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Postural control processes during standing and step initiation in autism spectrum disorder / Erin K. BOJANEK in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Postural control processes during standing and step initiation in autism spectrum disorder Type de document : texte imprimé Auteurs : Erin K. BOJANEK, Auteur ; Zheng WANG, Auteur ; Stormi P. WHITE, Auteur ; Matthew W. MOSCONI, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/physiopathology  Case-Control Studies  Child  Female  Gait/physiology  Humans  Male  Postural Balance/physiology  Standing Position  Young Adult  Anticipatory postural adjustments  Autism Spectrum disorder  Mutual information  Postural control  Stepping Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with autism spectrum disorder (ASD) show a reduced ability to maintain postural stability, though motor control mechanisms contributing to these issues and the extent to which they are associated with other gross motor activities (e.g., stepping) are not yet known. METHODS: Seventeen individuals with ASD and 20 typically developing (TD) controls (ages 6-19 years) completed three tests of postural control during standing. During the neutral stance, individuals stood with their feet shoulder width apart. During the Romberg one stance, they stood with feet close together. During the circular sway, participants stood with feet shoulder width apart and swayed in a circular motion. The standard deviation (SD) of their center of pressure (COP) in the mediolateral (ML) and anteroposterior (AP) directions and the COP trajectory length were examined for each stance. We also assessed mutual information (MI), or the shared dependencies between COP in the ML and AP directions. Participants also completed a stepping task in which they stepped forward from one force platform to an adjacent platform. The amplitude and duration of anticipatory postural adjustments (APAs) were examined, as were the maximum lateral sway, duration, and velocity of COP adjustments following the initial step. We examined stepping variables using separate one-way ANCOVAs with height as a covariate. The relationships between postural control and stepping measures and ASD symptom severity were assessed using Spearman correlations with scores on the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: Individuals with ASD showed increased COP trajectory length across stance conditions (p = 0.05) and reduced MI during circular sway relative to TD controls (p = 0.02). During stepping, groups did not differ on APA amplitude (p = 0.97) or duration (p = 0.41), but during their initial step, individuals with ASD showed reduced ML sway (p = 0.06), reduced body transfer duration (p < 0.01), and increased body transfer velocity (p = 0.02) compared to controls. Greater neutral stance COP(ML) variability (r = 0.55, p = 0.02) and decreased lateral sway (r = - 0.55, p = 0.02) when stepping were associated with more severe restricted and repetitive behaviors in participants with ASD. CONCLUSIONS: We found that individuals with ASD showed reduced MI during circular sway suggesting a reduced ability to effectively coordinate joint movements during dynamic postural adjustments. Additionally, individuals with ASD showed reduced lateral sway when stepping indicating that motor rigidity may interfere with balance and gait. Postural control and stepping deficits were related to repetitive behaviors in individuals with ASD indicating that motor rigidity and key clinical issues in ASD may represent overlapping pathological processes. En ligne : https://dx.doi.org/10.1186/s11689-019-9305-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Postural control processes during standing and step initiation in autism spectrum disorder [texte imprimé] / Erin K. BOJANEK, Auteur ; Zheng WANG, Auteur ; Stormi P. WHITE, Auteur ; Matthew W. MOSCONI, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Autism Spectrum Disorder/physiopathology  Case-Control Studies  Child  Female  Gait/physiology  Humans  Male  Postural Balance/physiology  Standing Position  Young Adult  Anticipatory postural adjustments  Autism Spectrum disorder  Mutual information  Postural control  Stepping Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with autism spectrum disorder (ASD) show a reduced ability to maintain postural stability, though motor control mechanisms contributing to these issues and the extent to which they are associated with other gross motor activities (e.g., stepping) are not yet known. METHODS: Seventeen individuals with ASD and 20 typically developing (TD) controls (ages 6-19 years) completed three tests of postural control during standing. During the neutral stance, individuals stood with their feet shoulder width apart. During the Romberg one stance, they stood with feet close together. During the circular sway, participants stood with feet shoulder width apart and swayed in a circular motion. The standard deviation (SD) of their center of pressure (COP) in the mediolateral (ML) and anteroposterior (AP) directions and the COP trajectory length were examined for each stance. We also assessed mutual information (MI), or the shared dependencies between COP in the ML and AP directions. Participants also completed a stepping task in which they stepped forward from one force platform to an adjacent platform. The amplitude and duration of anticipatory postural adjustments (APAs) were examined, as were the maximum lateral sway, duration, and velocity of COP adjustments following the initial step. We examined stepping variables using separate one-way ANCOVAs with height as a covariate. The relationships between postural control and stepping measures and ASD symptom severity were assessed using Spearman correlations with scores on the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: Individuals with ASD showed increased COP trajectory length across stance conditions (p = 0.05) and reduced MI during circular sway relative to TD controls (p = 0.02). During stepping, groups did not differ on APA amplitude (p = 0.97) or duration (p = 0.41), but during their initial step, individuals with ASD showed reduced ML sway (p = 0.06), reduced body transfer duration (p < 0.01), and increased body transfer velocity (p = 0.02) compared to controls. Greater neutral stance COP(ML) variability (r = 0.55, p = 0.02) and decreased lateral sway (r = - 0.55, p = 0.02) when stepping were associated with more severe restricted and repetitive behaviors in participants with ASD. CONCLUSIONS: We found that individuals with ASD showed reduced MI during circular sway suggesting a reduced ability to effectively coordinate joint movements during dynamic postural adjustments. Additionally, individuals with ASD showed reduced lateral sway when stepping indicating that motor rigidity may interfere with balance and gait. Postural control and stepping deficits were related to repetitive behaviors in individuals with ASD indicating that motor rigidity and key clinical issues in ASD may represent overlapping pathological processes. En ligne : https://dx.doi.org/10.1186/s11689-019-9305-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Guanfacine treatment improves ADHD phenotypes of impulsivity and hyperactivity in a neurofibromatosis type 1 mouse model / J.L. LUKKES in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Guanfacine treatment improves ADHD phenotypes of impulsivity and hyperactivity in a neurofibromatosis type 1 mouse model Type de document : texte imprimé Auteurs : J.L. LUKKES, Auteur ; H.P. DROZD, Auteur ; S D. FITZ, Auteur ; A.I. MOLOSH, Auteur ; D.W. CLAPP, Auteur ; A. SHEKHAR, Auteur Langues : Anglais (eng) Mots-clés : Adrenergic alpha-2 Receptor Agonists/pharmacology/therapeutic use  Animals  Attention Deficit Disorder with Hyperactivity/drug therapy  Disease Models, Animal  Guanfacine/pharmacology/therapeutic use  Impulsive Behavior/drug effects  Inhibition, Psychological  Male  Mice  Neurofibromatosis 1/complications  Phenotype  Reward  Adhd  Alpha 2A-adrenergic receptor agonist  Behavioral inhibition  Cliff avoidance reaction test  Delay discounting  Guanfacine  Hyperactivity  Impulsivity  Mouse  Neurofibromatosis type 1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a mutation in one copy of the neurofibromin gene (NF1(+/-)). Even though approximately 40-60% of children with NF1 meet the criteria for attention deficit hyperactivity disorder (ADHD), very few preclinical studies, if any, have investigated alterations in impulsivity and risk-taking behavior. Mice with deletion of a single NF1 gene (Nf1(+/-)) recapitulate many of the phenotypes of NF1 patients. METHODS: We compared wild-type (WT) and Nf1(+/-) mouse strains to investigate differences in impulsivity and hyperactivity using the delay discounting task (DDT), cliff avoidance reaction (CAR) test, and open field. We also investigated whether treatment with the clinically effective alpha-2A adrenergic receptor agonist, guanfacine (0.3 mg/kg, i.p.), would reverse deficits observed in behavioral inhibition. RESULTS: Nf1(+/-) mice chose a higher percentage of smaller rewards when both 10- and 20-s delays were administered compared to WT mice, suggesting Nf1(+/-) mice are more impulsive. When treated with guanfacine (0.3 mg/kg, i.p.), Nf1(+/-) mice exhibited decreased impulsive choice by waiting for the larger, delayed reward. Nf1(+/-) mice also exhibited deficits in behavioral inhibition compared to WT mice in the CAR test by repetitively entering the outer edge of the platform where they risk falling. Treatment with guanfacine ameliorated these deficits. In addition, Nf1(+/-) mice exhibited hyperactivity as increased distance was traveled compared to WT controls in the open field. This hyperactivity in Nf1(+/-) mice was reduced with guanfacine pre-treatment. CONCLUSIONS: Overall, our study confirms that Nf1(+/-) mice exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD, and can be used as a model system to identify alterations in neural circuitry associated with symptoms of ADHD in children with NF1. En ligne : https://dx.doi.org/10.1186/s11689-019-9304-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Guanfacine treatment improves ADHD phenotypes of impulsivity and hyperactivity in a neurofibromatosis type 1 mouse model [texte imprimé] / J.L. LUKKES, Auteur ; H.P. DROZD, Auteur ; S D. FITZ, Auteur ; A.I. MOLOSH, Auteur ; D.W. CLAPP, Auteur ; A. SHEKHAR, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adrenergic alpha-2 Receptor Agonists/pharmacology/therapeutic use  Animals  Attention Deficit Disorder with Hyperactivity/drug therapy  Disease Models, Animal  Guanfacine/pharmacology/therapeutic use  Impulsive Behavior/drug effects  Inhibition, Psychological  Male  Mice  Neurofibromatosis 1/complications  Phenotype  Reward  Adhd  Alpha 2A-adrenergic receptor agonist  Behavioral inhibition  Cliff avoidance reaction test  Delay discounting  Guanfacine  Hyperactivity  Impulsivity  Mouse  Neurofibromatosis type 1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a mutation in one copy of the neurofibromin gene (NF1(+/-)). Even though approximately 40-60% of children with NF1 meet the criteria for attention deficit hyperactivity disorder (ADHD), very few preclinical studies, if any, have investigated alterations in impulsivity and risk-taking behavior. Mice with deletion of a single NF1 gene (Nf1(+/-)) recapitulate many of the phenotypes of NF1 patients. METHODS: We compared wild-type (WT) and Nf1(+/-) mouse strains to investigate differences in impulsivity and hyperactivity using the delay discounting task (DDT), cliff avoidance reaction (CAR) test, and open field. We also investigated whether treatment with the clinically effective alpha-2A adrenergic receptor agonist, guanfacine (0.3 mg/kg, i.p.), would reverse deficits observed in behavioral inhibition. RESULTS: Nf1(+/-) mice chose a higher percentage of smaller rewards when both 10- and 20-s delays were administered compared to WT mice, suggesting Nf1(+/-) mice are more impulsive. When treated with guanfacine (0.3 mg/kg, i.p.), Nf1(+/-) mice exhibited decreased impulsive choice by waiting for the larger, delayed reward. Nf1(+/-) mice also exhibited deficits in behavioral inhibition compared to WT mice in the CAR test by repetitively entering the outer edge of the platform where they risk falling. Treatment with guanfacine ameliorated these deficits. In addition, Nf1(+/-) mice exhibited hyperactivity as increased distance was traveled compared to WT controls in the open field. This hyperactivity in Nf1(+/-) mice was reduced with guanfacine pre-treatment. CONCLUSIONS: Overall, our study confirms that Nf1(+/-) mice exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD, and can be used as a model system to identify alterations in neural circuitry associated with symptoms of ADHD in children with NF1. En ligne : https://dx.doi.org/10.1186/s11689-019-9304-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

A telehealth approach to improving clinical trial access for infants with tuberous sclerosis complex / Carly HYDE in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : A telehealth approach to improving clinical trial access for infants with tuberous sclerosis complex Type de document : texte imprimé Auteurs : Carly HYDE, Auteur ; Maria PIZZANO, Auteur ; Nicole M. MCDONALD, Auteur ; Charles A. 3rd NELSON, Auteur ; Connie KASARI, Auteur ; Elizabeth A. THIELE, Auteur ; Shafali S. JESTE, Auteur Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder/complications  Child, Preschool  Clinical Trials as Topic  Female  Humans  Infant  Male  Parents  Patient Selection  Telemedicine/methods  Tuberous Sclerosis/psychology  Videoconferencing  Autism spectrum disorder  Behavioral intervention  Clinical trial recruitment  Early intervention  Remote delivery  Telehealth  Tuberous sclerosis complex Index. décimale : PER Périodiques Résumé : BACKGROUND: Research in rare genetic syndromes associated with ASD is often hampered by the wide geographic distribution of families and the presence of medical comorbidities, such as epilepsy, that may preclude travel to clinical sites. These challenges can limit the sample size and generalizability of the cohorts included in both natural history studies and clinical trials. Tuberous sclerosis complex (TSC) is a rare genetic syndrome that confers an elevated risk for autism spectrum disorder (ASD), with social communication delays identified in this population as early as 12 months of age. Early identification of risk necessitates parallel testing of early intervention, prompting the first randomized controlled clinical trial of behavioral intervention for infants with TSC (NCT03422367). However, considerable early recruitment challenges have mandated the systematic identification of enrollment barriers followed by modification of the study design to address these barriers. METHODS: Caregivers were interviewed regarding barriers to enrollment (phase 1). Adaptations to the intervention were made to address these barriers (phase 2). Outcomes based on this modification to the study design were defined by enrollment rate and participant demographics. RESULTS: Qualitative reports from caregivers indicated that distance and time were the primary barriers to clinical trial enrollment. The intervention was then modified to a remote model, with at-home, parent-delivered intervention, and weekly video conferencing with interventionists at the study sites. Enrollment increased 10-fold (from 3 to 30 participants) within 1 year and included a more diverse and clinically representative cohort of infants. CONCLUSION: The design and implementation of more scalable methods to disseminate research remotely can substantially improve access to clinical trials in rare neurodevelopmental disorders. The lessons learned from this trial can serve as a model for future studies not only in rare conditions, but in other populations that lack adequate access, such as families with limited financial or clinical resources. Continued efforts will further refine delivery methods to enhance efficiency and ease of these delivery systems for families. En ligne : https://dx.doi.org/10.1186/s11689-019-9302-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] A telehealth approach to improving clinical trial access for infants with tuberous sclerosis complex [texte imprimé] / Carly HYDE, Auteur ; Maria PIZZANO, Auteur ; Nicole M. MCDONALD, Auteur ; Charles A. 3rd NELSON, Auteur ; Connie KASARI, Auteur ; Elizabeth A. THIELE, Auteur ; Shafali S. JESTE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adult  Autism Spectrum Disorder/complications  Child, Preschool  Clinical Trials as Topic  Female  Humans  Infant  Male  Parents  Patient Selection  Telemedicine/methods  Tuberous Sclerosis/psychology  Videoconferencing  Autism spectrum disorder  Behavioral intervention  Clinical trial recruitment  Early intervention  Remote delivery  Telehealth  Tuberous sclerosis complex Index. décimale : PER Périodiques Résumé : BACKGROUND: Research in rare genetic syndromes associated with ASD is often hampered by the wide geographic distribution of families and the presence of medical comorbidities, such as epilepsy, that may preclude travel to clinical sites. These challenges can limit the sample size and generalizability of the cohorts included in both natural history studies and clinical trials. Tuberous sclerosis complex (TSC) is a rare genetic syndrome that confers an elevated risk for autism spectrum disorder (ASD), with social communication delays identified in this population as early as 12 months of age. Early identification of risk necessitates parallel testing of early intervention, prompting the first randomized controlled clinical trial of behavioral intervention for infants with TSC (NCT03422367). However, considerable early recruitment challenges have mandated the systematic identification of enrollment barriers followed by modification of the study design to address these barriers. METHODS: Caregivers were interviewed regarding barriers to enrollment (phase 1). Adaptations to the intervention were made to address these barriers (phase 2). Outcomes based on this modification to the study design were defined by enrollment rate and participant demographics. RESULTS: Qualitative reports from caregivers indicated that distance and time were the primary barriers to clinical trial enrollment. The intervention was then modified to a remote model, with at-home, parent-delivered intervention, and weekly video conferencing with interventionists at the study sites. Enrollment increased 10-fold (from 3 to 30 participants) within 1 year and included a more diverse and clinically representative cohort of infants. CONCLUSION: The design and implementation of more scalable methods to disseminate research remotely can substantially improve access to clinical trials in rare neurodevelopmental disorders. The lessons learned from this trial can serve as a model for future studies not only in rare conditions, but in other populations that lack adequate access, such as families with limited financial or clinical resources. Continued efforts will further refine delivery methods to enhance efficiency and ease of these delivery systems for families. En ligne : https://dx.doi.org/10.1186/s11689-019-9302-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Health comorbidities and cognitive abilities across the lifespan in Down syndrome / Carla M. STARTIN in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Health comorbidities and cognitive abilities across the lifespan in Down syndrome Type de document : texte imprimé Auteurs : Carla M. STARTIN, Auteur ; Hana D'SOUZA, Auteur ; George BALL, Auteur ; Sarah HAMBURG, Auteur ; Rosalyn HITHERSAY, Auteur ; Kate M.O. HUGHES, Auteur ; Esha MASSAND, Auteur ; Annette KARMILOFF-SMITH, Auteur ; Michael S.C. THOMAS, Auteur ; LONDOWNS CONSORTIUM, Auteur ; Andre STRYDOM, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Aged  Aged, 80 and over  Child  Child, Preschool  Cognition  Comorbidity  Down Syndrome/epidemiology  Female  Humans  Infant  Language Development Disorders/epidemiology  Longevity  Male  Mental Disorders/epidemiology  Middle Aged  Sex Characteristics  United Kingdom/epidemiology  Young Adult  Cognitive outcomes  Down syndrome  Health comorbidities  Intellectual disability  Psychiatric comorbidities  Receptive language ability Index. décimale : PER Périodiques Résumé : BACKGROUND: Down syndrome (DS) is associated with variable intellectual disability and multiple health and psychiatric comorbidities. The impact of such comorbidities on cognitive outcomes is unknown. We aimed to describe patterns of physical health and psychiatric comorbidity prevalence, and receptive language ability, in DS across the lifespan, and determine relationships with cognitive outcomes. METHODS: Detailed medical histories were collected and cognitive abilities measured using standardised tests for 602 individuals with DS from England and Wales (age range 3 months to 73 years). Differences in prevalence rates between age groups and between males and females were determined using chi-squared or Fisher's exact tests. In adults, rates for psychiatric comorbidities were compared to expected population rates using standardised morbidity ratios (SMRs). Adapted ANCOVA functions were constructed to explore age and sex associations with receptive language ability across the lifespan, and regression analyses were performed to determine whether the presence of health comorbidities or physical phenotypes predicted cognitive abilities. RESULTS: Multiple comorbidities showed prevalence differences across the lifespan, though there were few sex differences. In adults, SMRs were increased in males and decreased in females with DS for schizophrenia, bipolar disorder, and anxiety. Further, SMRs were increased in both males and females with DS for dementia, autism, ADHD, and depression, with differences more pronounced in females for dementia and autism, and in males for depression. Across the lifespan, receptive language abilities increasingly deviated from age-typical levels, and males scored poorer than females. Only autism and epilepsy were associated with poorer cognitive ability in those aged 16-35 years, with no relationships for physical health comorbidities, including congenital heart defects. CONCLUSIONS: Our results indicate the prevalence of multiple comorbidities varies across the lifespan in DS, and in adults, rates for psychiatric comorbidities show different patterns for males and females relative to expected population rates. Further, most health comorbidities are not associated with poorer cognitive outcomes in DS, apart from autism and epilepsy. It is essential for clinicians to consider such differences to provide appropriate care and treatment for those with DS and to provide prognostic information relating to cognitive outcomes in those with comorbidities. En ligne : https://dx.doi.org/10.1186/s11689-019-9306-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Health comorbidities and cognitive abilities across the lifespan in Down syndrome [texte imprimé] / Carla M. STARTIN, Auteur ; Hana D'SOUZA, Auteur ; George BALL, Auteur ; Sarah HAMBURG, Auteur ; Rosalyn HITHERSAY, Auteur ; Kate M.O. HUGHES, Auteur ; Esha MASSAND, Auteur ; Annette KARMILOFF-SMITH, Auteur ; Michael S.C. THOMAS, Auteur ; LONDOWNS CONSORTIUM, Auteur ; Andre STRYDOM, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Adult  Aged  Aged, 80 and over  Child  Child, Preschool  Cognition  Comorbidity  Down Syndrome/epidemiology  Female  Humans  Infant  Language Development Disorders/epidemiology  Longevity  Male  Mental Disorders/epidemiology  Middle Aged  Sex Characteristics  United Kingdom/epidemiology  Young Adult  Cognitive outcomes  Down syndrome  Health comorbidities  Intellectual disability  Psychiatric comorbidities  Receptive language ability Index. décimale : PER Périodiques Résumé : BACKGROUND: Down syndrome (DS) is associated with variable intellectual disability and multiple health and psychiatric comorbidities. The impact of such comorbidities on cognitive outcomes is unknown. We aimed to describe patterns of physical health and psychiatric comorbidity prevalence, and receptive language ability, in DS across the lifespan, and determine relationships with cognitive outcomes. METHODS: Detailed medical histories were collected and cognitive abilities measured using standardised tests for 602 individuals with DS from England and Wales (age range 3 months to 73 years). Differences in prevalence rates between age groups and between males and females were determined using chi-squared or Fisher's exact tests. In adults, rates for psychiatric comorbidities were compared to expected population rates using standardised morbidity ratios (SMRs). Adapted ANCOVA functions were constructed to explore age and sex associations with receptive language ability across the lifespan, and regression analyses were performed to determine whether the presence of health comorbidities or physical phenotypes predicted cognitive abilities. RESULTS: Multiple comorbidities showed prevalence differences across the lifespan, though there were few sex differences. In adults, SMRs were increased in males and decreased in females with DS for schizophrenia, bipolar disorder, and anxiety. Further, SMRs were increased in both males and females with DS for dementia, autism, ADHD, and depression, with differences more pronounced in females for dementia and autism, and in males for depression. Across the lifespan, receptive language abilities increasingly deviated from age-typical levels, and males scored poorer than females. Only autism and epilepsy were associated with poorer cognitive ability in those aged 16-35 years, with no relationships for physical health comorbidities, including congenital heart defects. CONCLUSIONS: Our results indicate the prevalence of multiple comorbidities varies across the lifespan in DS, and in adults, rates for psychiatric comorbidities show different patterns for males and females relative to expected population rates. Further, most health comorbidities are not associated with poorer cognitive outcomes in DS, apart from autism and epilepsy. It is essential for clinicians to consider such differences to provide appropriate care and treatment for those with DS and to provide prognostic information relating to cognitive outcomes in those with comorbidities. En ligne : https://dx.doi.org/10.1186/s11689-019-9306-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months / Jessica B. GIRAULT in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months Type de document : texte imprimé Auteurs : Jessica B. GIRAULT, Auteur ; Meghan R. SWANSON, Auteur ; Shoba S. MEERA, Auteur ; Rebecca L. GRZADZINSKI, Auteur ; Mark D. SHEN, Auteur ; Catherine A. BURROWS, Auteur ; Jason J. WOLFF, Auteur ; Juhi PANDEY, Auteur ; Tanya ST JOHN, Auteur ; Annette ESTES, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Kelly N. BOTTERON, Auteur ; Heather C. HAZLETT, Auteur ; Stephen R. DAGER, Auteur ; Robert T. SCHULTZ, Auteur ; John N. CONSTANTINO, Auteur ; Joseph PIVEN, Auteur ; IBIS NETWORK, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Autism Spectrum Disorder/genetics  Child  Child, Preschool  Female  Humans  Infant  Male  Phenotype  Siblings  Autism  Communication  Development  Family study  Infant sibling  Language Index. décimale : PER Périodiques Résumé : BACKGROUND: Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. METHODS: Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. RESULTS: Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9-18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001). CONCLUSIONS: Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD. En ligne : https://dx.doi.org/10.1186/s11689-020-9308-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months [texte imprimé] / Jessica B. GIRAULT, Auteur ; Meghan R. SWANSON, Auteur ; Shoba S. MEERA, Auteur ; Rebecca L. GRZADZINSKI, Auteur ; Mark D. SHEN, Auteur ; Catherine A. BURROWS, Auteur ; Jason J. WOLFF, Auteur ; Juhi PANDEY, Auteur ; Tanya ST JOHN, Auteur ; Annette ESTES, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Kelly N. BOTTERON, Auteur ; Heather C. HAZLETT, Auteur ; Stephen R. DAGER, Auteur ; Robert T. SCHULTZ, Auteur ; John N. CONSTANTINO, Auteur ; Joseph PIVEN, Auteur ; IBIS NETWORK, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Autism Spectrum Disorder/genetics  Child  Child, Preschool  Female  Humans  Infant  Male  Phenotype  Siblings  Autism  Communication  Development  Family study  Infant sibling  Language Index. décimale : PER Périodiques Résumé : BACKGROUND: Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. METHODS: Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. RESULTS: Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9-18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001). CONCLUSIONS: Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD. En ligne : https://dx.doi.org/10.1186/s11689-020-9308-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Cognitive correlates of attention-deficit hyperactivity disorder in children and adolescents with high intellectual ability / María CADENAS