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04-1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64-37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88-9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective. CONCLUSIONS: This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology. En ligne : https://dx.doi.org/10.1186/s11689-022-09446-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

The importance of deep speech phenotyping for neurodevelopmental and genetic disorders: a conceptual review / Karen V. CHENAUSKY in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The importance of deep speech phenotyping for neurodevelopmental and genetic disorders: a conceptual review Type de document : texte imprimé Auteurs : Karen V. CHENAUSKY, Auteur ; Helen TAGER-FLUSBERG, Auteur Langues : Anglais (eng) Mots-clés : Apraxias/genetics  Child  Humans  Language  Language Development Disorders/complications/genetics  Speech  Speech Disorders/genetics/psychology  Childhood apraxia of speech  Motor speech disorders  Phenotype  Speech sound disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Speech is the most common modality through which language is communicated, and delayed, disordered, or absent speech production is a hallmark of many neurodevelopmental and genetic disorders. Yet, speech is not often carefully phenotyped in neurodevelopmental disorders. In this paper, we argue that such deep phenotyping, defined as phenotyping that is specific to speech production and not conflated with language or cognitive ability, is vital if we are to understand how genetic variations affect the brain regions that are associated with spoken language. Speech is distinct from language, though the two are related behaviorally and share neural substrates. We present a brief taxonomy of developmental speech production disorders, with particular emphasis on the motor speech disorders childhood apraxia of speech (a disorder of motor planning) and childhood dysarthria (a set of disorders of motor execution). We review the history of discoveries concerning the KE family, in whom a hereditary form of communication impairment was identified as childhood apraxia of speech and linked to dysfunction in the FOXP2 gene. The story demonstrates how instrumental deep phenotyping of speech production was in this seminal discovery in the genetics of speech and language. There is considerable overlap between the neural substrates associated with speech production and with FOXP2 expression, suggesting that further genes associated with speech dysfunction will also be expressed in similar brain regions. We then show how a biologically accurate computational model of speech production, in combination with detailed information about speech production in children with developmental disorders, can generate testable hypotheses about the nature, genetics, and neurology of speech disorders. CONCLUSIONS: Though speech and language are distinct, specific types of developmental speech disorder are associated with far-reaching effects on verbal communication in children with neurodevelopmental disorders. Therefore, detailed speech phenotyping, in collaboration with experts on pediatric speech development and disorders, can lead us to a new generation of discoveries about how speech development is affected in genetic disorders. En ligne : https://dx.doi.org/10.1186/s11689-022-09443-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] The importance of deep speech phenotyping for neurodevelopmental and genetic disorders: a conceptual review [texte imprimé] / Karen V. CHENAUSKY, Auteur ; Helen TAGER-FLUSBERG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Apraxias/genetics  Child  Humans  Language  Language Development Disorders/complications/genetics  Speech  Speech Disorders/genetics/psychology  Childhood apraxia of speech  Motor speech disorders  Phenotype  Speech sound disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Speech is the most common modality through which language is communicated, and delayed, disordered, or absent speech production is a hallmark of many neurodevelopmental and genetic disorders. Yet, speech is not often carefully phenotyped in neurodevelopmental disorders. In this paper, we argue that such deep phenotyping, defined as phenotyping that is specific to speech production and not conflated with language or cognitive ability, is vital if we are to understand how genetic variations affect the brain regions that are associated with spoken language. Speech is distinct from language, though the two are related behaviorally and share neural substrates. We present a brief taxonomy of developmental speech production disorders, with particular emphasis on the motor speech disorders childhood apraxia of speech (a disorder of motor planning) and childhood dysarthria (a set of disorders of motor execution). We review the history of discoveries concerning the KE family, in whom a hereditary form of communication impairment was identified as childhood apraxia of speech and linked to dysfunction in the FOXP2 gene. The story demonstrates how instrumental deep phenotyping of speech production was in this seminal discovery in the genetics of speech and language. There is considerable overlap between the neural substrates associated with speech production and with FOXP2 expression, suggesting that further genes associated with speech dysfunction will also be expressed in similar brain regions. We then show how a biologically accurate computational model of speech production, in combination with detailed information about speech production in children with developmental disorders, can generate testable hypotheses about the nature, genetics, and neurology of speech disorders. CONCLUSIONS: Though speech and language are distinct, specific types of developmental speech disorder are associated with far-reaching effects on verbal communication in children with neurodevelopmental disorders. Therefore, detailed speech phenotyping, in collaboration with experts on pediatric speech development and disorders, can lead us to a new generation of discoveries about how speech development is affected in genetic disorders. En ligne : https://dx.doi.org/10.1186/s11689-022-09443-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

An electronic health record (EHR) phenotype algorithm to identify patients with attention deficit hyperactivity disorders (ADHD) and psychiatric comorbidities / Isabella SLABY in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : An electronic health record (EHR) phenotype algorithm to identify patients with attention deficit hyperactivity disorders (ADHD) and psychiatric comorbidities Type de document : texte imprimé Auteurs : Isabella SLABY, Auteur ; Heather S. HAIN, Auteur ; Debra ABRAMS, Auteur ; Frank D. MENTCH, Auteur ; Joseph T. GLESSNER, Auteur ; Patrick M.A. SLEIMAN, Auteur ; Hakon HAKONARSON, Auteur Langues : Anglais (eng) Mots-clés : Algorithms  Attention Deficit Disorder with  Hyperactivity/complications/diagnosis/epidemiology  Case-Control Studies  Child  Comorbidity  Electronic Health Records  Humans  Phenotype  Prospective Studies  Retrospective Studies Index. décimale : PER Périodiques Résumé : BACKGROUND: In over half of pediatric cases, ADHD presents with comorbidities, and often, it is unclear whether the symptoms causing impairment are due to the comorbidity or the underlying ADHD. Comorbid conditions increase the likelihood for a more severe and persistent course and complicate treatment decisions. Therefore, it is highly important to establish an algorithm that identifies ADHD and comorbidities in order to improve research on ADHD using biorepository and other electronic record data. METHODS: It is feasible to accurately distinguish between ADHD in isolation from ADHD with comorbidities using an electronic algorithm designed to include other psychiatric disorders. We sought to develop an EHR phenotype algorithm to discriminate cases with ADHD in isolation from cases with ADHD with comorbidities more effectively for efficient future searches in large biorepositories. We developed a multi-source algorithm allowing for a more complete view of the patient's EHR, leveraging the biobank of the Center for Applied Genomics (CAG) at Children's Hospital of Philadelphia (CHOP). We mined EHRs from 2009 to 2016 using International Statistical Classification of Diseases and Related Health Problems (ICD) codes, medication history and keywords specific to ADHD, and comorbid psychiatric disorders to facilitate genotype-phenotype correlation efforts. Chart abstractions and behavioral surveys added evidence in support of the psychiatric diagnoses. Most notably, the algorithm did not exclude other psychiatric disorders, as is the case in many previous algorithms. Controls lacked psychiatric and other neurological disorders. Participants enrolled in various CAG studies at CHOP and completed a broad informed consent, including consent for prospective analyses of EHRs. We created and validated an EHR-based algorithm to classify ADHD and comorbid psychiatric status in a pediatric healthcare network to be used in future genetic analyses and discovery-based studies. RESULTS: In this retrospective case-control study that included data from 51,293 subjects, 5840 ADHD cases were discovered of which 46.1% had ADHD alone and 53.9% had ADHD with psychiatric comorbidities. Our primary study outcome was to examine whether the algorithm could identify and distinguish ADHD exclusive cases from ADHD comorbid cases. The results indicate ICD codes coupled with medication searches revealed the most cases. We discovered ADHD-related keywords did not increase yield. However, we found including ADHD-specific medications increased our number of cases by 21%. Positive predictive values (PPVs) were 95% for ADHD cases and 93% for controls. CONCLUSION: We established a new algorithm and demonstrated the feasibility of the electronic algorithm approach to accurately diagnose ADHD and comorbid conditions, verifying the efficiency of our large biorepository for further genetic discovery-based analyses. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02286817 . First posted on 10 November 2014. CLINICALTRIALS: gov, NCT02777931 . First posted on 19 May 2016. CLINICALTRIALS: gov, NCT03006367 . First posted on 30 December 2016. CLINICALTRIALS: gov, NCT02895906 . First posted on 12 September 2016. En ligne : https://dx.doi.org/10.1186/s11689-022-09447-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] An electronic health record (EHR) phenotype algorithm to identify patients with attention deficit hyperactivity disorders (ADHD) and psychiatric comorbidities [texte imprimé] / Isabella SLABY, Auteur ; Heather S. HAIN, Auteur ; Debra ABRAMS, Auteur ; Frank D. MENTCH, Auteur ; Joseph T. GLESSNER, Auteur ; Patrick M.A. SLEIMAN, Auteur ; Hakon HAKONARSON, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Algorithms  Attention Deficit Disorder with  Hyperactivity/complications/diagnosis/epidemiology  Case-Control Studies  Child  Comorbidity  Electronic Health Records  Humans  Phenotype  Prospective Studies  Retrospective Studies Index. décimale : PER Périodiques Résumé : BACKGROUND: In over half of pediatric cases, ADHD presents with comorbidities, and often, it is unclear whether the symptoms causing impairment are due to the comorbidity or the underlying ADHD. Comorbid conditions increase the likelihood for a more severe and persistent course and complicate treatment decisions. Therefore, it is highly important to establish an algorithm that identifies ADHD and comorbidities in order to improve research on ADHD using biorepository and other electronic record data. METHODS: It is feasible to accurately distinguish between ADHD in isolation from ADHD with comorbidities using an electronic algorithm designed to include other psychiatric disorders. We sought to develop an EHR phenotype algorithm to discriminate cases with ADHD in isolation from cases with ADHD with comorbidities more effectively for efficient future searches in large biorepositories. We developed a multi-source algorithm allowing for a more complete view of the patient's EHR, leveraging the biobank of the Center for Applied Genomics (CAG) at Children's Hospital of Philadelphia (CHOP). We mined EHRs from 2009 to 2016 using International Statistical Classification of Diseases and Related Health Problems (ICD) codes, medication history and keywords specific to ADHD, and comorbid psychiatric disorders to facilitate genotype-phenotype correlation efforts. Chart abstractions and behavioral surveys added evidence in support of the psychiatric diagnoses. Most notably, the algorithm did not exclude other psychiatric disorders, as is the case in many previous algorithms. Controls lacked psychiatric and other neurological disorders. Participants enrolled in various CAG studies at CHOP and completed a broad informed consent, including consent for prospective analyses of EHRs. We created and validated an EHR-based algorithm to classify ADHD and comorbid psychiatric status in a pediatric healthcare network to be used in future genetic analyses and discovery-based studies. RESULTS: In this retrospective case-control study that included data from 51,293 subjects, 5840 ADHD cases were discovered of which 46.1% had ADHD alone and 53.9% had ADHD with psychiatric comorbidities. Our primary study outcome was to examine whether the algorithm could identify and distinguish ADHD exclusive cases from ADHD comorbid cases. The results indicate ICD codes coupled with medication searches revealed the most cases. We discovered ADHD-related keywords did not increase yield. However, we found including ADHD-specific medications increased our number of cases by 21%. Positive predictive values (PPVs) were 95% for ADHD cases and 93% for controls. CONCLUSION: We established a new algorithm and demonstrated the feasibility of the electronic algorithm approach to accurately diagnose ADHD and comorbid conditions, verifying the efficiency of our large biorepository for further genetic discovery-based analyses. