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Ajouter le résultat dans votre panierAcute administration of NLX-101, a Serotonin 1A receptor agonist, improves auditory temporal processing during development in a mouse model of Fragile X Syndrome / Xin TAO in Journal of Neurodevelopmental Disorders, 17 (2025)
Titre : Acute administration of NLX-101, a Serotonin 1A receptor agonist, improves auditory temporal processing during development in a mouse model of Fragile X Syndrome Type de document : texte imprimé Auteurs : Xin TAO, Auteur ; Katilynne CROOM, Auteur ; Adrian NEWMAN-TANCREDI, Auteur ; Mark VARNEY, Auteur ; Khaleel A. RAZAK, Auteur Langues : Anglais (eng) Mots-clés : Animals Fragile X Syndrome/physiopathology Disease Models, Animal Mice, Knockout Mice Fragile X Mental Retardation Protein/genetics Male Electroencephalography Serotonin 5-HT1 Receptor Agonists/pharmacology/administration & dosage Auditory Perception/drug effects/physiology Female Mice, Inbred C57BL Evoked Potentials, Auditory/drug effects/physiology 5-HT1A receptors Autism spectrum disorders Fragile X syndrome Sensory hypersensitivity Serotonin Speech processing Temporal processing by Institutional Animal Care and Use Committee at the University of California, Riverside. Consent for publication: Not applicable. Competing interests: MV & AN-T are Shareholders in Neurolixis. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a leading known genetic cause of intellectual disability and autism spectrum disorders (ASD)-associated behaviors. A consistent and debilitating phenotype of FXS is auditory hypersensitivity that may lead to delayed language and high anxiety. Consistent with findings in FXS human studies, the mouse model of FXS, the Fmr1 knock out (KO) mouse, shows auditory hypersensitivity and temporal processing deficits. In electroencephalograph (EEG) recordings from humans and mice, these deficits manifest as increased N1 amplitudes in event-related potentials (ERP), increased gamma band single trial power (STP) and reduced phase locking to rapid temporal modulations of sound. In our previous study, we found that administration of the selective serotonin-1 A (5-HT(1A))receptor biased agonist, NLX-101, protected Fmr1 KO mice from auditory hypersensitivity-associated seizures. Here we tested the hypothesis that NLX-101 will normalize EEG phenotypes in developing Fmr1 KO mice. METHODS: To test this hypothesis, we examined the effect of NLX-101 on EEG phenotypes in male and female wildtype (WT) and Fmr1 KO mice. Using epidural electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at two ages, postnatal (P) 21 and 30 days, from both auditory and frontal cortices of awake, freely moving mice, following NLX-101 (at 1.8 mg/kg i.p.) or saline administration. RESULTS: Saline-injected Fmr1 KO mice showed increased N1 amplitudes, increased STP and reduced phase locking to auditory gap-in-noise stimuli versus wild-type mice, reproducing previously published EEG phenotypes. An acute injection of NLX-101 did not alter ERP amplitudes at either P21 or P30, but significantly reduces STP at P30. Inter-trial phase clustering was significantly increased in both age groups with NLX-101, indicating improved temporal processing. The differential effects of serotonin modulation on ERP, background power and temporal processing suggest different developmental mechanisms leading to these phenotypes. CONCLUSIONS: These results suggest that NLX-101 could constitute a promising treatment option for targeting post-synaptic 5-HT(1A) receptors to improve auditory temporal processing, which in turn may improve speech and language function in FXS. En ligne : https://dx.doi.org/10.1186/s11689-024-09587-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Acute administration of NLX-101, a Serotonin 1A receptor agonist, improves auditory temporal processing during development in a mouse model of Fragile X Syndrome [texte imprimé] / Xin TAO, Auteur ; Katilynne CROOM, Auteur ; Adrian NEWMAN-TANCREDI, Auteur ; Mark VARNEY, Auteur ; Khaleel A. RAZAK, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Animals Fragile X Syndrome/physiopathology Disease Models, Animal Mice, Knockout Mice Fragile X Mental Retardation Protein/genetics Male Electroencephalography Serotonin 5-HT1 Receptor Agonists/pharmacology/administration & dosage Auditory Perception/drug effects/physiology Female Mice, Inbred C57BL Evoked Potentials, Auditory/drug effects/physiology 5-HT1A receptors Autism spectrum disorders Fragile X syndrome Sensory hypersensitivity Serotonin Speech processing Temporal processing by Institutional Animal Care and Use Committee at the University of California, Riverside. Consent for publication: Not applicable. Competing interests: MV & AN-T are Shareholders in Neurolixis. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a leading known genetic cause of intellectual disability and autism spectrum disorders (ASD)-associated behaviors. A consistent and debilitating phenotype of FXS is auditory hypersensitivity that may lead to delayed language and high anxiety. Consistent with findings in FXS human studies, the mouse model of FXS, the Fmr1 knock out (KO) mouse, shows auditory hypersensitivity and temporal processing deficits. In electroencephalograph (EEG) recordings from humans and mice, these deficits manifest as increased N1 amplitudes in event-related potentials (ERP), increased gamma band single trial power (STP) and reduced phase locking to rapid temporal modulations of sound. In our previous study, we found that administration of the selective serotonin-1 A (5-HT(1A))receptor biased agonist, NLX-101, protected Fmr1 KO mice from auditory hypersensitivity-associated seizures. Here we tested the hypothesis that NLX-101 will normalize EEG phenotypes in developing Fmr1 KO mice. METHODS: To test this hypothesis, we examined the effect of NLX-101 on EEG phenotypes in male and female wildtype (WT) and Fmr1 KO mice. Using epidural electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at two ages, postnatal (P) 21 and 30 days, from both auditory and frontal cortices of awake, freely moving mice, following NLX-101 (at 1.8 mg/kg i.p.) or saline administration. RESULTS: Saline-injected Fmr1 KO mice showed increased N1 amplitudes, increased STP and reduced phase locking to auditory gap-in-noise stimuli versus wild-type mice, reproducing previously published EEG phenotypes. An acute injection of NLX-101 did not alter ERP amplitudes at either P21 or P30, but significantly reduces STP at P30. Inter-trial phase clustering was significantly increased in both age groups with NLX-101, indicating improved temporal processing. The differential effects of serotonin modulation on ERP, background power and temporal processing suggest different developmental mechanisms leading to these phenotypes. CONCLUSIONS: These results suggest that NLX-101 could constitute a promising treatment option for targeting post-synaptic 5-HT(1A) receptors to improve auditory temporal processing, which in turn may improve speech and language function in FXS. En ligne : https://dx.doi.org/10.1186/s11689-024-09587-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Resting state EEG in young children with Tuberous Sclerosis Complex: associations with medications and seizures Type de document : texte imprimé Auteurs : Caitlin C. CLEMENTS, Auteur ; Anne-Michelle ENGELSTAD, Auteur ; Carol L. WILKINSON, Auteur ; Carly HYDE, Auteur ; Megan HARTNEY, Auteur ; Alexandra SIMMONS, Auteur ; Helen TAGER-FLUSBERG, Auteur ; Shafali JESTE, Auteur ; Charles A. NELSON, Auteur Langues : Anglais (eng) Mots-clés : Humans Tuberous Sclerosis/physiopathology/drug therapy/complications Male Female Child, Preschool Electroencephalography Seizures/physiopathology/drug therapy/etiology Cross-Sectional Studies Anticonvulsants/therapeutic use/pharmacology Infant Biomarker Eeg Epilepsy GABA agonists Seizures Tuberous Sclerosis Complex participating families. Study procedures were approved by the Boston Children’s Hospital Institutional Review Board ( IRB P00017878 for JETS IRB P00018377 for ISP2). Consent for publication: All participating families consented to having the results of the research published in medical books or journals. Competing interests: SJ reports a relationship with TSC Alliance that includes board membership and travel reimbursement. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response. However, seizures and antiepileptic medications also affect resting neural oscillatory activity and could undermine the utility of resting state EEG features as biomarkers in neurodevelopmental disorders such as TSC. METHODS: This paper compares resting state EEG features in a cross-sectional cohort of young children with TSC (n = 49, ages 12-37 months) to 49 age- and sex-matched typically developing controls. Within children with TSC, associations were examined between resting state EEG features, seizure severity composite score, and use of GABA agonists. RESULTS: Compared to matched typically developing children, children with TSC showed significantly greater beta power in permutation cluster analyses. Children with TSC also showed significantly greater aperiodic offset (reflecting nonoscillatory neuronal firing) after power spectra were parameterized using SpecParam into aperiodic and periodic components. Within children with TSC, both greater seizure severity and use of GABAergic antiepileptic medication were significantly and independently associated with increased periodic peak beta power. CONCLUSIONS: The elevated peak beta power observed in children with TSC compared to matched typically developing controls may be driven by both seizures and GABA agonist use. It is recommended to collect seizure and medication data alongside EEG data for clinical trials. These results highlight the challenge of using resting state EEG features as biomarkers in trials with neurodevelopmental disabilities when epilepsy and anti-epileptic medication are common. En ligne : https://dx.doi.org/10.1186/s11689-025-09590-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Resting state EEG in young children with Tuberous Sclerosis Complex: associations with medications and seizures [texte imprimé] / Caitlin C. CLEMENTS, Auteur ; Anne-Michelle ENGELSTAD, Auteur ; Carol L. WILKINSON, Auteur ; Carly HYDE, Auteur ; Megan HARTNEY, Auteur ; Alexandra SIMMONS, Auteur ; Helen TAGER-FLUSBERG, Auteur ; Shafali JESTE, Auteur ; Charles A. NELSON, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Tuberous Sclerosis/physiopathology/drug therapy/complications Male Female Child, Preschool Electroencephalography Seizures/physiopathology/drug therapy/etiology Cross-Sectional Studies Anticonvulsants/therapeutic use/pharmacology Infant Biomarker Eeg Epilepsy GABA agonists Seizures Tuberous Sclerosis Complex participating families. Study procedures were approved by the Boston Children’s Hospital Institutional Review Board ( IRB P00017878 for JETS IRB P00018377 for ISP2). Consent for publication: All participating families consented to having the results of the research published in medical books or journals. Competing interests: SJ reports a relationship with TSC Alliance that includes board membership and travel reimbursement. Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response. However, seizures and antiepileptic medications also affect resting neural oscillatory activity and could undermine the utility of resting state EEG features as biomarkers in neurodevelopmental disorders such as TSC. METHODS: This paper compares resting state EEG features in a cross-sectional cohort of young children with TSC (n = 49, ages 12-37 months) to 49 age- and sex-matched typically developing controls. Within children with TSC, associations were examined between resting state EEG features, seizure severity composite score, and use of GABA agonists. RESULTS: Compared to matched typically developing children, children with TSC showed significantly greater beta power in permutation cluster analyses. Children with TSC also showed significantly greater aperiodic offset (reflecting nonoscillatory neuronal firing) after power spectra were parameterized using SpecParam into aperiodic and periodic components. Within children with TSC, both greater seizure severity and use of GABAergic antiepileptic medication were significantly and independently associated with increased periodic peak beta power. CONCLUSIONS: The elevated peak beta power observed in children with TSC compared to matched typically developing controls may be driven by both seizures and GABA agonist use. It is recommended to collect seizure and medication data alongside EEG data for clinical trials. These results highlight the challenge of using resting state EEG features as biomarkers in trials with neurodevelopmental disabilities when epilepsy and anti-epileptic medication are common. En ligne : https://dx.doi.org/10.1186/s11689-025-09590-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Reduced white matter integrity and disrupted brain network in children with type 2 and 3 spinal muscular atrophy Type de document : texte imprimé Auteurs : Huirong NIE, Auteur ; Shasha LAN, Auteur ; Huan WANG, Auteur ; Pei XIANG, Auteur ; Mengzhen YAN, Auteur ; Yang FAN, Auteur ; Wanqing SHEN, Auteur ; Yijuan LI, Auteur ; Wen TANG, Auteur ; Zhiyun YANG, Auteur ; Yujian LIANG, Auteur ; Yingqian CHEN, Auteur Langues : Anglais (eng) Mots-clés : Humans Male Female White Matter/diagnostic imaging/pathology Child Diffusion Tensor Imaging Spinal Muscular Atrophies of Childhood/diagnostic imaging/pathology Adolescent Brain/diagnostic imaging/pathology Nerve Net/diagnostic imaging/pathology Prospective Studies Spinal muscular atrophy Structural magnetic resonance imaging White matter The First Affiliated Hospital of Sun Yat-Sen University (No. [2021]710). Informed consent: Written informed consent was obtained from all subjects in this study. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Spinal muscular atrophy (SMA) is caused by reduced expression of survival motor neuron (SMN) protein. Previous studies indicated SMA causes not only lower motor neuron degeneration but also extensive brain involvement. This study aimed to investigate the changes of brain white matter and structural network using diffusion tensor imaging (DTI) in children with type 2 and 3 SMA. METHODS: Forty-two type 2 and 3 pediatric SMA patients and 42 age- and gender-matched healthy controls (HC) were prospectively enrolled in this study. The tract-based spatial statistics (TBSS) was used to assess white matter integrity and the structural network properties were calculated based on DTI white matter fiber tracking and the graph theory approach. A partial correlation was performed to explore the relationship between white matter parameters and clinical characteristics. RESULTS: In total, 42 patients (mean age, 10.86 ± 4.07 years; 23 men) were included. TBSS analysis revealed widespread white matter changes in SMA patients. The SMA patients showed changes in multiple small-world and network efficiency parameters. Compared to the HC group, SMA showed increased characteristic path length (L(p)), normalized clustering coefficient (γ), small-world characteristic (σ), and decreased global efficiency (E(glob)) (all p < 0.05). In the node properties, right supramarginal gyrus, right orbital part of superior frontal gyrus, right supplementary motor area, and left median cingulate and paracingulate gyri changed in SMA patients. A decreased axial diffusivity (AD) value was associated with lower Hammersmith Functional Motor Scale-Expanded scores (r = 0.45, p = 0.02), which means that the symptoms of SMA patients are more severe. CONCLUSIONS: This study found white matter and DTI-based brain network abnormalities in SMA patients, suggesting SMN protein deficiency may affect white matter development. En ligne : https://dx.doi.org/10.1186/s11689-025-09592-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Reduced white matter integrity and disrupted brain network in children with type 2 and 3 spinal muscular atrophy [texte imprimé] / Huirong NIE, Auteur ; Shasha LAN, Auteur ; Huan WANG, Auteur ; Pei XIANG, Auteur ; Mengzhen YAN, Auteur ; Yang FAN, Auteur ; Wanqing SHEN, Auteur ; Yijuan LI, Auteur ; Wen TANG, Auteur ; Zhiyun YANG, Auteur ; Yujian LIANG, Auteur ; Yingqian CHEN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Male Female White Matter/diagnostic imaging/pathology Child Diffusion Tensor Imaging Spinal Muscular Atrophies of Childhood/diagnostic imaging/pathology Adolescent Brain/diagnostic imaging/pathology Nerve Net/diagnostic imaging/pathology Prospective Studies Spinal muscular atrophy Structural magnetic resonance imaging White matter The First Affiliated Hospital of Sun Yat-Sen University (No. [2021]710). Informed consent: Written informed consent was obtained from all subjects in this study. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Spinal muscular atrophy (SMA) is caused by reduced expression of survival motor neuron (SMN) protein. Previous studies indicated SMA causes not only lower motor neuron degeneration but also extensive brain involvement. This study aimed to investigate the changes of brain white matter and structural network using diffusion tensor imaging (DTI) in children with type 2 and 3 SMA. METHODS: Forty-two type 2 and 3 pediatric SMA patients and 42 age- and gender-matched healthy controls (HC) were prospectively enrolled in this study. The tract-based spatial statistics (TBSS) was used to assess white matter integrity and the structural network properties were calculated based on DTI white matter fiber tracking and the graph theory approach. A partial correlation was performed to explore the relationship between white matter parameters and clinical characteristics. RESULTS: In total, 42 patients (mean age, 10.86 ± 4.07 years; 23 men) were included. TBSS analysis revealed widespread white matter changes in SMA patients. The SMA patients showed changes in multiple small-world and network efficiency parameters. Compared to the HC group, SMA showed increased characteristic path length (L(p)), normalized clustering coefficient (γ), small-world characteristic (σ), and decreased global efficiency (E(glob)) (all p < 0.05). In the node properties, right supramarginal gyrus, right orbital part of superior frontal gyrus, right supplementary motor area, and left median cingulate and paracingulate gyri changed in SMA patients. A decreased axial diffusivity (AD) value was associated with lower Hammersmith Functional Motor Scale-Expanded scores (r = 0.45, p = 0.02), which means that the symptoms of SMA patients are more severe. CONCLUSIONS: This study found white matter and DTI-based brain network abnormalities in SMA patients, suggesting SMN protein deficiency may affect white matter development. En ligne : https://dx.doi.org/10.1186/s11689-025-09592-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Regional hippocampal thinning and gyrification abnormalities and associated cognition in children with prenatal alcohol exposure Type de document : texte imprimé Auteurs : Blake A. GIMBEL, Auteur ; Jeffrey R. WOZNIAK, Auteur ; Bryon A. MUELLER, Auteur ; Kent A. TUOMINEN, Auteur ; Abigail M. ERNST, Auteur ; Mary E. ANTHONY, Auteur ; Erik DE WATER, Auteur ; CIFASD, Auteur ; Donovan J. ROEDIGER, Auteur Langues : Anglais (eng) Mots-clés : Humans Hippocampus/diagnostic imaging/pathology/abnormalities Female Child Adolescent Male Magnetic Resonance Imaging Fetal Alcohol Spectrum Disorders/diagnostic imaging/pathology Pregnancy Prenatal Exposure Delayed Effects/diagnostic imaging/pathology Neuropsychological Tests Cognition Fetal alcohol spectrum disorders Hippocampal gyrification Hippocampal thickness Memory Prenatal alcohol exposure study were approved by the University of Minnesota IRB and all participants' parents/guardians participated in a comprehensive informed consent procedure and signed consent forms. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal alcohol exposure (PAE) impacts hippocampal structure and function, contributing to deficits in memory and decision-making in affected individuals. Here, we evaluate hippocampal anomalies in children with PAE and an unexposed comparison group using advanced MRI methods that characterize hippocampal curvature and thickness. METHODS: Participants, ages 8 to 16 years, included children with PAE (n = 48) and an unexposed comparison group (n = 46) who underwent a dysmorphology exam, neuropsychological assessment, and an MRI scan. Height, weight, head circumference, and dysmorphic facial features were evaluated. Of those with PAE, 4.2% had fetal alcohol syndrome (FAS), 22.9% had partial FAS, and 72.9% had alcohol-related neurodevelopmental disorder. Neuropsychological testing included measures of intelligence and memory functioning. T1-weighted anatomical data were processed with the Hippunfold pipeline, which "unfolds" the complex hippocampal structure onto a template surface and provides measures of thickness and gyrification/curvature at each vertex. Permutation Analysis of Linear Models (PALM) was used to test for group differences (PAE vs. comparison) in hippocampal thickness and gyrification at each vertex and also to assess correlations with cognitive functioning. RESULTS: There were significant regional differences in thickness and gyrification across bilateral hippocampi, with the PAE group showing substantially thinner tissue and less curvature than the comparison group, especially in CA1 and subiculum regions. For those with PAE, thinner subicular tissue (bilateral) was associated with lower IQ. Also in the PAE group, lower episodic memory performance was associated with thinness in the right hippocampus, especially in the subiculum region. There were no significant regional hippocampal patterns that were associated with cognitive functioning for individuals in the unexposed comparison group. CONCLUSIONS: We used a novel MRI method to evaluate hippocampal structure in children with PAE and an unexposed comparison group. The data suggest that PAE disrupts hippocampal development, impacting both the early-stage folding of the structure and its ultimate thickness. The data also demonstrate that these developmental anomalies have functional consequences in terms of core memory functions as well as global intellectual functioning in children with PAE. En ligne : https://dx.doi.org/10.1186/s11689-025-09595-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Regional hippocampal thinning and gyrification abnormalities and associated cognition in children with prenatal alcohol exposure [texte imprimé] / Blake A. GIMBEL, Auteur ; Jeffrey R. WOZNIAK, Auteur ; Bryon A. MUELLER, Auteur ; Kent A. TUOMINEN, Auteur ; Abigail M. ERNST, Auteur ; Mary E. ANTHONY, Auteur ; Erik DE WATER, Auteur ; CIFASD, Auteur ; Donovan J. ROEDIGER, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Hippocampus/diagnostic imaging/pathology/abnormalities Female Child Adolescent Male Magnetic Resonance Imaging Fetal Alcohol Spectrum Disorders/diagnostic imaging/pathology Pregnancy Prenatal Exposure Delayed Effects/diagnostic imaging/pathology Neuropsychological Tests Cognition Fetal alcohol spectrum disorders Hippocampal gyrification Hippocampal thickness Memory Prenatal alcohol exposure study were approved by the University of Minnesota IRB and all participants' parents/guardians participated in a comprehensive informed consent procedure and signed consent forms. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal alcohol exposure (PAE) impacts hippocampal structure and function, contributing to deficits in memory and decision-making in affected individuals. Here, we evaluate hippocampal anomalies in children with PAE and an unexposed comparison group using advanced MRI methods that characterize hippocampal curvature and thickness. METHODS: Participants, ages 8 to 16 years, included children with PAE (n = 48) and an unexposed comparison group (n = 46) who underwent a dysmorphology exam, neuropsychological assessment, and an MRI scan. Height, weight, head circumference, and dysmorphic facial features were evaluated. Of those with PAE, 4.2% had fetal alcohol syndrome (FAS), 22.9% had partial FAS, and 72.9% had alcohol-related neurodevelopmental disorder. Neuropsychological testing included measures of intelligence and memory functioning. T1-weighted anatomical data were processed with the Hippunfold pipeline, which "unfolds" the complex hippocampal structure onto a template surface and provides measures of thickness and gyrification/curvature at each vertex. Permutation Analysis of Linear Models (PALM) was used to test for group differences (PAE vs. comparison) in hippocampal thickness and gyrification at each vertex and also to assess correlations with cognitive functioning. RESULTS: There were significant regional differences in thickness and gyrification across bilateral hippocampi, with the PAE group showing substantially thinner tissue and less curvature than the comparison group, especially in CA1 and subiculum regions. For those with PAE, thinner subicular tissue (bilateral) was associated with lower IQ. Also in the PAE group, lower episodic memory performance was associated with thinness in the right hippocampus, especially in the subiculum region. There were no significant regional hippocampal patterns that were associated with cognitive functioning for individuals in the unexposed comparison group. CONCLUSIONS: We used a novel MRI method to evaluate hippocampal structure in children with PAE and an unexposed comparison group. The data suggest that PAE disrupts hippocampal development, impacting both the early-stage folding of the structure and its ultimate thickness. The data also demonstrate that these developmental anomalies have functional consequences in terms of core memory functions as well as global intellectual functioning in children with PAE. En ligne : https://dx.doi.org/10.1186/s11689-025-09595-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Validation of the Food Safe Zone questionnaire for families of individuals with Prader-Willi syndrome Type de document : texte imprimé Auteurs : Elisabeth M. DYKENS, Auteur ; Elizabeth ROOF, Auteur ; Hailee HUNT-HAWKINS, Auteur ; Theresa V. STRONG, Auteur Langues : Anglais (eng) Mots-clés : Humans Prader-Willi Syndrome/psychology/complications Female Male Child Psychometrics Hyperphagia/etiology/psychology/diagnosis Surveys and Questionnaires Adult Adolescent Parents/psychology Child, Preschool Food Safety Reproducibility of Results Family/psychology Feeding Behavior Clinical trials Hyperphagia PWS food safety Prader-Willi syndrome this study was obtained by the Vanderbilt University Institutional Review Board, Integrated Science Committee, under the auspices of the University’s Human Research Protections Program. Vanderbilt participants provided written, informed consent using the e-consent function of RedCap, a secure, web-based data collection platform. After consenting, parents were invited to complete 3 questionnaires on RedCap. Additional study approval was obtained for participants recruited from the Foundation for Prader-Willi Research (FPWR) Patient Registry. Prior to collecting data from the Registry, the study was reviewed and approved by FPWR’s research committee and IRB. All registrants in FPWR’s Patient Registry gave approval for their de-identified data to be used for research purposes. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS), a genetic neurodevelopmental disorder, is characterized by hyperphagia and significant behavioral problems. Hyperphagic individuals with PWS are chronically hungry yet rarely feel sated, and often engage in food-seeking behaviors. To avoid life-threatening obesity in their children, families implement food security strategies (e.g., locking food sources, constant supervision around food, alerting others). Although widely used, these strategies have yet to be systematically examined. We thus developed and analyzed the psychometric properties of a new measure of these diverse strategies, the Food Safe Zone, and evaluated them in relation to hyperphagic symptoms and demographic variables. In doing so, we also shine a light on the extraordinary efforts of families in managing their children's hyperphagia. METHODS: Our team developed 20 FSZ items that were revised for clarity and completeness in an iterative feedback process with stakeholders, including parents, PWS specialists, and individuals with PWS. The FSZ was pilot tested, descriptive findings were reviewed by additional stakeholders, and then administered to 624 parents in a large-scale study. Based on an open-ended question, "Is there anything else you do to ensure food safety?" two additional items were added and evaluated in a follow-up study. RESULTS: Principal component analyses revealed that 21 FSZ items loaded onto 5 factors that were readily interpretable, accounting for 67% of test variance: Alerting Others and Food Supervision in the Community; Locking or Restricting Food Sources; Checking for Food; At Home Supervision and Meals; and Avoiding Food Settings. Internal consistency and test-rest reliability were robust. Convergent validity analyses revealed that parents implemented FSZ strategies in response to the severity of their child's hyperphagia, and not their child's age, gender or PWS genetic subtype. CONCLUSIONS: The psychometrically sound FSZ holds promise for future research, especially on the effects of food safety tactics on family members. In future clinical trials, the FSZ could also be used to help parents think critically about their food safety tactics in relation to their child's hyperphagia, or as an exploratory endpoint; if hyperphagia is lessened, so too may food safety tactics, thereby enhancing familial quality of life. En ligne : https://dx.doi.org/10.1186/s11689-024-09589-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Validation of the Food Safe Zone questionnaire for families of individuals with Prader-Willi syndrome [texte imprimé] / Elisabeth M. DYKENS, Auteur ; Elizabeth ROOF, Auteur ; Hailee HUNT-HAWKINS, Auteur ; Theresa V. STRONG, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Prader-Willi Syndrome/psychology/complications Female Male Child Psychometrics Hyperphagia/etiology/psychology/diagnosis Surveys and Questionnaires Adult Adolescent Parents/psychology Child, Preschool Food Safety Reproducibility of Results Family/psychology Feeding Behavior Clinical trials Hyperphagia PWS food safety Prader-Willi syndrome this study was obtained by the Vanderbilt University Institutional Review Board, Integrated Science Committee, under the auspices of the University’s Human Research Protections Program. Vanderbilt participants provided written, informed consent using the e-consent function of RedCap, a secure, web-based data collection platform. After consenting, parents were invited to complete 3 questionnaires on RedCap. Additional study approval was obtained for participants recruited from the Foundation for Prader-Willi Research (FPWR) Patient Registry. Prior to collecting data from the Registry, the study was reviewed and approved by FPWR’s research committee and IRB. All registrants in FPWR’s Patient Registry gave approval for their de-identified data to be used for research purposes. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Prader-Willi syndrome (PWS), a genetic neurodevelopmental disorder, is characterized by hyperphagia and significant behavioral problems. Hyperphagic individuals with PWS are chronically hungry yet rarely feel sated, and often engage in food-seeking behaviors. To avoid life-threatening obesity in their children, families implement food security strategies (e.g., locking food sources, constant supervision around food, alerting others). Although widely used, these strategies have yet to be systematically examined. We thus developed and analyzed the psychometric properties of a new measure of these diverse strategies, the Food Safe Zone, and evaluated them in relation to hyperphagic symptoms and demographic variables. In doing so, we also shine a light on the extraordinary efforts of families in managing their children's hyperphagia. METHODS: Our team developed 20 FSZ items that were revised for clarity and completeness in an iterative feedback process with stakeholders, including parents, PWS specialists, and individuals with PWS. The FSZ was pilot tested, descriptive findings were reviewed by additional stakeholders, and then administered to 624 parents in a large-scale study. Based on an open-ended question, "Is there anything else you do to ensure food safety?" two additional items were added and evaluated in a follow-up study. RESULTS: Principal component analyses revealed that 21 FSZ items loaded onto 5 factors that were readily interpretable, accounting for 67% of test variance: Alerting Others and Food Supervision in the Community; Locking or Restricting Food Sources; Checking for Food; At Home Supervision and Meals; and Avoiding Food Settings. Internal consistency and test-rest reliability were robust. Convergent validity analyses revealed that parents implemented FSZ strategies in response to the severity of their child's hyperphagia, and not their child's age, gender or PWS genetic subtype. CONCLUSIONS: The psychometrically sound FSZ holds promise for future research, especially on the effects of food safety tactics on family members. In future clinical trials, the FSZ could also be used to help parents think critically about their food safety tactics in relation to their child's hyperphagia, or as an exploratory endpoint; if hyperphagia is lessened, so too may food safety tactics, thereby enhancing familial quality of life. En ligne : https://dx.doi.org/10.1186/s11689-024-09589-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : An exploratory fetal MRI study examining the impact of 22q11.2 microdeletion syndrome on early brain growth Type de document : texte imprimé Auteurs : Daniel CROMB, Auteur ; Tom FINCK, Auteur ; Alexandra F. BONTHRONE, Auteur ; Alena UUS, Auteur ; Milou VAN POPPEL, Auteur ; Johannes STEINWEG, Auteur ; David F LLOYD, Auteur ; Kuberan PUSHPARAJAH, Auteur ; Reza RAZAVI, Auteur ; Serena J. COUNSELL, Auteur ; Mary. RUTHERFORD, Auteur Langues : Anglais (eng) Mots-clés : Humans Magnetic Resonance Imaging Female Brain/diagnostic imaging/growth & development/embryology/pathology DiGeorge Syndrome/diagnostic imaging Pregnancy Male Heart Defects, Congenital/diagnostic imaging Fetus/diagnostic imaging Adult Prenatal Diagnosis 22q deletion syndrome Fetal MRI authors declare no competing interests. Ethical approval: The National Research Ethics Service West London committee provided ethical approval (22qDS and CHD fetuses: 07/H0707/105 Control fetuses: 14/LO/1806). Informed, written consent was obtained from all participants before undergoing fetal MRI. We confirm that all methods were performed in accordance with the relevant guidelines and regulations. Index. décimale : PER Périodiques Résumé : BACKGROUND: Improved long-term outcomes, related to advances in surgical and clinical care of infants with congenital heart disease (CHD), has shifted focus onto the accompanying and later-onset cognitive and neuropsychiatric disorders in those who also have 22q11.2 deletion syndrome (22qDS). 