in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Cognitive correlates of attention-deficit hyperactivity disorder in children and adolescents with high intellectual ability Type de document : texte imprimé Auteurs : María CADENAS, Auteur ; Catharina HARTMAN, Auteur ; Stephen FARAONE, Auteur ; Kevin ANTSHEL, Auteur ; África BORGES, Auteur ; Lianne HOOGEVEEN, Auteur ; Nanda ROMMELSE, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Attention Deficit Disorder with Hyperactivity/psychology  Child  Cognition  Female  Humans  Intelligence  Intelligence Tests  Longitudinal Studies  Male  Netherlands  Adhd  Giftedness  High intelligence  Twice exceptional Index. décimale : PER Périodiques Résumé : BACKGROUND: There is an ongoing debate as to whether attention-deficit hyperactivity disorder (ADHD) in highly intelligent individuals has a similar presentation as in average intelligent individuals. The aim of this study was to examine the cognitive correlates of ADHD in highly intelligent children and adolescents with ADHD. METHOD: Two independent samples (N = 204 and N = 84) of (1) high intelligence quotient (IQ) (IQ ≥ 120) children and adolescents with ADHD were used, carefully matched on age, gender, ADHD severity, and IQ with (2) control participants with high intelligence, (3) participants with ADHD with an average intelligence (IQ 90-110), and (4) control participants with an average intelligence. These samples were selected from the Dutch node of the International Multicenter ADHD Genetics (NeuroIMAGE) and Tracking Adolescents' Individual Lives Survey (TRAILS) cohorts, respectively, in which a large battery of cognitive tasks was administered. Linear mixed models were used to examine the main effects of ADHD and IQ and their interaction on cognitive performance. RESULTS: ADHD-control group differences were not moderated by IQ; mostly equally large ADHD-control differences in cognitive performance were found for high versus average intelligent groups. The small moderating effects found mostly indicated somewhat milder cognitive problems in highly intelligent individuals with ADHD. Overall, highly intelligent children and adolescents with ADHD performed at the level of the average intelligent control children. CONCLUSIONS: Our findings indicate the cognitive profile of ADHD is similar in highly versus average intelligent individuals with ADHD, although ADHD-related cognitive deficits may be easily overlooked in the high intelligence population when compared to the typical (i.e., average intelligent) control group. En ligne : https://dx.doi.org/10.1186/s11689-020-9307-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Cognitive correlates of attention-deficit hyperactivity disorder in children and adolescents with high intellectual ability [texte imprimé] / María CADENAS, Auteur ; Catharina HARTMAN, Auteur ; Stephen FARAONE, Auteur ; Kevin ANTSHEL, Auteur ; África BORGES, Auteur ; Lianne HOOGEVEEN, Auteur ; Nanda ROMMELSE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Attention Deficit Disorder with Hyperactivity/psychology  Child  Cognition  Female  Humans  Intelligence  Intelligence Tests  Longitudinal Studies  Male  Netherlands  Adhd  Giftedness  High intelligence  Twice exceptional Index. décimale : PER Périodiques Résumé : BACKGROUND: There is an ongoing debate as to whether attention-deficit hyperactivity disorder (ADHD) in highly intelligent individuals has a similar presentation as in average intelligent individuals. The aim of this study was to examine the cognitive correlates of ADHD in highly intelligent children and adolescents with ADHD. METHOD: Two independent samples (N = 204 and N = 84) of (1) high intelligence quotient (IQ) (IQ ≥ 120) children and adolescents with ADHD were used, carefully matched on age, gender, ADHD severity, and IQ with (2) control participants with high intelligence, (3) participants with ADHD with an average intelligence (IQ 90-110), and (4) control participants with an average intelligence. These samples were selected from the Dutch node of the International Multicenter ADHD Genetics (NeuroIMAGE) and Tracking Adolescents' Individual Lives Survey (TRAILS) cohorts, respectively, in which a large battery of cognitive tasks was administered. Linear mixed models were used to examine the main effects of ADHD and IQ and their interaction on cognitive performance. RESULTS: ADHD-control group differences were not moderated by IQ; mostly equally large ADHD-control differences in cognitive performance were found for high versus average intelligent groups. The small moderating effects found mostly indicated somewhat milder cognitive problems in highly intelligent individuals with ADHD. Overall, highly intelligent children and adolescents with ADHD performed at the level of the average intelligent control children. CONCLUSIONS: Our findings indicate the cognitive profile of ADHD is similar in highly versus average intelligent individuals with ADHD, although ADHD-related cognitive deficits may be easily overlooked in the high intelligence population when compared to the typical (i.e., average intelligent) control group. En ligne : https://dx.doi.org/10.1186/s11689-020-9307-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Psychiatric illness and regression in individuals with Phelan-McDermid syndrome / Teresa M. KOHLENBERG in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Psychiatric illness and regression in individuals with Phelan-McDermid syndrome Type de document : texte imprimé Auteurs : Teresa M. KOHLENBERG, Auteur ; M. Pilar TRELLES, Auteur ; Brittany MCLARNEY, Auteur ; Catalina BETANCUR, Auteur ; Audrey THURM, Auteur ; Alexander KOLEVZON, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Bipolar Disorder/epidemiology  Catatonia/epidemiology  Chromosome Deletion  Chromosome Disorders/psychology  Chromosomes, Human, Pair 22  Female  Humans  Male  Mental Disorders/epidemiology  Middle Aged  Phenotype  Regression, Psychology  Young Adult  Bipolar disorder  Catatonia  Depression  Mania  Phelan-McDermid syndrome  Psychosis  Regression  SHANK3  Takeda, 5 AM Ventures, sema4, and LabCorp. The other authors declare that they  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic condition characterized by intellectual disability, speech and language deficits, hypotonia, autism spectrum disorder, and epilepsy. PMS is caused by 22q13.33 deletions or mutations affecting SHANK3, which codes for a critical scaffolding protein in excitatory synapses. SHANK3 variants are also known to be associated with an increased risk for regression, as well as for psychiatric disorders, including bipolar disorder and catatonia. This study aimed to further describe these phenomena in PMS and to explore any relationship between psychiatric illness and regression after early childhood. METHODS: Thirty-eight people with PMS were recruited to this study through the Phelan-McDermid Syndrome Foundation based on caregiver report of distinct development of psychiatric symptoms. Caregivers completed a clinician-administered semi-structured interview focused on eliciting psychiatric symptomatology. Data from the PMS International Registry were used to confirm genetic diagnoses of participants and to provide a larger sample for comparison. RESULTS: The mean age of the 38 participants was 24.7 years (range = 13 to 50; SD = 10.06). Females (31 of 38 cases; 82%) and sequence variants (15 of 38 cases; 39%) were over-represented in this sample, compared to base rates in the PMS International Registry. Onset of psychiatric symptoms occurred at a mean age of 15.4 years (range = 7 to 32), with presentations marked by prominent disturbances of mood. Enduring substantial loss of functional skills after onset of psychiatric changes was seen in 25 cases (66%). Symptomst indicative of catatonia occurred in 20 cases (53%). Triggers included infections, changes in hormonal status, and stressful life events. CONCLUSIONS: This study confirms that individuals with PMS are at risk of developing severe neuropsychiatric illness in adolescence or early adulthood, including bipolar disorder, catatonia, and lasting regression of skills. These findings should increase the awareness of these phenotypes and lead to earlier diagnosis and the implementation of appropriate interventions. Our findings also highlight the importance of genetic testing in the work-up of individuals with intellectual disability and acute psychiatric illness or regression. Future research is needed to clarify the prevalence and nature of psychiatric disorders and regression among larger unbiased samples of individuals with PMS. En ligne : https://dx.doi.org/10.1186/s11689-020-9309-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Psychiatric illness and regression in individuals with Phelan-McDermid syndrome [texte imprimé] / Teresa M. KOHLENBERG, Auteur ; M. Pilar TRELLES, Auteur ; Brittany MCLARNEY, Auteur ; Catalina BETANCUR, Auteur ; Audrey THURM, Auteur ; Alexander KOLEVZON, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Adult  Bipolar Disorder/epidemiology  Catatonia/epidemiology  Chromosome Deletion  Chromosome Disorders/psychology  Chromosomes, Human, Pair 22  Female  Humans  Male  Mental Disorders/epidemiology  Middle Aged  Phenotype  Regression, Psychology  Young Adult  Bipolar disorder  Catatonia  Depression  Mania  Phelan-McDermid syndrome  Psychosis  Regression  SHANK3  Takeda, 5 AM Ventures, sema4, and LabCorp. The other authors declare that they  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic condition characterized by intellectual disability, speech and language deficits, hypotonia, autism spectrum disorder, and epilepsy. PMS is caused by 22q13.33 deletions or mutations affecting SHANK3, which codes for a critical scaffolding protein in excitatory synapses. SHANK3 variants are also known to be associated with an increased risk for regression, as well as for psychiatric disorders, including bipolar disorder and catatonia. This study aimed to further describe these phenomena in PMS and to explore any relationship between psychiatric illness and regression after early childhood. METHODS: Thirty-eight people with PMS were recruited to this study through the Phelan-McDermid Syndrome Foundation based on caregiver report of distinct development of psychiatric symptoms. Caregivers completed a clinician-administered semi-structured interview focused on eliciting psychiatric symptomatology. Data from the PMS International Registry were used to confirm genetic diagnoses of participants and to provide a larger sample for comparison. RESULTS: The mean age of the 38 participants was 24.7 years (range = 13 to 50; SD = 10.06). Females (31 of 38 cases; 82%) and sequence variants (15 of 38 cases; 39%) were over-represented in this sample, compared to base rates in the PMS International Registry. Onset of psychiatric symptoms occurred at a mean age of 15.4 years (range = 7 to 32), with presentations marked by prominent disturbances of mood. Enduring substantial loss of functional skills after onset of psychiatric changes was seen in 25 cases (66%). Symptomst indicative of catatonia occurred in 20 cases (53%). Triggers included infections, changes in hormonal status, and stressful life events. CONCLUSIONS: This study confirms that individuals with PMS are at risk of developing severe neuropsychiatric illness in adolescence or early adulthood, including bipolar disorder, catatonia, and lasting regression of skills. These findings should increase the awareness of these phenotypes and lead to earlier diagnosis and the implementation of appropriate interventions. Our findings also highlight the importance of genetic testing in the work-up of individuals with intellectual disability and acute psychiatric illness or regression. Future research is needed to clarify the prevalence and nature of psychiatric disorders and regression among larger unbiased samples of individuals with PMS. En ligne : https://dx.doi.org/10.1186/s11689-020-9309-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

BOLD differences normally attributed to inhibitory control predict symptoms, not task-directed inhibitory control in ADHD / Andre CHEVRIER in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : BOLD differences normally attributed to inhibitory control predict symptoms, not task-directed inhibitory control in ADHD Type de document : texte imprimé Auteurs : Andre CHEVRIER, Auteur ; Russell J. SCHACHAR, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Attention Deficit Disorder with Hyperactivity/physiopathology  Brain/physiopathology  Child  Executive Function/physiology  Female  Humans  Inhibition, Psychological  Magnetic Resonance Imaging  Male  Neuropsychological Tests  Prefrontal Cortex/physiopathology  Reaction Time/physiology  Attention deficit hyperactivity disorder  Functional magnetic resonance imaging  Hyperactivity  Inattention  Inhibition  Stop signal reaction time  Stop signal task Index. décimale : PER Périodiques Résumé : BACKGROUND: Altered brain activity that has been observed in attention deficit hyperactivity disorder (ADHD) while performing cognitive control tasks like the stop signal task (SST) has generally been interpreted as reflecting either weak (under-active) or compensatory (over-active) versions of the same functions as in healthy controls. If so, then regional activities that correlate with the efficiency of inhibitory control (i.e. stop signal reaction time, SSRT) in healthy subjects should also correlate with SSRT in ADHD. Here we test the alternate hypothesis that BOLD (blood-oxygen-level-dependent) differences might instead reflect the redirection of neural processing resources normally used for task-directed inhibitory control, towards actively managing symptomatic behaviour. If so, then activities that correlate with SSRT in TD should instead correlate with inattentive and hyperactive symptoms in ADHD. METHODS: We used fMRI (functional magnetic resonance imaging) in 14 typically developing (TD) and 14 ADHD adolescents performing the SST, and in a replication sample of 14 healthy adults. First, we identified significant group BOLD differences during all phases of activity in the SST (i.e. warning, response, reactive inhibition, error detection and post-error slowing). Next, we correlated these phases of activity with SSRT in TD and with SSRT, inattentive and hyperactive symptom scores in ADHD. We then identified whole brain significant correlations in regions of significant group difference in activity. RESULTS: Only three regions of significant group difference were correlated with SSRT in TD and replication groups (left and right inferior frontal gyri (IFG) during error detection and hypothalamus during post-error slowing). Consistent with regions of altered activity managing symptomatic behaviour instead of task-directed behaviour, left IFG correlated with greater inattentive score, right IFG correlated with lower hyperactive score and hypothalamus correlated with greater inattentive score and oppositely correlated with SSRT compared to TD. CONCLUSIONS: Stimuli that elicit task-directed integration of neural processing in healthy subjects instead appear to be directing integrated function towards managing symptomatic behaviour in ADHD. The ability of the current approach to determine whether altered neural activities reflect comparable functions in ADHD and control groups has broad implications for the development and monitoring of therapeutic interventions. En ligne : https://dx.doi.org/10.1186/s11689-020-09311-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] BOLD differences normally attributed to inhibitory control predict symptoms, not task-directed inhibitory control in ADHD [texte imprimé] / Andre CHEVRIER, Auteur ; Russell J. SCHACHAR, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Attention Deficit Disorder with Hyperactivity/physiopathology  Brain/physiopathology  Child  Executive Function/physiology  Female  Humans  Inhibition, Psychological  Magnetic Resonance Imaging  Male  Neuropsychological Tests  Prefrontal Cortex/physiopathology  Reaction Time/physiology  Attention deficit hyperactivity disorder  Functional magnetic resonance imaging  Hyperactivity  Inattention  Inhibition  Stop signal reaction time  Stop signal task Index. décimale : PER Périodiques Résumé : BACKGROUND: Altered brain activity that has been observed in attention deficit hyperactivity disorder (ADHD) while performing cognitive control tasks like the stop signal task (SST) has generally been interpreted as reflecting either weak (under-active) or compensatory (over-active) versions of the same functions as in healthy controls. If so, then regional activities that correlate with the efficiency of inhibitory control (i.e. stop signal reaction time, SSRT) in healthy subjects should also correlate with SSRT in ADHD. Here we test the alternate hypothesis that BOLD (blood-oxygen-level-dependent) differences might instead reflect the redirection of neural processing resources normally used for task-directed inhibitory control, towards actively managing symptomatic behaviour. If so, then activities that correlate with SSRT in TD should instead correlate with inattentive and hyperactive symptoms in ADHD. METHODS: We used fMRI (functional magnetic resonance imaging) in 14 typically developing (TD) and 14 ADHD adolescents performing the SST, and in a replication sample of 14 healthy adults. First, we identified significant group BOLD differences during all phases of activity in the SST (i.e. warning, response, reactive inhibition, error detection and post-error slowing). Next, we correlated these phases of activity with SSRT in TD and with SSRT, inattentive and hyperactive symptom scores in ADHD. We then identified whole brain significant correlations in regions of significant group difference in activity. RESULTS: Only three regions of significant group difference were correlated with SSRT in TD and replication groups (left and right inferior frontal gyri (IFG) during error detection and hypothalamus during post-error slowing). Consistent with regions of altered activity managing symptomatic behaviour instead of task-directed behaviour, left IFG correlated with greater inattentive score, right IFG correlated with lower hyperactive score and hypothalamus correlated with greater inattentive score and oppositely correlated with SSRT compared to TD. CONCLUSIONS: Stimuli that elicit task-directed integration of neural processing in healthy subjects instead appear to be directing integrated function towards managing symptomatic behaviour in ADHD. The ability of the current approach to determine whether altered neural activities reflect comparable functions in ADHD and control groups has broad implications for the development and monitoring of therapeutic interventions. En ligne : https://dx.doi.org/10.1186/s11689-020-09311-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder / Jeffrey R. WOZNIAK in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder Type de document : texte imprimé Auteurs : Jeffrey R. WOZNIAK, Auteur ; Birgit A. FINK, Auteur ; Anita J. FUGLESTAD, Auteur ; Judith K. ECKERLE, Auteur ; Christopher J. BOYS, Auteur ; Kristin E. SANDNESS, Auteur ; Joshua P. RADKE, Auteur ; Neely C. MILLER, Auteur ; Christopher LINDGREN, Auteur ; Ann M. BREARLEY, Auteur ; Steven H. ZEISEL, Auteur ; Michael K. GEORGIEFF, Auteur Langues : Anglais (eng) Mots-clés : Child, Preschool  Choline/therapeutic use  Cognition/drug effects  Double-Blind Method  Female  Fetal Alcohol Spectrum Disorders/drug therapy  Follow-Up Studies  Humans  Intelligence/drug effects  Male  Memory, Short-Term/drug effects  Nootropic Agents/therapeutic use  Pregnancy  Prenatal Exposure Delayed Effects/drug therapy  Choline  Cognition  Fetal alcohol spectrum disorders  Longitudinal studies  Randomized controlled trials Index. décimale : PER Périodiques Résumé : BACKGROUND: Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial. METHODS: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2-5-year-olds with FASD. Participants include 31 children (16 placebo; 15 choline) seen 4 years after trial completion. The mean age at follow-up was 8.6 years. Diagnoses were 12.9% fetal alcohol syndrome (FAS), 41.9% partial FAS, and 45.1% alcohol-related neurodevelopmental disorder. The follow-up included measures of intelligence, memory, executive functioning, and behavior. RESULTS: Children who received choline had higher non-verbal intelligence, higher visual-spatial skill, higher working memory ability, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder than the placebo group. No differences were seen for verbal intelligence, visual memory, or other executive functions. CONCLUSIONS: These data support choline as a potential neurodevelopmental intervention for FASD and highlight the need for long-term follow-up to capture treatment effects on neurodevelopmental trajectories. TRIAL REGISTRATION: ClinicalTrials.Gov #NCT01149538; Registered: June 23, 2010; first enrollment July 2, 2010. En ligne : https://dx.doi.org/10.1186/s11689-020-09312-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder [texte imprimé] / Jeffrey R. WOZNIAK, Auteur ; Birgit A. FINK, Auteur ; Anita J. FUGLESTAD, Auteur ; Judith K. ECKERLE, Auteur ; Christopher J. BOYS, Auteur ; Kristin E. SANDNESS, Auteur ; Joshua P. RADKE, Auteur ; Neely C. MILLER, Auteur ; Christopher LINDGREN, Auteur ; Ann M. BREARLEY, Auteur ; Steven H. ZEISEL, Auteur ; Michael K. GEORGIEFF, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Child, Preschool  Choline/therapeutic use  Cognition/drug effects  Double-Blind Method  Female  Fetal Alcohol Spectrum Disorders/drug therapy  Follow-Up Studies  Humans  Intelligence/drug effects  Male  Memory, Short-Term/drug effects  Nootropic Agents/therapeutic use  Pregnancy  Prenatal Exposure Delayed Effects/drug therapy  Choline  Cognition  Fetal alcohol spectrum disorders  Longitudinal studies  Randomized controlled trials Index. décimale : PER Périodiques Résumé : BACKGROUND: Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial. METHODS: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2-5-year-olds with FASD. Participants include 31 children (16 placebo; 15 choline) seen 4 years after trial completion. The mean age at follow-up was 8.6 years. Diagnoses were 12.9% fetal alcohol syndrome (FAS), 41.9% partial FAS, and 45.1% alcohol-related neurodevelopmental disorder. The follow-up included measures of intelligence, memory, executive functioning, and behavior. RESULTS: Children who received choline had higher non-verbal intelligence, higher visual-spatial skill, higher working memory ability, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder than the placebo group. No differences were seen for verbal intelligence, visual memory, or other executive functions. CONCLUSIONS: These data support choline as a potential neurodevelopmental intervention for FASD and highlight the need for long-term follow-up to capture treatment effects on neurodevelopmental trajectories. TRIAL REGISTRATION: ClinicalTrials.Gov #NCT01149538; Registered: June 23, 2010; first enrollment July 2, 2010. En ligne : https://dx.doi.org/10.1186/s11689-020-09312-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity / Leonard ABBEDUTO in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity Type de document : texte imprimé Auteurs : Leonard ABBEDUTO, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Audra STERLING, Auteur ; Stephanie SHERMAN, Auteur ; Jamie O. EDGIN, Auteur ; Andrea MCDUFFIE, Auteur ; Anne HOFFMANN, Auteur ; Debra HAMILTON, Auteur ; Michael NELSON, Auteur ; Jeannie ASCHKENASY, Auteur ; Angela John THURMAN, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Autistic Disorder/diagnosis  Child  Feasibility Studies  Female  Fragile X Syndrome/therapy  Humans  Language Tests/statistics & numerical data  Male  Outcome Assessment, Health Care  Psychometrics  Reproducibility of Results  Young Adult  Clinical trials  Expressive language  Fragile X syndrome  Outcome measures  treatment  Pharmaceuticals Ltd., Fulcrum Therapeutics, and Lumind to consult on and  implement outcome measures in clinical trials for FXS and Down syndrome. EBK has  received funding from Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren,  Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin, Lumos, Ovid, AMO,  Yamo, Ionis, GeneTx, Acadia, Neurogene, Ultragenyx, and  Vtesse/Sucampo/Mallinkcrodt Pharmaceuticals to consult on trial design or  development strategies and/or conduct clinical trials in FXS or other genetic  Neurodevelopmental or neurodegenerative disorders, and from Asuragen Inc. to  develop testing standards for FMR1 testing. 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: The evaluation of treatment efficacy for individuals with fragile X syndrome (FXS) or intellectual disability (ID) more generally has been hampered by the lack of adequate outcome measures. We evaluated expressive language sampling (ELS) as a procedure for generating outcome measures for treatment research in FXS. We addressed: (a) feasibility, (b) practice effects over two administrations, (c) test-retest reliability over the repeated administrations, and (d) construct validity. We addressed these issues for the full sample as well as for subgroups defined by age, IQ, and ASD status. METHODS: Participants were 106 individuals with FXS between ages 6 and 23 years who had IQs within the range of intellectual disability (IQ < 70). ELS procedures for collecting samples in conversation and narration were followed and analyzed separately. Five measures were derived from transcripts segmented into C-units (i.e., an independent clause and its modifiers): number of C-units per minute (talkativeness), number of different word roots (vocabulary), C-unit length in morphemes (syntax), percentage of C-units containing dysfluency (utterance planning), and percentage of C-units that were fully or partly unintelligible (articulatory quality). ELS procedures were administered twice at 4-week intervals for each participant. Standardized tests and informant reports were administered and provided measures for evaluating construct validity of ELS measures. RESULTS: We found low rates of noncompliance, suggesting the task can be completed meaningfully by most individuals with FXS, although noncompliance was higher for younger, lower IQ, and more autistic participants. Minimal practice effects and strong test-retest reliability over the 4-week interval were observed for the full sample and across the range of ages, IQs, and autism symptom severity. Evidence of convergent construct validity was observed for the measures of vocabulary, syntax, and unintelligibility for the full sample and across the range of IQ and autism symptom severity, but not for participants under age 12. Conversation and narration yielded largely similar results in all analyses. CONCLUSIONS: The findings suggest that the ELS procedures are feasible and yield measures with adequate psychometric properties for a majority of 6 to 23 years with FXS who have ID. The procedures work equally well regardless of level of ID or degree of ASD severity. The procedures, however, are more challenging and have somewhat less adequate psychometric properties for individuals with FXS under age 12. En ligne : https://dx.doi.org/10.1186/s11689-020-09313-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity [texte imprimé] / Leonard ABBEDUTO, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Audra STERLING, Auteur ; Stephanie SHERMAN, Auteur ; Jamie O. EDGIN, Auteur ; Andrea MCDUFFIE, Auteur ; Anne HOFFMANN, Auteur ; Debra HAMILTON, Auteur ; Michael NELSON, Auteur ; Jeannie ASCHKENASY, Auteur ; Angela John THURMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Autistic Disorder/diagnosis  Child  Feasibility Studies  Female  Fragile X Syndrome/therapy  Humans  Language Tests/statistics & numerical data  Male  Outcome Assessment, Health Care  Psychometrics  Reproducibility of Results  Young Adult  Clinical trials  Expressive language  Fragile X syndrome  Outcome measures  treatment  Pharmaceuticals Ltd., Fulcrum Therapeutics, and Lumind to consult on and  implement outcome measures in clinical trials for FXS and Down syndrome. EBK has  received funding from Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren,  Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin, Lumos, Ovid, AMO,  Yamo, Ionis, GeneTx, Acadia, Neurogene, Ultragenyx, and  Vtesse/Sucampo/Mallinkcrodt Pharmaceuticals to consult on trial design or  development strategies and/or conduct clinical trials in FXS or other genetic  Neurodevelopmental or neurodegenerative disorders, and from Asuragen Inc. to  develop testing standards for FMR1 testing. 