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02286817 . First posted on 10 November 2014. CLINICALTRIALS: gov, NCT02777931 . First posted on 19 May 2016. CLINICALTRIALS: gov, NCT03006367 . First posted on 30 December 2016. CLINICALTRIALS: gov, NCT02895906 . First posted on 12 September 2016. En ligne : https://dx.doi.org/10.1186/s11689-022-09447-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Temporal stability of parent-reported behavior problems in late talkers over 2 years: a prospective case-control study from toddlerhood to preschool age / Hsin-Hui LU in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Temporal stability of parent-reported behavior problems in late talkers over 2 years: a prospective case-control study from toddlerhood to preschool age Type de document : texte imprimé Auteurs : Hsin-Hui LU, Auteur ; Jeng-Dau TSAI, Auteur ; Feng-Ming TSAO, Auteur Langues : Anglais (eng) Mots-clés : Case-Control Studies  Child, Preschool  Humans  Infant  Language Development  Language Development Disorders/etiology  Parents  Vocabulary  Behavior problems  Early identification  Late talkers  Temporal stability Index. décimale : PER Périodiques Résumé : BACKGROUND: Late talking (LT) in toddlers is a risk factor for language weakness that may interfere with the development of using language to regulate behavior and emotion and contribute to the development of behavior problems from early childhood. This study examined the temporal stability of parent-reported behavior problems among Mandarin-speaking LT toddlers from ages 2 to 4 in Taiwan. METHODS: Thirty-one LT and 31 typical language development (TLD) toddlers were assessed for their vocabulary production at age 2 with the Words and Sentences Forms of the MacArthur-Bates Communicative Developmental Inventories Toddler Form (Taiwan version). Additionally, participants' receptive and expressive language abilities were assessed using the receptive and expressive language subscales of the Bayley Scales of Infant and Toddler Development, Third Edition. At age 4, the Child Language Disorder Scale-Revised was applied and included the two core subtests for auditory comprehension and expressive communication. At ages 2 and 4 years, behavior problems were assessed with the Child Behavior Checklist. RESULTS: There was a higher percentage of participants with persistent behavior problems among LT toddlers than among TLD toddlers. Moreover, toddlers with larger vocabularies were less likely to develop withdrawal behaviors by preschool age. CONCLUSIONS: This study supported the temporal stability of parent-reported behavior problems among LT toddlers across early childhood. Early identification of and intervention for behavior problems associated with LT in toddlerhood is essential to alleviate their behavior problems later in preschool years. En ligne : https://dx.doi.org/10.1186/s11689-022-09445-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Temporal stability of parent-reported behavior problems in late talkers over 2 years: a prospective case-control study from toddlerhood to preschool age [texte imprimé] / Hsin-Hui LU, Auteur ; Jeng-Dau TSAI, Auteur ; Feng-Ming TSAO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Case-Control Studies  Child, Preschool  Humans  Infant  Language Development  Language Development Disorders/etiology  Parents  Vocabulary  Behavior problems  Early identification  Late talkers  Temporal stability Index. décimale : PER Périodiques Résumé : BACKGROUND: Late talking (LT) in toddlers is a risk factor for language weakness that may interfere with the development of using language to regulate behavior and emotion and contribute to the development of behavior problems from early childhood. This study examined the temporal stability of parent-reported behavior problems among Mandarin-speaking LT toddlers from ages 2 to 4 in Taiwan. METHODS: Thirty-one LT and 31 typical language development (TLD) toddlers were assessed for their vocabulary production at age 2 with the Words and Sentences Forms of the MacArthur-Bates Communicative Developmental Inventories Toddler Form (Taiwan version). Additionally, participants' receptive and expressive language abilities were assessed using the receptive and expressive language subscales of the Bayley Scales of Infant and Toddler Development, Third Edition. At age 4, the Child Language Disorder Scale-Revised was applied and included the two core subtests for auditory comprehension and expressive communication. At ages 2 and 4 years, behavior problems were assessed with the Child Behavior Checklist. RESULTS: There was a higher percentage of participants with persistent behavior problems among LT toddlers than among TLD toddlers. Moreover, toddlers with larger vocabularies were less likely to develop withdrawal behaviors by preschool age. CONCLUSIONS: This study supported the temporal stability of parent-reported behavior problems among LT toddlers across early childhood. Early identification of and intervention for behavior problems associated with LT in toddlerhood is essential to alleviate their behavior problems later in preschool years. En ligne : https://dx.doi.org/10.1186/s11689-022-09445-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Calculating genetic risk for dysfunction in pleiotropic biological processes using whole exome sequencing data / Olivia J. VEATCH in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Calculating genetic risk for dysfunction in pleiotropic biological processes using whole exome sequencing data Type de document : texte imprimé Auteurs : Olivia J. VEATCH, Auteur ; Diego R. MAZZOTTI, Auteur ; Robert T. SCHULTZ, Auteur ; Ted ABEL, Auteur ; Jacob J. MICHAELSON, Auteur ; Edward S. BRODKIN, Auteur ; Birkan TUNC, Auteur ; Susan G. ASSOULINE, Auteur ; Thomas NICKL-JOCKSCHAT, Auteur ; Beth A. MALOW, Auteur ; James S. SUTCLIFFE, Auteur ; Allan I. PACK, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/complications/genetics  Biological Phenomena  Child  Exome/genetics  Humans  Sleep Wake Disorders/complications/genetics  Exome Sequencing  Autism spectrum disorders  Genetic risk scores  Pleiotropy  Sleep duration  Systems biology Index. décimale : PER Périodiques Résumé : BACKGROUND: Numerous genes are implicated in autism spectrum disorder (ASD). ASD encompasses a wide-range and severity of symptoms and co-occurring conditions; however, the details of how genetic variation contributes to phenotypic differences are unclear. This creates a challenge for translating genetic evidence into clinically useful knowledge. Sleep disturbances are particularly prevalent co-occurring conditions in ASD, and genetics may inform treatment. Identifying convergent mechanisms with evidence for dysfunction that connect ASD and sleep biology could help identify better treatments for sleep disturbances in these individuals. METHODS: To identify mechanisms that influence risk for ASD and co-occurring sleep disturbances, we analyzed whole exome sequence data from individuals in the Simons Simplex Collection (n = 2380). We predicted protein damaging variants (PDVs) in genes currently implicated in either ASD or sleep duration in typically developing children. We predicted a network of ASD-related proteins with direct evidence for interaction with sleep duration-related proteins encoded by genes with PDVs. Overrepresentation analyses of Gene Ontology-defined biological processes were conducted on the resulting gene set. We calculated the likelihood of dysfunction in the top overrepresented biological process. We then tested if scores reflecting genetic dysfunction in the process were associated with parent-reported sleep duration. RESULTS: There were 29 genes with PDVs in the ASD dataset where variation was reported in the literature to be associated with both ASD and sleep duration. A network of 108 proteins encoded by ASD and sleep duration candidate genes with PDVs was identified. The mechanism overrepresented in PDV-containing genes that encode proteins in the interaction network with the most evidence for dysfunction was cerebral cortex development (GO:0,021,987). Scores reflecting dysfunction in this process were associated with sleep durations; the largest effects were observed in adolescents (p = 4.65 × 10(-3)). CONCLUSIONS: Our bioinformatic-driven approach detected a biological process enriched for genes encoding a protein-protein interaction network linking ASD gene products with sleep duration gene products where accumulation of potentially damaging variants in individuals with ASD was associated with sleep duration as reported by the parents. Specifically, genetic dysfunction impacting development of the cerebral cortex may affect sleep by disrupting sleep homeostasis which is evidenced to be regulated by this brain region. Future functional assessments and objective measurements of sleep in adolescents with ASD could provide the basis for more informed treatment of sleep problems in these individuals. En ligne : https://dx.doi.org/10.1186/s11689-022-09448-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Calculating genetic risk for dysfunction in pleiotropic biological processes using whole exome sequencing data [texte imprimé] / Olivia J. VEATCH, Auteur ; Diego R. MAZZOTTI, Auteur ; Robert T. SCHULTZ, Auteur ; Ted ABEL, Auteur ; Jacob J. MICHAELSON, Auteur ; Edward S. BRODKIN, Auteur ; Birkan TUNC, Auteur ; Susan G. ASSOULINE, Auteur ; Thomas NICKL-JOCKSCHAT, Auteur ; Beth A. MALOW, Auteur ; James S. SUTCLIFFE, Auteur ; Allan I. PACK, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Autism Spectrum Disorder/complications/genetics  Biological Phenomena  Child  Exome/genetics  Humans  Sleep Wake Disorders/complications/genetics  Exome Sequencing  Autism spectrum disorders  Genetic risk scores  Pleiotropy  Sleep duration  Systems biology Index. décimale : PER Périodiques Résumé : BACKGROUND: Numerous genes are implicated in autism spectrum disorder (ASD). ASD encompasses a wide-range and severity of symptoms and co-occurring conditions; however, the details of how genetic variation contributes to phenotypic differences are unclear. This creates a challenge for translating genetic evidence into clinically useful knowledge. Sleep disturbances are particularly prevalent co-occurring conditions in ASD, and genetics may inform treatment. Identifying convergent mechanisms with evidence for dysfunction that connect ASD and sleep biology could help identify better treatments for sleep disturbances in these individuals. METHODS: To identify mechanisms that influence risk for ASD and co-occurring sleep disturbances, we analyzed whole exome sequence data from individuals in the Simons Simplex Collection (n = 2380). We predicted protein damaging variants (PDVs) in genes currently implicated in either ASD or sleep duration in typically developing children. We predicted a network of ASD-related proteins with direct evidence for interaction with sleep duration-related proteins encoded by genes with PDVs. Overrepresentation analyses of Gene Ontology-defined biological processes were conducted on the resulting gene set. We calculated the likelihood of dysfunction in the top overrepresented biological process. We then tested if scores reflecting genetic dysfunction in the process were associated with parent-reported sleep duration. RESULTS: There were 29 genes with PDVs in the ASD dataset where variation was reported in the literature to be associated with both ASD and sleep duration. A network of 108 proteins encoded by ASD and sleep duration candidate genes with PDVs was identified. The mechanism overrepresented in PDV-containing genes that encode proteins in the interaction network with the most evidence for dysfunction was cerebral cortex development (GO:0,021,987). Scores reflecting dysfunction in this process were associated with sleep durations; the largest effects were observed in adolescents (p = 4.65 × 10(-3)). CONCLUSIONS: Our bioinformatic-driven approach detected a biological process enriched for genes encoding a protein-protein interaction network linking ASD gene products with sleep duration gene products where accumulation of potentially damaging variants in individuals with ASD was associated with sleep duration as reported by the parents. Specifically, genetic dysfunction impacting development of the cerebral cortex may affect sleep by disrupting sleep homeostasis which is evidenced to be regulated by this brain region. Future functional assessments and objective measurements of sleep in adolescents with ASD could provide the basis for more informed treatment of sleep problems in these individuals. En ligne : https://dx.doi.org/10.1186/s11689-022-09448-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications / Jennifer M. BAIN in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications Type de document : texte imprimé Auteurs : Jennifer M. BAIN, Auteur ; LeeAnne Green SNYDER, Auteur ; Katherine L. HELBIG, Auteur ; Dominique D. COOPER, Auteur ; Wendy K. CHUNG, Auteur ; Kimberly GOODSPEED, Auteur Langues : Anglais (eng) Mots-clés : Autistic Disorder  Epilepsy/genetics  GABA Plasma Membrane Transport Proteins/genetics  Humans  Neurodevelopmental Disorders/genetics  Parents  Autism  Epilepsy  Genetic  Hypotonia  Intellectual disability  Movement disorder  Neurodevelopmental disorder  SLC6A1  salary support for research from Simons Searchlight. The other authors declare  that they have no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: SLC6A1-related disorder is a recently identified, rare, genetic neurodevelopmental disorder that is associated with loss-of-function variants in SLC6A1. This gene encodes GABA transporter type I that is responsible for re-uptake of GABA from the synapse into the pre-synaptic terminal or circulating neuroglia. Based upon retrospective review of published cases and available research databases including Epi25 collective and SLC6A1 Connect patient database, the phenotypic spectrum is broad and includes developmental delay, epilepsy, and autism or autistic traits. SLC6A1 is one of the genes included in the Simons Searchlight registry, which includes standardized data collection across genetically identified neurodevelopmental conditions. METHODS: In this study, we compare parent-report measures of phenotypic features in the Simons Searchlight registry to previously published, provider-reported cases to assess if parent-report measures are consistent with what has been reported in the literature. RESULTS: There were 116 participants in the provider-reported dataset compared to 43 individuals in the caregiver-reported dataset. Carriers in Searchlight had 83 unique pathogenic or likely pathogenic variants in SLC6A1, which were predominantly missense or nonsense variants. There was no significant difference between groups for the prevalence of developmental delay, ASD, or ADHD. Caregivers more often reported hypotonia, while epilepsy was slightly more frequently reported by providers. CONCLUSIONS: We propose that standardized parent-report data collection methods are consistent with provider reports on many core features of SLC6A1-related disorder. The availability of patient registries and standardized natural history studies may fill an important need in clinical trial readiness programs, with larger sample sizes than smaller published case series. En ligne : https://dx.doi.org/10.1186/s11689-022-09449-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications [texte imprimé] / Jennifer M. BAIN, Auteur ; LeeAnne Green SNYDER, Auteur ; Katherine L. HELBIG, Auteur ; Dominique D. COOPER, Auteur ; Wendy K. CHUNG, Auteur ; Kimberly GOODSPEED, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autistic Disorder  Epilepsy/genetics  GABA Plasma Membrane Transport Proteins/genetics  Humans  Neurodevelopmental Disorders/genetics  Parents  Autism  Epilepsy  Genetic  Hypotonia  Intellectual disability  Movement disorder  Neurodevelopmental disorder  SLC6A1  salary support for research from Simons Searchlight. The other authors declare  that they have no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: SLC6A1-related disorder is a recently identified, rare, genetic neurodevelopmental disorder that is associated with loss-of-function variants in SLC6A1. This gene encodes GABA transporter type I that is responsible for re-uptake of GABA from the synapse into the pre-synaptic terminal or circulating neuroglia. Based upon retrospective review of published cases and available research databases including Epi25 collective and SLC6A1 Connect patient database, the phenotypic spectrum is broad and includes developmental delay, epilepsy, and autism or autistic traits. SLC6A1 is one of the genes included in the Simons Searchlight registry, which includes standardized data collection across genetically identified neurodevelopmental conditions. METHODS: In this study, we compare parent-report measures of phenotypic features in the Simons Searchlight registry to previously published, provider-reported cases to assess if parent-report measures are consistent with what has been reported in the literature. RESULTS: There were 116 participants in the provider-reported dataset compared to 43 individuals in the caregiver-reported dataset. Carriers in Searchlight had 83 unique pathogenic or likely pathogenic variants in SLC6A1, which were predominantly missense or nonsense variants. There was no significant difference between groups for the prevalence of developmental delay, ASD, or ADHD. Caregivers more often reported hypotonia, while epilepsy was slightly more frequently reported by providers. CONCLUSIONS: We propose that standardized parent-report data collection methods are consistent with provider reports on many core features of SLC6A1-related disorder. The availability of patient registries and standardized natural history studies may fill an important need in clinical trial readiness programs, with larger sample sizes than