22qDS is itself associated with neurodevelopmental impairments and altered brain growth. However, when brain growth in 22qDS first deviates from normal is unknown, and whether impaired brain development is primarily genetics-driven or a secondary consequence of the underlying CHD remains incompletely understood. METHODS: In this small, exploratory study, we use fetal MRI to assess volumetric brain development in 22qDS by comparing fetal brain morphometry to a set of gestation and sex-matched healthy controls, and a cohort of gestation and sex-matched fetuses with the same CHD diagnoses but without 22q11.2 deletion. Structural T2-weighted fetal brain images were acquired using a 1.5T MRI scanner. MR scanner and sequence parameters were identical in all cohorts. Motion-corrected images underwent segmentation using an automated pipeline developed for fetal brain MRI. Total brain tissue volumes, volumes for four different tissue regions (cortical grey matter, white matter, deep grey matter and cerebellum), cerebrospinal fluid and total intracranial volumes were calculated. RESULTS: Antenatal imaging was acquired between 29 and 35 weeks gestation. Thirty-three fetuses were included (7 22qDS; 14 isolated CHD; 12 healthy control). White matter volumes were significantly reduced in fetuses with 22qDS compared to control fetuses (p = 0.028), but not to those with CHD without 22q11.2 deletion (p = 0.09). Large effect-sizes were seen between the 22qDS and isolated CHD cohorts (D(Cohen) = 0.81), and between the 22qDS and control cohorts (D(Cohen) = 1.2) for white matter volumes. No significant differences were seen in volumes of other brain regions between groups. CONCLUSIONS: This exploratory study expands our existing knowledge on neurodevelopmental impairments in 22qDS to the fetal period by highlighting reduced white matter volumes compared to gestation and sex-matched control fetuses during this time-period. Our findings suggest that impaired white matter growth in fetuses with both 22qDS and CHD may not be fully explained by any underlying CHD. En ligne : https://dx.doi.org/10.1186/s11689-025-09594-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] An exploratory fetal MRI study examining the impact of 22q11.2 microdeletion syndrome on early brain growth [texte imprimé] / Daniel CROMB, Auteur ; Tom FINCK, Auteur ; Alexandra F. BONTHRONE, Auteur ; Alena UUS, Auteur ; Milou VAN POPPEL, Auteur ; Johannes STEINWEG, Auteur ; David F LLOYD, Auteur ; Kuberan PUSHPARAJAH, Auteur ; Reza RAZAVI, Auteur ; Serena J. COUNSELL, Auteur ; Mary. RUTHERFORD, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Magnetic Resonance Imaging Female Brain/diagnostic imaging/growth & development/embryology/pathology DiGeorge Syndrome/diagnostic imaging Pregnancy Male Heart Defects, Congenital/diagnostic imaging Fetus/diagnostic imaging Adult Prenatal Diagnosis 22q deletion syndrome Fetal MRI authors declare no competing interests. Ethical approval: The National Research Ethics Service West London committee provided ethical approval (22qDS and CHD fetuses: 07/H0707/105 Control fetuses: 14/LO/1806). Informed, written consent was obtained from all participants before undergoing fetal MRI. We confirm that all methods were performed in accordance with the relevant guidelines and regulations. Index. décimale : PER Périodiques Résumé : BACKGROUND: Improved long-term outcomes, related to advances in surgical and clinical care of infants with congenital heart disease (CHD), has shifted focus onto the accompanying and later-onset cognitive and neuropsychiatric disorders in those who also have 22q11.2 deletion syndrome (22qDS). 22qDS is itself associated with neurodevelopmental impairments and altered brain growth. However, when brain growth in 22qDS first deviates from normal is unknown, and whether impaired brain development is primarily genetics-driven or a secondary consequence of the underlying CHD remains incompletely understood. METHODS: In this small, exploratory study, we use fetal MRI to assess volumetric brain development in 22qDS by comparing fetal brain morphometry to a set of gestation and sex-matched healthy controls, and a cohort of gestation and sex-matched fetuses with the same CHD diagnoses but without 22q11.2 deletion. Structural T2-weighted fetal brain images were acquired using a 1.5T MRI scanner. MR scanner and sequence parameters were identical in all cohorts. Motion-corrected images underwent segmentation using an automated pipeline developed for fetal brain MRI. Total brain tissue volumes, volumes for four different tissue regions (cortical grey matter, white matter, deep grey matter and cerebellum), cerebrospinal fluid and total intracranial volumes were calculated. RESULTS: Antenatal imaging was acquired between 29 and 35 weeks gestation. Thirty-three fetuses were included (7 22qDS; 14 isolated CHD; 12 healthy control). White matter volumes were significantly reduced in fetuses with 22qDS compared to control fetuses (p = 0.028), but not to those with CHD without 22q11.2 deletion (p = 0.09). Large effect-sizes were seen between the 22qDS and isolated CHD cohorts (D(Cohen) = 0.81), and between the 22qDS and control cohorts (D(Cohen) = 1.2) for white matter volumes. No significant differences were seen in volumes of other brain regions between groups. CONCLUSIONS: This exploratory study expands our existing knowledge on neurodevelopmental impairments in 22qDS to the fetal period by highlighting reduced white matter volumes compared to gestation and sex-matched control fetuses during this time-period. Our findings suggest that impaired white matter growth in fetuses with both 22qDS and CHD may not be fully explained by any underlying CHD. En ligne : https://dx.doi.org/10.1186/s11689-025-09594-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : The striatal matrix compartment is expanded in autism spectrum disorder Type de document : texte imprimé Auteurs : Jeff L. WAUGH, Auteur ; Asim O.A. HASSAN, Auteur ; Adrian T. FUNK, Auteur ; Joseph A. MALDJIAN, Auteur Langues : Anglais (eng) Mots-clés : Humans Autism Spectrum Disorder/diagnostic imaging/pathology Male Child Female Corpus Striatum/diagnostic imaging/pathology Adult Adolescent Diffusion Tensor Imaging Young Adult Cohort Studies Autism Connectivity-based Parcellation Matrix Striatum Striosome Tractography and supervised by our Institutional Review Board. All analyses were carried out on de-identified MRI data. Consent was obtained by the studies that originated that MRI data. Consent for publication: No individually-identifiable data is presented in this manuscript. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is the second-most common neurodevelopmental disorder in childhood. This complex developmental disorder manifests with restricted interests, repetitive behaviors, and difficulties in communication and social awareness. The inherited and acquired causes of ASD impact many and diverse brain regions, challenging efforts to identify a shared neuroanatomical substrate for this range of symptoms. The striatum and its connections are among the most implicated sites of abnormal structure and/or function in ASD. Striatal projection neurons develop in segregated tissue compartments, the matrix and striosome, that are histochemically, pharmacologically, and functionally distinct. Immunohistochemical assessment of ASD and animal models of autism described abnormal matrix:striosome volume ratios, with an possible shift from striosome to matrix volume. Shifting the matrix:striosome ratio could result from expansion in matrix, reduction in striosome, spatial redistribution of the compartments, or a combination of these changes. Each type of ratio-shifting abnormality may predispose to ASD but yield different combinations of ASD features. METHODS: We developed a cohort of 426 children and adults (213 matched ASD-control pairs) and performed connectivity-based parcellation (diffusion tractography) of the striatum. This identified voxels with matrix-like and striosome-like patterns of structural connectivity. RESULTS: Matrix-like volume was increased in ASD, with no evident change in the volume or organization of the striosome-like compartment. The inter-compartment volume difference (matrix minus striosome) within each individual was 31% larger in ASD. Matrix-like volume was increased in both caudate and putamen, and in somatotopic zones throughout the rostral-caudal extent of the striatum. Subjects with moderate elevations in ADOS (Autism Diagnostic Observation Schedule) scores had increased matrix-like volume, but those with highly elevated ADOS scores had 3.7-fold larger increases in matrix-like volume. CONCLUSIONS: Matrix and striosome are embedded in distinct structural and functional networks, suggesting that compartment-selective injury or maldevelopment may mediate specific and distinct clinical features. Previously, assessing the striatal compartments in humans required post mortem tissue. Striatal parcellation provides a means to assess neuropsychiatric diseases for compartment-specific abnormalities. While this ASD cohort had increased matrix-like volume, other mechanisms that shift the matrix:striosome ratio may also increase the chance of developing the diverse social, sensory, and motor phenotypes of ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09596-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] The striatal matrix compartment is expanded in autism spectrum disorder [texte imprimé] / Jeff L. WAUGH, Auteur ; Asim O.A. HASSAN, Auteur ; Adrian T. FUNK, Auteur ; Joseph A. MALDJIAN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Autism Spectrum Disorder/diagnostic imaging/pathology Male Child Female Corpus Striatum/diagnostic imaging/pathology Adult Adolescent Diffusion Tensor Imaging Young Adult Cohort Studies Autism Connectivity-based Parcellation Matrix Striatum Striosome Tractography and supervised by our Institutional Review Board. All analyses were carried out on de-identified MRI data. Consent was obtained by the studies that originated that MRI data. Consent for publication: No individually-identifiable data is presented in this manuscript. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is the second-most common neurodevelopmental disorder in childhood. This complex developmental disorder manifests with restricted interests, repetitive behaviors, and difficulties in communication and social awareness. The inherited and acquired causes of ASD impact many and diverse brain regions, challenging efforts to identify a shared neuroanatomical substrate for this range of symptoms. The striatum and its connections are among the most implicated sites of abnormal structure and/or function in ASD. Striatal projection neurons develop in segregated tissue compartments, the matrix and striosome, that are histochemically, pharmacologically, and functionally distinct. Immunohistochemical assessment of ASD and animal models of autism described abnormal matrix:striosome volume ratios, with an possible shift from striosome to matrix volume. Shifting the matrix:striosome ratio could result from expansion in matrix, reduction in striosome, spatial redistribution of the compartments, or a combination of these changes. Each type of ratio-shifting abnormality may predispose to ASD but yield different combinations of ASD features. METHODS: We developed a cohort of 426 children and adults (213 matched ASD-control pairs) and performed connectivity-based parcellation (diffusion tractography) of the striatum. This identified voxels with matrix-like and striosome-like patterns of structural connectivity. RESULTS: Matrix-like volume was increased in ASD, with no evident change in the volume or organization of the striosome-like compartment. The inter-compartment volume difference (matrix minus striosome) within each individual was 31% larger in ASD. Matrix-like volume was increased in both caudate and putamen, and in somatotopic zones throughout the rostral-caudal extent of the striatum. Subjects with moderate elevations in ADOS (Autism Diagnostic Observation Schedule) scores had increased matrix-like volume, but those with highly elevated ADOS scores had 3.7-fold larger increases in matrix-like volume. CONCLUSIONS: Matrix and striosome are embedded in distinct structural and functional networks, suggesting that compartment-selective injury or maldevelopment may mediate specific and distinct clinical features. Previously, assessing the striatal compartments in humans required post mortem tissue. Striatal parcellation provides a means to assess neuropsychiatric diseases for compartment-specific abnormalities. While this ASD cohort had increased matrix-like volume, other mechanisms that shift the matrix:striosome ratio may also increase the chance of developing the diverse social, sensory, and motor phenotypes of ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09596-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Atypical audio-visual neural synchrony and speech processing in early autism Type de document : texte imprimé Auteurs : Xiaoyue WANG, Auteur ; Sophie BOUTON, Auteur ; Nada KOJOVIC, Auteur ; Anne-Lise GIRAUD, Auteur ; Marie SCHAER, Auteur Langues : Anglais (eng) Mots-clés : Humans Female Male Speech Perception/physiology Autism Spectrum Disorder/physiopathology Child, Preschool Electroencephalography Visual Perception/physiology Auditory Perception/physiology Eye-Tracking Technology Child Photic Stimulation Brain/physiopathology Acoustic Stimulation Audio-visual Autism spectrum disorders (ASD) Gaze direction Oscillation phase entrainment Speech envelope Visual motion Ethics approval and consent to participate: Informed consent was obtained from the parents of all participants prior to inclusion in the study. The research was conducted with the ethical standards set forth by the Ethics Committee of the Faculty of Medicine at the University of Geneva Hospital and adhered to the principles outlined in the Declaration of Helsinki. Competing interests: The authors declare no conflict of interest. Preprint servers: The manuscript was deposited as a preprint in bioRxiv with the license CC BY-NC-ND 4.0. Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with Autism Spectrum disorder (ASD) often exhibit communication difficulties that may stem from basic auditory temporal integration impairment but also be aggravated by an audio-visual integration deficit, resulting in a lack of interest in face-to-face communication. This study addresses whether speech processing anomalies in young autistic children (mean age 3.09-year-old) are associated with alterations of audio-visual temporal integration. METHODS: We used high-density electroencephalography (HD-EEG) and eye tracking to record brain activity and gaze patterns in 31 children with ASD (6 females) and 33 typically developing (TD) children (11 females), while they watched cartoon videos. Neural responses to temporal audio-visual stimuli were analyzed using Temporal Response Functions model and phase analyses for audiovisual temporal coordination. RESULTS: The reconstructability of speech signals from auditory responses was reduced in children with ASD compared to TD, but despite more restricted gaze patterns in ASD it was similar for visual responses in both groups. Speech reception was most strongly affected when visual speech information was also present, an interference that was not seen in TD children. These differences were associated with a broader phase angle distribution (exceeding pi/2) in the EEG theta range in children with ASD, signaling reduced reliability of audio-visual temporal alignment. CONCLUSION: These findings show that speech processing anomalies in ASD do not stand alone and that they are associated already at a very early development stage with audio-visual imbalance with poor auditory response encoding and disrupted audio-visual temporal coordination. En ligne : https://dx.doi.org/10.1186/s11689-025-09593-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Atypical audio-visual neural synchrony and speech processing in early autism [texte imprimé] / Xiaoyue WANG, Auteur ; Sophie BOUTON, Auteur ; Nada KOJOVIC, Auteur ; Anne-Lise GIRAUD, Auteur ; Marie SCHAER, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Female Male Speech Perception/physiology Autism Spectrum Disorder/physiopathology Child, Preschool Electroencephalography Visual Perception/physiology Auditory Perception/physiology Eye-Tracking Technology Child Photic Stimulation Brain/physiopathology Acoustic Stimulation Audio-visual Autism spectrum disorders (ASD) Gaze direction Oscillation phase entrainment Speech envelope Visual motion Ethics approval and consent to participate: Informed consent was obtained from the parents of all participants prior to inclusion in the study. The research was conducted with the ethical standards set forth by the Ethics Committee of the Faculty of Medicine at the University of Geneva Hospital and adhered to the principles outlined in the Declaration of Helsinki. Competing interests: The authors declare no conflict of interest. Preprint servers: The manuscript was deposited as a preprint in bioRxiv with the license CC BY-NC-ND 4.0. Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with Autism Spectrum disorder (ASD) often exhibit communication difficulties that may stem from basic auditory temporal integration impairment but also be aggravated by an audio-visual integration deficit, resulting in a lack of interest in face-to-face communication. This study addresses whether speech processing anomalies in young autistic children (mean age 3.09-year-old) are associated with alterations of audio-visual temporal integration. METHODS: We used high-density electroencephalography (HD-EEG) and eye tracking to record brain activity and gaze patterns in 31 children with ASD (6 females) and 33 typically developing (TD) children (11 females), while they watched cartoon videos. Neural responses to temporal audio-visual stimuli were analyzed using Temporal Response Functions model and phase analyses for audiovisual temporal coordination. RESULTS: The reconstructability of speech signals from auditory responses was reduced in children with ASD compared to TD, but despite more restricted gaze patterns in ASD it was similar for visual responses in both groups. Speech reception was most strongly affected when visual speech information was also present, an interference that was not seen in TD children. These differences were associated with a broader phase angle distribution (exceeding pi/2) in the EEG theta range in children with ASD, signaling reduced reliability of audio-visual temporal alignment. CONCLUSION: These findings show that speech processing anomalies in ASD do not stand alone and that they are associated already at a very early development stage with audio-visual imbalance with poor auditory response encoding and disrupted audio-visual temporal coordination. En ligne : https://dx.doi.org/10.1186/s11689-025-09593-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : DNA