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: The evaluation of treatment efficacy for individuals with fragile X syndrome (FXS) or intellectual disability (ID) more generally has been hampered by the lack of adequate outcome measures. We evaluated expressive language sampling (ELS) as a procedure for generating outcome measures for treatment research in FXS. We addressed: (a) feasibility, (b) practice effects over two administrations, (c) test-retest reliability over the repeated administrations, and (d) construct validity. We addressed these issues for the full sample as well as for subgroups defined by age, IQ, and ASD status. METHODS: Participants were 106 individuals with FXS between ages 6 and 23 years who had IQs within the range of intellectual disability (IQ < 70). ELS procedures for collecting samples in conversation and narration were followed and analyzed separately. Five measures were derived from transcripts segmented into C-units (i.e., an independent clause and its modifiers): number of C-units per minute (talkativeness), number of different word roots (vocabulary), C-unit length in morphemes (syntax), percentage of C-units containing dysfluency (utterance planning), and percentage of C-units that were fully or partly unintelligible (articulatory quality). ELS procedures were administered twice at 4-week intervals for each participant. Standardized tests and informant reports were administered and provided measures for evaluating construct validity of ELS measures. RESULTS: We found low rates of noncompliance, suggesting the task can be completed meaningfully by most individuals with FXS, although noncompliance was higher for younger, lower IQ, and more autistic participants. Minimal practice effects and strong test-retest reliability over the 4-week interval were observed for the full sample and across the range of ages, IQs, and autism symptom severity. Evidence of convergent construct validity was observed for the measures of vocabulary, syntax, and unintelligibility for the full sample and across the range of IQ and autism symptom severity, but not for participants under age 12. Conversation and narration yielded largely similar results in all analyses. CONCLUSIONS: The findings suggest that the ELS procedures are feasible and yield measures with adequate psychometric properties for a majority of 6 to 23 years with FXS who have ID. The procedures work equally well regardless of level of ID or degree of ASD severity. The procedures, however, are more challenging and have somewhat less adequate psychometric properties for individuals with FXS under age 12. En ligne : https://dx.doi.org/10.1186/s11689-020-09313-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Correction to: Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity / Leonard ABBEDUTO in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Correction to: Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity Type de document : texte imprimé Auteurs : Leonard ABBEDUTO, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Audra STERLING, Auteur ; Stephanie SHERMAN, Auteur ; Jamie O. EDGIN, Auteur ; Andrea MCDUFFIE, Auteur ; Anne HOFFMANN, Auteur ; Debra HAMILTON, Auteur ; Michael NELSON, Auteur ; Jeannie ASCHKENASY, Auteur ; Angela John THURMAN, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : In the original publication of this article [1], the author name Leonard Abbeduto was misspelled as Leonardkk Abbeduto. The original article has been corrected. En ligne : https://dx.doi.org/10.1186/s11689-020-09314-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Correction to: Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity [texte imprimé] / Leonard ABBEDUTO, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Audra STERLING, Auteur ; Stephanie SHERMAN, Auteur ; Jamie O. EDGIN, Auteur ; Andrea MCDUFFIE, Auteur ; Anne HOFFMANN, Auteur ; Debra HAMILTON, Auteur ; Michael NELSON, Auteur ; Jeannie ASCHKENASY, Auteur ; Angela John THURMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Index. décimale : PER Périodiques Résumé : In the original publication of this article [1], the author name Leonard Abbeduto was misspelled as Leonardkk Abbeduto. The original article has been corrected. En ligne : https://dx.doi.org/10.1186/s11689-020-09314-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome / Angela John THURMAN in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome Type de document : texte imprimé Auteurs : Angela John THURMAN, Auteur ; Laura A. POTTER, Auteur ; Kyoungmi KIM, Auteur ; Flora TASSONE, Auteur ; Amy BANASIK, Auteur ; Sarah Nelson POTTER, Auteur ; Lauren BULLARD, Auteur ; Vivian NGUYEN, Auteur ; Andrea MCDUFFIE, Auteur ; Randi HAGERMAN, Auteur ; Leonard ABBEDUTO, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  California  Child  Communication  Double-Blind Method  Female  Fragile X Syndrome/therapy  Humans  Language  Language Therapy/methods  Lovastatin/therapeutic use  Male  Mothers/education  Outcome Assessment, Health Care  Telecommunications  Distance teleconferencing  Expressive language sampling  Fragile X syndrome  Lovastatin  Narrative storytelling  Pili  Parent-implemented language intervention  outcome measures from Fulcrum Therapeutics and the Azrieli Foundation. FT has  received funding from the Azrieli Foundation, Zynerba, and Asuragen, Inc., for  studies in FXS. RH has received funding from Zynerba, Ovid, and the Azrieli  Foundation for treatment studies in children and adults with FXS. She has also  consulted with Zynerba and Fulcrum regarding treatment studies in FXS. LA has  received funding for the development and implementation of treatment outcome  measures from the F. Hoffmann-La Roche Ltd., Roche TCRC, Inc., Neuren  Pharmaceuticals Ltd., Fulcrum Therapeutics, Azrieli Foundation, and LuMind IDSC  Foundation. Index. décimale : PER Périodiques Résumé : BACKGROUND: The purpose of this study was to conduct a 20-week controlled trial of lovastatin (10 to 40 mg/day) in youth with fragile X syndrome (FXS) ages 10 to 17 years, combined with an open-label treatment of a parent-implemented language intervention (PILI), delivered via distance video teleconferencing to both treatment groups, lovastatin and placebo. METHOD: A randomized, double-blind trial was conducted at one site in the Sacramento, California, metropolitan area. Fourteen participants were assigned to the lovastatin group; two participants terminated early from the study. Sixteen participants were assigned to the placebo group. Lovastatin or placebo was administered orally in a capsule form, starting at 10 mg and increasing weekly or as tolerated by 10 mg increments, up to a maximum dose of 40 mg daily. A PILI was delivered to both groups for 12 weeks, with 4 activities per week, through video teleconferencing by an American Speech-Language Association-certified Speech-Language Pathologist, in collaboration with a Board-Certified Behavior Analyst. Parents were taught to use a set of language facilitation strategies while interacting with their children during a shared storytelling activity. The main outcome measures included absolute change from baseline to final visit in the means for youth total number of story-related utterances, youth number of different word roots, and parent total number of story-related utterances. RESULTS: Significant increases in all primary outcome measures were observed in both treatment groups. Significant improvements were also observed in parent reports of the severity of spoken language and social impairments in both treatment groups. In all cases, the amount of change observed did not differ across the two treatment groups. Although gains in parental use of the PILI-targeted intervention strategies were observed in both treatment groups, parental use of the PILI strategies was correlated with youth gains in the placebo group and not in the lovastatin group. CONCLUSION: Participants in both groups demonstrated significant changes in the primary outcome measures. The magnitude of change observed across the two groups was comparable, providing additional support for the efficacy of the use of PILI in youth with FXS. TRIAL REGISTRATION: US National Institutes of Health (ClinicalTrials.gov), NCT02642653. Registered 12/30/2015. En ligne : https://dx.doi.org/10.1186/s11689-020-09315-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome [texte imprimé] / Angela John THURMAN, Auteur ; Laura A. POTTER, Auteur ; Kyoungmi KIM, Auteur ; Flora TASSONE, Auteur ; Amy BANASIK, Auteur ; Sarah Nelson POTTER, Auteur ; Lauren BULLARD, Auteur ; Vivian NGUYEN, Auteur ; Andrea MCDUFFIE, Auteur ; Randi HAGERMAN, Auteur ; Leonard ABBEDUTO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  California  Child  Communication  Double-Blind Method  Female  Fragile X Syndrome/therapy  Humans  Language  Language Therapy/methods  Lovastatin/therapeutic use  Male  Mothers/education  Outcome Assessment, Health Care  Telecommunications  Distance teleconferencing  Expressive language sampling  Fragile X syndrome  Lovastatin  Narrative storytelling  Pili  Parent-implemented language intervention  outcome measures from Fulcrum Therapeutics and the Azrieli Foundation. FT has  received funding from the Azrieli Foundation, Zynerba, and Asuragen, Inc., for  studies in FXS. RH has received funding from Zynerba, Ovid, and the Azrieli  Foundation for treatment studies in children and adults with FXS. She has also  consulted with Zynerba and Fulcrum regarding treatment studies in FXS. LA has  received funding for the development and implementation of treatment outcome  measures from the F. Hoffmann-La Roche Ltd., Roche TCRC, Inc., Neuren  Pharmaceuticals Ltd., Fulcrum Therapeutics, Azrieli Foundation, and LuMind IDSC  Foundation. Index. décimale : PER Périodiques Résumé : BACKGROUND: The purpose of this study was to conduct a 20-week controlled trial of lovastatin (10 to 40 mg/day) in youth with fragile X syndrome (FXS) ages 10 to 17 years, combined with an open-label treatment of a parent-implemented language intervention (PILI), delivered via distance video teleconferencing to both treatment groups, lovastatin and placebo. METHOD: A randomized, double-blind trial was conducted at one site in the Sacramento, California, metropolitan area. Fourteen participants were assigned to the lovastatin group; two participants terminated early from the study. Sixteen participants were assigned to the placebo group. Lovastatin or placebo was administered orally in a capsule form, starting at 10 mg and increasing weekly or as tolerated by 10 mg increments, up to a maximum dose of 40 mg daily. A PILI was delivered to both groups for 12 weeks, with 4 activities per week, through video teleconferencing by an American Speech-Language Association-certified Speech-Language Pathologist, in collaboration with a Board-Certified Behavior Analyst. Parents were taught to use a set of language facilitation strategies while interacting with their children during a shared storytelling activity. The main outcome measures included absolute change from baseline to final visit in the means for youth total number of story-related utterances, youth number of different word roots, and parent total number of story-related utterances. RESULTS: Significant increases in all primary outcome measures were observed in both treatment groups. Significant improvements were also observed in parent reports of the severity of spoken language and social impairments in both treatment groups. In all cases, the amount of change observed did not differ across the two treatment groups. Although gains in parental use of the PILI-targeted intervention strategies were observed in both treatment groups, parental use of the PILI strategies was correlated with youth gains in the placebo group and not in the lovastatin group. CONCLUSION: Participants in both groups demonstrated significant changes in the primary outcome measures. The magnitude of change observed across the two groups was comparable, providing additional support for the efficacy of the use of PILI in youth with FXS. TRIAL REGISTRATION: US National Institutes of Health (ClinicalTrials.gov), NCT02642653. Registered 12/30/2015. En ligne : https://dx.doi.org/10.1186/s11689-020-09315-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Developmental studies in fragile X syndrome / Khaleel A. RAZAK in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Developmental studies in fragile X syndrome Type de document : texte imprimé Auteurs : Khaleel A. RAZAK, Auteur ; Kelli C. DOMINICK, Auteur ; Craig A. ERICKSON, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Animals  Child  Child, Preschool  Disease Models, Animal  Female  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/genetics  Humans  Infant  Male  Mice  Mice, Knockout  Young Adult Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is the most common single gene cause of autism and intellectual disabilities. Humans with FXS exhibit increased anxiety, sensory hypersensitivity, seizures, repetitive behaviors, cognitive inflexibility, and social behavioral impairments. The main purpose of this review is to summarize developmental studies of FXS in humans and in the mouse model, the Fmr1 knockout mouse. The literature presents considerable evidence that a number of early developmental deficits can be identified and that these early deficits chart a course of altered developmental experience leading to symptoms well characterized in adolescents and adults. Nevertheless, a number of critical issues remain unclear or untested regarding the development of symptomology and underlying mechanisms. First, what is the role of FMRP, the protein product of Fmr1 gene, during different developmental ages? Does the absence of FMRP during early development lead to irreversible changes, or could reintroduction of FMRP or therapeutics aimed at FMRP-interacting proteins/pathways hold promise when provided in adults? These questions have implications for clinical trial designs in terms of optimal treatment windows, but few studies have systematically addressed these issues in preclinical and clinical work. Published studies also point to complex trajectories of symptom development, leading to the conclusion that single developmental time point studies are unlikely to disambiguate effects of genetic mutation from effects of altered developmental experience and compensatory plasticity. We conclude by suggesting a number of experiments needed to address these major gaps in the field. En ligne : https://dx.doi.org/10.1186/s11689-020-09310-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Developmental studies in fragile X syndrome [texte imprimé] / Khaleel A. RAZAK, Auteur ; Kelli C. DOMINICK, Auteur ; Craig A. ERICKSON, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Animals  Child  Child, Preschool  Disease Models, Animal  Female  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/genetics  Humans  Infant  Male  Mice  Mice, Knockout  Young Adult Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is the most common single gene cause of autism and intellectual disabilities. Humans with FXS exhibit increased anxiety, sensory hypersensitivity, seizures, repetitive behaviors, cognitive inflexibility, and social behavioral impairments. The main purpose of this review is to summarize developmental studies of FXS in humans and in the mouse model, the Fmr1 knockout mouse. The literature presents considerable evidence that a number of early developmental deficits can be identified and that these early deficits chart a course of altered developmental experience leading to symptoms well characterized in adolescents and adults. Nevertheless, a number of critical issues remain unclear or untested regarding the development of symptomology and underlying mechanisms. First, what is the role of FMRP, the protein product of Fmr1 gene, during different developmental ages? Does the absence of FMRP during early development lead to irreversible changes, or could reintroduction of FMRP or therapeutics aimed at FMRP-interacting proteins/pathways hold promise when provided in adults? These questions have implications for clinical trial designs in terms of optimal treatment windows, but few studies have systematically addressed these issues in preclinical and clinical work. Published studies also point to complex trajectories of symptom development, leading to the conclusion that single developmental time point studies are unlikely to disambiguate effects of genetic mutation from effects of altered developmental experience and compensatory plasticity. We conclude by suggesting a number of experiments needed to address these major gaps in the field. En ligne : https://dx.doi.org/10.1186/s11689-020-09310-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations / Hequn LIU in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations Type de document : texte imprimé Auteurs : Hequn LIU, Auteur ; Jesse BARNES, Auteur ; Erika PEDROSA, Auteur ; Nathaniel S. HERMAN, Auteur ; Franklin SALAS, Auteur ; Ping WANG, Auteur ; Deyou ZHENG, Auteur ; Herbert M. LACHMAN, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Cataract/genetics  Cells, Cultured  Child  Endosomes/metabolism  Extracellular Matrix Proteins/genetics  Eye Diseases/genetics  Gene Expression Profiling  Glaucoma/genetics  Humans  Induced Pluripotent Stem Cells/metabolism  Male  Mutation  Neural Stem Cells/metabolism  Oculocerebrorenal Syndrome/genetics/metabolism/physiopathology  Phosphoric Monoester Hydrolases/genetics/metabolism  Reelin Protein  Sequence Analysis, RNA  Young Adult  Cataracts  Dpp10  Dent disease  Efemp1  Glaucoma  Kv4.2  Lowe syndrome  Meis2  Macular degeneration  Ocrl  Spon1  Tmem132 Index. décimale : PER Périodiques Résumé : BACKGROUND: Lowe syndrome (LS) is caused by loss-of-function mutations in the X-linked gene OCRL, which codes for an inositol polyphosphate 5-phosphatase that plays a key role in endosome recycling, clathrin-coated pit formation, and actin polymerization. It is characterized by congenital cataracts, intellectual and developmental disability, and renal proximal tubular dysfunction. Patients are also at high risk for developing glaucoma and seizures. We recently developed induced pluripotent stem cell (iPSC) lines from three patients with LS who have hypomorphic variants affecting the 3' end of the gene, and their neurotypical brothers to serve as controls. METHODS: In this study, we used RNA sequencing (RNA-seq) to obtain transcriptome profiles in LS and control neural progenitor cells (NPCs). RESULTS: In a comparison of the patient and control NPCs (n = 3), we found 16 differentially expressed genes (DEGs) at the multiple test adjusted p value (padj) < 0.1, with nine at padj < 0.05. Using nominal p value < 0.05, 319 DEGs were detected. The relatively small number of DEGs could be due to the fact that OCRL is not a transcription factor per se, although it could have secondary effects on gene expression through several different mechanisms. Although the number of DEGs passing multiple test correction was small, those that were found are quite consistent with some of the known molecular effects of OCRL protein, and the clinical manifestations of LS. Furthermore, using gene set enrichment analysis (GSEA), we found that genes increased expression in the patient NPCs showed enrichments of several gene ontology (GO) terms (false discovery rate < 0.25): telencephalon development, pallium development, NPC proliferation, and cortex development, which are consistent with a condition characterized by intellectual disabilities and psychiatric manifestations. In addition, a significant enrichment among the nominal DEGs for genes implicated in autism spectrum disorder (ASD) was found (e.g., AFF2, DNER, DPP6, DPP10, RELN, CACNA1C), as well as several that are strong candidate genes for the development of eye problems found in LS, including glaucoma. The most notable example is EFEMP1, a well-known candidate gene for glaucoma and other eye pathologies. CONCLUSION: Overall, the RNA-seq findings present several candidate genes that could help explain the underlying basis for the neurodevelopmental and eye problems seen in boys with LS. En ligne : https://dx.doi.org/10.1186/s11689-020-09317-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations [texte imprimé] / Hequn LIU, Auteur ; Jesse BARNES, Auteur ; Erika PEDROSA, Auteur ; Nathaniel S. HERMAN, Auteur ; Franklin SALAS, Auteur ; Ping WANG, Auteur ; Deyou ZHENG, Auteur ; Herbert M. LACHMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Adult  Cataract/genetics  Cells, Cultured  Child  Endosomes/metabolism  Extracellular Matrix Proteins/genetics  Eye Diseases/genetics  Gene Expression Profiling  Glaucoma/genetics  Humans  Induced Pluripotent Stem Cells/metabolism  Male  Mutation  Neural Stem Cells/metabolism  Oculocerebrorenal Syndrome/genetics/metabolism/physiopathology  Phosphoric Monoester Hydrolases/genetics/metabolism  Reelin Protein  Sequence Analysis, RNA  Young Adult  Cataracts  Dpp10  Dent disease  Efemp1  Glaucoma  Kv4.2  Lowe syndrome  Meis2  Macular degeneration  Ocrl  Spon1  Tmem132 Index. décimale : PER Périodiques Résumé : BACKGROUND: Lowe syndrome (LS) is caused by loss-of-function mutations in the X-linked gene OCRL, which codes for an inositol polyphosphate 5-phosphatase that plays a key role in endosome recycling, clathrin-coated pit formation, and actin polymerization. It is characterized by congenital cataracts, intellectual and developmental disability, and renal proximal tubular dysfunction. Patients are also at high risk for developing glaucoma and seizures. We recently developed induced pluripotent stem cell (iPSC) lines from three patients with LS who have hypomorphic variants affecting the 3' end of the gene, and their neurotypical brothers to serve as controls. METHODS: In this study, we used RNA sequencing (RNA-seq) to obtain transcriptome profiles in LS and control neural progenitor cells (NPCs). RESULTS: In a comparison of the patient and control NPCs (n = 3), we found 16 differentially expressed genes (DEGs) at the multiple test adjusted p value (padj) < 0.1, with nine at padj < 0.05. Using nominal p value < 0.05, 319 DEGs were detected. The relatively small number of DEGs could be due to the fact that OCRL is not a transcription factor per se, although it could have secondary effects on gene expression through several different mechanisms. Although the number of DEGs passing multiple test correction was small, those that were found are quite consistent with some of the known molecular effects of OCRL protein, and the clinical manifestations of LS. Furthermore, using gene set enrichment analysis (GSEA), we found that genes increased expression in the patient NPCs showed enrichments of several gene ontology (GO) terms (false discovery rate < 0.25): telencephalon development, pallium development, NPC proliferation, and cortex development, which are consistent with a condition characterized by intellectual disabilities and psychiatric manifestations. In addition, a significant enrichment among the nominal DEGs for genes implicated in autism spectrum disorder (ASD) was found (e.g., AFF2, DNER, DPP6, DPP10, RELN, CACNA1C), as well as several that are strong candidate genes for the development of eye problems found in LS, including glaucoma. The most notable example is EFEMP1, a well-known candidate gene for glaucoma and other eye pathologies. CONCLUSION: Overall, the RNA-seq findings present several candidate genes that could help explain the underlying basis for the neurodevelopmental and eye problems seen in boys with LS. En ligne : https://dx.doi.org/10.1186/s11689-020-09317-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Hippocampal transcriptome analysis following maternal separation implicates altered RNA processing in a mouse model of fetal alcohol spectrum disorder / Bonnie L.J. ALBERRY in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Hippocampal transcriptome analysis following maternal separation implicates altered RNA processing in a mouse model of fetal alcohol spectrum disorder Type de document : texte imprimé Auteurs : Bonnie L.J. ALBERRY, Auteur ; Christina A. CASTELLANI, Auteur ; Shiva M. SINGH, Auteur Langues : Anglais (eng) Mots-clés : Alcohol Drinking/genetics  Animals  Animals, Newborn  Anxiety  Canada  Disease Models, Animal  Ethanol/administration & dosage/metabolism  Female  Fetal Alcohol Spectrum Disorders/genetics/metabolism  Gene Expression Profiling  Gene Expression Regulation  Hippocampus/metabolism  Maternal Deprivation  Mice  Pregnancy  Prenatal Exposure Delayed Effects/genetics/metabolism  RNA Processing, Post-Transcriptional  Transcriptome  Fetal alcohol spectrum disorder  Gene expression  Hippocampus  Maternal separation  Prenatal alcohol  Wgcna Index. décimale : PER Périodiques Résumé : BACKGROUND: Fetal alcohol spectrum disorders (FASD) are common, seen in 1-5% of the population in the USA and Canada. Children diagnosed with FASD are not likely to remain with their biological parents, facing early maternal separation and foster placements throughout childhood. METHODS: We model FASD in mice via prenatal alcohol exposure and further induce early life stress through maternal separation. We use RNA-seq followed by clustering of expression profiles through weighted gene co-expression network analysis (WGCNA) to analyze transcriptomic changes that result from the treatments. We use reverse transcription qPCR to validate these changes in the mouse hippocampus. RESULTS: We report an association between adult hippocampal gene expression and prenatal ethanol exposure followed by postnatal separation stress that is related to behavioral changes. Expression profile clustering using WGCNA identifies a set of transcripts, module 19, associated with anxiety-like behavior (r = 0.79, p = 0.002) as well as treatment group (r = 0.68, p = 0.015). Genes in this module are overrepresented by genes involved in transcriptional regulation and other pathways related to neurodevelopment. Interestingly, one member of this module, Polr2a, polymerase (RNA) II (DNA directed) polypeptide A, is downregulated by the combination of prenatal ethanol and postnatal stress in an RNA-Seq experiment and qPCR validation (q = 2e-12, p = 0.004, respectively). CONCLUSIONS: Together, transcriptional control in the hippocampus is implicated as a potential underlying mechanism leading to anxiety-like behavior via environmental insults. Further research is required to elucidate the mechanism involved and use this insight towards early diagnosis and amelioration strategies involving children born with FASD. En ligne : https://dx.doi.org/10.1186/s11689-020-09316-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Hippocampal transcriptome analysis following maternal separation implicates altered RNA processing in a mouse model of fetal alcohol spectrum disorder [texte imprimé] / Bonnie L.J. ALBERRY, Auteur ; Christina A. CASTELLANI, Auteur ; Shiva M. SINGH, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Alcohol Drinking/genetics  Animals  Animals, Newborn  Anxiety  Canada  Disease Models, Animal  Ethanol/administration & dosage/metabolism  Female  Fetal Alcohol Spectrum Disorders/genetics/metabolism  Gene Expression Profiling  Gene Expression Regulation  Hippocampus/metabolism  Maternal Deprivation  Mice  Pregnancy  Prenatal Exposure Delayed Effects/genetics/metabolism  RNA Processing, Post-Transcriptional  Transcriptome  Fetal alcohol spectrum disorder  Gene expression  Hippocampus  Maternal separation  Prenatal alcohol  Wgcna Index. décimale : PER Périodiques Résumé : BACKGROUND: Fetal alcohol spectrum disorders (FASD) are common, seen in 1-5% of the population in the USA and Canada. Children diagnosed with FASD are not likely to remain with their biological parents, facing early maternal separation and foster placements throughout childhood. METHODS: We model FASD in mice via prenatal alcohol exposure and further induce early life stress through maternal separation. We use RNA-seq followed by clustering of expression profiles through weighted gene co-expression network analysis (WGCNA) to analyze transcriptomic changes that result from the treatments. We use reverse transcription qPCR to validate these changes in the mouse hippocampus. RESULTS: We report an association between adult hippocampal gene expression and prenatal ethanol exposure followed by postnatal separation stress that is related to behavioral changes. Expression profile clustering using WGCNA identifies a set of transcripts, module 19, associated with anxiety-like behavior (r = 0.79, p = 0.002) as well as treatment group (r = 0.68, p = 0.015). Genes in this module are overrepresented by genes involved in transcriptional regulation and other pathways related to neurodevelopment. Interestingly, one member of this module, Polr2a, polymerase (RNA) II (DNA directed) polypeptide A, is downregulated by the combination of prenatal ethanol and postnatal stress in an RNA-Seq experiment and qPCR validation (q = 2e-12, p = 0.004, respectively). CONCLUSIONS: Together, transcriptional control in the hippocampus is implicated as a potential underlying mechanism leading to anxiety-like behavior via environmental insults. Further research is required to elucidate the mechanism involved and use this insight towards early diagnosis and amelioration strategies involving children born with FASD. En ligne : https://dx.doi.org/10.1186/s11689-020-09316-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Using generalizability theory to evaluate the comparative reliability of developmental measures in neurogenetic syndrome and low-risk populations / Lisa R. HAMRICK in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Using generalizability theory to evaluate the comparative reliability of developmental