smaller published case series. En ligne : https://dx.doi.org/10.1186/s11689-022-09449-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Copy number variation at the 22q11.2 locus influences prevalence, severity, and psychiatric impact of sleep disturbance / Kathleen P. O'HORA in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Copy number variation at the 22q11.2 locus influences prevalence, severity, and psychiatric impact of sleep disturbance Type de document : texte imprimé Auteurs : Kathleen P. O'HORA, Auteur ; Amy LIN, Auteur ; Leila KUSHAN-WELLS, Auteur ; Carrie E. BEARDEN, Auteur Langues : Anglais (eng) Mots-clés : Abnormalities, Multiple  Child  Chromosome Duplication  Chromosomes, Human, Pair 22  DNA Copy Number Variations/genetics  DiGeorge Syndrome  Female  Humans  Male  Prevalence  Sleep  Sleep Wake Disorders/complications/epidemiology/genetics  22q11.2 locus  Autism spectrum disorder  Behavioral problems  Copy number variation  Developmental neuropsychiatric disorders  Executive function  Psychosis  Psychosis-risk symptoms  Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disturbance is common, impairing, and may affect symptomatology in developmental neuropsychiatric disorders. Here, we take a genetics-first approach to study the complex role of sleep in psychopathology. Specifically, we examine severity of sleep disturbance in individuals with a reciprocal copy number variant (CNV) at the 22q11.2 locus and determine sleep's effect on psychiatric symptoms. CNVs (deletion or duplication) at this locus confer some of the greatest known risks of neuropsychiatric disorders; recent studies suggest the 22q11.2 deletion negatively impacts sleep, but sleep disruption associated with 22q11.2 duplication has not been investigated. METHODS: We compared subjective sleep disturbance and its relationship to psychiatric symptoms cross-sectionally and longitudinally over 1 year in 107 22q11.2 deletion (22qDel) carriers (14.56±8.0 years; 50% male), 42 22q11.2 duplication (22qDup) carriers (16.26±13.1 years; 54.8% male), and 88 age- and sex-matched controls (14.65±7.4 years; 47.1% male). Linear mixed models were used to compare sleep disturbance, assessed via the Structured Interview for Psychosis-Risk Syndromes (SIPS), across groups. Next, CNV carriers were categorized as good or poor sleepers to investigate sleep effects on multiple neurobehavioral traits: psychosis-risk symptoms (SIPS), autism-related behaviors (Repetitive Behavior Scale (RBS) and Social Responsiveness Scale (SRS)), real-world executive function (Behavior Rating Inventory of Executive Function (BRIEF)), and emotional/behavioral problems (Child Behavior Checklist (CBCL)). Linear mixed models tested the effect of sleep category and a group-by-sleep interaction on each measure, cross-sectionally and longitudinally. RESULTS: 22qDel and 22qDup carriers both reported poorer sleep than controls, but did not differ from each other. Cross-sectionally and longitudinally, poor sleepers scored higher on positive symptoms, anxious/depressed, somatic complaints, thought problems, and aggressive behavior, as well as RBS and SRS total scores. There were significant group-by-sleep interactions for positive symptoms and the majority of CBCL subdomains, in which the difference between good and poor sleepers was larger in 22qDel compared to 22qDup. CONCLUSIONS: Our findings indicate that CNVs at the 22q11.2 locus impact sleep which, in turn, influences psychopathology. Sleep disturbances can differentially impact psychopathology, depending on 22q11.2 gene dosage. Our findings serve as a starting point for exploring a genetic basis for sleep disturbance in developmental neuropsychiatric disorders. En ligne : https://dx.doi.org/10.1186/s11689-022-09450-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Copy number variation at the 22q11.2 locus influences prevalence, severity, and psychiatric impact of sleep disturbance [texte imprimé] / Kathleen P. O'HORA, Auteur ; Amy LIN, Auteur ; Leila KUSHAN-WELLS, Auteur ; Carrie E. BEARDEN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Abnormalities, Multiple  Child  Chromosome Duplication  Chromosomes, Human, Pair 22  DNA Copy Number Variations/genetics  DiGeorge Syndrome  Female  Humans  Male  Prevalence  Sleep  Sleep Wake Disorders/complications/epidemiology/genetics  22q11.2 locus  Autism spectrum disorder  Behavioral problems  Copy number variation  Developmental neuropsychiatric disorders  Executive function  Psychosis  Psychosis-risk symptoms  Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disturbance is common, impairing, and may affect symptomatology in developmental neuropsychiatric disorders. Here, we take a genetics-first approach to study the complex role of sleep in psychopathology. Specifically, we examine severity of sleep disturbance in individuals with a reciprocal copy number variant (CNV) at the 22q11.2 locus and determine sleep's effect on psychiatric symptoms. CNVs (deletion or duplication) at this locus confer some of the greatest known risks of neuropsychiatric disorders; recent studies suggest the 22q11.2 deletion negatively impacts sleep, but sleep disruption associated with 22q11.2 duplication has not been investigated. METHODS: We compared subjective sleep disturbance and its relationship to psychiatric symptoms cross-sectionally and longitudinally over 1 year in 107 22q11.2 deletion (22qDel) carriers (14.56±8.0 years; 50% male), 42 22q11.2 duplication (22qDup) carriers (16.26±13.1 years; 54.8% male), and 88 age- and sex-matched controls (14.65±7.4 years; 47.1% male). Linear mixed models were used to compare sleep disturbance, assessed via the Structured Interview for Psychosis-Risk Syndromes (SIPS), across groups. Next, CNV carriers were categorized as good or poor sleepers to investigate sleep effects on multiple neurobehavioral traits: psychosis-risk symptoms (SIPS), autism-related behaviors (Repetitive Behavior Scale (RBS) and Social Responsiveness Scale (SRS)), real-world executive function (Behavior Rating Inventory of Executive Function (BRIEF)), and emotional/behavioral problems (Child Behavior Checklist (CBCL)). Linear mixed models tested the effect of sleep category and a group-by-sleep interaction on each measure, cross-sectionally and longitudinally. RESULTS: 22qDel and 22qDup carriers both reported poorer sleep than controls, but did not differ from each other. Cross-sectionally and longitudinally, poor sleepers scored higher on positive symptoms, anxious/depressed, somatic complaints, thought problems, and aggressive behavior, as well as RBS and SRS total scores. There were significant group-by-sleep interactions for positive symptoms and the majority of CBCL subdomains, in which the difference between good and poor sleepers was larger in 22qDel compared to 22qDup. CONCLUSIONS: Our findings indicate that CNVs at the 22q11.2 locus impact sleep which, in turn, influences psychopathology. Sleep disturbances can differentially impact psychopathology, depending on 22q11.2 gene dosage. Our findings serve as a starting point for exploring a genetic basis for sleep disturbance in developmental neuropsychiatric disorders. En ligne : https://dx.doi.org/10.1186/s11689-022-09450-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Steady-state visual evoked potentials in children with neurofibromatosis type 1: associations with behavioral rating scales and impact of psychostimulant medication / Eve LALANCETTE in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Steady-state visual evoked potentials in children with neurofibromatosis type 1: associations with behavioral rating scales and impact of psychostimulant medication Type de document : texte imprimé Auteurs : Eve LALANCETTE, Auteur ; Audrey-Rose CHARLEBOIS-POIRIER, Auteur ; Kristian AGBOGBA, Auteur ; Inga Sophia KNOTH, Auteur ; Emily J.H. JONES, Auteur ; Luke MASON, Auteur ; Sébastien PERREAULT, Auteur ; Sarah LIPPE, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Behavior Rating Scale  Child  Child, Preschool  Electroencephalography  Evoked Potentials, Visual  Humans  Neurofibromatosis 1/complications  Photic Stimulation  Inattention symptoms  Neurofibromatosis type 1  Psychostimulant medication  Steady-state visual evoked potentials Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder often associated with cognitive dysfunctions, including a high occurrence of deficits in visuoperceptual skills. The neural underpinnings of these visuoperceptual deficits are not fully understood. We used steady-state visual evoked potentials (SSVEPs) to investigate possible alterations in the synchronization of neural activity in the occipital cortex of children with NF1. METHODS: SSVEPs were measured using electroencephalography and compared between children with NF1 (n = 28) and neurotypical controls (n = 28) aged between 4 and 13 years old. SSVEPs were recorded during visual stimulation with coloured icons flickering at three different frequencies (6 Hz, 10 Hz, and 15 Hz) and analyzed in terms of signal-to-noise ratios. A mixed design ANCOVA was performed to compare SSVEP responses between groups at the three stimulation frequencies. Pearson's correlations with levels of intellectual functioning as well as with symptoms of ADHD, ASD and emotional/behavioral problems were performed. The impact of psychostimulant medication on the SSVEP responses was analyzed in a subset of the NF1 group (n = 8) with paired t-tests. RESULTS: We observed reduced signal-to-noise ratios of the SSVEP responses in children with NF1. The SSVEP responses were negatively correlated with symptoms of inattention and with symptoms of emotional/behavioral problems in the NF1 group. The SSVEP response generated by the lowest stimulation frequency (i.e., 6 Hz) was rescued with the intake of psychostimulant medication. CONCLUSIONS: Impaired processing of rhythmic visual stimulation was evidenced in children with NF1 through measures of SSVEP responses. Those responses seem to be more reduced in children with NF1 who exhibit more symptoms of inattention and emotional/behavioral problems in their daily life. SSVEPs are potentially sensitive electrophysiological markers that could be included in future studies investigating the impact of medication on brain activity and cognitive functioning in children with NF1. En ligne : https://dx.doi.org/10.1186/s11689-022-09452-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Steady-state visual evoked potentials in children with neurofibromatosis type 1: associations with behavioral rating scales and impact of psychostimulant medication [texte imprimé] / Eve LALANCETTE, Auteur ; Audrey-Rose CHARLEBOIS-POIRIER, Auteur ; Kristian AGBOGBA, Auteur ; Inga Sophia KNOTH, Auteur ; Emily J.H. JONES, Auteur ; Luke MASON, Auteur ; Sébastien PERREAULT, Auteur ; Sarah LIPPE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adolescent  Behavior Rating Scale  Child  Child, Preschool  Electroencephalography  Evoked Potentials, Visual  Humans  Neurofibromatosis 1/complications  Photic Stimulation  Inattention symptoms  Neurofibromatosis type 1  Psychostimulant medication  Steady-state visual evoked potentials Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder often associated with cognitive dysfunctions, including a high occurrence of deficits in visuoperceptual skills. The neural underpinnings of these visuoperceptual deficits are not fully understood. We used steady-state visual evoked potentials (SSVEPs) to investigate possible alterations in the synchronization of neural activity in the occipital cortex of children with NF1. METHODS: SSVEPs were measured using electroencephalography and compared between children with NF1 (n = 28) and neurotypical controls (n = 28) aged between 4 and 13 years old. SSVEPs were recorded during visual stimulation with coloured icons flickering at three different frequencies (6 Hz, 10 Hz, and 15 Hz) and analyzed in terms of signal-to-noise ratios. A mixed design ANCOVA was performed to compare SSVEP responses between groups at the three stimulation frequencies. Pearson's correlations with levels of intellectual functioning as well as with symptoms of ADHD, ASD and emotional/behavioral problems were performed. The impact of psychostimulant medication on the SSVEP responses was analyzed in a subset of the NF1 group (n = 8) with paired t-tests. RESULTS: We observed reduced signal-to-noise ratios of the SSVEP responses in children with NF1. The SSVEP responses were negatively correlated with symptoms of inattention and with symptoms of emotional/behavioral problems in the NF1 group. The SSVEP response generated by the lowest stimulation frequency (i.e., 6 Hz) was rescued with the intake of psychostimulant medication. CONCLUSIONS: Impaired processing of rhythmic visual stimulation was evidenced in children with NF1 through measures of SSVEP responses. Those responses seem to be more reduced in children with NF1 who exhibit more symptoms of inattention and emotional/behavioral problems in their daily life. SSVEPs are potentially sensitive electrophysiological markers that could be included in future studies investigating the impact of medication on brain activity and cognitive functioning in children with NF1. En ligne : https://dx.doi.org/10.1186/s11689-022-09452-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Identifying and describing subtypes of spontaneous empathic facial expression production in autistic adults / Jennifer QUINDE-ZLIBUT in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Identifying and describing subtypes of spontaneous empathic facial expression production in autistic adults Type de document : texte imprimé Auteurs : Jennifer QUINDE-ZLIBUT, Auteur ; Anabil MUNSHI, Auteur ; Gautam BISWAS, Auteur ; Carissa J. CASCIO, Auteur Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/psychology  Autistic Disorder/complications  Emotions  Empathy  Facial Expression  Humans  Autism spectrum disorder  Facial expression production  Nonverbal communication Index. décimale : PER Périodiques Résumé : BACKGROUND: It is unclear whether atypical patterns of facial expression production metrics in autism reflect the dynamic and nuanced nature of facial expressions across people or a true diagnostic difference. Furthermore, the heterogeneity observed across autism symptomatology suggests a need for more adaptive and personalized social skills programs. Towards this goal, it would be useful to have a more concrete and empirical understanding of the different expressiveness profiles within the autistic population and how they differ from neurotypicals. METHODS: We used automated facial coding and an unsupervised clustering approach to limit inter-individual variability in facial expression production that may have otherwise obscured group differences in previous studies, allowing an "apples-to-apples" comparison between autistic and neurotypical adults. Specifically, we applied k-means clustering to identify subtypes of facial expressiveness in an autism group (N = 27) and a neurotypical control group (N = 57) separately. The two most stable clusters from these analyses were then further characterized and compared based on their expressiveness and emotive congruence to emotionally charged stimuli. RESULTS: Our main finding was that a subset of autistic adults in our sample show heightened spontaneous facial expressions irrespective of image valence. We did not find evidence for greater incongruous (i.e., inappropriate) facial expressions in autism. Finally, we found a negative trend between expressiveness and emotion recognition within the autism group. CONCLUSION: The results from our previous study on self-reported empathy and current expressivity findings point to a higher degree of facial expressions recruited for emotional resonance in autism that may not always be adaptive (e.g., experiencing similar emotional resonance regardless of valence). These findings also build on previous work indicating that facial expression intensity is not diminished in autism and suggest the