measures in neurogenetic syndrome and low-risk populations Type de document : texte imprimé Auteurs : Lisa R. HAMRICK, Auteur ; Alison M. HANEY, Auteur ; Bridgette L. KELLEHER, Auteur ; Sean P. LANE, Auteur Langues : Anglais (eng) Mots-clés : Analysis of Variance  Angelman Syndrome/psychology  Child, Preschool  Communication  Female  Generalization, Psychological  Humans  Infant  Longitudinal Studies  Male  Prader-Willi Syndrome/psychology  Psychometrics/standards  Reproducibility of Results  Risk  Williams Syndrome/psychology  Angelman  Communication and Symbolic Behavior Scales  Generalizability theory  Neurogenetic  Prader-Willi  Reliability  Social communication  Williams Index. décimale : PER Périodiques Résumé : BACKGROUND: The lack of available measures that can reliably characterize early developmental skills in children with neurogenetic syndromes (NGS) poses a significant challenge for research on early development in these populations. Although syndrome-specific measures may sometimes be necessary, a more cost- and time-efficient solution would be to identify existing measures that are appropriate for use in special populations or optimize existing measures to be used in these groups. Reliability is an important metric of psychometric rigor to consider when auditing and optimizing assessment tools for NGS. In this study, we use Generalizability Theory, an extension of classical test theory, as a novel approach for more comprehensively characterizing the reliability of existing measures and making decisions about their use in the field of NGS research. METHODS: We conducted generalizability analyses on a popular early social communication screener, the Communication and Symbolic Behavior Scales-Infant-Toddler Checklist (CSBS-ITC), collected on 172 children (41 Angelman syndrome, 30 Prader-Willi syndrome, 42 Williams syndrome, 59 low-risk controls). RESULTS: Overall, the CSBS-ITC demonstrated at least adequate reliability in the NGS groups included in this study, particularly for the Prader-Willi and Williams syndrome groups. However, the sources of systematic error variance in the CSBS-ITC varied greatly between the low-risk control and NGS groups. Moreover, as unassessed in previous research, the CSBS-ITC demonstrated substantial differences in variance sources among the NGS groups. Reliability of CSBS-ITC scores was highest when averaging across all measurement points for a given child and was generally similar or better in the NGS groups compared to the low-risk control group. CONCLUSIONS: Our findings suggest that the CSBS-ITC communicates different information about the reliability of stability versus change, in low-risk control and NGS samples, respectively, and that psychometric approaches like Generalizability Theory can provide more complete information about the reliability of existing measures and inform decisions about how measures are used in research on early development in NGS. En ligne : https://dx.doi.org/10.1186/s11689-020-09318-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Using generalizability theory to evaluate the comparative reliability of developmental measures in neurogenetic syndrome and low-risk populations [texte imprimé] / Lisa R. HAMRICK, Auteur ; Alison M. HANEY, Auteur ; Bridgette L. KELLEHER, Auteur ; Sean P. LANE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Analysis of Variance  Angelman Syndrome/psychology  Child, Preschool  Communication  Female  Generalization, Psychological  Humans  Infant  Longitudinal Studies  Male  Prader-Willi Syndrome/psychology  Psychometrics/standards  Reproducibility of Results  Risk  Williams Syndrome/psychology  Angelman  Communication and Symbolic Behavior Scales  Generalizability theory  Neurogenetic  Prader-Willi  Reliability  Social communication  Williams Index. décimale : PER Périodiques Résumé : BACKGROUND: The lack of available measures that can reliably characterize early developmental skills in children with neurogenetic syndromes (NGS) poses a significant challenge for research on early development in these populations. Although syndrome-specific measures may sometimes be necessary, a more cost- and time-efficient solution would be to identify existing measures that are appropriate for use in special populations or optimize existing measures to be used in these groups. Reliability is an important metric of psychometric rigor to consider when auditing and optimizing assessment tools for NGS. In this study, we use Generalizability Theory, an extension of classical test theory, as a novel approach for more comprehensively characterizing the reliability of existing measures and making decisions about their use in the field of NGS research. METHODS: We conducted generalizability analyses on a popular early social communication screener, the Communication and Symbolic Behavior Scales-Infant-Toddler Checklist (CSBS-ITC), collected on 172 children (41 Angelman syndrome, 30 Prader-Willi syndrome, 42 Williams syndrome, 59 low-risk controls). RESULTS: Overall, the CSBS-ITC demonstrated at least adequate reliability in the NGS groups included in this study, particularly for the Prader-Willi and Williams syndrome groups. However, the sources of systematic error variance in the CSBS-ITC varied greatly between the low-risk control and NGS groups. Moreover, as unassessed in previous research, the CSBS-ITC demonstrated substantial differences in variance sources among the NGS groups. Reliability of CSBS-ITC scores was highest when averaging across all measurement points for a given child and was generally similar or better in the NGS groups compared to the low-risk control group. CONCLUSIONS: Our findings suggest that the CSBS-ITC communicates different information about the reliability of stability versus change, in low-risk control and NGS samples, respectively, and that psychometric approaches like Generalizability Theory can provide more complete information about the reliability of existing measures and inform decisions about how measures are used in research on early development in NGS. En ligne : https://dx.doi.org/10.1186/s11689-020-09318-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice / Nicole MARTIN-KENNY in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice Type de document : texte imprimé Auteurs : Nicole MARTIN-KENNY, Auteur ; Nathalie G. BÉRUBÉ, Auteur Langues : Anglais (eng) Mots-clés : Animals  Autistic Disorder/genetics  Chromatin Assembly and Disassembly  Female  Male  X-Linked Intellectual Disability/genetics  Mice  Mice, Knockout  Mutation  Neurons/metabolism  Postpartum Period  X-linked Nuclear Protein  alpha-Thalassemia/genetics  Atrx  Autism spectrum disorder  Cre/loxP system  Genetically engineered mice  Repetitive behaviours  Social behaviours  Startle response Index. décimale : PER Périodiques Résumé : BACKGROUND: Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours. METHODS: Male and female mice with a postnatal conditional ablation of ATRX were generated using the Cre/lox system under the control of the αCaMKII gene promoter. These mice were tested in a battery of behavioural tests that assess autistic-like features. We utilized paradigms that measure social behaviour, repetitive, and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak's multiple comparison test or unpaired Student's t tests as indicated. RESULTS: The behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits. CONCLUSION: The postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice. En ligne : https://dx.doi.org/10.1186/s11689-020-09319-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice [texte imprimé] / Nicole MARTIN-KENNY, Auteur ; Nathalie G. BÉRUBÉ, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Autistic Disorder/genetics  Chromatin Assembly and Disassembly  Female  Male  X-Linked Intellectual Disability/genetics  Mice  Mice, Knockout  Mutation  Neurons/metabolism  Postpartum Period  X-linked Nuclear Protein  alpha-Thalassemia/genetics  Atrx  Autism spectrum disorder  Cre/loxP system  Genetically engineered mice  Repetitive behaviours  Social behaviours  Startle response Index. décimale : PER Périodiques Résumé : BACKGROUND: Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours. METHODS: Male and female mice with a postnatal conditional ablation of ATRX were generated using the Cre/lox system under the control of the αCaMKII gene promoter. These mice were tested in a battery of behavioural tests that assess autistic-like features. We utilized paradigms that measure social behaviour, repetitive, and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak's multiple comparison test or unpaired Student's t tests as indicated. RESULTS: The behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits. CONCLUSION: The postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice. En ligne : https://dx.doi.org/10.1186/s11689-020-09319-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Expressive language development in adolescents with Down syndrome and fragile X syndrome: change over time and the role of family-related factors / Laura DEL HOYO SORIANO in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Expressive language development in adolescents with Down syndrome and fragile X syndrome: change over time and the role of family-related factors Type de document : texte imprimé Auteurs : Laura DEL HOYO SORIANO, Auteur ; Angela John THURMAN, Auteur ; Danielle HARVEY, Auteur ; Sara T. KOVER, Auteur ; Leonard ABBEDUTO, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Child  Cognition  Down Syndrome/psychology  Family/psychology  Fragile X Syndrome/psychology  Humans  Intellectual Disability/psychology  Language Development  Language Development Disorders/complications  Language Tests  Longitudinal Studies  Male  Mother-Child Relations/psychology  Mothers/psychology  Vocabulary  Adolescence  Conversation  Down syndrome  Expressive language development  Family-related factors  Fragile X syndrome  Longitudinal  Narration Index. décimale : PER Périodiques Résumé : BACKGROUND: It is well known that individuals with Down syndrome (DS) or fragile X syndrome (FXS) demonstrate expressive language difficulties beginning early in childhood. It is less clear, however, whether expressive language skills change during the adolescent period in these individuals, and if any of these changes are syndrome specific. Studying this, as well as the role of maternal and family-related factors in expressive language development, may provide the foundation for efficacious interventions for adolescents with DS or FXS. METHODS: In this study, we examined expressive language trajectories, assessed through conversation and narration, in 57 adolescent males with intellectual disability (ID) (20 DS and 37 FXS) in relation to the diagnostic group (DS vs. FXS) and family-related factors (maternal IQ, maternal psychological distress, closeness in the mother-child relationship, family income, and maternal and paternal education) after adjusting for chronological age (CA) and nonverbal cognition. RESULTS: Changes over repeated annual assessments for males with DS or FXS were observed only during conversation, such as an increase in talkativeness, but a decrease in syntax complexity and lexical diversity. We found a diagnosis-related effect in the change over time in conversational talkativeness favoring those with FXS. Finally, a closer mother-child relationship predicted less decrease over time in lexical diversity during conversation, and participants of mothers who graduated college showed a greater increase in conversational talkativeness over time compared to those of mothers with a high school education. CONCLUSIONS: Our results suggest that, during the adolescent period for males with DS or FXS, there is an increase in the amount of talk produced in conversational contexts, but also a decrease in the quality of the language produced. In addition, our results indicate syndrome-specificity for aspects of expressive language development and reinforce the protective role of family-related factors. En ligne : https://dx.doi.org/10.1186/s11689-020-09320-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Expressive language development in adolescents with Down syndrome and fragile X syndrome: change over time and the role of family-related factors [texte imprimé] / Laura DEL HOYO SORIANO, Auteur ; Angela John THURMAN, Auteur ; Danielle HARVEY, Auteur ; Sara T. KOVER, Auteur ; Leonard ABBEDUTO, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Child  Cognition  Down Syndrome/psychology  Family/psychology  Fragile X Syndrome/psychology  Humans  Intellectual Disability/psychology  Language Development  Language Development Disorders/complications  Language Tests  Longitudinal Studies  Male  Mother-Child Relations/psychology  Mothers/psychology  Vocabulary  Adolescence  Conversation  Down syndrome  Expressive language development  Family-related factors  Fragile X syndrome  Longitudinal  Narration Index. décimale : PER Périodiques Résumé : BACKGROUND: It is well known that individuals with Down syndrome (DS) or fragile X syndrome (FXS) demonstrate expressive language difficulties beginning early in childhood. It is less clear, however, whether expressive language skills change during the adolescent period in these individuals, and if any of these changes are syndrome specific. Studying this, as well as the role of maternal and family-related factors in expressive language development, may provide the foundation for efficacious interventions for adolescents with DS or FXS. METHODS: In this study, we examined expressive language trajectories, assessed through conversation and narration, in 57 adolescent males with intellectual disability (ID) (20 DS and 37 FXS) in relation to the diagnostic group (DS vs. FXS) and family-related factors (maternal IQ, maternal psychological distress, closeness in the mother-child relationship, family income, and maternal and paternal education) after adjusting for chronological age (CA) and nonverbal cognition. RESULTS: Changes over repeated annual assessments for males with DS or FXS were observed only during conversation, such as an increase in talkativeness, but a decrease in syntax complexity and lexical diversity. We found a diagnosis-related effect in the change over time in conversational talkativeness favoring those with FXS. Finally, a closer mother-child relationship predicted less decrease over time in lexical diversity during conversation, and participants of mothers who graduated college showed a greater increase in conversational talkativeness over time compared to those of mothers with a high school education. CONCLUSIONS: Our results suggest that, during the adolescent period for males with DS or FXS, there is an increase in the amount of talk produced in conversational contexts, but also a decrease in the quality of the language produced. In addition, our results indicate syndrome-specificity for aspects of expressive language development and reinforce the protective role of family-related factors. En ligne : https://dx.doi.org/10.1186/s11689-020-09320-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Cortisol profiles and clinical severity in MECP2 duplication syndrome / Sarika U. PETERS in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Cortisol profiles and clinical severity in MECP2 duplication syndrome Type de document : texte imprimé Auteurs : Sarika U. PETERS, Auteur ; Cary FU, Auteur ; Jeffrey L. NEUL, Auteur ; Douglas A. GRANGER, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Biomarkers  Child  Child, Preschool  Chromosome Duplication  Female  Humans  Hydrocortisone/metabolism  Male  X-Linked Intellectual Disability/metabolism  Saliva  Severity of Illness Index  Young Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder primarily affecting males which is caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2 gene. Core clinical features of MDS include choreiform movements, progressive spasticity, recurrent respiratory infections, developmental delays in the first 6 months of life, hypotonia, vasomotor disturbances, constipation, drooling, and bruxism. Prior studies suggest that HPA axis activity may be altered in MDS and measures of HPA axis activity may offer insight into disease severity. METHODS: To ascertain whether cortisol profiles are a potential biomarker of clinical severity, diurnal profiles of cortisol and the cortisol awakening response were examined from saliva samples in 31 participants with MDS (ages 2-24 years), and 27 of these samples were usable. Documentation of a positive diagnostic test for MECP2 duplication was required for entry into the study. Samples were collected on each of two consecutive weekdays at four time points during the day: immediately after waking, 30 min after waking, between 3 and 4 PM, and in the evening before bedtime. Correlations with duplication size, clinical severity, sleep problems, and behavior were also examined. RESULTS: Results revealed that a majority of participants with MDS exhibit a declining cortisol awakening response (n = 17). A declining CAR was significantly associated with increased clinical severity scores (r = - .508; p = .03), larger duplication size, waking later, and an increased number of hospitalizations for infections. CONCLUSIONS: Future mechanistic studies will have to determine whether the declining CAR in MDS is attributable to problems with "flip-flop switching" of regional brain activation (involving the suprachiasmatic nucleus and the hippocampus, and the HPA axis) that is responsible for the switch from reduced to increased adrenal sensitivity. Taken together, results suggest the possibility that cortisol profiles could potentially be a biomarker of clinical severity and utilized for the purposes of patient stratification for future clinical trials in MDS. En ligne : https://dx.doi.org/10.1186/s11689-020-09322-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Cortisol profiles and clinical severity in MECP2 duplication syndrome [texte imprimé] / Sarika U. PETERS, Auteur ; Cary FU, Auteur ; Jeffrey L. NEUL, Auteur ; Douglas A. GRANGER, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Biomarkers  Child  Child, Preschool  Chromosome Duplication  Female  Humans  Hydrocortisone/metabolism  Male  X-Linked Intellectual Disability/metabolism  Saliva  Severity of Illness Index  Young Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder primarily affecting males which is caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2 gene. Core clinical features of MDS include choreiform movements, progressive spasticity, recurrent respiratory infections, developmental delays in the first 6 months of life, hypotonia, vasomotor disturbances, constipation, drooling, and bruxism. Prior studies suggest that HPA axis activity may be altered in MDS and measures of HPA axis activity may offer insight into disease severity. METHODS: To ascertain whether cortisol profiles are a potential biomarker of clinical severity, diurnal profiles of cortisol and the cortisol awakening response were examined from saliva samples in 31 participants with MDS (ages 2-24 years), and 27 of these samples were usable. Documentation of a positive diagnostic test for MECP2 duplication was required for entry into the study. Samples were collected on each of two consecutive weekdays at four time points during the day: immediately after waking, 30 min after waking, between 3 and 4 PM, and in the evening before bedtime. Correlations with duplication size, clinical severity, sleep problems, and behavior were also examined. RESULTS: Results revealed that a majority of participants with MDS exhibit a declining cortisol awakening response (n = 17). A declining CAR was significantly associated with increased clinical severity scores (r = - .508; p = .03), larger duplication size, waking later, and an increased number of hospitalizations for infections. CONCLUSIONS: Future mechanistic studies will have to determine whether the declining CAR in MDS is attributable to problems with "flip-flop switching" of regional brain activation (involving the suprachiasmatic nucleus and the hippocampus, and the HPA axis) that is responsible for the switch from reduced to increased adrenal sensitivity. Taken together, results suggest the possibility that cortisol profiles could potentially be a biomarker of clinical severity and utilized for the purposes of patient stratification for future clinical trials in MDS. En ligne : https://dx.doi.org/10.1186/s11689-020-09322-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Towards greater transparency in neurodevelopmental disorders research: use of a proposed workflow and propensity scores to facilitate selection of matched groups / Janet Y. BANG in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Towards greater transparency in neurodevelopmental disorders research: use of a proposed workflow and propensity scores to facilitate selection of matched groups Type de document : texte imprimé Auteurs : Janet Y. BANG, Auteur ; Megha SHARDA, Auteur ; Aparna S. NADIG, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/psychology  Bias  Child  Data Interpretation, Statistical  Female  Humans  Male  Neurodevelopmental Disorders  Patient Selection  Propensity Score  Reproducibility of Results  Research Design  Workflow  Covariate  Group comparison  Matching  Propensity score  Reproducibility  Transparency Index. décimale : PER Périodiques Résumé : BACKGROUND: Matching is one commonly utilized method in quasi-experimental designs involving individuals with neurodevelopmental disorders (NDD). This method ensures two or more groups (e.g., individuals with an NDD versus neurotypical individuals) are balanced on pre-existing covariates (e.g., IQ), enabling researchers to interpret performance on outcome measures as being attributed to group membership. While much attention has been paid to the statistical criteria of how to assess whether groups are well-matched, relatively little attention has been given to a crucial prior step: the selection of the individuals that are included in matched groups. The selection of individuals is often an undocumented process, which can invite unintentional, arbitrary, and biased decision-making. Limited documentation can result in findings that have limited reproducibility and replicability and thereby have poor potential for generalization to the broader population. Especially given the heterogeneity of individuals with NDDs, interpretation of research findings depends on minimizing bias at all stages of data collection and analysis. RESULTS: In the spirit of open science, this tutorial demonstrates how a workflow can be used to provide a transparent, reproducible, and replicable process to select individuals for matched groups. Our workflow includes the following key steps: Assess data, Select covariates, Conduct matching, and Diagnose matching. Our sample dataset is from children with autism spectrum disorder (ASD; n = 25) and typically developing children (n = 43) but can be adapted to comparisons of any two groups in quasi-experimental designs. We work through this method to conduct and document matching using propensity scores implemented with the R package MatchIt. Data and code are publicly available, and a template for this workflow is provided in the Additional file 1 as well as on a public repository. CONCLUSIONS: It is important to provide clear documentation regarding the selection process to establish matched groups. This documentation ensures better transparency in participant selection and data analysis in NDD research. We hope the adoption of such a workflow will ultimately advance our ability to replicate findings and help improve the lives of individuals with NDDs. En ligne : https://dx.doi.org/10.1186/s11689-020-09321-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Towards greater transparency in neurodevelopmental disorders research: use of a proposed workflow and propensity scores to facilitate selection of matched groups [texte imprimé] / Janet Y. BANG, Auteur ; Megha SHARDA, Auteur ; Aparna S. NADIG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Autism Spectrum Disorder/psychology  Bias  Child  Data Interpretation, Statistical  Female  Humans  Male  Neurodevelopmental Disorders  Patient Selection  Propensity Score  Reproducibility of Results  Research Design  Workflow  Covariate  Group comparison  Matching  Propensity score  Reproducibility  Transparency Index. décimale : PER Périodiques Résumé : BACKGROUND: Matching is one commonly utilized method in quasi-experimental designs involving individuals with neurodevelopmental disorders (NDD). This method ensures two or more groups (e.g., individuals with an NDD versus neurotypical individuals) are balanced on pre-existing covariates (e.g., IQ), enabling researchers to interpret performance on outcome measures as being attributed to group membership. While much attention has been paid to the statistical criteria of how to assess whether groups are well-matched, relatively little attention has been given to a crucial prior step: the selection of the individuals that are included in matched groups. The selection of individuals is often an undocumented process, which can invite unintentional, arbitrary, and biased decision-making. Limited documentation can result in findings that have limited reproducibility and replicability and thereby have poor potential for generalization to the broader population. Especially given the heterogeneity of individuals with NDDs, interpretation of research findings depends on minimizing bias at all stages of data collection and analysis. RESULTS: In the spirit of open science, this tutorial demonstrates how a workflow can be used to provide a transparent, reproducible, and replicable process to select individuals for matched groups. Our workflow includes the following key steps: Assess data, Select covariates, Conduct matching, and Diagnose matching. Our sample dataset is from children with autism spectrum disorder (ASD; n = 25) and typically developing children (n = 43) but can be adapted to comparisons of any two groups in quasi-experimental designs. We work through this method to conduct and document matching using propensity scores implemented with the R package MatchIt. Data and code are publicly available, and a template for this workflow is provided in the Additional file 1 as well as on a public repository. CONCLUSIONS: It is important to provide clear documentation regarding the selection process to establish matched groups. This documentation ensures better transparency in participant selection and data analysis in NDD research. We hope the adoption of such a workflow will ultimately advance our ability to replicate findings and help improve the lives of individuals with NDDs. En ligne : https://dx.doi.org/10.1186/s11689-020-09321-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader-Willi syndrome / Rui-Ni WU in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader-Willi syndrome Type de document : texte imprimé Auteurs : Rui-Ni WU, Auteur ; Wei-Chen HUNG, Auteur ; Ching-Tsuey CHEN, Auteur ; Li-Ping TSAI, Auteur ; Wen-Sung LAI, Auteur ; Ming-Yuan MIN, Auteur ; Shi-Bing WONG, Auteur Langues : Anglais (eng) Mots-clés : Adrenergic Neurons/metabolism  Animals  Animals, Newborn  Disease Models, Animal  Female  Gene Expression Regulation, Developmental  Locus Coeruleus/metabolism  Mice  Nerve Tissue Proteins  Nuclear Proteins  Prader-Willi Syndrome/metabolism  A-type potassium current  Hypercapnia  Hypotonia  Locus coeruleus  Necdin  Prader–Willi syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS. METHODS: Heterozygous necdin-deficient mice (B6.Cg-Ndn(tm1ky)) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/-p) animals, which were examined of LC-NE neuronal activity, developmental reflexes, and plethysmography. RESULTS: On slice electrophysiology, LC-NE neurons of Ndn(tm1ky) mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndn(tm1ky) mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia. CONCLUSIONS: LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis. En ligne : https://dx.doi.org/10.1186/s11689-020-09323-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader-Willi syndrome [texte imprimé] / Rui-Ni WU, Auteur ; Wei-Chen HUNG, Auteur ; Ching-Tsuey CHEN, Auteur ; Li-Ping TSAI, Auteur ; Wen-Sung LAI, Auteur ; Ming-Yuan MIN, Auteur ; Shi-Bing WONG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adrenergic Neurons/metabolism  Animals  Animals, Newborn  Disease Models, Animal  Female  Gene Expression Regulation, Developmental  Locus Coeruleus/metabolism  Mice  Nerve Tissue Proteins  Nuclear Proteins  Prader-Willi Syndrome/metabolism  A-type potassium current  Hypercapnia  Hypotonia  Locus coeruleus  Necdin  Prader–Willi syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS. METHODS: Heterozygous necdin-deficient mice (B6.Cg-Ndn(tm1ky)) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/-p) animals, which were examined of LC-NE neuronal activity, developmental reflexes, and plethysmography. RESULTS: On slice electrophysiology, LC-NE neurons of Ndn(tm1ky) mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndn(tm1ky) mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia. CONCLUSIONS: LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis. En ligne : https://dx.doi.org/10.1186/s11689-020-09323-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Properties of beta oscillations in Dup15q syndrome / Vidya SARAVANAPANDIAN in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Properties of beta oscillations in Dup15q syndrome Type de document : texte imprimé Auteurs : Vidya SARAVANAPANDIAN, Auteur ; Joel FROHLICH, Auteur ; Joerg F. HIPP, Auteur ; Carly HYDE, Auteur ; Aaron W. SCHEFFLER, Auteur ; Peyman GOLSHANI, Auteur ; Edwin H. COOK, Auteur ; Lawrence T. REITER, Auteur ; Damla SENTURK, Auteur ; Shafali S. JESTE, Auteur Langues : Anglais (eng) Mots-clés : Child  Child, Preschool  Electroencephalography  Epilepsy  Follow-Up Studies  Humans  Infant  Intellectual Disability  Reproducibility of Results  Autism  Biomarkers  Dup15q syndrome  Eeg  Gaba  Neurodevelopmental disorders  UBE3A  of F. Hoffmann-La Roche Ltd. (October 2016–July 2017). Joerg F. Hipp is an  employee of F. Hoffmann-La Roche Ltd. Carly Hyde: no competing interests Aaron W.  Scheffler: no competing interests Peyman Golshani: no competing interests Edwin  H. Cook: no competing interests Lawrence T. Reiter: no competing interests Damla  Senturk: no competing interests Shafali Jeste serves as a consultant for and has  received funding from F. Hoffmann-La Roche Ltd. and Yamo Pharmaceuticals Index. décimale : PER Périodiques Résumé : BACKGROUND: Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism, intellectual disability, hypotonia, and epilepsy. The 15q region harbors genes critical for brain development, particularly UBE3A and a cluster of gamma-aminobutyric acid type A receptor (GABA(A)R) genes. We recently described an electrophysiological biomarker of the syndrome, characterized by excessive beta oscillations (12-30 Hz), resembling electroencephalogram (EEG) changes induced by allosteric modulation of GABA(A)Rs. In this follow-up study, we tested a larger cohort of children with Dup15q syndrome to comprehensively examine properties of this EEG biomarker that would inform its use in future clinical trials, specifically, its (1) relation to basic clinical features, such as age, duplication type, and epilepsy; (2) relation to behavioral characteristics, such as cognition and adaptive function; (3) stability over time; and (4) reproducibility of the signal in clinical EEG recordings. METHODS: We computed EEG power and beta peak frequency (BPF) in a cohort of children with Dup15q syndrome (N = 41, age range 9-189 months). To relate EEG parameters to clinical (study 1) and behavioral features (study 2), we examined age, duplication type, epilepsy, cognition, and daily living skills (DLS) as predictors of beta power and BPF. To evaluate stability over time (study 3), we derived the intraclass correlation coefficients (ICC) from beta power and BPF computed from children with multiple EEG recordings (N = 10, age range 18-161 months). To evaluate reproducibility in a clinical setting (study 4), we derived ICCs from beta power computed from children (N = 8, age range 19-96 months), who had undergone both research EEG and clinical EEG. RESULTS: The most promising relationships between EEG and clinical traits were found using BPF. BPF was predicted both by epilepsy status (R(2) = 0.11, p = 0.038) and the DLS component of the Vineland Adaptive Behavior Scale (R(2) = 0.17, p = 0.01). Beta power and peak frequency showed high stability across repeated visits (beta power ICC = 0.93, BPF ICC = 0.92). A reproducibility analysis revealed that beta power estimates are comparable between research and clinical EEG (ICC = 0.94). CONCLUSIONS: In this era of precision health, with pharmacological and neuromodulatory therapies being developed and tested for specific genetic etiologies of neurodevelopmental disorders, quantification and examination of mechanistic biomarkers can greatly improve clinical trials. To this end, the robust beta oscillations evident in Dup15q syndrome are clinically reproducible and stable over time. With future preclinical and computational studies that will help disentangle the underlying mechanism, it is possible that this biomarker could serve as a robust measure of drug target engagement or a proximal outcome measure in future disease modifying intervention trials. En ligne : https://dx.doi.org/10.1186/s11689-020-09326-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Properties of beta oscillations in Dup15q syndrome [texte imprimé] / Vidya SARAVANAPANDIAN, Auteur ; Joel FROHLICH, Auteur ; Joerg F. HIPP, Auteur ; Carly HYDE, Auteur ; Aaron W. SCHEFFLER, Auteur ; Peyman GOLSHANI, Auteur ; Edwin H. COOK, Auteur ; Lawrence T. REITER, Auteur ; Damla SENTURK, Auteur ; Shafali S. JESTE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Child  Child, Preschool  Electroencephalography  Epilepsy  Follow-Up Studies  Humans  Infant  Intellectual Disability  Reproducibility of Results  Autism  Biomarkers  Dup15q syndrome  Eeg  Gaba  Neurodevelopmental disorders  UBE3A  of F. Hoffmann-La Roche Ltd. (October 2016–July 2017). Joerg F. Hipp is an  employee of F. Hoffmann-La Roche Ltd. Carly Hyde: no competing interests Aaron W.  Scheffler: no competing interests Peyman Golshani: no competing interests Edwin  H. Cook: no competing interests Lawrence T. Reiter: no competing interests Damla  Senturk: no competing interests Shafali Jeste serves as a consultant for and has  received funding from F. Hoffmann-La Roche Ltd. and Yamo Pharmaceuticals Index. décimale : PER Périodiques Résumé : BACKGROUND: Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism, intellectual disability, hypotonia, and epilepsy. The 15q region harbors genes critical for brain development, particularly UBE3A and a cluster of gamma-aminobutyric acid type A receptor (GABA(A)R) genes. We recently described an electrophysiological biomarker of the syndrome, characterized by excessive beta oscillations (12-30 Hz), resembling electroencephalogram (EEG) changes induced by allosteric modulation of GABA(A)Rs. In this follow-up study, we tested a larger cohort of children with Dup15q syndrome to comprehensively examine properties of this EEG biomarker that would inform its use in future clinical trials, specifically, its (1) relation to basic clinical features, such as age, duplication type, and epilepsy; (2) relation to behavioral characteristics, such as cognition and adaptive function; (3) stability over time; and (4) reproducibility of the signal in clinical EEG recordings. METHODS: We computed EEG power and beta peak frequency (BPF) in a cohort of children with Dup15q syndrome (N = 41, age range 9-189 months). To relate EEG parameters to clinical (study 1) and behavioral features (study 2), we examined age, duplication type, epilepsy, cognition, and daily living skills (DLS) as predictors of beta power and BPF. To evaluate stability over time (study 3), we derived the intraclass correlation coefficients (ICC) from beta power and BPF computed from children with multiple EEG recordings (N = 10, age range 18-161 months). To evaluate reproducibility in a clinical setting (study 4), we derived ICCs from beta power computed from children (N = 8, age range 19-96 months), who had undergone both research EEG and clinical EEG. RESULTS: The most promising relationships between EEG and clinical traits were found using BPF. BPF was predicted both by epilepsy status (R(2) = 0.11, p = 0.038) and the DLS component of the Vineland Adaptive Behavior Scale (R(2) = 0.17, p = 0.01). Beta power and peak frequency showed high stability across repeated visits (beta power ICC = 0.93, BPF ICC = 0.92). A reproducibility analysis revealed that beta power estimates are comparable between research and clinical EEG (ICC = 0.94). CONCLUSIONS: In this era of precision health, with pharmacological and neuromodulatory therapies being developed and tested for specific genetic etiologies of neurodevelopmental disorders, quantification and examination of mechanistic biomarkers can greatly improve clinical trials. To this end, the robust beta oscillations evident in Dup15q syndrome are clinically reproducible and stable over time. With future preclinical and computational studies that will help disentangle the underlying mechanism, it is possible that this biomarker could serve as a robust measure of drug target engagement or a proximal outcome measure in future disease modifying intervention trials. En ligne : https://dx.doi.org/10.1186/s11689-020-09326-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation / Sarah J. GOODMAN in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation Type de document : texte imprimé Auteurs : Sarah J. GOODMAN, Auteur ; Christie L. BURTON, Auteur ; Darci T. BUTCHER, Auteur ; Michelle T. SIU, Auteur ; Mathieu LEMIRE, Auteur ; Eric CHATER-DIEHL, Auteur ; Andrei L. TURINSKY, Auteur ; Michael BRUDNO, Auteur ; Noam SORENI, Auteur ; David ROSENBERG, Auteur ; Kate D. FITZGERALD, Auteur ; Gregory L. HANNA, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Paul D. ARNOLD, Auteur ; Jennifer CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; Rosanna WEKSBERG, Auteur Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  DNA Methylation/genetics  Genetic Variation/genetics  Humans  Obsessive-Compulsive Disorder/genetics  Adhd  Biomarker  DNA methylation  Epigenetics  Ocd Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). METHODS: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4-18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. RESULTS: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. CONCLUSIONS: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09324-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation [texte imprimé] / Sarah J. GOODMAN, Auteur ; Christie L. BURTON, Auteur ; Darci T. BUTCHER, Auteur ; Michelle T. SIU, Auteur ; Mathieu LEMIRE, Auteur ; Eric CHATER-DIEHL, Auteur ; Andrei L. TURINSKY, Auteur ; Michael BRUDNO, Auteur ; Noam SORENI, Auteur ; David ROSENBERG, Auteur ; Kate D. FITZGERALD, Auteur ; Gregory L. HANNA, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Paul D. ARNOLD, Auteur ; Jennifer CROSBIE, Auteur ; Russell SCHACHAR, Auteur ; Rosanna WEKSBERG, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics  DNA Methylation/genetics  Genetic Variation/genetics  Humans  Obsessive-Compulsive Disorder/genetics  Adhd  Biomarker  DNA methylation  Epigenetics  Ocd Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs). METHODS: We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4-18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders. RESULTS: Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample. CONCLUSIONS: Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09324-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project / Petrus J. DE VRIES in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project Type de document : texte imprimé Auteurs : Petrus J. DE VRIES, Auteur ; Elena BELOUSOVA, Auteur ; Mirjana P. BENEDIK, Auteur ; Tom CARTER, Auteur ; Vincent COTTIN, Auteur ; Paolo CURATOLO, Auteur ; Lisa D'AMATO, Auteur ; Guillaume BEURE D'AUGÈRES, Auteur ; José C. FERREIRA, Auteur ; Martha FEUCHT, Auteur ; Carla FLADROWSKI, Auteur ; Christoph HERTZBERG, Auteur ; Sergiusz JOZWIAK, Auteur ; John A. LAWSON, Auteur ; Alfons MACAYA, Auteur ; Ruben MARQUES, Auteur ; Rima NABBOUT, Auteur ; Finbar O'CALLAGHAN, Auteur ; Jiong QIN, Auteur ; Valentin SANDER, Auteur ; Matthias SAUTER, Auteur ; Seema SHAH, Auteur ; Yukitoshi TAKAHASHI, Auteur ; Renaud TOURAINE, Auteur ; Sotiris YOUROUKOS, Auteur ; Bernard ZONNENBERG, Auteur ; J Chris KINGSWOOD, Auteur ; Anna C. JANSEN, Auteur ; TOSCA CONSORTIUM AND TOSCA INVESTIGATORS, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/epidemiology/etiology  Checklist  Cognitive Dysfunction  Feasibility Studies  Female  Humans  Male  Tuberous Sclerosis/complications/epidemiology  Asd  Cluster analysis  Factor analysis  Natural TAND clusters  Neuropsychiatric  Registry  Tand  Tosca  Tuberous sclerosis complex  AM, SY, MPB, BZ, and ACJ received honoraria and travel support from Novartis. VC  received personal fees for consulting  lecture fees and travel from Actelion,  Bayer, Biogen Idec, Boehringer Ingelheim, Gilead, GSK, MSD, Novartis, Pfizer,  Roche, and Sanofi  grants from Actelion, Boehringer Ingelheim, GSK, Pfizer, and  Roche  and personal fees for developing educational material from Boehringer  Ingelheim and Roche. PJdV has been on the steering group of the EXIST-1, 2, and 3  studies sponsored by Novartis and co-PI on two investigator-initiated studies  part-funded by Novartis. RN received grant support, paid to her institution, from  Eisai and lecture fees from Nutricia, Eisai, Advicenne, and GW Pharma. YT  received personal fees from Novartis for lecture and for copyright of referential  figures from the journals and grant from the Japanese government for intractable  epilepsy research. SJ was partly financed by the EC Seventh Framework Programme  (FP7/2007-2013  EPISTOP, grant agreement no. 602391), the Polish Ministerial  funds for science (years 2013–2018) for the implementation of international  co-financed project, and the grant EPIMARKER of the Polish National Center for  Research and Development No. STRATEGMED3/306306/4/2016. JCK, PC, CH, JAL, and JQ  received research grants from Novartis. RM and SS are employees of Novartis. LD’A  was an employee of Novartis at the time of manuscript concept approval. VS  reported no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters. RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions. CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters. En ligne : https://dx.doi.org/10.1186/s11689-020-09327-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project [texte imprimé] / Petrus J. DE VRIES, Auteur ; Elena BELOUSOVA, Auteur ; Mirjana P. BENEDIK, Auteur ; Tom CARTER, Auteur ; Vincent COTTIN, Auteur ; Paolo CURATOLO, Auteur ; Lisa D'AMATO, Auteur ; Guillaume BEURE D'AUGÈRES, Auteur ; José C. FERREIRA, Auteur ; Martha FEUCHT, Auteur ; Carla FLADROWSKI, Auteur ; Christoph HERTZBERG, Auteur ; Sergiusz JOZWIAK, Auteur ; John A. LAWSON, Auteur ; Alfons MACAYA, Auteur ; Ruben MARQUES, Auteur ; Rima NABBOUT, Auteur ; Finbar O'CALLAGHAN, Auteur ; Jiong QIN, Auteur ; Valentin SANDER, Auteur ; Matthias SAUTER, Auteur ; Seema SHAH, Auteur ; Yukitoshi TAKAHASHI, Auteur ; Renaud TOURAINE, Auteur ; Sotiris YOUROUKOS, Auteur ; Bernard ZONNENBERG, Auteur ; J Chris KINGSWOOD, Auteur ; Anna C. JANSEN, Auteur ; TOSCA CONSORTIUM AND TOSCA INVESTIGATORS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Autism Spectrum Disorder/epidemiology/etiology  Checklist  Cognitive Dysfunction  Feasibility Studies  Female  Humans  Male  Tuberous Sclerosis/complications/epidemiology  Asd  Cluster analysis  Factor analysis  Natural TAND clusters  Neuropsychiatric  Registry  Tand  Tosca  Tuberous sclerosis complex  AM, SY, MPB, BZ, and ACJ received honoraria and travel support from Novartis. VC  received personal fees for consulting  lecture fees and travel from Actelion,  Bayer, Biogen Idec, Boehringer Ingelheim, Gilead, GSK, MSD, Novartis, Pfizer,  Roche, and Sanofi  grants from Actelion, Boehringer Ingelheim, GSK, Pfizer, and  Roche  and personal fees for developing educational material from Boehringer  Ingelheim and Roche. PJdV has been on the steering group of the EXIST-1, 2, and 3  studies sponsored by Novartis and co-PI on two investigator-initiated studies  part-funded by Novartis. RN received grant support, paid to her institution, from  Eisai and lecture fees from Nutricia, Eisai, Advicenne, and GW Pharma. YT  received personal fees from Novartis for lecture and for copyright of referential  figures from the journals and grant from the Japanese government for intractable  epilepsy research. SJ was partly financed by the EC Seventh Framework Programme  (FP7/2007-2013  EPISTOP, grant agreement no. 602391), the Polish Ministerial  funds for science (years 2013–2018) for the implementation of international  co-financed project, and the grant EPIMARKER of the Polish National Center for  Research and Development No. STRATEGMED3/306306/4/2016. JCK, PC, CH, JAL, and JQ  received research grants from Novartis. RM and SS are employees of Novartis. LD’A  was an employee of Novartis at the time of manuscript concept approval. VS  reported no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters. RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions. CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters. En ligne : https://dx.doi.org/10.1186/s11689-020-09327-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia / Kanako ISHIZUKA in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia Type de document : texte imprimé Auteurs : Kanako ISHIZUKA, Auteur ; Tomoyuki YOSHIDA, Auteur ; Takeshi KAWABATA, Auteur ; Ayako IMAI, Auteur ; Hisashi MORI, Auteur ; Hiroki KIMURA, Auteur ; Toshiya INADA, Auteur ; Yuko OKAHISA, Auteur ; Jun EGAWA, Auteur ; Masahide USAMI, Auteur ; Itaru KUSHIMA, Auteur ; Mako MORIKAWA, Auteur ; Takashi OKADA, Auteur ; Masashi IKEDA, Auteur ; Aleksic BRANKO, Auteur ; Daisuke MORI, Auteur ; Toshiyuki SOMEYA, Auteur ; Nakao IWATA, Auteur ; Norio OZAKI, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/genetics  Calcium-Binding Proteins/genetics  Exons  Heterozygote  Humans  Mutation  Neural Cell Adhesion Molecules/genetics  Schizophrenia/genetics  Autism spectrum disorders  Genotype-phenotype  Missense variants  Nrxn1  Neurodevelopmental disorder  Schizophrenia  Targeted resequencing  Ultra-rare variants Index. décimale : PER Périodiques Résumé : BACKGROUND: Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. METHODS: To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. RESULTS: Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. CONCLUSIONS: The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ. En ligne : https://dx.doi.org/10.1186/s11689-020-09325-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia [texte imprimé] / Kanako ISHIZUKA, Auteur ; Tomoyuki YOSHIDA, Auteur ; Takeshi KAWABATA, Auteur ; Ayako IMAI, Auteur ; Hisashi MORI, Auteur ; Hiroki KIMURA, Auteur ; Toshiya INADA, Auteur ; Yuko OKAHISA, Auteur ; Jun EGAWA, Auteur ; Masahide USAMI, Auteur ; Itaru KUSHIMA, Auteur ; Mako MORIKAWA, Auteur ; Takashi OKADA, Auteur ; Masashi IKEDA, Auteur ; Aleksic BRANKO, Auteur ; Daisuke MORI, Auteur ; Toshiyuki SOMEYA, Auteur ; Nakao IWATA, Auteur ; Norio OZAKI, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Autism Spectrum Disorder/genetics  Calcium-Binding Proteins/genetics  Exons  Heterozygote  Humans  Mutation  Neural Cell Adhesion Molecules/genetics  Schizophrenia/genetics  Autism spectrum disorders  Genotype-phenotype  Missense variants  Nrxn1  Neurodevelopmental disorder  Schizophrenia  Targeted resequencing  Ultra-rare variants Index. décimale : PER Périodiques Résumé : BACKGROUND: Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. METHODS: To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. RESULTS: Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. CONCLUSIONS: The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ. En ligne : https://dx.doi.org/10.1186/s11689-020-09325-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Deficits in skilled motor and auditory learning in a rat model of Rett syndrome / Katherine S. ADCOCK in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Deficits in skilled motor and auditory learning in a rat model of Rett syndrome Type de document : texte imprimé Auteurs : Katherine S. ADCOCK, Auteur ; Abigail E. BLOUNT, Auteur ; Robert A. MORRISON, Auteur ; Amanda ALVAREZ-DIEPPA, Auteur ; Michael P. KILGARD, Auteur ; Crystal T. ENGINEER, Auteur ; Seth A. HAYS, Auteur Langues : Anglais (eng) Mots-clés : Animals  Auditory Perception  Female  Learning  Methyl-CpG-Binding Protein 2/genetics  Mice  Mice, Transgenic  Rats  Rett Syndrome/complications/genetics  Auditory  MeCP2  Motor  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2. Individuals with Rett syndrome display developmental regression at an early age, and develop a range of motor, auditory, cognitive, and social impairments. Several studies have successfully modeled some aspects of dysfunction and Rett syndrome-like phenotypes in transgenic mouse and rat models bearing mutations in the MECP2 gene. Here, we sought to extend these findings and characterize skilled learning, a more complex behavior known to be altered in Rett syndrome. METHODS: We evaluated the acquisition and performance of auditory and motor function on two complex tasks in heterozygous female Mecp2 rats. Animals were trained to perform a speech discrimination task or a skilled forelimb reaching task. RESULTS: Our results reveal that Mecp2 rats display slower acquisition and reduced performance on an auditory discrimination task than wild-type (WT) littermates. Similarly, Mecp2 rats exhibit impaired learning rates and worse performance on a skilled forelimb motor task compared to WT. CONCLUSIONS: Together, these findings illustrate novel deficits in skilled learning consistent with clinical manifestation of Rett syndrome and provide a framework for development of therapeutic strategies to improve these complex behaviors. En ligne : https://dx.doi.org/10.1186/s11689-020-09330-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Deficits in skilled motor and auditory learning in a rat model of Rett syndrome [texte imprimé] / Katherine S. ADCOCK, Auteur ; Abigail E. BLOUNT, Auteur ; Robert A. MORRISON, Auteur ; Amanda ALVAREZ-DIEPPA, Auteur ; Michael P. KILGARD, Auteur ; Crystal T. ENGINEER, Auteur ; Seth A. HAYS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Auditory Perception  Female  Learning  Methyl-CpG-Binding Protein 2/genetics  Mice  Mice, Transgenic  Rats  Rett Syndrome/complications/genetics  Auditory  MeCP2  Motor  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome is an X-linked neurodevelopmental disorder caused by a mutation in the gene MECP2. Individuals with Rett syndrome display developmental regression at an early age, and develop a range of motor, auditory, cognitive, and social impairments. Several studies have successfully modeled some aspects of dysfunction and Rett syndrome-like phenotypes in transgenic mouse and rat models bearing mutations in the MECP2 gene. Here, we sought to extend these findings and characterize skilled learning, a more complex behavior known to be altered in Rett syndrome. METHODS: We evaluated the acquisition and performance of auditory and motor function on two complex tasks in heterozygous female Mecp2 rats. Animals were trained to perform a speech discrimination task or a skilled forelimb reaching task. RESULTS: Our results reveal that Mecp2 rats display slower acquisition and reduced performance on an auditory discrimination task than wild-type (WT) littermates. Similarly, Mecp2 rats exhibit impaired learning rates and worse performance on a skilled forelimb motor task compared to WT. CONCLUSIONS: Together, these findings illustrate novel deficits in skilled learning consistent with clinical manifestation of Rett syndrome and provide a framework for development of therapeutic strategies to improve these complex behaviors. En ligne : https://dx.doi.org/10.1186/s11689-020-09330-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Protective role of mirtazapine in adult female Mecp2(+/-) mice and patients with Rett syndrome / Javier FLORES GUTIÉRREZ in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Protective role of mirtazapine in adult female Mecp2(+/-) mice and patients with Rett syndrome Type de document : texte imprimé Auteurs : Javier FLORES GUTIÉRREZ, Auteur ; Claudio DE FELICE, Auteur ; Giulia NATALI, Auteur ; Silvia LEONCINI, Auteur ; Cinzia SIGNORINI, Auteur ; Joussef HAYEK, Auteur ; Enrico TONGIORGI, Auteur Langues : Anglais (eng) Mots-clés : Animals  Disease Models, Animal  Female  Humans  Methyl-CpG-Binding Protein 2/genetics  Mice  Mirtazapine  Retrospective Studies  Rett Syndrome/genetics  Antidepressants  Intellectual disability disorders  Irritability/aggressiveness  Motor learning deficits  Parvalbumin neurons  Rett syndrome  Somatosensory cortex Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT), an X-linked neurodevelopmental rare disease mainly caused by MECP2-gene mutations, is a prototypic intellectual disability disorder. Reversibility of RTT-like phenotypes in an adult mouse model lacking the Mecp2-gene has given hope of treating the disease at any age. However, adult RTT patients still urge for new treatments. Given the relationship between RTT and monoamine deficiency, we investigated mirtazapine (MTZ), a noradrenergic and specific-serotonergic antidepressant, as a potential treatment. METHODS: Adult heterozygous-Mecp2 (HET) female mice (6-months old) were treated for 30 days with 10 mg/kg MTZ and assessed for general health, motor skills, motor learning, and anxiety. Motor cortex, somatosensory cortex, and amygdala were analyzed for parvalbumin expression. Eighty RTT adult female patients harboring a pathogenic MECP2 mutation were randomly assigned to treatment to MTZ for insomnia and mood disorders (mean age = 23.1 ± 7.5 years, range = 16-47 years; mean MTZ-treatment duration = 1.64 ± 1.0 years, range = 0.08-5.0 years). Rett clinical severity scale (RCSS) and motor behavior assessment scale (MBAS) were retrospectively analyzed. RESULTS: In HET mice, MTZ preserved motor learning from deterioration and normalized parvalbumin levels in the primary motor cortex. Moreover, MTZ rescued the aberrant open-arm preference behavior observed in HET mice in the elevated plus-maze (EPM) and normalized parvalbumin expression in the barrel cortex. Since whisker clipping also abolished the EPM-related phenotype, we propose it is due to sensory hypersensitivity. In patients, MTZ slowed disease progression or induced significant improvements for 10/16 MBAS-items of the M1 social behavior area: 4/7 items of the M2 oro-facial/respiratory area and 8/14 items of the M3 motor/physical signs area. CONCLUSIONS: This study provides the first evidence that long-term treatment of adult female heterozygous Mecp2(tm1.1Bird) mice and adult Rett patients with the antidepressant mirtazapine is well tolerated and that it protects from disease progression and improves motor, sensory, and behavioral symptoms. En ligne : https://dx.doi.org/10.1186/s11689-020-09328-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Protective role of mirtazapine in adult female Mecp2(+/-) mice and patients with Rett syndrome [texte imprimé] / Javier FLORES GUTIÉRREZ, Auteur ; Claudio DE FELICE, Auteur ; Giulia NATALI, Auteur ; Silvia LEONCINI, Auteur ; Cinzia SIGNORINI, Auteur ; Joussef HAYEK, Auteur ; Enrico TONGIORGI, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Disease Models, Animal  Female  Humans  Methyl-CpG-Binding Protein 2/genetics  Mice  Mirtazapine  Retrospective Studies  Rett Syndrome/genetics  Antidepressants  Intellectual disability disorders  Irritability/aggressiveness  Motor learning deficits  Parvalbumin neurons  Rett syndrome  Somatosensory cortex Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT), an X-linked neurodevelopmental rare disease mainly caused by MECP2-gene mutations, is a prototypic intellectual disability disorder. Reversibility of RTT-like phenotypes in an adult mouse model lacking the Mecp2-gene has given hope of treating the disease at any age. However, adult RTT patients still urge for new treatments. Given the relationship between RTT and monoamine deficiency, we investigated mirtazapine (MTZ), a noradrenergic and specific-serotonergic antidepressant, as a potential treatment. METHODS: Adult heterozygous-Mecp2 (HET) female mice (6-months old) were treated for 30 days with 10 mg/kg MTZ and assessed for general health, motor skills, motor learning, and anxiety. Motor cortex, somatosensory cortex, and amygdala were analyzed for parvalbumin expression. Eighty RTT adult female patients harboring a pathogenic MECP2 mutation were randomly assigned to treatment to MTZ for insomnia and mood disorders (mean age = 23.1 ± 7.5 years, range = 16-47 years; mean MTZ-treatment duration = 1.64 ± 1.0 years, range = 0.08-5.0 years). Rett clinical severity scale (RCSS) and motor behavior assessment scale (MBAS) were retrospectively analyzed. RESULTS: In HET mice, MTZ preserved motor learning from deterioration and normalized parvalbumin levels in the primary motor cortex. Moreover, MTZ rescued the aberrant open-arm preference behavior observed in HET mice in the elevated plus-maze (EPM) and normalized parvalbumin expression in the barrel cortex. Since whisker clipping also abolished the EPM-related phenotype, we propose it is due to sensory hypersensitivity. In patients, MTZ slowed disease progression or induced significant improvements for 10/16 MBAS-items of the M1 social behavior area: 4/7 items of the M2 oro-facial/respiratory area and 8/14 items of the M3 motor/physical signs area. CONCLUSIONS: This study provides the first evidence that long-term treatment of adult female heterozygous Mecp2(tm1.1Bird) mice and adult Rett patients with the antidepressant mirtazapine is well tolerated and that it protects from disease progression and improves motor, sensory, and behavioral symptoms. En ligne : https://dx.doi.org/10.1186/s11689-020-09328-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Deficits in higher visual area representations in a mouse model of Angelman syndrome / Leah B. TOWNSEND in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Deficits in higher visual area representations in a mouse model of Angelman syndrome Type de document : texte imprimé Auteurs : Leah B. TOWNSEND, Auteur ; Kelly A. JONES, Auteur ; Christopher R. DORSETT, Auteur ; Benjamin D. PHILPOT, Auteur ; Spencer L. SMITH, Auteur Langues : Anglais (eng) Mots-clés : Angelman Syndrome/genetics  Animals  Disease Models, Animal  Mice  Neurons  Visual Cortex Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, "higher" sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs). METHODS: Here, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli. RESULTS: We found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS. CONCLUSION: Assaying downstream, or "higher" circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders. TRIAL REGISTRATION: Not applicable. En ligne : https://dx.doi.org/10.1186/s11689-020-09329-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Deficits in higher visual area representations in a mouse model of Angelman syndrome [texte imprimé] / Leah B. TOWNSEND, Auteur ; Kelly A. JONES, Auteur ; Christopher R. DORSETT, Auteur ; Benjamin D. PHILPOT, Auteur ; Spencer L. SMITH, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Angelman Syndrome/genetics  Animals  Disease Models, Animal  Mice  Neurons  Visual Cortex Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, "higher" sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs). METHODS: Here, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli. RESULTS: We found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS. CONCLUSION: Assaying downstream, or "higher" circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders. TRIAL REGISTRATION: Not applicable. En ligne : https://dx.doi.org/10.1186/s11689-020-09329-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