need for intervention programs to focus on emotion recognition and social skills in the context of both negative and positive emotions. En ligne : https://dx.doi.org/10.1186/s11689-022-09451-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Identifying and describing subtypes of spontaneous empathic facial expression production in autistic adults [texte imprimé] / Jennifer QUINDE-ZLIBUT, Auteur ; Anabil MUNSHI, Auteur ; Gautam BISWAS, Auteur ; Carissa J. CASCIO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Adult  Autism Spectrum Disorder/psychology  Autistic Disorder/complications  Emotions  Empathy  Facial Expression  Humans  Autism spectrum disorder  Facial expression production  Nonverbal communication Index. décimale : PER Périodiques Résumé : BACKGROUND: It is unclear whether atypical patterns of facial expression production metrics in autism reflect the dynamic and nuanced nature of facial expressions across people or a true diagnostic difference. Furthermore, the heterogeneity observed across autism symptomatology suggests a need for more adaptive and personalized social skills programs. Towards this goal, it would be useful to have a more concrete and empirical understanding of the different expressiveness profiles within the autistic population and how they differ from neurotypicals. METHODS: We used automated facial coding and an unsupervised clustering approach to limit inter-individual variability in facial expression production that may have otherwise obscured group differences in previous studies, allowing an "apples-to-apples" comparison between autistic and neurotypical adults. Specifically, we applied k-means clustering to identify subtypes of facial expressiveness in an autism group (N = 27) and a neurotypical control group (N = 57) separately. The two most stable clusters from these analyses were then further characterized and compared based on their expressiveness and emotive congruence to emotionally charged stimuli. RESULTS: Our main finding was that a subset of autistic adults in our sample show heightened spontaneous facial expressions irrespective of image valence. We did not find evidence for greater incongruous (i.e., inappropriate) facial expressions in autism. Finally, we found a negative trend between expressiveness and emotion recognition within the autism group. CONCLUSION: The results from our previous study on self-reported empathy and current expressivity findings point to a higher degree of facial expressions recruited for emotional resonance in autism that may not always be adaptive (e.g., experiencing similar emotional resonance regardless of valence). These findings also build on previous work indicating that facial expression intensity is not diminished in autism and suggest the need for intervention programs to focus on emotion recognition and social skills in the context of both negative and positive emotions. En ligne : https://dx.doi.org/10.1186/s11689-022-09451-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

The impact of sex chromosome trisomies (XXX, XXY, XYY) on gaze towards faces and affect recognition: a cross-sectional eye tracking study / Nienke BOUW in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The impact of sex chromosome trisomies (XXX, XXY, XYY) on gaze towards faces and affect recognition: a cross-sectional eye tracking study Type de document : texte imprimé Auteurs : Nienke BOUW, Auteur ; Hanna SWAAB, Auteur ; Nicole TARTAGLIA, Auteur ; Lisa CORDEIRO, Auteur ; Sophie VAN RIJN, Auteur Langues : Anglais (eng) Mots-clés : Child  Child, Preschool  Cross-Sectional Studies  Eye-Tracking Technology  Humans  Infant  Recognition, Psychology  Sex Chromosomes  Trisomy  Affect recognition  Eye gaze to faces  Eye tracking  Sex chromosome trisomies  Young children Index. décimale : PER Périodiques Résumé : BACKGROUND: About 1:650-1000 children are born with an extra X or Y chromosome (47,XXX; 47,XXY; 47,XYY), which results in a sex chromosome trisomy (SCT). This international cross-sectional study was designed to investigate gaze towards faces and affect recognition during early life of children with SCT, with the aim to find indicators for support and treatment. METHODS: A group of 101 children with SCT (aged 1-7 years old; M(age)= 3.7 years) was included in this study, as well as a population-based sample of 98 children without SCT (M(age)= 3.7). Eye gaze patterns to faces were measured using an eye tracking method that quantifies first fixations and fixation durations on eyes of static faces and fixation durations on eyes and faces in a dynamic paradigm (with two conditions: single face and multiple faces). Affect recognition was measured using the subtest Affect Recognition of the NEPSY-II neuropsychological test battery. Recruitment and assessment took place in the Netherlands and the USA. RESULTS: Eye tracking results reveal that children with SCT show lower proportion fixation duration on faces already from the age of 3 years, compared to children without SCT. Also, impairments in the clinical range for affect recognition were found (32.2% of the SCT group scored in the well below average range). CONCLUSIONS: These results highlight the importance to further explore the development of social cognitive skills of children with SCT in a longitudinal design, the monitoring of affect recognition skills, and the implementation of (preventive) interventions aiming to support the development of attention to social important information and affect recognition. En ligne : https://dx.doi.org/10.1186/s11689-022-09453-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] The impact of sex chromosome trisomies (XXX, XXY, XYY) on gaze towards faces and affect recognition: a cross-sectional eye tracking study [texte imprimé] / Nienke BOUW, Auteur ; Hanna SWAAB, Auteur ; Nicole TARTAGLIA, Auteur ; Lisa CORDEIRO, Auteur ; Sophie VAN RIJN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Child  Child, Preschool  Cross-Sectional Studies  Eye-Tracking Technology  Humans  Infant  Recognition, Psychology  Sex Chromosomes  Trisomy  Affect recognition  Eye gaze to faces  Eye tracking  Sex chromosome trisomies  Young children Index. décimale : PER Périodiques Résumé : BACKGROUND: About 1:650-1000 children are born with an extra X or Y chromosome (47,XXX; 47,XXY; 47,XYY), which results in a sex chromosome trisomy (SCT). This international cross-sectional study was designed to investigate gaze towards faces and affect recognition during early life of children with SCT, with the aim to find indicators for support and treatment. METHODS: A group of 101 children with SCT (aged 1-7 years old; M(age)= 3.7 years) was included in this study, as well as a population-based sample of 98 children without SCT (M(age)= 3.7). Eye gaze patterns to faces were measured using an eye tracking method that quantifies first fixations and fixation durations on eyes of static faces and fixation durations on eyes and faces in a dynamic paradigm (with two conditions: single face and multiple faces). Affect recognition was measured using the subtest Affect Recognition of the NEPSY-II neuropsychological test battery. Recruitment and assessment took place in the Netherlands and the USA. RESULTS: Eye tracking results reveal that children with SCT show lower proportion fixation duration on faces already from the age of 3 years, compared to children without SCT. Also, impairments in the clinical range for affect recognition were found (32.2% of the SCT group scored in the well below average range). CONCLUSIONS: These results highlight the importance to further explore the development of social cognitive skills of children with SCT in a longitudinal design, the monitoring of affect recognition skills, and the implementation of (preventive) interventions aiming to support the development of attention to social important information and affect recognition. En ligne : https://dx.doi.org/10.1186/s11689-022-09453-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

A framework for characterizing heterogeneity in neurodevelopmental data using latent profile analysis in a sample of children with ADHD / Anne B. ARNETT in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : A framework for characterizing heterogeneity in neurodevelopmental data using latent profile analysis in a sample of children with ADHD Type de document : texte imprimé Auteurs : Anne B. ARNETT, Auteur ; Brian P. FLAHERTY, Auteur Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/psychology  Child  Electroencephalography  Humans  Neurodevelopmental Disorders/complications Index. décimale : PER Périodiques Résumé : BACKGROUND: Heterogeneity in neurodevelopmental disorders, and attention deficit hyperactivity disorder (ADHD) in particular, is increasingly identified as a barrier to identifying biomarkers and developing standards for clinical care. Clustering analytic methods have previously been used across a variety of data types with the goal of identifying meaningful subgroups of individuals with ADHD. However, these analyses have often relied on algorithmic approaches which assume no error in group membership and have not made associations between patterns of behavioral, neurocognitive, and genetic indicators. More sophisticated latent classification models are often not utilized in neurodevelopmental research due to the difficulty of working with these models in small sample sizes. METHODS: In the current study, we propose a framework for evaluating mixture models in sample sizes typical of neurodevelopmental research. We describe a combination of qualitative and quantitative model fit evaluation procedures. We test our framework using latent profile analysis (LPA) in a case study of 120 children with and without ADHD, starting with well-understood neuropsychological indicators, and building toward integration of electroencephalogram (EEG) measures. RESULTS: We identified a stable five-class LPA model using seven neuropsychological indicators. Although we were not able to identify a stable multimethod indicator model, we did successfully extrapolate results of the neuropsychological model to identify distinct patterns of resting EEG power across five frequency bands. CONCLUSIONS: Our approach, which emphasizes theoretical as well as empirical evaluation of mixture models, could make these models more accessible to clinical researchers and may be a useful approach to parsing heterogeneity in neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-022-09454-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] A framework for characterizing heterogeneity in neurodevelopmental data using latent profile analysis in a sample of children with ADHD [texte imprimé] / Anne B. ARNETT, Auteur ; Brian P. FLAHERTY, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Attention Deficit Disorder with Hyperactivity/psychology  Child  Electroencephalography  Humans  Neurodevelopmental Disorders/complications Index. décimale : PER Périodiques Résumé : BACKGROUND: Heterogeneity in neurodevelopmental disorders, and attention deficit hyperactivity disorder (ADHD) in particular, is increasingly identified as a barrier to identifying biomarkers and developing standards for clinical care. Clustering analytic methods have previously been used across a variety of data types with the goal of identifying meaningful subgroups of individuals with ADHD. However, these analyses have often relied on algorithmic approaches which assume no error in group membership and have not made associations between patterns of behavioral, neurocognitive, and genetic indicators. More sophisticated latent classification models are often not utilized in neurodevelopmental research due to the difficulty of working with these models in small sample sizes. METHODS: In the current study, we propose a framework for evaluating mixture models in sample sizes typical of neurodevelopmental research. We describe a combination of qualitative and quantitative model fit evaluation procedures. We test our framework using latent profile analysis (LPA) in a case study of 120 children with and without ADHD, starting with well-understood neuropsychological indicators, and building toward integration of electroencephalogram (EEG) measures. RESULTS: We identified a stable five-class LPA model using seven neuropsychological indicators. Although we were not able to identify a stable multimethod indicator model, we did successfully extrapolate results of the neuropsychological model to identify distinct patterns of resting EEG power across five frequency bands. CONCLUSIONS: Our approach, which emphasizes theoretical as well as empirical evaluation of mixture models, could make these models more accessible to clinical researchers and may be a useful approach to parsing heterogeneity in neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-022-09454-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Is the dolphin a fish? ERP evidence for the impact of typicality during early visual processing in ultra-rapid semantic categorization in autism spectrum disorder / Ann-Kathrin BECK in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Is the dolphin a fish? ERP evidence for the impact of typicality during early visual processing in ultra-rapid semantic categorization in autism spectrum disorder Type de document : texte imprimé Auteurs : Ann-Kathrin BECK, Auteur ; Daniela CZERNOCHOWSKI, Auteur ; Thomas LACHMANN, Auteur ; Bernardo BARAHONA-CORREA, Auteur ; Joana C. CARMO, Auteur Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder  Cognition  Dolphins  Male  Semantics  Visual Perception  Autistic spectrum  D prime  Eeg  Erp  High functioning  Presentation time Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurotypical individuals categorize items even during ultra-rapid presentations (20 ms; see Thorpe et al. Nature 381: 520, 1996). In cognitively able autistic adults, these semantic categorization processes may be impaired and/or may require additional time, specifically for the categorization of atypical compared to typical items. Here, we investigated how typicality structures influence ultra-rapid categorization in cognitively able autistic and neurotypical male adults. METHODS: Images representing typical or atypical exemplars of two different categories (food/animals) were presented for 23.5 vs. 82.3 ms (short/long). We analyzed detection rates, reaction times, and the event-related potential components dN150, N1, P2, N2, and P3 for each group. RESULTS: Behavioral results suggest slower and less correct responses to atypical compared to typical images. This typicality effect was larger for the category with less distinct boundaries (food) and observed in both groups. However, electrophysiological data indicate a different time course of typicality effects, suggesting that neurotypical adults categorize atypical images based on simple features (P2), whereas cognitively able autistic adults categorize later, based on arbitrary features of atypical images (P3). CONCLUSIONS: We found evidence that all three factors under investigation - category, typicality, and presentation time - modulated specific aspects of semantic categorization. Additionally, we observed a qualitatively different pattern in the autistic adults, which suggests that they relied on different cognitive processes to complete the task. En ligne : https://dx.doi.org/10.1186/s11689-022-09457-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Is the dolphin a fish? ERP evidence for the impact of typicality during early visual processing in ultra-rapid semantic categorization in autism spectrum disorder [texte imprimé] / Ann-Kathrin BECK, Auteur ; Daniela CZERNOCHOWSKI, Auteur ; Thomas LACHMANN, Auteur ; Bernardo BARAHONA-CORREA, Auteur ; Joana C. CARMO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Animals  Autism Spectrum Disorder  Cognition  Dolphins  Male  Semantics  Visual Perception  Autistic spectrum  D prime  Eeg  Erp  High functioning  Presentation time Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurotypical individuals categorize items even during ultra-rapid presentations (20 ms; see Thorpe et al. Nature 381: 520, 1996). In cognitively able autistic adults, these semantic categorization processes may be impaired and/or may require additional time, specifically for the categorization of atypical compared to typical items. Here, we investigated how typicality structures influence ultra-rapid categorization in cognitively able autistic and neurotypical male adults. METHODS: Images representing typical or atypical exemplars of two different categories (food/animals) were presented for 23.5 vs. 82.3 ms (short/long). We analyzed detection rates, reaction times, and the event-related potential components dN150, N1, P2, N2, and P3 for each group. RESULTS: Behavioral results suggest slower and less correct responses to atypical compared to typical images. This typicality effect was larger for the category with less distinct boundaries (food) and observed in both groups. However, electrophysiological data indicate a different time course of typicality effects, suggesting that neurotypical adults categorize atypical images based on simple features (P2), whereas cognitively able autistic adults categorize later, based on arbitrary features of atypical images (P3). CONCLUSIONS: We found evidence that all three factors under investigation - category, typicality, and presentation time - modulated specific aspects of semantic categorization. Additionally, we observed a qualitatively different pattern in the autistic adults, which suggests that they relied on different cognitive processes to complete the task. En ligne : https://dx.doi.org/10.1186/s11689-022-09457-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism / Prany WANTZEN in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism Type de document : texte imprimé Auteurs : Prany WANTZEN, Auteur ; Patrice CLOCHON, Auteur ; Franck DOIDY, Auteur ; Fabrice WALLOIS, Auteur ; Mahdi MAHMOUDZADEH, Auteur ; Pierre DESAUNAY, Auteur ; Mille CHRISTIAN, Auteur ; Jean-Marc GUILE, Auteur ; Fabian GUENOLE, Auteur ; Francis EUSTACHE, Auteur ; Jean-Marc BALEYTE, Auteur ; Bérengère GUILLERY-GIRARD, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder  Autistic Disorder  Brain Mapping  Electroencephalography  Humans  Magnetic Resonance Imaging  Neural Pathways  Alpha  Autism spectrum disorder  Connectivity  Dan  Dmn  Eeg  Integration  Resting state  Smn Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), the sensorimotor network (SMN), and the dorsal attention network (DAN). These functional connectivity analyses provide relevant insight into the neurophysiological correlates of multimodal integration in ASD. METHODS: Using high temporal resolution EEG, the present study investigates the functional connectivity in the alpha band within and between the DMN, SMN, and the DAN. We examined eyes-closed EEG alpha lagged phase synchronization, using standardized low-resolution brain electromagnetic tomography (sLORETA) in 29 participants with ASD and 38 developing (TD) controls (age, sex, and IQ matched). RESULTS: We observed reduced functional connectivity in the ASD group relative to TD controls, within and between the DMN, the SMN, and the DAN. We identified three hubs of dysconnectivity in ASD: the posterior cingulate cortex, the precuneus, and the medial frontal gyrus. These three regions also presented decreased current source density in the alpha band. CONCLUSION: These results shed light on possible multimodal integration impairments affecting the communication between bottom-up and top-down information. The observed hypoconnectivity between the DMN, SMN, and DAN could also be related to difficulties in switching between externally oriented attention and internally oriented thoughts. En ligne : https://dx.doi.org/10.1186/s11689-022-09456-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism [texte imprimé] / Prany WANTZEN, Auteur ; Patrice CLOCHON, Auteur ; Franck DOIDY, Auteur ; Fabrice WALLOIS, Auteur ; Mahdi MAHMOUDZADEH, Auteur ; Pierre DESAUNAY, Auteur ; Mille CHRISTIAN, Auteur ; Jean-Marc GUILE, Auteur ; Fabian GUENOLE, Auteur ; Francis EUSTACHE, Auteur ; Jean-Marc BALEYTE, Auteur ; Bérengère GUILLERY-GIRARD, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder  Autistic Disorder  Brain Mapping  Electroencephalography  Humans  Magnetic Resonance Imaging  Neural Pathways  Alpha  Autism spectrum disorder  Connectivity  Dan  Dmn  Eeg  Integration  Resting state  Smn Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), the sensorimotor network (SMN), and the dorsal attention network (DAN). These functional connectivity analyses provide relevant insight into the neurophysiological correlates of multimodal integration in ASD. METHODS: Using high temporal resolution EEG, the present study investigates the functional connectivity in the alpha band within and between the DMN, SMN, and the DAN. We examined eyes-closed EEG alpha lagged phase synchronization, using standardized low-resolution brain electromagnetic tomography (sLORETA) in 29 participants with ASD and 38 developing (TD) controls (age, sex, and IQ matched). RESULTS: We observed reduced functional connectivity in the ASD group relative to TD controls, within and between the DMN, the SMN, and the DAN. We identified three hubs of dysconnectivity in ASD: the posterior cingulate cortex, the precuneus, and the medial frontal gyrus. These three regions also presented decreased current source density in the alpha band. CONCLUSION: These results shed light on possible multimodal integration impairments affecting the communication between bottom-up and top-down information. The observed hypoconnectivity between the DMN, SMN, and DAN could also be related to difficulties in switching between externally oriented attention and internally oriented thoughts. En ligne : https://dx.doi.org/10.1186/s11689-022-09456-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Auditory processing in rodent models of autism: a systematic review / Maya WILDE in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Auditory processing in rodent models of autism: a systematic review Type de document : texte imprimé Auteurs : Maya WILDE, Auteur ; Lena CONSTANTIN, Auteur ; Peter R THORNE, Auteur ; Johanna M MONTGOMERY, Auteur ; Ethan K SCOTT, Auteur ; Juliette E CHEYNE, Auteur Langues : Anglais (eng) Mots-clés : Animals  Auditory Perception/physiology  Autistic Disorder  Electroencephalography/methods  Evoked Potentials, Auditory, Brain Stem  Humans  Mice  Rats  Rodentia  Auditory  Auditory brainstem recordings  Autism spectrum disorder  Cortical event-related potentials  Rodent models Index. décimale : PER Périodiques Résumé : Autism is a complex condition with many traits, including differences in auditory sensitivity. Studies in human autism are plagued by the difficulty of controlling for aetiology, whereas studies in individual rodent models cannot represent the full spectrum of human autism. This systematic review compares results in auditory studies across a wide range of established rodent models of autism to mimic the wide range of aetiologies in the human population. A search was conducted in the PubMed and Web of Science databases to find primary research articles in mouse or rat models of autism which investigate central auditory processing. A total of 88 studies were included. These used non-invasive measures of auditory function, such as auditory brainstem response recordings, cortical event-related potentials, electroencephalography, and behavioural tests, which are translatable to human studies. They also included invasive measures, such as electrophysiology and histology, which shed insight on the origins of the phenotypes found in the non-invasive studies. The most consistent results across these studies were increased latency of the N1 peak of event-related potentials, decreased power and coherence of gamma activity in the auditory cortex, and increased auditory startle responses to high sound levels. Invasive studies indicated loss of subcortical inhibitory neurons, hyperactivity in the lateral superior olive and auditory thalamus, and reduced specificity of responses in the auditory cortex. This review compares the auditory phenotypes across rodent models and highlights those that mimic findings in human studies, providing a framework and avenues for future studies to inform understanding of the auditory system in autism. En ligne : https://dx.doi.org/10.1186/s11689-022-09458-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Auditory processing in rodent models of autism: a systematic review [texte imprimé] / Maya WILDE, Auteur ; Lena CONSTANTIN, Auteur ; Peter R THORNE, Auteur ; Johanna M MONTGOMERY, Auteur ; Ethan K SCOTT, Auteur ; Juliette E CHEYNE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Animals  Auditory Perception/physiology  Autistic Disorder  Electroencephalography/methods  Evoked Potentials, Auditory, Brain Stem  Humans  Mice  Rats  Rodentia  Auditory  Auditory brainstem recordings  Autism spectrum disorder  Cortical event-related potentials  Rodent models Index. décimale : PER Périodiques Résumé : Autism is a complex condition with many traits, including differences in auditory sensitivity. Studies in human autism are plagued by the difficulty of controlling for aetiology, whereas studies in individual rodent models cannot represent the full spectrum of human autism. This systematic review compares results in auditory studies across a wide range of established rodent models of autism to mimic the wide range of aetiologies in the human population. A search was conducted in the PubMed and Web of Science databases to find primary research articles in mouse or rat models of autism which investigate central auditory processing. A total of 88 studies were included. These used non-invasive measures of auditory function, such as auditory brainstem response recordings, cortical event-related potentials, electroencephalography, and behavioural tests, which are translatable to human studies. They also included invasive measures, such as electrophysiology and histology, which shed insight on the origins of the phenotypes found in the non-invasive studies. The most consistent results across these studies were increased latency of the N1 peak of event-related potentials, decreased power and coherence of gamma activity in the auditory cortex, and increased auditory startle responses to high sound levels. Invasive studies indicated loss of subcortical inhibitory neurons, hyperactivity in the lateral superior olive and auditory thalamus, and reduced specificity of responses in the auditory cortex. This review compares the auditory phenotypes across rodent models and highlights those that mimic findings in human studies, providing a framework and avenues for future studies to inform understanding of the auditory system in autism. En ligne : https://dx.doi.org/10.1186/s11689-022-09458-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Phenotypic characteristics and variability in CHARGE syndrome: a PRISMA compliant systematic review and meta-analysis / Andrea T. THOMAS in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Phenotypic characteristics and variability in CHARGE syndrome: a PRISMA compliant systematic review and meta-analysis Type de document : texte imprimé Auteurs : Andrea T. THOMAS, Auteur ; Jane WAITE, Auteur ; Caitlin A. WILLIAMS, Auteur ; Jeremy KIRK, Auteur ; Chris OLIVER, Auteur ; Caroline RICHARDS, Auteur Langues : Anglais (eng) Mots-clés : Aggression  CHARGE Syndrome/complications/epidemiology  Humans  Intellectual Disability/complications/epidemiology/psychology  Self-Injurious Behavior/epidemiology/psychology  Sleep Wake Disorders  Aggressive behaviour  Behavioural phenotype  CHARGE syndrome  Intellectual disability  Self-injurious behaviour  Sensory impairment  Sleep Index. décimale : PER Périodiques Résumé : BACKGROUND: CHARGE syndrome (OMIM #214800) is a phenotypically complex genetic condition characterised by multi-system, multi-sensory impairments. Behavioural, psychological, cognitive and sleep difficulties are not well delineated and are likely associated with biopsychosocial factors. METHODS: This meta-analysis investigated the prevalence of clinical features, physical characteristics and conditions, behavioural, psychological, cognitive and sleep characteristics in CHARGE syndrome, and statistically evaluated directional associations between these characteristics. Pooled prevalence estimates were calculated using reliable, prespecified quality weighting criteria, and meta-regression was conducted to identify associations between characteristics. RESULTS: Of the 42 eligible studies, data could be extracted for 1675 participants. Prevalence estimates were highest for developmental delay (84%), intellectual disability (64%), aggressive behaviour (48%), self-injurious behaviour (44%) and sleep difficulties (45%). Meta-regression indicated significant associations between intellectual disability and choanal atresia, intellectual disability and inner ear anomalies, sleep difficulties and growth deficiency, and sleep difficulties and gross motor difficulties. CONCLUSIONS: Our comprehensive review of clinical features, behavioural, psychological, cognitive and physical characteristics, conditions and comorbidities in CHARGE syndrome provides an empirically based foundation to further research and practice. En ligne : https://dx.doi.org/10.1186/s11689-022-09459-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Phenotypic characteristics and variability in CHARGE syndrome: a PRISMA compliant systematic review and meta-analysis [texte imprimé] / Andrea T. THOMAS, Auteur ; Jane WAITE, Auteur ; Caitlin A. WILLIAMS, Auteur ; Jeremy KIRK, Auteur ; Chris OLIVER, Auteur ; Caroline RICHARDS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Aggression  CHARGE Syndrome/complications/epidemiology  Humans  Intellectual Disability/complications/epidemiology/psychology  Self-Injurious Behavior/epidemiology/psychology  Sleep Wake Disorders  Aggressive behaviour  Behavioural phenotype  CHARGE syndrome  Intellectual disability  Self-injurious behaviour  Sensory impairment  Sleep Index. décimale : PER Périodiques Résumé : BACKGROUND: CHARGE syndrome (OMIM #214800) is a phenotypically complex genetic condition characterised by multi-system, multi-sensory impairments. Behavioural, psychological, cognitive and sleep difficulties are not well delineated and are likely associated with biopsychosocial factors. METHODS: This meta-analysis investigated the prevalence of clinical features, physical characteristics and conditions, behavioural, psychological, cognitive and sleep characteristics in CHARGE syndrome, and statistically evaluated directional associations between these characteristics. Pooled prevalence estimates were calculated using reliable, prespecified quality weighting criteria, and meta-regression was conducted to identify associations between characteristics. RESULTS: Of the 42 eligible studies, data could be extracted for 1675 participants. Prevalence estimates were highest for developmental delay (84%), intellectual disability (64%), aggressive behaviour (48%), self-injurious behaviour (44%) and sleep difficulties (45%). Meta-regression indicated significant associations between intellectual disability and choanal atresia, intellectual disability and inner ear anomalies, sleep difficulties and growth deficiency, and sleep difficulties and gross motor difficulties. CONCLUSIONS: Our comprehensive review of clinical features, behavioural, psychological, cognitive and physical characteristics, conditions and comorbidities in CHARGE syndrome provides an empirically based foundation to further research and practice. En ligne : https://dx.doi.org/10.1186/s11689-022-09459-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Focus on your locus with a massively parallel reporter assay / Jessica C. MCAFEE in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Focus on your locus with a