A small-molecule screen reveals novel modulators of MeCP2 and X-chromosome inactivation maintenance / Hyeong-Min LEE in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : A small-molecule screen reveals novel modulators of MeCP2 and X-chromosome inactivation maintenance Type de document : texte imprimé Auteurs : Hyeong-Min LEE, Auteur ; M Bram KUIJER, Auteur ; Nerea RUIZ BLANES, Auteur ; Ellen P. CLARK, Auteur ; Megumi AITA, Auteur ; Lorena GALIANO ARJONA, Auteur ; Agnieszka KOKOT, Auteur ; Noah SCIAKY, Auteur ; Jeremy M. SIMON, Auteur ; Sanchita BHATNAGAR, Auteur ; Benjamin D. PHILPOT, Auteur ; Andrea CERASE, Auteur Langues : Anglais (eng) Mots-clés : Animals  Chromosomes  Female  Male  Methyl-CpG-Binding Protein 2/genetics/metabolism  Mice  Mutation  Rett Syndrome/drug therapy/genetics  X Chromosome Inactivation  Ag490  Jak/stat  Janus Kinase  Janus Kinase inhibitors  MeCP2  PI3K/ATK pathways  Rett syndrome  X-chromosome inactivation Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. While MeCP2 mutations are lethal in most males, females survive birth but show severe neurological defects. Because X-chromosome inactivation (XCI) is a random process, approximately 50% of the cells silence the wild-type (WT) copy of the MeCP2 gene. Thus, reactivating the silent WT copy of MeCP2 could provide therapeutic intervention for RTT. METHODS: Toward this goal, we screened ~ 28,000 small-molecule compounds from several libraries using a MeCP2-luciferase reporter cell line and cortical neurons from a MeCP2-EGFP mouse model. We used gain/increase of luminescence or fluorescence as a readout of MeCP2 reactivation and tested the efficacy of these drugs under different drug regimens, conditions, and cellular contexts. RESULTS: We identified inhibitors of the JAK/STAT pathway as XCI-reactivating agents, both by in vitro and ex vivo assays. In particular, we show that AG-490, a Janus Kinase 2 (JAK2) kinase inhibitor, and Jaki, a pan JAK/STAT inhibitor, are capable of reactivating MeCP2 from the inactive X chromosome, in different cellular contexts. CONCLUSIONS: Our results suggest that inhibition of the JAK/STAT pathway is a new potential pathway to reinstate MeCP2 gene expression as an efficient RTT treatment. En ligne : https://dx.doi.org/10.1186/s11689-020-09332-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] A small-molecule screen reveals novel modulators of MeCP2 and X-chromosome inactivation maintenance [texte imprimé] / Hyeong-Min LEE, Auteur ; M Bram KUIJER, Auteur ; Nerea RUIZ BLANES, Auteur ; Ellen P. CLARK, Auteur ; Megumi AITA, Auteur ; Lorena GALIANO ARJONA, Auteur ; Agnieszka KOKOT, Auteur ; Noah SCIAKY, Auteur ; Jeremy M. SIMON, Auteur ; Sanchita BHATNAGAR, Auteur ; Benjamin D. PHILPOT, Auteur ; Andrea CERASE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Chromosomes  Female  Male  Methyl-CpG-Binding Protein 2/genetics/metabolism  Mice  Mutation  Rett Syndrome/drug therapy/genetics  X Chromosome Inactivation  Ag490  Jak/stat  Janus Kinase  Janus Kinase inhibitors  MeCP2  PI3K/ATK pathways  Rett syndrome  X-chromosome inactivation Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. While MeCP2 mutations are lethal in most males, females survive birth but show severe neurological defects. Because X-chromosome inactivation (XCI) is a random process, approximately 50% of the cells silence the wild-type (WT) copy of the MeCP2 gene. Thus, reactivating the silent WT copy of MeCP2 could provide therapeutic intervention for RTT. METHODS: Toward this goal, we screened ~ 28,000 small-molecule compounds from several libraries using a MeCP2-luciferase reporter cell line and cortical neurons from a MeCP2-EGFP mouse model. We used gain/increase of luminescence or fluorescence as a readout of MeCP2 reactivation and tested the efficacy of these drugs under different drug regimens, conditions, and cellular contexts. RESULTS: We identified inhibitors of the JAK/STAT pathway as XCI-reactivating agents, both by in vitro and ex vivo assays. In particular, we show that AG-490, a Janus Kinase 2 (JAK2) kinase inhibitor, and Jaki, a pan JAK/STAT inhibitor, are capable of reactivating MeCP2 from the inactive X chromosome, in different cellular contexts. CONCLUSIONS: Our results suggest that inhibition of the JAK/STAT pathway is a new potential pathway to reinstate MeCP2 gene expression as an efficient RTT treatment. En ligne : https://dx.doi.org/10.1186/s11689-020-09332-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Affective and psychotic reactivity to daily-life stress in adults with 22q11DS: a study using the experience sampling method / Maude SCHNEIDER in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Affective and psychotic reactivity to daily-life stress in adults with 22q11DS: a study using the experience sampling method Type de document : texte imprimé Auteurs : Maude SCHNEIDER, Auteur ; Thomas VAESSEN, Auteur ; Esther D.A. VAN DUIN, Auteur ; Zuzana KASANOVA, Auteur ; Wolfgang VIECHTBAUER, Auteur ; Ulrich REININGHAUS, Auteur ; Claudia VINGERHOETS, Auteur ; Jan BOOIJ, Auteur ; Ann SWILLEN, Auteur ; Jacob A.S. VORSTMAN, Auteur ; Thérèse VAN AMELSVOORT, Auteur ; Inez MYIN-GERMEYS, Auteur Langues : Anglais (eng) Mots-clés : Adult  DiGeorge Syndrome  Ecological Momentary Assessment  Humans  Mental Disorders  Psychotic Disorders/complications  Stress, Psychological/complications  22q11.2 deletion syndrome  Experience sampling method  Momentary psychotic experiences  Negative affect  Positive affect  Stress reactivity Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with an increased risk of psychiatric disorders. Vulnerability for psychopathology has been related to an increased reactivity to stress. Here, we examined affective states, perceived stress, affective and psychotic reactivity to various sources of environmental stress using the experience sampling method (ESM), a structured diary technique allowing repeated assessments in the context of daily life. METHODS: Adults with 22q11DS (n = 31; age, 34.1 years) and matched healthy controls (HCs; n = 24; age, 39.9 years) were included. ESM was used to assess affective states, perceived stress, and stress reactivity. Data were analyzed using multilevel regression models. RESULTS: Adults with 22q11DS displayed overall higher levels of negative affect but comparable levels of positive affect compared to HCs. Higher levels of perceived stress were reported by individuals with 22q11DS. Comparable affective and psychotic reactivity in relation to all types of environmental stress was observed between the two groups. CONCLUSION: The results point toward higher levels of negative affect and differences in the perception of daily hassles in 22q11DS but no difference in affective or psychotic reactivity to stress. This study contributes to the growing literature regarding the impact of stress on the development of psychopathology in the 22q11DS population. En ligne : https://dx.doi.org/10.1186/s11689-020-09333-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Affective and psychotic reactivity to daily-life stress in adults with 22q11DS: a study using the experience sampling method [texte imprimé] / Maude SCHNEIDER, Auteur ; Thomas VAESSEN, Auteur ; Esther D.A. VAN DUIN, Auteur ; Zuzana KASANOVA, Auteur ; Wolfgang VIECHTBAUER, Auteur ; Ulrich REININGHAUS, Auteur ; Claudia VINGERHOETS, Auteur ; Jan BOOIJ, Auteur ; Ann SWILLEN, Auteur ; Jacob A.S. VORSTMAN, Auteur ; Thérèse VAN AMELSVOORT, Auteur ; Inez MYIN-GERMEYS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adult  DiGeorge Syndrome  Ecological Momentary Assessment  Humans  Mental Disorders  Psychotic Disorders/complications  Stress, Psychological/complications  22q11.2 deletion syndrome  Experience sampling method  Momentary psychotic experiences  Negative affect  Positive affect  Stress reactivity Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with an increased risk of psychiatric disorders. Vulnerability for psychopathology has been related to an increased reactivity to stress. Here, we examined affective states, perceived stress, affective and psychotic reactivity to various sources of environmental stress using the experience sampling method (ESM), a structured diary technique allowing repeated assessments in the context of daily life. METHODS: Adults with 22q11DS (n = 31; age, 34.1 years) and matched healthy controls (HCs; n = 24; age, 39.9 years) were included. ESM was used to assess affective states, perceived stress, and stress reactivity. Data were analyzed using multilevel regression models. RESULTS: Adults with 22q11DS displayed overall higher levels of negative affect but comparable levels of positive affect compared to HCs. Higher levels of perceived stress were reported by individuals with 22q11DS. Comparable affective and psychotic reactivity in relation to all types of environmental stress was observed between the two groups. CONCLUSION: The results point toward higher levels of negative affect and differences in the perception of daily hassles in 22q11DS but no difference in affective or psychotic reactivity to stress. This study contributes to the growing literature regarding the impact of stress on the development of psychopathology in the 22q11DS population. En ligne : https://dx.doi.org/10.1186/s11689-020-09333-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Sleep characteristics and problems of 2-year-olds with Williams syndrome: relations with language and behavior / Caroline GREINER DE MAGALHÃES in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Sleep characteristics and problems of 2-year-olds with Williams syndrome: relations with language and behavior Type de document : texte imprimé Auteurs : Caroline GREINER DE MAGALHÃES, Auteur ; Louise M. O'BRIEN, Auteur ; Carolyn B. MERVIS, Auteur Langues : Anglais (eng) Mots-clés : Child, Preschool  Humans  Parents  Sleep  Sleep Wake Disorders  Surveys and Questionnaires  Williams Syndrome  Behavior problems  Language development  Neurodevelopmental disorders  Pediatrics  Sleep problems  Sleep-related breathing disorders  Sleepiness  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep problems have been shown to have a negative impact on language development and behavior for both typically developing children and children with a range of neurodevelopmental disorders. The relation of sleep characteristics and problems to language and behavior for children with Williams syndrome (WS) is unclear. The goal of this study was to address these relations for 2-year-olds with WS. Associations of nonverbal reasoning ability, nighttime sleep duration, and excessive daytime sleepiness with language ability and behavior problems were considered. METHOD: Ninety-six 2-year-olds with genetically confirmed classic-length WS deletions participated. Parents completed the Pediatric Sleep Questionnaire, which includes a Sleep-Related Breathing Disorder (SRBD) scale with a subscale measuring excessive daytime sleepiness, to assess sleep characteristics and problems. Parents also completed the Child Behavior Checklist (CBCL) and the MacArthur-Bates Communicative Development Inventory: Words and Sentences to assess behavior problems and expressive vocabulary, respectively. Children completed the Mullen Scales of Early Learning to measure nonverbal reasoning and language abilities. RESULTS: Parents indicated that children slept an average of 10.36 h per night (SD = 1.09, range 7.3-13.3), not differing significantly from the mean reported by Bell and Zimmerman (2010) for typically developing toddlers (p = .787). Sixteen percent of participants screened positive for SRBD and 30% for excessive daytime sleepiness. Children who screened positive for SRBD had significantly more behavior problems on all CBCL scales than children who screened negative. Children with excessive daytime sleepiness had significantly more attention/hyperactivity, stress, and externalizing problems than those who did not have daytime sleepiness. Individual differences in parent-reported nighttime sleep duration and directly measured nonverbal reasoning abilities accounted for unique variance in expressive language, receptive language, and internalizing problems. Individual differences in parent-reported daytime sleepiness accounted for unique variance in externalizing problems. CONCLUSIONS: The relations of nighttime sleep duration, positive screens for SRBD, and excessive daytime sleepiness to language and behavior in toddlers with WS parallel prior findings for typically developing toddlers. These results highlight the importance of screening young children with WS for sleep problems. Studies investigating the efficacy of behavioral strategies for improving sleep in children with WS are warranted. En ligne : https://dx.doi.org/10.1186/s11689-020-09336-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Sleep characteristics and problems of 2-year-olds with Williams syndrome: relations with language and behavior [texte imprimé] / Caroline GREINER DE MAGALHÃES, Auteur ; Louise M. O'BRIEN, Auteur ; Carolyn B. MERVIS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Child, Preschool  Humans  Parents  Sleep  Sleep Wake Disorders  Surveys and Questionnaires  Williams Syndrome  Behavior problems  Language development  Neurodevelopmental disorders  Pediatrics  Sleep problems  Sleep-related breathing disorders  Sleepiness  Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep problems have been shown to have a negative impact on language development and behavior for both typically developing children and children with a range of neurodevelopmental disorders. The relation of sleep characteristics and problems to language and behavior for children with Williams syndrome (WS) is unclear. The goal of this study was to address these relations for 2-year-olds with WS. Associations of nonverbal reasoning ability, nighttime sleep duration, and excessive daytime sleepiness with language ability and behavior problems were considered. METHOD: Ninety-six 2-year-olds with genetically confirmed classic-length WS deletions participated. Parents completed the Pediatric Sleep Questionnaire, which includes a Sleep-Related Breathing Disorder (SRBD) scale with a subscale measuring excessive daytime sleepiness, to assess sleep characteristics and problems. Parents also completed the Child Behavior Checklist (CBCL) and the MacArthur-Bates Communicative Development Inventory: Words and Sentences to assess behavior problems and expressive vocabulary, respectively. Children completed the Mullen Scales of Early Learning to measure nonverbal reasoning and language abilities. RESULTS: Parents indicated that children slept an average of 10.36 h per night (SD = 1.09, range 7.3-13.3), not differing significantly from the mean reported by Bell and Zimmerman (2010) for typically developing toddlers (p = .787). Sixteen percent of participants screened positive for SRBD and 30% for excessive daytime sleepiness. Children who screened positive for SRBD had significantly more behavior problems on all CBCL scales than children who screened negative. Children with excessive daytime sleepiness had significantly more attention/hyperactivity, stress, and externalizing problems than those who did not have daytime sleepiness. Individual differences in parent-reported nighttime sleep duration and directly measured nonverbal reasoning abilities accounted for unique variance in expressive language, receptive language, and internalizing problems. Individual differences in parent-reported daytime sleepiness accounted for unique variance in externalizing problems. CONCLUSIONS: The relations of nighttime sleep duration, positive screens for SRBD, and excessive daytime sleepiness to language and behavior in toddlers with WS parallel prior findings for typically developing toddlers. These results highlight the importance of screening young children with WS for sleep problems. Studies investigating the efficacy of behavioral strategies for improving sleep in children with WS are warranted. En ligne : https://dx.doi.org/10.1186/s11689-020-09336-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Telehealth-enabled behavioral treatment for problem behaviors in boys with fragile X syndrome: a randomized controlled trial / Scott S. HALL in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Telehealth-enabled behavioral treatment for problem behaviors in boys with fragile X syndrome: a randomized controlled trial Type de document : texte imprimé Auteurs : Scott S. HALL, Auteur ; Katerina D. MONLUX, Auteur ; Arlette Bujanda RODRIGUEZ, Auteur ; Booil JO, Auteur ; Joy S. POLLARD, Auteur Langues : Anglais (eng) Mots-clés : Behavior Therapy  Child  Fragile X Syndrome/therapy  Humans  Male  Problem Behavior  Quality of Life  Telemedicine  Behavioral treatment  Fragile X syndrome  Functional analysis  Problem behavior  Randomized controlled trial Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with fragile X syndrome (FXS) are at increased risk for exhibiting problem behaviors such as aggression and self-injury. However, many children with FXS have limited access to behavioral treatments that have known efficacy due to the low availability of treatment providers and the wide geographical dispersion of families with FXS across the country. Telehealth may offer a cost-effective and practical solution to overcome these significant barriers. We examined the effect of administering an established behavior analytic intervention called functional communication training (FCT) via telehealth on levels of problem behaviors exhibited by boys with FXS. We also examined treatment acceptability, as well as the effect of the treatment on levels of parenting stress. METHODS: Boys with FXS, aged 3 to 10 years, who displayed problem behaviors daily, were randomized to receive FCT via telehealth (n = 30) or treatment as usual (n = 27) over 12 weeks. Outcome measures included in-session observations of problem behavior, the Aberrant Behavior Checklist-Community (ABC-C), the Treatment Acceptability Rating Form-Revised (TARF-R), and the Parenting Stress Index, 4th edition (PSI-4). RESULTS: Intention-to-treat analyses indicated that scores on the irritability subscale of the ABC-C, our primary outcome measure, decreased significantly for boys who received FCT via telehealth compared to boys who received treatment as usual (p < .001, Cohen's d = 0.65). In-session observations conducted for those who received treatment showed that levels of problem behavior decreased by 91% from baseline. Levels of parenting stress related to child behavioral problems were also lower following FCT treatment, and caregivers reported that the intervention was acceptable. CONCLUSIONS: These findings support telehealth-enabled FCT as a framework for expanding access to behavioral treatments for problem behaviors in children with FXS. Expanded delivery of behavior analytic treatment via telehealth also has the potential to lower healthcare costs, improve child and family quality of life, and lead to advances in the treatment of problem behavior in the broader population of individuals with neurodevelopmental disorders. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03510156 . Registered 27 April 2018. En ligne : https://dx.doi.org/10.1186/s11689-020-09331-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Telehealth-enabled behavioral treatment for problem behaviors in boys with fragile X syndrome: a randomized controlled trial [texte imprimé] / Scott S. HALL, Auteur ; Katerina D. MONLUX, Auteur ; Arlette Bujanda RODRIGUEZ, Auteur ; Booil JO, Auteur ; Joy S. POLLARD, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Behavior Therapy  Child  Fragile X Syndrome/therapy  Humans  Male  Problem Behavior  Quality of Life  Telemedicine  Behavioral treatment  Fragile X syndrome  Functional analysis  Problem behavior  Randomized controlled trial Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with fragile X syndrome (FXS) are at increased risk for exhibiting problem behaviors such as aggression and self-injury. However, many children with FXS have limited access to behavioral treatments that have known efficacy due to the low availability of treatment providers and the wide geographical dispersion of families with FXS across the country. Telehealth may offer a cost-effective and practical solution to overcome these significant barriers. We examined the effect of administering an established behavior analytic intervention called functional communication training (FCT) via telehealth on levels of problem behaviors exhibited by boys with FXS. We also examined treatment acceptability, as well as the effect of the treatment on levels of parenting stress. METHODS: Boys with FXS, aged 3 to 10 years, who displayed problem behaviors daily, were randomized to receive FCT via telehealth (n = 30) or treatment as usual (n = 27) over 12 weeks. Outcome measures included in-session observations of problem behavior, the Aberrant Behavior Checklist-Community (ABC-C), the Treatment Acceptability Rating Form-Revised (TARF-R), and the Parenting Stress Index, 4th edition (PSI-4). RESULTS: Intention-to-treat analyses indicated that scores on the irritability subscale of the ABC-C, our primary outcome measure, decreased significantly for boys who received FCT via telehealth compared to boys who received treatment as usual (p < .001, Cohen's d = 0.65). In-session observations conducted for those who received treatment showed that levels of problem behavior decreased by 91% from baseline. Levels of parenting stress related to child behavioral problems were also lower following FCT treatment, and caregivers reported that the intervention was acceptable. CONCLUSIONS: These findings support telehealth-enabled FCT as a framework for expanding access to behavioral treatments for problem behaviors in children with FXS. Expanded delivery of behavior analytic treatment via telehealth also has the potential to lower healthcare costs, improve child and family quality of life, and lead to advances in the treatment of problem behavior in the broader population of individuals with neurodevelopmental disorders. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03510156 . Registered 27 April 2018. En ligne : https://dx.doi.org/10.1186/s11689-020-09331-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Risk of neurodevelopmental disorders in children born from different ART treatments: a systematic review and meta-analysis / Tono DJUWANTONO in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Risk of neurodevelopmental disorders in children born from different ART treatments: a systematic review and meta-analysis Type de document : texte imprimé Auteurs : Tono DJUWANTONO, Auteur ; Jenifer Kiem AVIANI, Auteur ; Wiryawan PERMADI, Auteur ; Tri Hanggono ACHMAD, Auteur ; Danny HALIM, Auteur Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/epidemiology  Child  Female  Humans  Infant, Newborn  Neurodevelopmental Disorders/epidemiology/etiology  Pregnancy  Premature Birth  Reproductive Techniques, Assisted/adverse effects  Sperm Injections, Intracytoplasmic  Assisted reproductive treatments  Autism spectrum disorder  Cerebral palsy  Frozen embryo transfer  In vitro fertilization  Intellectual disability  Intracytoplasmic sperm injection  Long-term outcome  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Various techniques in assisted reproductive technology (ART) have been developed as solutions for specific infertility problems. It is important to gain consensual conclusions on the actual risks of neurodevelopmental disorders among children who are born from ART. This study aimed to quantify the relative risks of cerebral palsy, intellectual disability, autism spectrum disorder (ASD), and behavioral problems in children from different ART methods by using systematic review and meta-analysis. Healthcare providers could use the results of this study to suggest the suitable ART technique and plan optimum postnatal care. METHODS: Pubmed, Google Scholar, and Scopus databases were used to search for studies up to January 2020. Of the 181 screened full manuscripts, 17 studies (9.39%) fulfilled the selection criteria. Based on the Newcastle-Ottawa scale ratings, 7 studies were excluded, resulting in 10 studies that were eventually included in the meta-analyses. Mantel-Haenszel risk ratio model was used in the meta-analysis, and the results are described using forest plot with 95% confidence interval. Heterogeneity was assessed using the I(2) value. RESULTS: Pooled evaluation of 10 studies showed that the risk of cerebral palsy in children from assisted reproductive technology (ART) is higher than children from natural conceptions (risk ratio [RR] 1.82, [1.41, 2.34]; P = 0.00001). Risk of intellectual disability (RR 1.46, [1.03, 2.08]; P = 0.03) and ASD (RR 1.49 [1.05, 2.11]; P = 0.03) are higher in intracytoplasmic sperm injection (ICSI) children compared to conventional in vitro fertilization (IVF) children. The differences in the risk of neurodevelopmental disorders in children born after frozen and fresh embryo transfers are not significant. Analysis on potential cofounder effects, including multiple birth, preterm birth, and low birth body weight highlight possibilities of significant correlation to the risks of neurodevelopmental disorders. CONCLUSIONS: Pooled estimates suggest that children born after ART are at higher risk of acquiring cerebral palsy. ICSI treatment causes higher risk of intellectual disability and ASD. These findings suggest the importance of the availability of intensive care unit at the time of delivery and long-term developmental evaluation particularly in children from ICSI. En ligne : https://dx.doi.org/10.1186/s11689-020-09347-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Risk of neurodevelopmental disorders in children born from different ART treatments: a systematic review and meta-analysis [texte imprimé] / Tono DJUWANTONO, Auteur ; Jenifer Kiem AVIANI, Auteur ; Wiryawan PERMADI, Auteur ; Tri Hanggono ACHMAD, Auteur ; Danny HALIM, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Autism Spectrum Disorder/epidemiology  Child  Female  Humans  Infant, Newborn  Neurodevelopmental Disorders/epidemiology/etiology  Pregnancy  Premature Birth  Reproductive Techniques, Assisted/adverse effects  Sperm Injections, Intracytoplasmic  Assisted reproductive treatments  Autism spectrum disorder  Cerebral palsy  Frozen embryo transfer  In vitro fertilization  Intellectual disability  Intracytoplasmic sperm injection  Long-term outcome  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Various techniques in assisted reproductive technology (ART) have been developed as solutions for specific infertility problems. It is important to gain consensual conclusions on the actual risks of neurodevelopmental disorders among children who are born from ART. This study aimed to quantify the relative risks of cerebral palsy, intellectual disability, autism spectrum disorder (ASD), and behavioral problems in children from different ART methods by using systematic review and meta-analysis. Healthcare providers could use the results of this study to suggest the suitable ART technique and plan optimum postnatal care. METHODS: Pubmed, Google Scholar, and Scopus databases were used to search for studies up to January 2020. Of the 181 screened full manuscripts, 17 studies (9.39%) fulfilled the selection criteria. Based on the Newcastle-Ottawa scale ratings, 7 studies were excluded, resulting in 10 studies that were eventually included in the meta-analyses. Mantel-Haenszel risk ratio model was used in the meta-analysis, and the results are described using forest plot with 95% confidence interval. Heterogeneity was assessed using the I(2) value. RESULTS: Pooled evaluation of 10 studies showed that the risk of cerebral palsy in children from assisted reproductive technology (ART) is higher than children from natural conceptions (risk ratio [RR] 1.82, [1.41, 2.34]; P = 0.00001). Risk of intellectual disability (RR 1.46, [1.03, 2.08]; P = 0.03) and ASD (RR 1.49 [1.05, 2.11]; P = 0.03) are higher in intracytoplasmic sperm injection (ICSI) children compared to conventional in vitro fertilization (IVF) children. The differences in the risk of neurodevelopmental disorders in children born after frozen and fresh embryo transfers are not significant. Analysis on potential cofounder effects, including multiple birth, preterm birth, and low birth body weight highlight possibilities of significant correlation to the risks of neurodevelopmental disorders. CONCLUSIONS: Pooled estimates suggest that children born after ART are at higher risk of acquiring cerebral palsy. ICSI treatment causes higher risk of intellectual disability and ASD. These findings suggest the importance of the availability of intensive care unit at the time of delivery and long-term developmental evaluation particularly in children from ICSI. En ligne : https://dx.doi.org/10.1186/s11689-020-09347-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos / Elizabeth L. BERG in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos Type de document : texte imprimé Auteurs : Elizabeth L. BERG, Auteur ; Tianna M. CHING, Auteur ; Donald A. BRUUN, Auteur ; Josef K. RIVERA, Auteur ; Milo CAREAGA, Auteur ; Jacob ELLEGOOD, Auteur ; Jason P. LERCH, Auteur ; Markus WÖHR, Auteur ; Pamela J. LEIN, Auteur ; Jill L. SILVERMAN, Auteur Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder  Brain  Chlorpyrifos/toxicity  Female  Male  Pregnancy  Prenatal Exposure Delayed Effects  Rats  Rats, Sprague-Dawley  United States  Animal models  Autism  Behavior  Chlorpyrifos  Imaging  Neurodevelopment  Pesticides  Rat  Social  Toxicology  Usv  Vocalization Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs), including intellectual disability, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), are pervasive, lifelong disorders for which pharmacological interventions are not readily available. Substantial increases in the prevalence of NDDs over a relatively short period may not be attributed solely to genetic factors and/or improved diagnostic criteria. There is now a consensus that multiple genetic loci combined with environmental risk factors during critical periods of neurodevelopment influence NDD susceptibility and symptom severity. Organophosphorus (OP) pesticides have been identified as potential environmental risk factors. Epidemiological studies suggest that children exposed prenatally to the OP pesticide chlorpyrifos (CPF) have significant mental and motor delays and strong positive associations for the development of a clinical diagnosis of intellectual delay or disability, ADHD, or ASD. METHODS: We tested the hypothesis that developmental CPF exposure impairs behavior relevant to NDD phenotypes (i.e., deficits in social communication and repetitive, restricted behavior). Male and female rat pups were exposed to CPF at 0.1, 0.3, or 1.0 mg/kg (s.c.) from postnatal days 1-4. RESULTS: These CPF doses did not significantly inhibit acetylcholinesterase activity in the blood or brain but significantly impaired pup ultrasonic vocalizations (USV) in both sexes. Social communication in juveniles via positive affiliative 50-kHz USV playback was absent in females exposed to CPF at 0.3 mg/kg and 1.0 mg/kg. In contrast, this CPF exposure paradigm had no significant effect on gross locomotor abilities or contextual and cued fear memory. Ex vivo magnetic resonance imaging largely found no differences between the CPF-exposed rats and the corresponding vehicle controls using strict false discovery correction; however, there were interesting trends in females in the 0.3 mg/kg dose group. CONCLUSIONS: This work generated and characterized a rat model of developmental CPF exposure that exhibits adverse behavioral phenotypes resulting from perinatal exposures at levels that did not significantly inhibit acetylcholinesterase activity in the brain or blood. These data suggest that current regulations regarding safe levels of CPF need to be reconsidered. En ligne : https://dx.doi.org/10.1186/s11689-020-09342-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Translational outcomes relevant to neurodevelopmental disorders following early life exposure of rats to chlorpyrifos [texte imprimé] / Elizabeth L. BERG, Auteur ; Tianna M. CHING, Auteur ; Donald A. BRUUN, Auteur ; Josef K. RIVERA, Auteur ; Milo CAREAGA, Auteur ; Jacob ELLEGOOD, Auteur ; Jason P. LERCH, Auteur ; Markus WÖHR, Auteur ; Pamela J. LEIN, Auteur ; Jill L. SILVERMAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Autism Spectrum Disorder  Brain  Chlorpyrifos/toxicity  Female  Male  Pregnancy  Prenatal Exposure Delayed Effects  Rats  Rats, Sprague-Dawley  United States  Animal models  Autism  Behavior  Chlorpyrifos  Imaging  Neurodevelopment  Pesticides  Rat  Social  Toxicology  Usv  Vocalization Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs), including intellectual disability, attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), are pervasive, lifelong disorders for which pharmacological interventions are not readily available. Substantial increases in the prevalence of NDDs over a relatively short period may not be attributed solely to genetic factors and/or improved diagnostic criteria. There is now a consensus that multiple genetic loci combined with environmental risk factors during critical periods of neurodevelopment influence NDD susceptibility and symptom severity. Organophosphorus (OP) pesticides have been identified as potential environmental risk factors. Epidemiological studies suggest that children exposed prenatally to the OP pesticide chlorpyrifos (CPF) have significant mental and motor delays and strong positive associations for the development of a clinical diagnosis of intellectual delay or disability, ADHD, or ASD. METHODS: We tested the hypothesis that developmental CPF exposure impairs behavior relevant to NDD phenotypes (i.e., deficits in social communication and repetitive, restricted behavior). Male and female rat pups were exposed to CPF at 0.1, 0.3, or 1.0 mg/kg (s.c.) from postnatal days 1-4. RESULTS: These CPF doses did not significantly inhibit acetylcholinesterase activity in the blood or brain but significantly impaired pup ultrasonic vocalizations (USV) in both sexes. Social communication in juveniles via positive affiliative 50-kHz USV playback was absent in females exposed to CPF at 0.3 mg/kg and 1.0 mg/kg. In contrast, this CPF exposure paradigm had no significant effect on gross locomotor abilities or contextual and cued fear memory. Ex vivo magnetic resonance imaging largely found no differences between the CPF-exposed rats and the corresponding vehicle controls using strict false discovery correction; however, there were interesting trends in females in the 0.3 mg/kg dose group. CONCLUSIONS: This work generated and characterized a rat model of developmental CPF exposure that exhibits adverse behavioral phenotypes resulting from perinatal exposures at levels that did not significantly inhibit acetylcholinesterase activity in the brain or blood. These data suggest that current regulations regarding safe levels of CPF need to be reconsidered. En ligne : https://dx.doi.org/10.1186/s11689-020-09342-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Developmental exposure to diesel exhaust upregulates transcription factor expression, decreases hippocampal neurogenesis, and alters cortical lamina organization: relevance to neurodevelopmental disorders / Toby B. COLE in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Developmental exposure to diesel exhaust upregulates transcription factor expression, decreases hippocampal neurogenesis, and alters cortical lamina organization: relevance to neurodevelopmental disorders Type de document : texte imprimé Auteurs : Toby B. COLE, Auteur ; Yu-Chi CHANG, Auteur ; Khoi DAO, Auteur ; Ray DAZA, Auteur ; Robert HEVNER, Auteur ; Lucio G. COSTA, Auteur Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder  Cerebral Cortex  Female  Hippocampus/metabolism  Male  Mice  Mice, Inbred C57BL  Neurogenesis  Transcription Factors  Vehicle Emissions  Adult neurogenesis  Air pollution  Autism spectrum disorder  Cortical lamina organization  Developmental neurotoxicity  Diesel exhaust Index. décimale : PER Périodiques Résumé : BACKGROUND: Exposure to traffic-related air pollution (TRAP) during development and/or in adulthood has been associated in many human studies with both neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorder (ASD) and Alzheimer's disease (AD) or Parkinson's disease (PD). METHODS: In the present study, C57BL/6 J mice were exposed to environmentally relevant levels (250+/-50 μg/m(3)) of diesel exhaust (DE) or filtered air (FA) during development (E0 to PND21). The expression of several transcription factors relevant for CNS development was assessed on PND3. To address possible mechanistic underpinnings of previously observed behavioral effects of DE exposure, adult neurogenesis in the hippocampus and laminar organization of neurons in the somatosensory cortex were analyzed on PND60. Results were analyzed separately for male and female mice. RESULTS: Developmental DE exposure caused a male-specific upregulation of Pax6, Tbr1, Tbr2, Sp1, and Creb1 on PND3. In contrast, in both males and females, Tbr2(+) intermediate progenitor cells in the PND60 hippocampal dentate gyrus were decreased, as an indication of reduced adult neurogenesis. In the somatosensory region of the cerebral cortex, laminar distribution of Trb1, calbindin, and parvalbumin (but not of Ctip2 or Cux1) was altered by developmental DE exposure. CONCLUSIONS: These results provide additional evidence to previous findings indicating the ability of developmental DE exposure to cause biochemical/molecular and behavioral alterations that may be involved in neurodevelopmental disorders such as ASD. En ligne : https://dx.doi.org/10.1186/s11689-020-09340-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Developmental exposure to diesel exhaust upregulates transcription factor expression, decreases hippocampal neurogenesis, and alters cortical lamina organization: relevance to neurodevelopmental disorders [texte imprimé] / Toby B. COLE, Auteur ; Yu-Chi CHANG, Auteur ; Khoi DAO, Auteur ; Ray DAZA, Auteur ; Robert HEVNER, Auteur ; Lucio G. COSTA, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Autism Spectrum Disorder  Cerebral Cortex  Female  Hippocampus/metabolism  Male  Mice  Mice, Inbred C57BL  Neurogenesis  Transcription Factors  Vehicle Emissions  Adult neurogenesis  Air pollution  Autism spectrum disorder  Cortical lamina organization  Developmental neurotoxicity  Diesel exhaust Index. décimale : PER Périodiques Résumé : BACKGROUND: Exposure to traffic-related air pollution (TRAP) during development and/or in adulthood has been associated in many human studies with both neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorder (ASD) and Alzheimer's disease (AD) or Parkinson's disease (PD). METHODS: In the present study, C57BL/6 J mice were exposed to environmentally relevant levels (250+/-50 μg/m(3)) of diesel exhaust (DE) or filtered air (FA) during development (E0 to PND21). The expression of several transcription factors relevant for CNS development was assessed on PND3. To address possible mechanistic underpinnings of previously observed behavioral effects of DE exposure, adult neurogenesis in the hippocampus and laminar organization of neurons in the somatosensory cortex were analyzed on PND60. Results were analyzed separately for male and female mice. RESULTS: Developmental DE exposure caused a male-specific upregulation of Pax6, Tbr1, Tbr2, Sp1, and Creb1 on PND3. In contrast, in both males and females, Tbr2(+) intermediate progenitor cells in the PND60 hippocampal dentate gyrus were decreased, as an indication of reduced adult neurogenesis. In the somatosensory region of the cerebral cortex, laminar distribution of Trb1, calbindin, and parvalbumin (but not of Ctip2 or Cux1) was altered by developmental DE exposure. CONCLUSIONS: These results provide additional evidence to previous findings indicating the ability of developmental DE exposure to cause biochemical/molecular and behavioral alterations that may be involved in neurodevelopmental disorders such as ASD. En ligne : https://dx.doi.org/10.1186/s11689-020-09340-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Epigenetics modifiers: potential hub for understanding and treating neurodevelopmental disorders from hypoxic injury / Ana G. CRISTANCHO in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Epigenetics modifiers: potential hub for understanding and treating neurodevelopmental disorders from hypoxic injury Type de document : texte imprimé Auteurs : Ana G. CRISTANCHO, Auteur ; Eric D. MARSH, Auteur Langues : Anglais (eng) Mots-clés : Brain  Child  DNA Methylation  Epigenesis, Genetic  Humans  Hypoxia  Infant, Newborn  Neurodevelopmental Disorders  Brain development  Epigenetics  Histone modification  Hypoxia  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: The fetal brain is adapted to the hypoxic conditions present during normal in utero development. Relatively more hypoxic states, either chronic or acute, are pathologic and can lead to significant long-term neurodevelopmental sequelae. In utero hypoxic injury is associated with neonatal mortality and millions of lives lived with varying degrees of disability. MAIN BODY: Genetic studies of children with neurodevelopmental disease indicate that epigenetic modifiers regulating DNA methylation and histone remodeling are critical for normal brain development. Epigenetic modifiers are also regulated by environmental stimuli, such as hypoxia. Indeed, epigenetic modifiers that are mutated in children with genetic neurodevelopmental diseases are regulated by hypoxia in a number of preclinical models and may be part of the mechanism for the long-term neurodevelopmental sequelae seem in children with hypoxic brain injury. Thus, a comprehensive understanding the role of DNA methylation and histone modifications in hypoxic injury is critical for developing novel strategies to treat children with hypoxic injury. CONCLUSIONS: This review focuses on our current understanding of the intersection between epigenetics, brain development, and hypoxia. Opportunities for the use of epigenetics as biomarkers of neurodevelopmental disease after hypoxic injury and potential clinical epigenetics targets to improve outcomes after injury are also discussed. While there have been many published studies on the epigenetics of hypoxia, more are needed in the developing brain in order to determine which epigenetic pathways may be most important for mitigating the long-term consequences of hypoxic brain injury. En ligne : https://dx.doi.org/10.1186/s11689-020-09344-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Epigenetics modifiers: potential hub for understanding and treating neurodevelopmental disorders from hypoxic injury [texte imprimé] / Ana G. CRISTANCHO, Auteur ; Eric D. MARSH, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Brain  Child  DNA Methylation  Epigenesis, Genetic  Humans  Hypoxia  Infant, Newborn  Neurodevelopmental Disorders  Brain development  Epigenetics  Histone modification  Hypoxia  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: The fetal brain is adapted to the hypoxic conditions present during normal in utero development. Relatively more hypoxic states, either chronic or acute, are pathologic and can lead to significant long-term neurodevelopmental sequelae. In utero hypoxic injury is associated with neonatal mortality and millions of lives lived with varying degrees of disability. MAIN BODY: Genetic studies of children with neurodevelopmental disease indicate that epigenetic modifiers regulating DNA methylation and histone remodeling are critical for normal brain development. Epigenetic modifiers are also regulated by environmental stimuli, such as hypoxia. Indeed, epigenetic modifiers that are mutated in children with genetic neurodevelopmental diseases are regulated by hypoxia in a number of preclinical models and may be part of the mechanism for the long-term neurodevelopmental sequelae seem in children with hypoxic brain injury. Thus, a comprehensive understanding the role of DNA methylation and histone modifications in hypoxic injury is critical for developing novel strategies to treat children with hypoxic injury. CONCLUSIONS: This review focuses on our current understanding of the intersection between epigenetics, brain development, and hypoxia. Opportunities for the use of epigenetics as biomarkers of neurodevelopmental disease after hypoxic injury and potential clinical epigenetics targets to improve outcomes after injury are also discussed. While there have been many published studies on the epigenetics of hypoxia, more are needed in the developing brain in order to determine which epigenetic pathways may be most important for mitigating the long-term consequences of hypoxic brain injury. En ligne : https://dx.doi.org/10.1186/s11689-020-09344-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Stunting and lead: using causal mediation analysis to better understand how environmental lead exposure affects cognitive outcomes in children / Kelsey M. GLEASON in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Stunting and lead: using causal mediation analysis to better understand how environmental lead exposure affects cognitive outcomes in children Type de document : texte imprimé Auteurs : Kelsey M. GLEASON, Auteur ; Linda VALERI, Auteur ; Anuraj H. SHANKAR, Auteur ; John F. OBRYCKI, Auteur ; Md Omar Sharif IBNE HASAN, Auteur ; Golam MOSTOFA, Auteur ; Quazi QUAMRUZZAMAN, Auteur ; Robert O. WRIGHT, Auteur ; David C. CHRISTIANI, Auteur ; David C. BELLINGER, Auteur ; Maitreyi MAZUMDAR, Auteur Langues : Anglais (eng) Mots-clés : Bangladesh  Child, Preschool  Cognition  Female  Growth Disorders/chemically induced  Humans  Infant  Infant, Newborn  Lead/adverse effects  Mediation Analysis  Pregnancy  Bayley Scales of Infant Development  Blood lead  Cognitive development  Mediation analysis  Stunting Index. décimale : PER Périodiques Résumé : BACKGROUND: Many children in Bangladesh experience poor nutritional status and environmental lead exposure, both of which are associated with lower scores on neurodevelopmental assessments. Recent studies have suggested that part of lead's adverse effects on neurodevelopment are caused in part by lead's effect on growth. New statistical methods are now available to evaluate potential causal pathways in observational studies. This study used a novel statistical method to test the hypothesis that stunting, a measure of linear growth related to poor nutrition, is a mediator and/or an effect modifier of the lead exposure's adverse effect on cognitive development. METHODS: Participants were 734 children from a longitudinal birth cohort established in rural Bangladesh to study the health effects of prenatal and early childhood environmental metal exposures. Lead exposure was estimated using umbilical cord blood samples obtained at birth and blood obtained via venipuncture at age 20-40 months. Stunting was determined using the World Health Organization's standards. Neurodevelopment was assessed at age 20-40 months years using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). We evaluated the effect of lead on stunting and whether the effect of lead on cognitive scores is modified by stunting status in multivariable regression analyses. We then conducted a novel 4-way mediation analysis that allows for exposure-mediator interaction to assess how much of the effect of lead on cognitive scores is explained by the pathway through stunting (mediation) and how much is explained by the interaction between lead and stunt (effect modification). RESULTS: Stunting was not a mediator of the effect of lead in our analyses. Results suggested effect modification by stunting. In an area of Bangladesh with lower lead exposures (median umbilical cord blood lead concentration, 1.7 μg/dL), stunting modified the relationship between prenatal blood lead concentrations and cognitive score at age 2-3 years. A 1-unit increase in natural log cord blood lead concentration in the presence of stunting was associated with a 2.1-unit decrease in cognitive scores (β = - 2.10, SE = 0.71, P = 0.003). This interaction was not found in a second study site where lead exposures were higher (median umbilical cord blood lead concentration, 6.1 μg/dL, β = - 0.45, SE = 0.49, P = 0.360). CONCLUSIONS: We used a novel method of mediation analysis to test whether stunting mediated the adverse effect of prenatal lead exposure on cognitive outcomes in Bangladesh. While we did not find that stunting acted as mediator of lead's effect on cognitive development, we found significant effect modification by stunting. Our results suggest that children with stunting are more vulnerable to the adverse effects of low-level lead exposure. En ligne : https://dx.doi.org/10.1186/s11689-020-09346-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Stunting and lead: using causal mediation analysis to better understand how environmental lead exposure affects cognitive outcomes in children [texte imprimé] / Kelsey M. GLEASON, Auteur ; Linda VALERI, Auteur ; Anuraj H. SHANKAR, Auteur ; John F. OBRYCKI, Auteur ; Md Omar Sharif IBNE HASAN, Auteur ; Golam MOSTOFA, Auteur ; Quazi QUAMRUZZAMAN, Auteur ; Robert O. WRIGHT, Auteur ; David C. CHRISTIANI, Auteur ; David C. BELLINGER, Auteur ; Maitreyi MAZUMDAR, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Bangladesh  Child, Preschool  Cognition  Female  Growth Disorders/chemically induced  Humans  Infant  Infant, Newborn  Lead/adverse effects  Mediation Analysis  Pregnancy  Bayley Scales of Infant Development  Blood lead  Cognitive development  Mediation analysis  Stunting Index. décimale : PER Périodiques Résumé : BACKGROUND: Many children in Bangladesh experience poor nutritional status and environmental lead exposure, both of which are associated with lower scores on neurodevelopmental assessments. Recent studies have suggested that part of lead's adverse effects on neurodevelopment are caused in part by lead's effect on growth. New statistical methods are now available to evaluate potential causal pathways in observational studies. This study used a novel statistical method to test the hypothesis that stunting, a measure of linear growth related to poor nutrition, is a mediator and/or an effect modifier of the lead exposure's adverse effect on cognitive development. METHODS: Participants were 734 children from a longitudinal birth cohort established in rural Bangladesh to study the health effects of prenatal and early childhood environmental metal exposures. Lead exposure was estimated using umbilical cord blood samples obtained at birth and blood obtained via venipuncture at age 20-40 months. Stunting was determined using the World Health Organization's standards. Neurodevelopment was assessed at age 20-40 months years using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). We evaluated the effect of lead on stunting and whether the effect of lead on cognitive scores is modified by stunting status in multivariable regression analyses. We then conducted a novel 4-way mediation analysis that allows for exposure-mediator interaction to assess how much of the effect of lead on cognitive scores is explained by the pathway through stunting (mediation) and how much is explained by the interaction between lead and stunt (effect modification). RESULTS: Stunting was not a mediator of the effect of lead in our analyses. Results suggested effect modification by stunting. In an area of Bangladesh with lower lead exposures (median umbilical cord blood lead concentration, 1.7 μg/dL), stunting modified the relationship between prenatal blood lead concentrations and cognitive score at age 2-3 years. A 1-unit increase in natural log cord blood lead concentration in the presence of stunting was associated with a 2.1-unit decrease in cognitive scores (β = - 2.10, SE = 0.71, P = 0.003). This interaction was not found in a second study site where lead exposures were higher (median umbilical cord blood lead concentration, 6.1 μg/dL, β = - 0.45, SE = 0.49, P = 0.360). CONCLUSIONS: We used a novel method of mediation analysis to test whether stunting mediated the adverse effect of prenatal lead exposure on cognitive outcomes in Bangladesh. While we did not find that stunting acted as mediator of lead's effect on cognitive development, we found significant effect modification by stunting. Our results suggest that children with stunting are more vulnerable to the adverse effects of low-level lead exposure. En ligne : https://dx.doi.org/10.1186/s11689-020-09346-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Psychosocial deprivation and receptive language ability: a two-sample study / Kathryn L. HUMPHREYS in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Psychosocial deprivation and receptive language ability: a two-sample study Type de document : texte imprimé Auteurs : Kathryn L. HUMPHREYS, Auteur ; Laura S. MACHLIN, Auteur ; Katherine L. GUYON-HARRIS, Auteur ; Charles A. NELSON, Auteur ; Nathan A. FOX, Auteur ; Charles H ZEANAH, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Child  Child, Preschool  Foster Home Care  Humans  Language  Language Development  Prospective Studies  Psychosocial Deprivation  Romania  Deprivation  Neglect  Receptive language  Socioeconomic status Index. décimale : PER Périodiques Résumé : BACKGROUND: The quality of early caregiving experiences is a known contributor to the quality of the language experiences young children receive. What is unknown is whether, and if so, how psychosocial deprivation early in life is associated with long-lasting receptive language outcomes. METHODS: Two prospective longitudinal studies examining early psychosocial deprivation/neglect in different contexts (i.e., deprivation due to institutional care or deprivation experienced by children residing within US families) and receptive language as assessed via the Peabody Picture Vocabulary Test (PPVT) were used to assess the magnitude of these associations. First, 129 participants from the Bucharest Early Intervention Project, a randomized controlled trial of foster care as an alternative to institutional care in Romania, completed a receptive language assessment at age 18 years. Second, from the USA, 3342 participants from the Fragile Families and Child Wellbeing Study were assessed from infancy until middle childhood. RESULTS: Children exposed to early institutional care, on average, had lower receptive language scores than their never institutionalized counterparts in late adolescence. While randomization to an early foster care intervention had no long-lasting association with PPVT scores, the duration of childhood exposure to institutional care was negatively associated with receptive language. Psychosocial deprivation in US families was also negatively associated with receptive language longitudinally, and this association remained statistically significant even after accounting for measures of socioeconomic status. CONCLUSION: Experiences of psychosocial deprivation may have long-lasting consequences for receptive language ability, extending to age 18 years. Psychosocial deprivation is an important prospective predictor of poorer receptive language. TRIAL REGISTRATION: Bucharest Early Intervention Project ClinicalTrials.gov Identifier: NCT00747396. En ligne : https://dx.doi.org/10.1186/s11689-020-09341-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Psychosocial deprivation and receptive language ability: a two-sample study [texte imprimé] / Kathryn L. HUMPHREYS, Auteur ; Laura S. MACHLIN, Auteur ; Katherine L. GUYON-HARRIS, Auteur ; Charles A. NELSON, Auteur ; Nathan A. FOX, Auteur ; Charles H ZEANAH, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Child  Child, Preschool  Foster Home Care  Humans  Language  Language Development  Prospective Studies  Psychosocial Deprivation  Romania  Deprivation  Neglect  Receptive language  Socioeconomic status Index. décimale : PER Périodiques Résumé : BACKGROUND: The quality of early caregiving experiences is a known contributor to the quality of the language experiences young children receive. What is unknown is whether, and if so, how psychosocial deprivation early in life is associated with long-lasting receptive language outcomes. METHODS: Two prospective longitudinal studies examining