massively parallel reporter assay Type de document : texte imprimé Auteurs : Jessica C. MCAFEE, Auteur ; Jessica L. BELL, Auteur ; Oleh KRUPA, Auteur ; Nana MATOBA, Auteur ; Jason L. STEIN, Auteur ; Hyejung WON, Auteur Langues : Anglais (eng) Mots-clés : Gene Expression Regulation  Genome-Wide Association Study  High-Throughput Nucleotide Sequencing/methods  Humans  Regulatory Sequences, Nucleic Acid  Functional validation  Gwas  Gene regulation  Gene-environment interactions  Mpra  Neurodevelopmental disorders  Noncoding genome  Posttranscriptional regulation  Wgs Index. décimale : PER Périodiques Résumé : A growing number of variants associated with risk for neurodevelopmental disorders have been identified by genome-wide association and whole genome sequencing studies. As common risk variants often fall within large haplotype blocks covering long stretches of the noncoding genome, the causal variants within an associated locus are often unknown. Similarly, the effect of rare noncoding risk variants identified by whole genome sequencing on molecular traits is seldom known without functional assays. A massively parallel reporter assay (MPRA) is an assay that can functionally validate thousands of regulatory elements simultaneously using high-throughput sequencing and barcode technology. MPRA has been adapted to various experimental designs that measure gene regulatory effects of genetic variants within cis- and trans-regulatory elements as well as posttranscriptional processes. This review discusses different MPRA designs that have been or could be used in the future to experimentally validate genetic variants associated with neurodevelopmental disorders. Though MPRA has limitations such as it does not model genomic context, this assay can help narrow down the underlying genetic causes of neurodevelopmental disorders by screening thousands of sequences in one experiment. We conclude by describing future directions of this technique such as applications of MPRA for gene-by-environment interactions and pharmacogenetics. En ligne : https://dx.doi.org/10.1186/s11689-022-09461-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Focus on your locus with a massively parallel reporter assay [texte imprimé] / Jessica C. MCAFEE, Auteur ; Jessica L. BELL, Auteur ; Oleh KRUPA, Auteur ; Nana MATOBA, Auteur ; Jason L. STEIN, Auteur ; Hyejung WON, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Gene Expression Regulation  Genome-Wide Association Study  High-Throughput Nucleotide Sequencing/methods  Humans  Regulatory Sequences, Nucleic Acid  Functional validation  Gwas  Gene regulation  Gene-environment interactions  Mpra  Neurodevelopmental disorders  Noncoding genome  Posttranscriptional regulation  Wgs Index. décimale : PER Périodiques Résumé : A growing number of variants associated with risk for neurodevelopmental disorders have been identified by genome-wide association and whole genome sequencing studies. As common risk variants often fall within large haplotype blocks covering long stretches of the noncoding genome, the causal variants within an associated locus are often unknown. Similarly, the effect of rare noncoding risk variants identified by whole genome sequencing on molecular traits is seldom known without functional assays. A massively parallel reporter assay (MPRA) is an assay that can functionally validate thousands of regulatory elements simultaneously using high-throughput sequencing and barcode technology. MPRA has been adapted to various experimental designs that measure gene regulatory effects of genetic variants within cis- and trans-regulatory elements as well as posttranscriptional processes. This review discusses different MPRA designs that have been or could be used in the future to experimentally validate genetic variants associated with neurodevelopmental disorders. Though MPRA has limitations such as it does not model genomic context, this assay can help narrow down the underlying genetic causes of neurodevelopmental disorders by screening thousands of sequences in one experiment. We conclude by describing future directions of this technique such as applications of MPRA for gene-by-environment interactions and pharmacogenetics. En ligne : https://dx.doi.org/10.1186/s11689-022-09461-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Default mode and fronto-parietal network associations with IQ development across childhood in autism / Joshua K. LEE in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Default mode and fronto-parietal network associations with IQ development across childhood in autism Type de document : texte imprimé Auteurs : Joshua K. LEE, Auteur ; An Chuen Billy CHO, Auteur ; Derek S. ANDREWS, Auteur ; Sally OZONOFF, Auteur ; Sally J. ROGERS, Auteur ; David G. AMARAL, Auteur ; Marjorie SOLOMON, Auteur ; Christine Wu NORDAHL, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications/diagnostic imaging  Autistic Disorder/diagnostic imaging  Brain/diagnostic imaging  Brain Mapping  Female  Humans  Intellectual Disability/complications  Autism spectrum disorder  Default mode  Fronto-parietal  Iq  Intellectual disability  Longitudinal  MRI  Inc., and Axial Therapeutics. The other authors declare that they have competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intellectual disability affects approximately one third of individuals with autism spectrum disorder (autism). Yet, a major unresolved neurobiological question is what differentiates autistic individuals with and without intellectual disability. Intelligence quotients (IQs) are highly variable during childhood. We previously identified three subgroups of autistic children with different trajectories of intellectual development from early (2-3½ years) to middle childhood (9-12 years): (a) persistently high: individuals whose IQs remained in the normal range; (b) persistently low: individuals whose IQs remained in the range of intellectual disability (IQ < 70); and (c) changers: individuals whose IQs began in the range of intellectual disability but increased to the normal IQ range. The frontoparietal (FPN) and default mode (DMN) networks have established links to intellectual functioning. Here, we tested whether brain regions within the FPN and DMN differed volumetrically between these IQ trajectory groups in early childhood. METHODS: We conducted multivariate distance matrix regression to examine the brain regions within the FPN (11 regions x 2 hemispheres) and the DMN (12 regions x 2 hemispheres) in 48 persistently high (18 female), 108 persistently low (32 female), and 109 changers (39 female) using structural MRI acquired at baseline. FPN and DMN regions were defined using networks identified in Smith et al. (Proc Natl Acad Sci U S A 106:13040-5, 2009). IQ trajectory groups were defined by IQ measurements from up to three time points spanning early to middle childhood (mean age time 1: 3.2 years; time 2: 5.4 years; time 3: 11.3 years). RESULTS: The changers group exhibited volumetric differences in the DMN compared to both the persistently low and persistently high groups at time 1. However, the persistently high group did not differ from the persistently low group, suggesting that DMN structure may be an early predictor for change in IQ trajectory. In contrast, the persistently high group exhibited differences in the FPN compared to both the persistently low and changers groups, suggesting differences related more to concurrent IQ and the absence of intellectual disability. CONCLUSIONS: Within autism, volumetric differences of brain regions within the DMN in early childhood may differentiate individuals with persistently low IQ from those with low IQ that improves through childhood. Structural differences in brain networks between these three IQ-based subgroups highlight distinct neural underpinnings of these autism sub-phenotypes. En ligne : https://dx.doi.org/10.1186/s11689-022-09460-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Default mode and fronto-parietal network associations with IQ development across childhood in autism [texte imprimé] / Joshua K. LEE, Auteur ; An Chuen Billy CHO, Auteur ; Derek S. ANDREWS, Auteur ; Sally OZONOFF, Auteur ; Sally J. ROGERS, Auteur ; David G. AMARAL, Auteur ; Marjorie SOLOMON, Auteur ; Christine Wu NORDAHL, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Autism Spectrum Disorder/complications/diagnostic imaging  Autistic Disorder/diagnostic imaging  Brain/diagnostic imaging  Brain Mapping  Female  Humans  Intellectual Disability/complications  Autism spectrum disorder  Default mode  Fronto-parietal  Iq  Intellectual disability  Longitudinal  MRI  Inc., and Axial Therapeutics. The other authors declare that they have competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intellectual disability affects approximately one third of individuals with autism spectrum disorder (autism). Yet, a major unresolved neurobiological question is what differentiates autistic individuals with and without intellectual disability. Intelligence quotients (IQs) are highly variable during childhood. We previously identified three subgroups of autistic children with different trajectories of intellectual development from early (2-3½ years) to middle childhood (9-12 years): (a) persistently high: individuals whose IQs remained in the normal range; (b) persistently low: individuals whose IQs remained in the range of intellectual disability (IQ < 70); and (c) changers: individuals whose IQs began in the range of intellectual disability but increased to the normal IQ range. The frontoparietal (FPN) and default mode (DMN) networks have established links to intellectual functioning. Here, we tested whether brain regions within the FPN and DMN differed volumetrically between these IQ trajectory groups in early childhood. METHODS: We conducted multivariate distance matrix regression to examine the brain regions within the FPN (11 regions x 2 hemispheres) and the DMN (12 regions x 2 hemispheres) in 48 persistently high (18 female), 108 persistently low (32 female), and 109 changers (39 female) using structural MRI acquired at baseline. FPN and DMN regions were defined using networks identified in Smith et al. (Proc Natl Acad Sci U S A 106:13040-5, 2009). IQ trajectory groups were defined by IQ measurements from up to three time points spanning early to middle childhood (mean age time 1: 3.2 years; time 2: 5.4 years; time 3: 11.3 years). RESULTS: The changers group exhibited volumetric differences in the DMN compared to both the persistently low and persistently high groups at time 1. However, the persistently high group did not differ from the persistently low group, suggesting that DMN structure may be an early predictor for change in IQ trajectory. In contrast, the persistently high group exhibited differences in the FPN compared to both the persistently low and changers groups, suggesting differences related more to concurrent IQ and the absence of intellectual disability. CONCLUSIONS: Within autism, volumetric differences of brain regions within the DMN in early childhood may differentiate individuals with persistently low IQ from those with low IQ that improves through childhood. Structural differences in brain networks between these three IQ-based subgroups highlight distinct neural underpinnings of these autism sub-phenotypes. En ligne : https://dx.doi.org/10.1186/s11689-022-09460-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome / Carrie R. JONAK in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome Type de document : texte imprimé Auteurs : Carrie R. JONAK, Auteur ; Ernest V. PEDAPATI, Auteur ; Lauren M. SCHMITT, Auteur ; Samantha A. ASSAD, Auteur ; Manbir S. SANDHU, Auteur ; Lisa DESTEFANO, Auteur ; Lauren ETHRIDGE, Auteur ; Khaleel A. RAZAK, Auteur ; John A. SWEENEY, Auteur ; Devin K. BINDER, Auteur ; Craig A. ERICKSON, Auteur Langues : Anglais (eng) Mots-clés : Animals  Baclofen/pharmacology  Disease Models, Animal  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/complications/drug therapy  Humans  Male  Mice  Mice, Knockout  Autism  Baclofen  Biomarker  Electroencephalography  Fragile X syndrome  Multielectrode array  in fragile X syndrome held by the Cincinnati Children’s Research Foundation  (CCRF) and licensed out at the discretion of CCRF. CAE is a current consultant to  Impel, Stalicla, and Scioto Bioscience. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. METHODS: In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABA(B) selective agonist racemic baclofen (RBAC). RESULTS: In Fmr1 KO mice and in humans with FXS, baclofen use was associated with suppression of elevated gamma power and increase in low-frequency power at rest. In the Fmr1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted. CONCLUSIONS: Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field. TRIAL REGISTRATION: The human experiments are registered under NCT02998151. En ligne : https://dx.doi.org/10.1186/s11689-022-09455-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome [texte imprimé] / Carrie R. JONAK, Auteur ; Ernest V. PEDAPATI, Auteur ; Lauren M. SCHMITT, Auteur ; Samantha A. ASSAD, Auteur ; Manbir S. SANDHU, Auteur ; Lisa DESTEFANO, Auteur ; Lauren ETHRIDGE, Auteur ; Khaleel A. RAZAK, Auteur ; John A. SWEENEY, Auteur ; Devin K. BINDER, Auteur ; Craig A. ERICKSON, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Animals  Baclofen/pharmacology  Disease Models, Animal  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/complications/drug therapy  Humans  Male  Mice  Mice, Knockout  Autism  Baclofen  Biomarker  Electroencephalography  Fragile X syndrome  Multielectrode array  in fragile X syndrome held by the Cincinnati Children’s Research Foundation  (CCRF) and licensed out at the discretion of CCRF. CAE is a current consultant to  Impel, Stalicla, and Scioto Bioscience. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. METHODS: In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABA(B) selective agonist racemic baclofen (RBAC). RESULTS: In Fmr1 KO mice and in humans with FXS, baclofen use was associated with suppression of elevated gamma power and increase in low-frequency power at rest. In the Fmr1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted. CONCLUSIONS: Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field. TRIAL REGISTRATION: The human experiments are registered under NCT02998151. En ligne : https://dx.doi.org/10.1186/s11689-022-09455-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Long-term follow-up of telehealth-enabled behavioral treatment for challenging behaviors in boys with fragile X syndrome / Scott S. HALL in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Long-term follow-up of telehealth-enabled behavioral treatment for challenging behaviors in boys with fragile X syndrome Type de document : texte imprimé Auteurs : Scott S. HALL, Auteur ; Arlette Bujanda RODRIGUEZ, Auteur ; Booil JO, Auteur ; Joy S. POLLARD, Auteur Langues : Anglais (eng) Mots-clés : Behavior Therapy  Child  Follow-Up Studies  Fragile X Syndrome/complications/therapy  Humans  Male  Parents/education  Telemedicine Index. décimale : PER Périodiques Résumé : BACKGROUND: A significant proportion of boys with fragile X syndrome (FXS), the most common known genetic cause of intellectual disability, exhibit challenging behaviors such as aggression and self-injury that can cause significant distress to families. Recent evidence suggests that coaching caregivers to implement functional communication training (FCT) with their child via telehealth can help to ameliorate these behaviors in FXS. In the present study, we followed families who had participated in our previous randomized controlled trial of FCT to evaluate the longer-term effects of FCT on challenging behaviors in this population. METHODS: In study 1, follow-up emails, phone calls, text messages, and letters were sent to caregivers of 48 boys with FXS who had completed our previous study conducted between 2016 and 2019. The main outcome measures administered at follow-up were the Aberrant Behavior Checklist-Community (ABC-C) and the Parenting Stress Index, 4th Edition (PSI-4). In study 2, families who had received FCT treatment but whose child exhibited challenging behaviors daily at follow-up received a 1-h parent training booster session to determine whether the intervention effect could be recovered. RESULTS: Sixteen (66.7%) of 24 families who had received FCT treatment and 18 (75.0%) of 24 families who had received treatment as usual were traced and consented between March and August 2021. The mean follow-up time was 3.1 years (range, 1.4 to 4.2 years). Longitudinal mixed effects analyses indicated that boys who had received FCT were more likely to show improvements on the irritability and lethargy/social withdrawal subscales of the ABC-C over the follow-up interval compared to boys who had continued with treatment as usual. Four of the six boys who had received the booster parent training session via telehealth were reported to exhibit fewer forms of challenging behavior at a 4-week follow-up. CONCLUSIONS: Empowering parents to implement behavior analytic treatments with their child in their own home can have durable effects on maintaining low levels of challenging behaviors in boys with FXS. These data further support the need to implement parent-mediated interventions for challenging behaviors in this population at an early age. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03510156) . Registered 27 April 2018. En ligne : https://dx.doi.org/10.1186/s11689-022-09463-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Long-term follow-up of telehealth-enabled behavioral treatment for challenging behaviors in boys with fragile X syndrome [texte imprimé] / Scott S. HALL, Auteur ; Arlette Bujanda RODRIGUEZ, Auteur ; Booil JO, Auteur ; Joy S. POLLARD, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Behavior Therapy  Child  Follow-Up Studies  Fragile X Syndrome/complications/therapy  Humans  Male  Parents/education  Telemedicine Index. décimale : PER Périodiques Résumé : BACKGROUND: A significant proportion of boys with fragile X syndrome (FXS), the most common known genetic cause of intellectual disability, exhibit challenging behaviors such as aggression and self-injury that can cause significant distress to families. Recent evidence suggests that coaching caregivers to implement functional communication training (FCT) with their child via telehealth can help to ameliorate these behaviors in FXS. In the present study, we followed families who had participated in our previous randomized controlled trial of FCT to evaluate the longer-term effects of FCT on challenging behaviors in this population. METHODS: In study 1, follow-up emails, phone calls, text messages, and letters were sent to caregivers of 48 boys with FXS who had completed our previous study conducted between 2016 and 2019. The main outcome measures administered at follow-up were the Aberrant Behavior Checklist-Community (ABC-C) and the Parenting Stress Index, 4th Edition (PSI-4). In study 2, families who had received FCT treatment but whose child exhibited challenging behaviors daily at follow-up received a 1-h parent training booster session to determine whether the intervention effect could be recovered. RESULTS: Sixteen (66.7%) of 24 families who had received FCT treatment and 18 (75.0%) of 24 families who had received treatment as usual were traced and consented between March and August 2021. The mean follow-up time was 3.1 years (range, 1.4 to 4.2 years). Longitudinal mixed effects analyses indicated that boys who had received FCT were more likely to show improvements on the irritability and lethargy/social withdrawal subscales of the ABC-C over the follow-up interval compared to boys who had continued with treatment as usual. Four of the six boys who had received the booster parent training session via telehealth were reported to exhibit fewer forms of challenging behavior at a 4-week follow-up. CONCLUSIONS: Empowering parents to implement behavior analytic treatments with their child in their own home can have durable effects on maintaining low levels of challenging behaviors in boys with FXS. These data further support the need to implement parent-mediated interventions for challenging behaviors in this population at an early age. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03510156) . Registered 27 April 2018. En ligne : https://dx.doi.org/10.1186/s11689-022-09463-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Divergent presentation of anxiety in high-risk groups within the intellectual disability population / Laura GROVES in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Divergent presentation of anxiety in high-risk groups within the intellectual disability population Type de document : texte imprimé Auteurs : Laura GROVES, Auteur ; Joanna MOSS, Auteur ; Chris OLIVER, Auteur ; Rachel ROYSTON, Auteur ; Jane WAITE, Auteur ; Hayley CRAWFORD, Auteur Langues : Anglais (eng) Mots-clés : Anxiety/complications/epidemiology  Anxiety Disorders/complications/diagnosis/epidemiology  Autism Spectrum Disorder/complications/epidemiology/psychology  De Lange Syndrome/complications  Fragile X Syndrome/complications  Humans  Intellectual Disability/complications/diagnosis/epidemiology  Prospective Studies  Anxiety  Cornelia de Lange syndrome  Fragile X syndrome  Genetic syndromes  Intellectual disability Index. décimale : PER Périodiques Résumé : BACKGROUND: Anxiety symptomatology is common in individuals with intellectual disability (ID). Symptomatology includes both traditional Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) anxiety disorders and autism spectrum disorder (ASD)-related anxiety traits. Some genetic disorders such as Cornelia de Lange (CdLS) and fragile X syndromes (FXS) are at very high risk of anxiety and afford the opportunity to examine prevalence, profiles and associated person characteristics. However, prevalence and associated characteristics of anxiety in these high-risk groups remain poorly described and understood. The aim of the current study was to examine the prevalence and profile of DSM-5 and ASD-related anxiety symptomatology in individuals with CdLS and FXS and associated behavioural and cognitive characteristics. METHODS: Questionnaires and interviews assessing DSM-5 and ASD-related anxiety were conducted with caregivers of individuals with CdLS (n = 49) and FXS (n = 36). RESULTS: DSM-5 anxiety symptomatology was present in both groups with high co-morbidity across anxiety diagnoses. ASD-related anxiety was also prevalent with specific difficulties related to intolerance of uncertainty identified in both groups. Symptomatology was persistent over the lifespan for both groups. Anxiety type was partially associated with repetitive behaviour but not measures of overall ASD phenomenology in CdLS. CONCLUSIONS: DSM-5 and ASD-related anxiety are common in these high-risk syndromes associated with ID. Prospective syndrome specific presentations and associations, which may implicate specific underlying mechanisms, are discussed. Clinicians should be aware of the risk and difficulties involved in assessment of anxiety in individuals with ID, including atypical types, to ensure these individuals do not "miss" diagnoses and support in general clinical practice. En ligne : https://dx.doi.org/10.1186/s11689-022-09462-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Divergent presentation of anxiety in high-risk groups within the intellectual disability population [texte imprimé] / Laura GROVES, Auteur ; Joanna MOSS, Auteur ; Chris OLIVER, Auteur ; Rachel ROYSTON, Auteur ; Jane WAITE, Auteur ; Hayley CRAWFORD, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Anxiety/complications/epidemiology  Anxiety Disorders/complications/diagnosis/epidemiology  Autism Spectrum Disorder/complications/epidemiology/psychology  De Lange Syndrome/complications  Fragile X Syndrome/complications  Humans  Intellectual Disability/complications/diagnosis/epidemiology  Prospective Studies  Anxiety  Cornelia de Lange syndrome  Fragile X syndrome  Genetic syndromes  Intellectual disability Index. décimale : PER Périodiques Résumé : BACKGROUND: Anxiety symptomatology is common in individuals with intellectual disability (ID). Symptomatology includes both traditional Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) anxiety disorders and autism spectrum disorder (ASD)-related anxiety traits. Some genetic disorders such as Cornelia de Lange (CdLS) and fragile X syndromes (FXS) are at very high risk of anxiety and afford the opportunity to examine prevalence, profiles and associated person characteristics. However, prevalence and associated characteristics of anxiety in these high-risk groups remain poorly described and understood. The aim of the current study was to examine the prevalence and profile of DSM-5 and ASD-related anxiety symptomatology in individuals with CdLS and FXS and associated behavioural and cognitive characteristics. METHODS: Questionnaires and interviews assessing DSM-5 and ASD-related anxiety were conducted with caregivers of individuals with CdLS (n = 49) and FXS (n = 36). RESULTS: DSM-5 anxiety symptomatology was present in both groups with high co-morbidity across anxiety diagnoses. ASD-related anxiety was also prevalent with specific difficulties related to intolerance of uncertainty identified in both groups. Symptomatology was persistent over the lifespan for both groups. Anxiety type was partially associated with repetitive behaviour but not measures of overall ASD phenomenology in CdLS. CONCLUSIONS: DSM-5 and ASD-related anxiety are common in these high-risk syndromes associated with ID. Prospective syndrome specific presentations and associations, which may implicate specific underlying mechanisms, are discussed. Clinicians should be aware of the risk and difficulties involved in assessment of anxiety in individuals with ID, including atypical types, to ensure these individuals do not "miss" diagnoses and support in general clinical practice. En ligne : https://dx.doi.org/10.1186/s11689-022-09462-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Correction: EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism / Prany WANTZEN in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Correction: EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism Type de document : texte imprimé Auteurs : Prany WANTZEN, Auteur ; Patrice CLOCHON, Auteur ; Franck DOIDY, Auteur ; Fabrice WALLOIS, Auteur ; Mahdi MAHMOUDZADEH, Auteur ; Pierre DESAUNAY, Auteur ; Christian MILLE, Auteur ; Jean-Marc GUILE, Auteur ; Fabian GUENOLE, Auteur ; Francis EUSTACHE, Auteur ; Jean-Marc BALEYTE, Auteur ; Bérengère GUILLERY-GIRARD, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-022-09464-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Correction: EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism [texte imprimé] / Prany WANTZEN, Auteur ; Patrice CLOCHON, Auteur ; Franck DOIDY, Auteur ; Fabrice WALLOIS, Auteur ; Mahdi MAHMOUDZADEH, Auteur ; Pierre DESAUNAY, Auteur ; Christian MILLE, Auteur ; Jean-Marc GUILE, Auteur ; Fabian GUENOLE, Auteur ; Francis EUSTACHE, Auteur ; Jean-Marc BALEYTE, Auteur ; Bérengère GUILLERY-GIRARD, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-022-09464-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX) / Elizabeth BERRY-KRAVIS in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX) Type de document : texte imprimé Auteurs : Elizabeth BERRY-KRAVIS, Auteur ; Randi HAGERMAN, Auteur ; Dejan BUDIMIROVIC, Auteur ; Craig ERICKSON, Auteur ; Helen HEUSSLER, Auteur ; Nicole TARTAGLIA, Auteur ; Jonathan COHEN, Auteur ; Flora TASSONE, Auteur ; Thomas DOBBINS, Auteur ; Elizabeth MERIKLE, Auteur ; Terri SEBREE, Auteur ; Nancy TICH, Auteur ; Joseph M. PALUMBO, Auteur ; Stephen O'QUINN, Auteur Langues : Anglais (eng) Mots-clés : Child  Male  Humans  Adolescent  Female  Fragile X Syndrome/drug therapy/genetics  Cannabidiol/pharmacology/therapeutic use  DNA Methylation  Behavioral Symptoms  Gels/therapeutic use  Fragile X Mental Retardation Protein/genetics  Cannabidiol  Clinical trial  Endocannabinoid system  Fragile X syndrome  for the conduct of the study as investigators and are on scientific advisory  board for fragile X syndrome for Zynerba Pharmaceuticals. DB, HH, JC, and FT have  received funding from Zynerba Pharmaceuticals for the conduct of the study as  investigators. TD and EM are paid consultants for Zynerba Pharmaceuticals. TS,  NTich, and SO’Q are employees of Zynerba Pharmaceuticals. JMP was an employee of  Zynerba Pharmaceuticals at the time of the study. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy. DESIGN: CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS. METHODS: Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist-Community Edition FXS (ABC-C(FXS)) SA subscale in a full cohort of patients with a FXS full mutation, regardless of the FMR1 methylation status. Ad hoc analyses assessed efficacy in patients with ≥ 90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely. RESULTS: A total of 212 patients, mean age 9.7 years, 75% males, were enrolled. A total of 169 (79.7%) patients presented with ≥ 90% methylation of the FMR1 promoter and full mutation of FMR1. Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥ 90% methylation of FMR1 (nominal P = 0.020). This group also achieved statistically significant improvements in Caregiver Global Impression-Change in SA and isolation, irritable and disruptive behaviors, and social interactions (nominal P-values: P = 0.038, P = 0.028, and P = 0.002). Similar results were seen in patients with 100% methylation of FMR1. ZYN002 was safe and well tolerated. All treatment-emergent adverse events (TEAEs) were mild or moderate. The most common treatment-related TEAE was application site pain (ZYN002: 6.4%; placebo: 1.0%). CONCLUSIONS: In CONNECT-FX, ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe. TRIAL REGISTRATION: The CONNECT-FX trial is registered on Clinicaltrials.gov (NCT03614663). En ligne : https://dx.doi.org/10.1186/s11689-022-09466-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX) [texte imprimé] / Elizabeth BERRY-KRAVIS, Auteur ; Randi HAGERMAN, Auteur ; Dejan BUDIMIROVIC, Auteur ; Craig ERICKSON, Auteur ; Helen HEUSSLER, Auteur ; Nicole TARTAGLIA, Auteur ; Jonathan COHEN, Auteur ; Flora TASSONE, Auteur ; Thomas DOBBINS, Auteur ; Elizabeth MERIKLE, Auteur ; Terri SEBREE, Auteur ; Nancy TICH, Auteur ; Joseph M. PALUMBO, Auteur ; Stephen O'QUINN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Child  Male  Humans  Adolescent  Female  Fragile X Syndrome/drug therapy/genetics  Cannabidiol/pharmacology/therapeutic use  DNA Methylation  Behavioral Symptoms  Gels/therapeutic use  Fragile X Mental Retardation Protein/genetics  Cannabidiol  Clinical trial  Endocannabinoid system  Fragile X syndrome  for the conduct of the study as investigators and are on scientific advisory  board for fragile X syndrome for Zynerba Pharmaceuticals. DB, HH, JC, and FT have  received funding from Zynerba Pharmaceuticals for the conduct of the study as  investigators. TD and EM are paid consultants for Zynerba Pharmaceuticals. TS,  NTich, and SO’Q are employees of Zynerba Pharmaceuticals. JMP was an employee of  Zynerba Pharmaceuticals at the time of the study. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy. DESIGN: CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS. METHODS: Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care. The primary endpoint assessed change in social avoidance (SA) measured by the Aberrant Behavior Checklist-Community Edition FXS (ABC-C(FXS)) SA subscale in a full cohort of patients with a FXS full mutation, regardless of the FMR1 methylation status. Ad hoc analyses assessed efficacy in patients with ≥ 90% and 100% methylation of the promoter region of the FMR1 gene, in whom FMR1 gene silencing is most likely. RESULTS: A total of 212 patients, mean age 9.7 years, 75% males, were enrolled. A total of 169 (79.7%) patients presented with ≥ 90% methylation of the FMR1 promoter and full mutation of FMR1. Although statistical significance for the primary endpoint was not achieved in the full cohort, significant improvement was demonstrated in patients with ≥ 90% methylation of FMR1 (nominal P = 0.020). This group also achieved statistically significant improvements in Caregiver Global Impression-Change in SA and isolation, irritable and disruptive behaviors, and social interactions (nominal P-values: P = 0.038, P = 0.028, and P = 0.002). Similar results were seen in patients with 100% methylation of FMR1. ZYN002 was safe and well tolerated. All treatment-emergent adverse events (TEAEs) were mild or moderate. The most common treatment-related TEAE was application site pain (ZYN002: 6.4%; placebo: 1.0%). CONCLUSIONS: In CONNECT-FX, ZYN002 was well tolerated in patients with FXS and demonstrated evidence of efficacy with a favorable benefit risk relationship in patients with ≥ 90% methylation of the FMR1 gene, in whom gene silencing is most likely, and the impact of FXS is typically most severe. TRIAL REGISTRATION: The CONNECT-FX trial is registered on Clinicaltrials.gov (NCT03614663). En ligne : https://dx.doi.org/10.1186/s11689-022-09466-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

The feasibility and utility of hair follicle sampling to measure FMRP and FMR1 mRNA in children with or without fragile X syndrome: a pilot study / Isha JALNAPURKAR in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The feasibility and utility of hair follicle sampling to measure FMRP and FMR1 mRNA in children with or without fragile X syndrome: a pilot study Type de document : texte imprimé Auteurs : Isha JALNAPURKAR, Auteur ; Jean A. FRAZIER, Auteur ; Mark ROTH, Auteur ; David M. COCHRAN, Auteur ; Ann FOLEY, Auteur ; Taylor MERK, Auteur ; Lauren VENUTI, Auteur ; Lucienne RONCO, Auteur ; Shane RAINES, Auteur ; Diego CADAVID, Auteur Langues : Anglais (eng) Mots-clés : Male  Humans  Fragile X Syndrome/genetics  Fragile X Mental Retardation Protein/genetics  RNA, Messenger/genetics/metabolism  Hair Follicle/metabolism  Pilot Projects  Clinical biomarker  FMR1 mRNA  Fmrp  Fragile X  Hair follicle  during the experimental work and writing of the manuscript. They are no longer  with Fulcrum Therapeutics, but they own equity in Fulcrum Therapeutics. D. C. and  M. R. are currently full-time employees of X4 Pharmaceuticals, which is not  related to this work. J. A. F. receives research support from Healx, Tetra, and  Quadrant. D. M. C. consults with Abbvie Inc. The other authors declare that they  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (> 200 base pairs) on the promotor region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, fragile X messenger ribonucleoprotein 1 (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this, it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 mRNA and FMRP. METHODS: Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules. RESULTS: There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants and lowest in the FXS boys. Measurement of FMR1 mRNA and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab. CONCLUSION: Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home, and office settings, is feasible, repeatable, and can be used for measurement of FMR1 mRNA and FMRP in longitudinal studies. En ligne : https://dx.doi.org/10.1186/s11689-022-09465-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] The feasibility and utility of hair follicle sampling to measure FMRP and FMR1 mRNA in children with or without fragile X syndrome: a pilot study [texte imprimé] / Isha JALNAPURKAR, Auteur ; Jean A. FRAZIER, Auteur ; Mark ROTH, Auteur ; David M. COCHRAN, Auteur ; Ann FOLEY, Auteur ; Taylor MERK, Auteur ; Lauren VENUTI, Auteur ; Lucienne RONCO, Auteur ; Shane RAINES, Auteur ; Diego CADAVID, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Male  Humans  Fragile X Syndrome/genetics  Fragile X Mental Retardation Protein/genetics  RNA, Messenger/genetics/metabolism  Hair Follicle/metabolism  Pilot Projects  Clinical biomarker  FMR1 mRNA  Fmrp  Fragile X  Hair follicle  during the experimental work and writing of the manuscript. They are no longer  with Fulcrum Therapeutics, but they own equity in Fulcrum Therapeutics. D. C. and  M. R. are currently full-time employees of X4 Pharmaceuticals, which is not  related to this work. J. A. F. receives research support from Healx, Tetra, and  Quadrant. D. M. C. consults with Abbvie Inc. The other authors declare that they  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (> 200 base pairs) on the promotor region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, fragile X messenger ribonucleoprotein 1 (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this, it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 mRNA and FMRP. METHODS: Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules. RESULTS: There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants and lowest in the FXS boys. Measurement of FMR1 mRNA and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab. CONCLUSION: Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home, and office settings, is feasible, repeatable, and can be used for measurement of FMR1 mRNA and FMRP in longitudinal studies. En ligne : https://dx.doi.org/10.1186/s11689-022-09465-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Social attention during object engagement: toward a cross-species measure of preferential social orienting / Claire WEICHSELBAUM in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Social attention during object engagement: toward a cross-species measure of preferential social orienting Type de document : texte imprimé Auteurs : Claire WEICHSELBAUM, Auteur ; Nicole HENDRIX, Auteur ; Jordan ALBRIGHT, Auteur ; Joseph D. DOUGHERTY, Auteur ; Kelly N. BOTTERON, Auteur ; John N. CONSTANTINO, Auteur ; Natasha MARRUS, Auteur Langues : Anglais (eng) Mots-clés : Infant  Humans  Animals  Dogs  Autism Spectrum Disorder/psychology  Social Behavior  Prospective Studies  Attention  Cognition  Autism  Cross-species  Social attention  Social motivation  Social orienting  Responsiveness Scale. The other authors declare that they have no competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: A central challenge in preclinical research investigating the biology of autism spectrum disorder (ASD) is the translation of ASD-related social phenotypes across humans and animal models. Social orienting, an observable, evolutionarily conserved behavior, represents a promising cross-species ASD phenotype given that disrupted social orienting is an early-emerging ASD feature with evidence for predicting familial recurrence. Here, we adapt a competing-stimulus social orienting task from domesticated dogs to naturalistic play behavior in human toddlers and test whether this approach indexes decreased social orienting in ASD. METHODS: Play behavior was coded from the Autism Diagnostic Observation Schedule (ADOS) in two samples of toddlers, each with and without ASD. Sample 1 (n = 16) consisted of community-ascertained research participants, while Sample 2 involved a prospective study of infants at a high or low familial liability for ASD (n = 67). Coding quantified the child's looks towards the experimenter and caregiver, a social stimulus, while playing with high-interest toys, a non-social stimulus. A competing-stimulus measure of "Social Attention During Object Engagement" (SADOE) was calculated by dividing the number of social looks by total time spent playing with toys. SADOE was compared based on ASD diagnosis and differing familial liability for ASD. RESULTS: In both samples, toddlers with ASD exhibited significantly lower SADOE compared to toddlers without ASD, with large effect sizes (Hedges' g ≥ 0.92) driven by a lower frequency of child-initiated spontaneous looks. Among toddlers at high familial likelihood of ASD, toddlers with ASD showed lower SADOE than toddlers without ASD, while SADOE did not differ based on presence or absence of familial ASD risk alone. SADOE correlated negatively with ADOS social affect calibrated severity scores and positively with the Communication and Symbolic Behavior Scales social subscale. In a binary logistic regression model, SADOE alone correctly classified 74.1% of cases, which rose to 85.2% when combined with cognitive development. CONCLUSIONS: This work suggests that a brief behavioral measure pitting a high-interest nonsocial stimulus against the innate draw of social partners can serve as a feasible cross-species measure of social orienting, with implications for genetically informative behavioral phenotyping of social deficits in ASD and other neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-022-09467-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Social attention during object engagement: toward a cross-species measure of preferential social orienting [texte imprimé] / Claire WEICHSELBAUM, Auteur ; Nicole HENDRIX, Auteur ; Jordan ALBRIGHT, Auteur ; Joseph D. DOUGHERTY, Auteur ; Kelly N. BOTTERON, Auteur ; John N. CONSTANTINO, Auteur ; Natasha MARRUS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Infant  Humans  Animals  Dogs  Autism Spectrum Disorder/psychology  Social Behavior  Prospective Studies  Attention  Cognition  Autism  Cross-species  Social attention  Social motivation  Social orienting  Responsiveness Scale. The other authors declare that they have no competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: A central challenge in preclinical research investigating the biology of autism spectrum disorder (ASD) is the translation of ASD-related social phenotypes across humans and animal models. Social orienting, an observable, evolutionarily conserved behavior, represents a promising cross-species ASD phenotype given that disrupted social orienting is an early-emerging ASD feature with evidence for predicting familial recurrence. Here, we adapt a competing-stimulus social orienting task from domesticated dogs to naturalistic play behavior in human toddlers and test whether this approach indexes decreased social orienting in ASD. METHODS: Play behavior was coded from the Autism Diagnostic Observation Schedule (ADOS) in two samples of toddlers, each with and without ASD. Sample 1 (n = 16) consisted of community-ascertained research participants, while Sample 2 involved a prospective study of infants at a high or low familial liability for ASD (n = 67). Coding quantified the child's looks towards the experimenter and caregiver, a social stimulus, while playing with high-interest toys, a non-social stimulus. A competing-stimulus measure of "Social Attention During Object Engagement" (SADOE) was calculated by dividing the number of social looks by total time spent playing with toys. SADOE was compared based on ASD diagnosis and differing familial liability for ASD. RESULTS: In both samples, toddlers with ASD exhibited significantly lower SADOE compared to toddlers without ASD, with large effect sizes (Hedges' g ≥ 0.92) driven by a lower frequency of child-initiated spontaneous looks. Among toddlers at high familial likelihood of ASD, toddlers with ASD showed lower SADOE than toddlers without ASD, while SADOE did not differ based on presence or absence of familial ASD risk alone. SADOE correlated negatively with ADOS social affect calibrated severity scores and positively with the Communication and Symbolic Behavior Scales social subscale. In a binary logistic regression model, SADOE alone correctly classified 74.1% of cases, which rose to 85.2% when combined with cognitive development. CONCLUSIONS: This work suggests that a brief behavioral measure pitting a high-interest nonsocial stimulus against the innate draw of social partners can serve as a feasible cross-species measure of social orienting, with implications for genetically informative behavioral phenotyping of social deficits in ASD and other neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-022-09467-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes / Blake A. GIMBEL in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes Type de document : texte imprimé Auteurs : Blake A. GIMBEL, Auteur ; Mary E. ANTHONY, Auteur ; Abigail M. ERNST, Auteur ; Donovan J. ROEDIGER, Auteur ; Erik DE WATER, Auteur ; Judith K. ECKERLE, Auteur ; Christopher J. BOYS, Auteur ; Joshua P. RADKE, Auteur ; Bryon A. MUELLER, Auteur ; Anita J. FUGLESTAD, Auteur ; Steven H. ZEISEL, Auteur ; Michael K. GEORGIEFF, Auteur ; Jeffrey R. WOZNIAK, Auteur Langues : Anglais (eng) Mots-clés : Child  Pregnancy  Female  Humans  Child, Preschool  Fetal Alcohol Spectrum Disorders/drug therapy  Choline/therapeutic use  Corpus Callosum/diagnostic imaging  Follow-Up Studies  White Matter/diagnostic imaging  Choline  Cognition  Diffusion MRI  Fetal alcohol spectrum disorders  Longitudinal studies  Neurite orientation dispersion and density imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. METHODS: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5 to 5 year olds with FASD. Participants in this long-term follow-up study include 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11.0 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up included measures of executive functioning and an MRI scan. RESULTS: Children who received choline had better performance on several tasks of lower-order executive function (e.g., processing speed) and showed higher white matter microstructure organization (i.e., greater axon coherence) in the splenium of the corpus callosum compared to the placebo group. CONCLUSIONS: These preliminary findings, although exploratory at this stage, highlight potential long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that choline may affect white matter development, representing a potential target of choline in this population. TRIAL REGISTRATION: Prior to enrollment, this trial was registered with clinicaltrials.gov ( NCT01149538 ) on June 23, 2010. En ligne : https://dx.doi.org/10.1186/s11689-022-09470-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes [texte imprimé] / Blake A. GIMBEL, Auteur ; Mary E. ANTHONY, Auteur ; Abigail M. ERNST, Auteur ; Donovan J. ROEDIGER, Auteur ; Erik DE WATER, Auteur ; Judith K. ECKERLE, Auteur ; Christopher J. BOYS, Auteur ; Joshua P. RADKE, Auteur ; Bryon A. MUELLER, Auteur ; Anita J. FUGLESTAD, Auteur ; Steven H. ZEISEL, Auteur ; Michael K. GEORGIEFF, Auteur ; Jeffrey R. WOZNIAK, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Child  Pregnancy  Female  Humans  Child, Preschool  Fetal Alcohol Spectrum Disorders/drug therapy  Choline/therapeutic use  Corpus Callosum/diagnostic imaging  Follow-Up Studies  White Matter/diagnostic imaging  Choline  Cognition  Diffusion MRI  Fetal alcohol spectrum disorders  Longitudinal studies  Neurite orientation dispersion and density imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. METHODS: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5 to 5 year olds with FASD. Participants in this long-term follow-up study include 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11.0 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up included measures of executive functioning and an MRI scan. RESULTS: Children who received choline had better performance on several tasks of lower-order executive function (e.g., processing speed) and showed higher white matter microstructure organization (i.e., greater axon coherence) in the splenium of the corpus callosum compared to the placebo group. CONCLUSIONS: These preliminary findings, although exploratory at this stage, highlight potential long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that choline may affect white matter development, representing a potential target of choline in this population. TRIAL REGISTRATION: Prior to enrollment, this trial was registered with clinicaltrials.gov ( NCT01149538 ) on June 23, 2010. En ligne : https://dx.doi.org/10.1186/s11689-022-09470-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575