early psychosocial deprivation/neglect in different contexts (i.e., deprivation due to institutional care or deprivation experienced by children residing within US families) and receptive language as assessed via the Peabody Picture Vocabulary Test (PPVT) were used to assess the magnitude of these associations. First, 129 participants from the Bucharest Early Intervention Project, a randomized controlled trial of foster care as an alternative to institutional care in Romania, completed a receptive language assessment at age 18 years. Second, from the USA, 3342 participants from the Fragile Families and Child Wellbeing Study were assessed from infancy until middle childhood. RESULTS: Children exposed to early institutional care, on average, had lower receptive language scores than their never institutionalized counterparts in late adolescence. While randomization to an early foster care intervention had no long-lasting association with PPVT scores, the duration of childhood exposure to institutional care was negatively associated with receptive language. Psychosocial deprivation in US families was also negatively associated with receptive language longitudinally, and this association remained statistically significant even after accounting for measures of socioeconomic status. CONCLUSION: Experiences of psychosocial deprivation may have long-lasting consequences for receptive language ability, extending to age 18 years. Psychosocial deprivation is an important prospective predictor of poorer receptive language. TRIAL REGISTRATION: Bucharest Early Intervention Project ClinicalTrials.gov Identifier: NCT00747396. En ligne : https://dx.doi.org/10.1186/s11689-020-09341-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Exploratory spatial analysis of autism rates in New York school districts: role of sociodemographic and language differences / Kathleen MCGRATH in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Exploratory spatial analysis of autism rates in New York school districts: role of sociodemographic and language differences Type de document : texte imprimé Auteurs : Kathleen MCGRATH, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder  Autistic Disorder/epidemiology  Child  Child, Preschool  Female  Humans  Language  Male  New York/epidemiology  Schools  Socioeconomic Factors  Spatial Analysis  Young Adult  Autism  Disability  English Language Learners  Geographic information systems  Sociodemographics Index. décimale : PER Périodiques Résumé : BACKGROUND: Literature on autism spectrum disorder (ASD) suggests lower ASD prevalence and higher age of diagnosis among children of color, from lower socioeconomic backgrounds, and from families with lower educational levels. These disparities have been attributed to factors such as limited access to diagnostic and treatment services, less opportunity for upward mobility to locales with ample resources, and linguistic barriers. However, few studies describe prevalence and geographic differences of ASD diagnoses by English Language Learner (ELL) status. OBJECTIVES: The primary objectives of this study are to (1) spatially explore the prevalence of ASD among New York State school districts and (2) examine differences of ASD prevalence rates between ELLs and native English-speaking peers. METHODS: Using the 2016-2017 district-level data on public and non-public school age students (3-21 years old) receiving special education services in New York, we analyzed sociodemographic trends among school districts with varying percentages (low, medium, and high ranges) of students with ASD and ELLs. To do this, we conducted exploratory spatial analyses using GIS software, analysis of school district level demographic data, and multivariate linear regression. RESULTS: In contrast to prior research on ASD prevalence among minority groups, we found disproportionately higher rates of ASD among school districts with higher proportions of Black and Hispanic students. Geographic analysis revealed statistically significant clustering of school districts with high ASD rates in New York City and Albany. Higher proportions of ELLs tended to be concentrated in densely populated, urban, and geographically smaller school districts and had higher proportions of Black, Hispanic, and Asian students. CONCLUSIONS: Schools with higher rates of ASD and ELL students tend to be concentrated in urban regions throughout New York and have higher representation of Black and Hispanic/Latino students, as well as higher rates of learning disabilities in general. Further research is warranted to explore possible reasons for this phenomenon. En ligne : https://dx.doi.org/10.1186/s11689-020-09338-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Exploratory spatial analysis of autism rates in New York school districts: role of sociodemographic and language differences [texte imprimé] / Kathleen MCGRATH, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder  Autistic Disorder/epidemiology  Child  Child, Preschool  Female  Humans  Language  Male  New York/epidemiology  Schools  Socioeconomic Factors  Spatial Analysis  Young Adult  Autism  Disability  English Language Learners  Geographic information systems  Sociodemographics Index. décimale : PER Périodiques Résumé : BACKGROUND: Literature on autism spectrum disorder (ASD) suggests lower ASD prevalence and higher age of diagnosis among children of color, from lower socioeconomic backgrounds, and from families with lower educational levels. These disparities have been attributed to factors such as limited access to diagnostic and treatment services, less opportunity for upward mobility to locales with ample resources, and linguistic barriers. However, few studies describe prevalence and geographic differences of ASD diagnoses by English Language Learner (ELL) status. OBJECTIVES: The primary objectives of this study are to (1) spatially explore the prevalence of ASD among New York State school districts and (2) examine differences of ASD prevalence rates between ELLs and native English-speaking peers. METHODS: Using the 2016-2017 district-level data on public and non-public school age students (3-21 years old) receiving special education services in New York, we analyzed sociodemographic trends among school districts with varying percentages (low, medium, and high ranges) of students with ASD and ELLs. To do this, we conducted exploratory spatial analyses using GIS software, analysis of school district level demographic data, and multivariate linear regression. RESULTS: In contrast to prior research on ASD prevalence among minority groups, we found disproportionately higher rates of ASD among school districts with higher proportions of Black and Hispanic students. Geographic analysis revealed statistically significant clustering of school districts with high ASD rates in New York City and Albany. Higher proportions of ELLs tended to be concentrated in densely populated, urban, and geographically smaller school districts and had higher proportions of Black, Hispanic, and Asian students. CONCLUSIONS: Schools with higher rates of ASD and ELL students tend to be concentrated in urban regions throughout New York and have higher representation of Black and Hispanic/Latino students, as well as higher rates of learning disabilities in general. Further research is warranted to explore possible reasons for this phenomenon. En ligne : https://dx.doi.org/10.1186/s11689-020-09338-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Long-term spatial tracking of cells affected by environmental insults / Shahid MOHAMMAD in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Long-term spatial tracking of cells affected by environmental insults Type de document : texte imprimé Auteurs : Shahid MOHAMMAD, Auteur ; Stephen J. PAGE, Auteur ; Toru SASAKI, Auteur ; Nicholas AYVAZIAN, Auteur ; Pasko RAKIC, Auteur ; Yuka Imamura KAWASAWA, Auteur ; Kazue HASHIMOTO-TORII, Auteur ; Masaaki TORII, Auteur Langues : Anglais (eng) Mots-clés : Animals  Brain/embryology/growth & development  Environment  Female  Mice  Mice, Transgenic  Neurons  Pregnancy  Prenatal Exposure Delayed Effects  Brain development  Environmental stress  Heat shock signaling  Lineage tracing  Reporter Index. décimale : PER Périodiques Résumé : BACKGROUND: Harsh environments surrounding fetuses and children can induce cellular damage in the developing brain, increasing the risk of intellectual disability and other neurodevelopmental disorders such as schizophrenia. However, the mechanisms by which early damage leads to disease manifestation in later life remain largely unknown. Previously, we demonstrated that the activation of heat shock (HS) signaling can be utilized as a unique reporter to label the cells that undergo specific molecular/cellular changes upon exposure to environmental insults throughout the body. Since the activation of HS signaling is an acute and transient event, this approach was not intended for long-term tracing of affected cells after the activation has diminished. In the present study, we generated new reporter transgenic mouse lines as a novel tool to achieve systemic and long-term tracking of affected cells and their progeny. METHODS: The reporter transgenic mouse system was designed so that the activation of HS signaling through HS response element (HSE) drives flippase (FLPo)-flippase recognition target (FRT) recombination-mediated permanent expression of the red fluorescent protein (RFP), tdTomato. With a priority on consistent and efficient assessment of the reporter system, we focused on intraperitoneal (i.p.) injection models of high-dose, short prenatal exposure to alcohol (ethanol) and sodium arsenite (ethanol at 4.0 g/kg/day and sodium arsenite at 5.0 mg/kg/day, at embryonic day (E) 12 and 13). Long-term reporter expression was examined in the brain of reporter mice that were prenatally exposed to these insults. Electrophysiological properties were compared between RFP(+) and RFP(-) cortical neurons in animals prenatally exposed to arsenite. RESULTS: We detected RFP(+) neurons and glia in the brains of postnatal mice that had been prenatally exposed to alcohol or sodium arsenite. In animals prenatally exposed to sodium arsenite, we also detected reduced excitability in RFP(+) cortical neurons. CONCLUSION: The reporter transgenic mice allowed us to trace the cells that once responded to prenatal environmental stress and the progeny derived from these cells long after the exposure in postnatal animals. Tracing of these cells indicates that the impact of prenatal exposure on neural progenitor cells can lead to functional abnormalities in their progeny cells in the postnatal brain. Further studies using more clinically relevant exposure models are warranted to explore this mechanism. En ligne : https://dx.doi.org/10.1186/s11689-020-09339-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Long-term spatial tracking of cells affected by environmental insults [texte imprimé] / Shahid MOHAMMAD, Auteur ; Stephen J. PAGE, Auteur ; Toru SASAKI, Auteur ; Nicholas AYVAZIAN, Auteur ; Pasko RAKIC, Auteur ; Yuka Imamura KAWASAWA, Auteur ; Kazue HASHIMOTO-TORII, Auteur ; Masaaki TORII, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Brain/embryology/growth & development  Environment  Female  Mice  Mice, Transgenic  Neurons  Pregnancy  Prenatal Exposure Delayed Effects  Brain development  Environmental stress  Heat shock signaling  Lineage tracing  Reporter Index. décimale : PER Périodiques Résumé : BACKGROUND: Harsh environments surrounding fetuses and children can induce cellular damage in the developing brain, increasing the risk of intellectual disability and other neurodevelopmental disorders such as schizophrenia. However, the mechanisms by which early damage leads to disease manifestation in later life remain largely unknown. Previously, we demonstrated that the activation of heat shock (HS) signaling can be utilized as a unique reporter to label the cells that undergo specific molecular/cellular changes upon exposure to environmental insults throughout the body. Since the activation of HS signaling is an acute and transient event, this approach was not intended for long-term tracing of affected cells after the activation has diminished. In the present study, we generated new reporter transgenic mouse lines as a novel tool to achieve systemic and long-term tracking of affected cells and their progeny. METHODS: The reporter transgenic mouse system was designed so that the activation of HS signaling through HS response element (HSE) drives flippase (FLPo)-flippase recognition target (FRT) recombination-mediated permanent expression of the red fluorescent protein (RFP), tdTomato. With a priority on consistent and efficient assessment of the reporter system, we focused on intraperitoneal (i.p.) injection models of high-dose, short prenatal exposure to alcohol (ethanol) and sodium arsenite (ethanol at 4.0 g/kg/day and sodium arsenite at 5.0 mg/kg/day, at embryonic day (E) 12 and 13). Long-term reporter expression was examined in the brain of reporter mice that were prenatally exposed to these insults. Electrophysiological properties were compared between RFP(+) and RFP(-) cortical neurons in animals prenatally exposed to arsenite. RESULTS: We detected RFP(+) neurons and glia in the brains of postnatal mice that had been prenatally exposed to alcohol or sodium arsenite. In animals prenatally exposed to sodium arsenite, we also detected reduced excitability in RFP(+) cortical neurons. CONCLUSION: The reporter transgenic mice allowed us to trace the cells that once responded to prenatal environmental stress and the progeny derived from these cells long after the exposure in postnatal animals. Tracing of these cells indicates that the impact of prenatal exposure on neural progenitor cells can lead to functional abnormalities in their progeny cells in the postnatal brain. Further studies using more clinically relevant exposure models are warranted to explore this mechanism. En ligne : https://dx.doi.org/10.1186/s11689-020-09339-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Early life stress and development: potential mechanisms for adverse outcomes / Karen E. SMITH in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Early life stress and development: potential mechanisms for adverse outcomes Type de document : texte imprimé Auteurs : Karen E. SMITH, Auteur ; Seth D. POLLAK, Auteur Langues : Anglais (eng) Mots-clés : Adverse Childhood Experiences  Amygdala  Child  Humans  Hypothalamo-Hypophyseal System  Pituitary-Adrenal System  Stress, Psychological  Developmental disorders  Early adversity  Early life stress  Neurobiological development Index. décimale : PER Périodiques Résumé : BACKGROUND: Chronic and/or extreme stress in early life, often referred to as early adversity, childhood trauma, or early life stress, has been associated with a wide range of adverse effects on development. However, while early life stress has been linked to negative effects on a number of neural systems, the specific mechanisms through which early life stress influences development and individual differences in children's outcomes are still not well understood. MAIN TEXT: The current paper reviews the existing literature on the neurobiological effects of early life stress and their ties to children's psychological and behavioral development. CONCLUSIONS: Early life stress has persistent and pervasive effects on prefrontal-hypothalamic-amygdala and dopaminergic circuits that are at least partially mediated by alterations in hypothalamic-pituitary-adrenal axis function. However, to date, this research has primarily utilized methods of assessment that focus solely on children's event exposures. Incorporating assessment of factors that influence children's interpretation of stressors, along with stressful events, has the potential to provide further insight into the mechanisms contributing to individual differences in neurodevelopmental effects of early life stress. This can aid in further elucidating specific mechanisms through which these neurobiological changes influence development and contribute to risk for psychopathology and health disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09337-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Early life stress and development: potential mechanisms for adverse outcomes [texte imprimé] / Karen E. SMITH, Auteur ; Seth D. POLLAK, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adverse Childhood Experiences  Amygdala  Child  Humans  Hypothalamo-Hypophyseal System  Pituitary-Adrenal System  Stress, Psychological  Developmental disorders  Early adversity  Early life stress  Neurobiological development Index. décimale : PER Périodiques Résumé : BACKGROUND: Chronic and/or extreme stress in early life, often referred to as early adversity, childhood trauma, or early life stress, has been associated with a wide range of adverse effects on development. However, while early life stress has been linked to negative effects on a number of neural systems, the specific mechanisms through which early life stress influences development and individual differences in children's outcomes are still not well understood. MAIN TEXT: The current paper reviews the existing literature on the neurobiological effects of early life stress and their ties to children's psychological and behavioral development. CONCLUSIONS: Early life stress has persistent and pervasive effects on prefrontal-hypothalamic-amygdala and dopaminergic circuits that are at least partially mediated by alterations in hypothalamic-pituitary-adrenal axis function. However, to date, this research has primarily utilized methods of assessment that focus solely on children's event exposures. Incorporating assessment of factors that influence children's interpretation of stressors, along with stressful events, has the potential to provide further insight into the mechanisms contributing to individual differences in neurodevelopmental effects of early life stress. This can aid in further elucidating specific mechanisms through which these neurobiological changes influence development and contribute to risk for psychopathology and health disorders. En ligne : https://dx.doi.org/10.1186/s11689-020-09337-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Investigating the impact of the environment on neurodevelopmental disorder / Heather VOLK in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Investigating the impact of the environment on neurodevelopmental disorder Type de document : texte imprimé Auteurs : Heather VOLK, Auteur ; Margaret A. SHERIDAN, Auteur Langues : Anglais (eng) Mots-clés : Environment  Humans  Neurodevelopmental Disorders Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-020-09345-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Investigating the impact of the environment on neurodevelopmental disorder [texte imprimé] / Heather VOLK, Auteur ; Margaret A. SHERIDAN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Environment  Humans  Neurodevelopmental Disorders Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-020-09345-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Maternal immune response and air pollution exposure during pregnancy: insights from the Early Markers for Autism (EMA) study / Heather E. VOLK in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Maternal immune response and air pollution exposure during pregnancy: insights from the Early Markers for Autism (EMA) study Type de document : texte imprimé Auteurs : Heather E. VOLK, Auteur ; Bo PARK, Auteur ; Calliope HOLLINGUE, Auteur ; Karen L. JONES, Auteur ; Paul ASHWOOD, Auteur ; Gayle C. WINDHAM, Auteur ; Fred LURMAN, Auteur ; Stacey E. ALEXEEFF, Auteur ; Martin KHARRAZI, Auteur ; Michelle PEARL, Auteur ; Judy VAN DE WATER, Auteur ; Lisa A. CROEN, Auteur Langues : Anglais (eng) Mots-clés : Air Pollution/adverse effects  Autistic Disorder  Biomarkers  Case-Control Studies  Child  Female  Humans  Immunity  Male  Pregnancy/immunology  Prenatal Exposure Delayed Effects  United States  Air pollution  Autism spectrum disorder  Immune response  Intellectual disability  Prenatal exposure  declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. OBJECTIVES: To assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study. METHODS: EMA is a population-based, nested case-control study which linked archived maternal serum samples collected during weeks 15-19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency's Air Quality System data using the maternal residential address reported during the prenatal screening visit. RESULTS: Previous month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from - 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure. CONCLUSION: This study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring. En ligne : https://dx.doi.org/10.1186/s11689-020-09343-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Maternal immune response and air pollution exposure during pregnancy: insights from the Early Markers for Autism (EMA) study [texte imprimé] / Heather E. VOLK, Auteur ; Bo PARK, Auteur ; Calliope HOLLINGUE, Auteur ; Karen L. JONES, Auteur ; Paul ASHWOOD, Auteur ; Gayle C. WINDHAM, Auteur ; Fred LURMAN, Auteur ; Stacey E. ALEXEEFF, Auteur ; Martin KHARRAZI, Auteur ; Michelle PEARL, Auteur ; Judy VAN DE WATER, Auteur ; Lisa A. CROEN, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Air Pollution/adverse effects  Autistic Disorder  Biomarkers  Case-Control Studies  Child  Female  Humans  Immunity  Male  Pregnancy/immunology  Prenatal Exposure Delayed Effects  United States  Air pollution  Autism spectrum disorder  Immune response  Intellectual disability  Prenatal exposure  declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Perinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy. OBJECTIVES: To assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study. METHODS: EMA is a population-based, nested case-control study which linked archived maternal serum samples collected during weeks 15-19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency's Air Quality System data using the maternal residential address reported during the prenatal screening visit. RESULTS: Previous month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from - 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurodevelopmental outcome. IL-6 remained associated with ASD with ID even after adjusting for air pollution exposure. CONCLUSION: This study suggests that maternal immune activation is associated with risk for neurodevelopmental disorders. Furthermore, that prenatal air pollution exposure is associated with small, but perhaps biologically relevant, effects on maternal immune system function during pregnancy. Additional studies are needed to better evaluate how prenatal exposure to air pollution affects the trajectory of maternal immune activation during pregnancy, if windows of heightened susceptibility can be identified, and how these factors influence neurodevelopment of the offspring. En ligne : https://dx.doi.org/10.1186/s11689-020-09343-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

Medications for attention-deficit/hyperactivity disorder in individuals with or without coexisting autism spectrum disorder: analysis of data from the Swedish prescribed drug register / Viktoria JOHANSSON in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Medications for attention-deficit/hyperactivity disorder in individuals with or without coexisting autism spectrum disorder: analysis of data from the Swedish prescribed drug register Type de document : texte imprimé Auteurs : Viktoria JOHANSSON, Auteur ; Sven SANDIN, Auteur ; Zheng CHANG, Auteur ; Mark J. TAYLOR, Auteur ; Paul LICHTENSTEIN, Auteur ; Brian M. D'ONOFRIO, Auteur ; Henrik LARSSON, Auteur ; Clara HELLNER, Auteur ; Linda HALLDNER, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Aged  Aged, 80 and over  Attention Deficit Disorder with Hyperactivity/complications/drug  therapy/epidemiology  Autism Spectrum Disorder/complications/drug therapy/epidemiology  Child  Child, Preschool  Humans  Methylphenidate/therapeutic use  Middle Aged  Pharmaceutical Preparations  Sweden/epidemiology  Young Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinical studies found that medication for attention-deficit/hyperactivity disorder (ADHD) is effective in coexisting autism spectrum disorder (ASD), but current research is based on small clinical studies mainly performed on children or adolescents. We here use register data to examine if individuals with ADHD and coexisting ASD present differences in the prescribing patterns of ADHD medication when compared to individuals with pure ADHD. METHODS: Data with information on filled prescriptions and diagnoses was retrieved from the Swedish Prescribed Drug Register and the National Patient Register. We identified 34,374 individuals with pure ADHD and 5012 individuals with ADHD and coexisting ASD, aged between 3 and 80 years. The first treatment episode with ADHD medications (≥ 2 filled prescriptions within 90 days) and daily doses of methylphenidate during a 3-year period was measured. Odds ratios (ORs) were calculated for the likelihood of being prescribed ADHD medication in individuals with and without ASD and Wilcoxon rank-sum test was used to compare group differences in dose per day. RESULTS: Individuals with ADHD and coexisting ASD were less likely to start continuous treatment with ADHD medication (ADHD 80.5%; ADHD with ASD 76.2%; OR, 0.80; 95% confidence interval, 0.75-0.86), were less likely to be prescribed methylphenidate, and were more commonly prescribed second line treatments such as dexamphetamine, amphetamine, or modafinil. No group difference was observed for atomoxetine. In adults with ADHD and coexisting ASD, methylphenidate was prescribed in lower daily doses over three years as compared to individuals with pure ADHD. CONCLUSIONS: The findings indicate that there are differences in the medical treatment of individuals with or without ASD. If these differences are due to different medication responses in ASD or due to other factors such as clinicians' perceptions of medication effects in patients with ASD, needs to be further studied. En ligne : https://dx.doi.org/10.1186/s11689-020-09352-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Medications for attention-deficit/hyperactivity disorder in individuals with or without coexisting autism spectrum disorder: analysis of data from the Swedish prescribed drug register [texte imprimé] / Viktoria JOHANSSON, Auteur ; Sven SANDIN, Auteur ; Zheng CHANG, Auteur ; Mark J. TAYLOR, Auteur ; Paul LICHTENSTEIN, Auteur ; Brian M. D'ONOFRIO, Auteur ; Henrik LARSSON, Auteur ; Clara HELLNER, Auteur ; Linda HALLDNER, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Adolescent  Adult  Aged  Aged, 80 and over  Attention Deficit Disorder with Hyperactivity/complications/drug  therapy/epidemiology  Autism Spectrum Disorder/complications/drug therapy/epidemiology  Child  Child, Preschool  Humans  Methylphenidate/therapeutic use  Middle Aged  Pharmaceutical Preparations  Sweden/epidemiology  Young Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinical studies found that medication for attention-deficit/hyperactivity disorder (ADHD) is effective in coexisting autism spectrum disorder (ASD), but current research is based on small clinical studies mainly performed on children or adolescents. We here use register data to examine if individuals with ADHD and coexisting ASD present differences in the prescribing patterns of ADHD medication when compared to individuals with pure ADHD. METHODS: Data with information on filled prescriptions and diagnoses was retrieved from the Swedish Prescribed Drug Register and the National Patient Register. We identified 34,374 individuals with pure ADHD and 5012 individuals with ADHD and coexisting ASD, aged between 3 and 80 years. The first treatment episode with ADHD medications (≥ 2 filled prescriptions within 90 days) and daily doses of methylphenidate during a 3-year period was measured. Odds ratios (ORs) were calculated for the likelihood of being prescribed ADHD medication in individuals with and without ASD and Wilcoxon rank-sum test was used to compare group differences in dose per day. RESULTS: Individuals with ADHD and coexisting ASD were less likely to start continuous treatment with ADHD medication (ADHD 80.5%; ADHD with ASD 76.2%; OR, 0.80; 95% confidence interval, 0.75-0.86), were less likely to be prescribed methylphenidate, and were more commonly prescribed second line treatments such as dexamphetamine, amphetamine, or modafinil. No group difference was observed for atomoxetine. In adults with ADHD and coexisting ASD, methylphenidate was prescribed in lower daily doses over three years as compared to individuals with pure ADHD. CONCLUSIONS: The findings indicate that there are differences in the medical treatment of individuals with or without ASD. If these differences are due to different medication responses in ASD or due to other factors such as clinicians' perceptions of medication effects in patients with ASD, needs to be further studied. En ligne : https://dx.doi.org/10.1186/s11689-020-09352-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573