methylation biomarkers of intellectual/developmental disability across the lifespan Type de document : texte imprimé Auteurs : Janine M. LASALLE, Auteur Langues : Anglais (eng) Mots-clés : Humans DNA Methylation Intellectual Disability/genetics/diagnosis/metabolism Developmental Disabilities/genetics/diagnosis/metabolism Biomarkers/metabolism Epigenesis, Genetic Female Pregnancy Aging Autism Biomarkers Cell free DNA Cord blood DNA methylation Down syndrome Dup15q syndrome Epigenetic clock Epigenetics Exposure Genomic Placenta for publication: Not applicable. Competing interests: Dr. LaSalle is a co-founder and Chief Scientific Officer at 2C Bioscience Inc. Index. décimale : PER Périodiques Résumé : Epigenetic mechanisms, including DNA methylation, act at the interface of genes and environment by allowing a static genome to respond and adapt to a dynamic environment during the lifespan of an individual. Genome-wide DNA methylation analyses on a wide range of human biospecimens are beginning to identify epigenetic biomarkers that can predict risk of intellectual/developmental disabilities (IDD). DNA methylation-based epigenetic signatures are becoming clinically useful in categorizing benign from pathogenic genetic variants following exome sequencing. While DNA methylation marks differ by tissue source, recent studies have shown that accessible perinatal tissues, such as placenta, cord blood, newborn blood spots, and cell free DNA may serve as accessible surrogate tissues for testing epigenetic biomarkers relevant to understanding genetic, environmental, and gene by environment interactions on the developing brain. These DNA methylation signatures may also provide important information about the biological pathways that become dysregulated prior to disease progression that could be used to develop early pharmacological interventions. Future applications could involve preventative screenings using DNA methylation biomarkers during pregnancy or the newborn period for IDDs and other neurodevelopmental disorders. DNA methylation biomarkers in adolescence and adulthood are also likely to be clinically useful for tracking biological aging or co-occurring health conditions that develop across the lifespan. In conclusion, DNA methylation biomarkers are expected to become more common in clinical diagnoses of IDD, to improve understanding of complex IDD etiologies, to improve endpoints for clinical trials, and to monitor potential health concerns for individuals with IDD as they age. En ligne : https://dx.doi.org/10.1186/s11689-025-09598-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] DNA methylation biomarkers of intellectual/developmental disability across the lifespan [texte imprimé] / Janine M. LASALLE, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans DNA Methylation Intellectual Disability/genetics/diagnosis/metabolism Developmental Disabilities/genetics/diagnosis/metabolism Biomarkers/metabolism Epigenesis, Genetic Female Pregnancy Aging Autism Biomarkers Cell free DNA Cord blood DNA methylation Down syndrome Dup15q syndrome Epigenetic clock Epigenetics Exposure Genomic Placenta for publication: Not applicable. Competing interests: Dr. LaSalle is a co-founder and Chief Scientific Officer at 2C Bioscience Inc. Index. décimale : PER Périodiques Résumé : Epigenetic mechanisms, including DNA methylation, act at the interface of genes and environment by allowing a static genome to respond and adapt to a dynamic environment during the lifespan of an individual. Genome-wide DNA methylation analyses on a wide range of human biospecimens are beginning to identify epigenetic biomarkers that can predict risk of intellectual/developmental disabilities (IDD). DNA methylation-based epigenetic signatures are becoming clinically useful in categorizing benign from pathogenic genetic variants following exome sequencing. While DNA methylation marks differ by tissue source, recent studies have shown that accessible perinatal tissues, such as placenta, cord blood, newborn blood spots, and cell free DNA may serve as accessible surrogate tissues for testing epigenetic biomarkers relevant to understanding genetic, environmental, and gene by environment interactions on the developing brain. These DNA methylation signatures may also provide important information about the biological pathways that become dysregulated prior to disease progression that could be used to develop early pharmacological interventions. Future applications could involve preventative screenings using DNA methylation biomarkers during pregnancy or the newborn period for IDDs and other neurodevelopmental disorders. DNA methylation biomarkers in adolescence and adulthood are also likely to be clinically useful for tracking biological aging or co-occurring health conditions that develop across the lifespan. In conclusion, DNA methylation biomarkers are expected to become more common in clinical diagnoses of IDD, to improve understanding of complex IDD etiologies, to improve endpoints for clinical trials, and to monitor potential health concerns for individuals with IDD as they age. En ligne : https://dx.doi.org/10.1186/s11689-025-09598-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Differences in sleep EEG coherence and spindle metrics in toddlers with and without receptive/expressive language delay: a prospective observational study Type de document : texte imprimé Auteurs : Xinyi HONG, Auteur ; Cristan FARMER, Auteur ; Nataliia KOZHEMIAKO, Auteur ; Gregory L. HOLMES, Auteur ; Lauren THOMPSON, Auteur ; Stacy MANWARING, Auteur ; Audrey THURM, Auteur ; Ashura BUCKLEY, Auteur Langues : Anglais (eng) Mots-clés : Humans Electroencephalography Female Male Infant Language Development Disorders/physiopathology Child, Preschool Sleep/physiology Prospective Studies Brain/physiopathology Brain Waves/physiology Brain development Cognitive function Diagnostic markers Language delay Neurophysiology Sleep architecture by the NIH Institutional Review Board (protocol 11-M-0144 NCT01339767). Consent was obtained from parents or guardians of participants prior to their participation. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Changes in brain connectivity during development are thought to reflect organizational and maturational processes that correspond to skill acquisition in domains like motor, language, and cognition. This theory is supported by findings in typically developing children as well as observations of abnormal connectivity among children with neurodevelopmental differences. However, few coherence studies have capitalized on the potential of sleep electroencephalogram (EEG) to examine the developing brain, especially among very young children for whom formal neurodevelopmental diagnosis is not yet possible. Sleep microarchitecture in young children may offer key insights into neurophysiological abnormalities associated with neurodevelopmental trajectories and potentially aid in early detection and intervention. In this study, we explored sleep EEG coherence and sleep spindles in typically developing toddlers and toddlers at increased risk of later neurodevelopmental diagnoses. METHODS: We investigated EEG coherence and sleep spindles in 16 toddlers with receptive and expressive language delay (LangD) and 39 typically developing (TD) toddlers. Participants were aged 12-22 months at baseline, and 34 (LangD, n=11; TD, n=23) participants were evaluated again at 36 months of age. RESULTS: Average EEG coherence was stronger in the LangD group than the TD group, with differences most prominent during slow-wave sleep. Some age-related increases in coherence were observed, but these did not differ between groups. Sleep spindle density, duration, and frequency changed between baseline and follow-up for both groups, with the LangD group demonstrating a smaller magnitude of change than the TD group. The direction of change was frequency band-dependent for both groups. CONCLUSIONS: These findings indicate that atypical sleep EEG connectivity and sleep spindle development can be detected in toddlers at risk of later neurodevelopmental diagnoses. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT01339767 ; Registration date: 4/20/2011. En ligne : https://dx.doi.org/10.1186/s11689-024-09586-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Differences in sleep EEG coherence and spindle metrics in toddlers with and without receptive/expressive language delay: a prospective observational study [texte imprimé] / Xinyi HONG, Auteur ; Cristan FARMER, Auteur ; Nataliia KOZHEMIAKO, Auteur ; Gregory L. HOLMES, Auteur ; Lauren THOMPSON, Auteur ; Stacy MANWARING, Auteur ; Audrey THURM, Auteur ; Ashura BUCKLEY, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Electroencephalography Female Male Infant Language Development Disorders/physiopathology Child, Preschool Sleep/physiology Prospective Studies Brain/physiopathology Brain Waves/physiology Brain development Cognitive function Diagnostic markers Language delay Neurophysiology Sleep architecture by the NIH Institutional Review Board (protocol 11-M-0144 NCT01339767). Consent was obtained from parents or guardians of participants prior to their participation. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Changes in brain connectivity during development are thought to reflect organizational and maturational processes that correspond to skill acquisition in domains like motor, language, and cognition. This theory is supported by findings in typically developing children as well as observations of abnormal connectivity among children with neurodevelopmental differences. However, few coherence studies have capitalized on the potential of sleep electroencephalogram (EEG) to examine the developing brain, especially among very young children for whom formal neurodevelopmental diagnosis is not yet possible. Sleep microarchitecture in young children may offer key insights into neurophysiological abnormalities associated with neurodevelopmental trajectories and potentially aid in early detection and intervention. In this study, we explored sleep EEG coherence and sleep spindles in typically developing toddlers and toddlers at increased risk of later neurodevelopmental diagnoses. METHODS: We investigated EEG coherence and sleep spindles in 16 toddlers with receptive and expressive language delay (LangD) and 39 typically developing (TD) toddlers. Participants were aged 12-22 months at baseline, and 34 (LangD, n=11; TD, n=23) participants were evaluated again at 36 months of age. RESULTS: Average EEG coherence was stronger in the LangD group than the TD group, with differences most prominent during slow-wave sleep. Some age-related increases in coherence were observed, but these did not differ between groups. Sleep spindle density, duration, and frequency changed between baseline and follow-up for both groups, with the LangD group demonstrating a smaller magnitude of change than the TD group. The direction of change was frequency band-dependent for both groups. CONCLUSIONS: These findings indicate that atypical sleep EEG connectivity and sleep spindle development can be detected in toddlers at risk of later neurodevelopmental diagnoses. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT01339767 ; Registration date: 4/20/2011. En ligne : https://dx.doi.org/10.1186/s11689-024-09586-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Disrupted visual attention relates to cognitive development in infants with Neurofibromatosis Type 1 Type de document : texte imprimé Auteurs : Jannath BEGUM-ALI, Auteur ; Luke MASON, Auteur ; Tony CHARMAN, Auteur ; Mark H. JOHNSON, Auteur ; Jonathan GREEN, Auteur ; Shruti GARG, Auteur ; Emily J.H. JONES, Auteur ; THE STAARS AND EDEN TEAMS, Auteur Langues : Anglais (eng) Mots-clés : Humans Neurofibromatosis 1/complications/physiopathology Infant Attention/physiology Male Female Child Development/physiology Longitudinal Studies Visual Perception/physiology Attention Deficit Disorder with Hyperactivity/physiopathology Cognition/physiology Autism Spectrum Disorder/physiopathology Attention deficit hyperactivity disorder Autism spectrum disorder Eye tracking Longitudinal Neurofibromatosis Type 1 Visual attention consent was provided by the parent(s) prior to the commencement of the study. The testing only took place if the infants were in a content and alert state. Ethical approval was granted by the National Research Ethics Service and the Research Ethics Committee of the Department of Psychological Sciences, Birkbeck, University of London. Consent for publication: Not applicable. Competing interests: Dr Jannath Begum Ali declares no conflict of interest. Dr Luke Mason declares no conflict of interest. Professor Tony Charman has served as a paid consultant to F. Hoffmann-La Roche Ltd and Servier. He has received royalties from Sage Publications and Guildford Publications. . Dr Shruti Garg declares no conflict of interest. Professor Jonathan Green declares no conflict of interest. Professor Mark H. Johnson declares no conflict of interest. Professor Emily J.H. Jones declares no conflict of interest. The STAARS team declares no conflict of interest. The EDEN team declares no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurofibromatosis Type 1 is a genetic condition diagnosed in infancy that substantially increases the likelihood of a child experiencing cognitive and developmental difficulties, including Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). Children with NF1 show clear differences in attention, but whether these differences emerge in early development and how they relate to broader difficulties with cognitive and learning skills is unclear. To address this question requires longitudinal prospective studies from infancy, where the relation between domains of visual attention (including exogenous and endogenous shifting) and cognitive development can be mapped over time. METHODS: We report data from 28 infants with NF1 tested longitudinally at 5, 10 and 14 months compared to cohorts of 29 typical likelihood infants (with no history of NF1 or ASD and/or ADHD), and 123 infants with a family history of ASD and/or ADHD. We used an eyetracking battery to measure both exogenous and endogenous control of visual attention. RESULTS: Infants with NF1 demonstrated intact social orienting, but slower development of endogenous visual foraging. This slower development presented as prolonged engagement with a salient stimulus in a static display relative to typically developing infants. In terms of exogenous attention shifting, NF1 infants showed faster saccadic reaction times than typical likelihood infants. However, the NF1 group demonstrated a slower developmental improvement from 5 to 14 months of age. Individual differences in foraging and saccade times were concurrently related to visual reception abilities within the full infant cohort (NF1, typical likelihood and those with a family history of ASD/ADHD). CONCLUSIONS: Our results provide preliminary evidence that alterations in saccadic reaction time and visual foraging may contribute to learning difficulties in infants with NF1. En ligne : https://dx.doi.org/10.1186/s11689-025-09599-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Disrupted visual attention relates to cognitive development in infants with Neurofibromatosis Type 1 [texte imprimé] / Jannath BEGUM-ALI, Auteur ; Luke MASON, Auteur ; Tony CHARMAN, Auteur ; Mark H. JOHNSON, Auteur ; Jonathan GREEN, Auteur ; Shruti GARG, Auteur ; Emily J.H. JONES, Auteur ; THE STAARS AND EDEN TEAMS, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Neurofibromatosis 1/complications/physiopathology Infant Attention/physiology Male Female Child Development/physiology Longitudinal Studies Visual Perception/physiology Attention Deficit Disorder with Hyperactivity/physiopathology Cognition/physiology Autism Spectrum Disorder/physiopathology Attention deficit hyperactivity disorder Autism spectrum disorder Eye tracking Longitudinal Neurofibromatosis Type 1 Visual attention consent was provided by the parent(s) prior to the commencement of the study. The testing only took place if the infants were in a content and alert state. Ethical approval was granted by the National Research Ethics Service and the Research Ethics Committee of the Department of Psychological Sciences, Birkbeck, University of London. Consent for publication: Not applicable. Competing interests: Dr Jannath Begum Ali declares no conflict of interest. Dr Luke Mason declares no conflict of interest. Professor Tony Charman has served as a paid consultant to F. Hoffmann-La Roche Ltd and Servier. He has received royalties from Sage Publications and Guildford Publications. . Dr Shruti Garg declares no conflict of interest. Professor Jonathan Green declares no conflict of interest. Professor Mark H. Johnson declares no conflict of interest. Professor Emily J.H. Jones declares no conflict of interest. The STAARS team declares no conflict of interest. The EDEN team declares no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurofibromatosis Type 1 is a genetic condition diagnosed in infancy that substantially increases the likelihood of a child experiencing cognitive and developmental difficulties, including Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). Children with NF1 show clear differences in attention, but whether these differences emerge in early development and how they relate to broader difficulties with cognitive and learning skills is unclear. To address this question requires longitudinal prospective studies from infancy, where the relation between domains of visual attention (including exogenous and endogenous shifting) and cognitive development can be mapped over time. METHODS: We report data from 28 infants with NF1 tested longitudinally at 5, 10 and 14 months compared to cohorts of 29 typical likelihood infants (with no history of NF1 or ASD and/or ADHD), and 123 infants with a family history of ASD and/or ADHD. We used an eyetracking battery to measure both exogenous and endogenous control of visual attention. RESULTS: Infants with NF1 demonstrated intact social orienting, but slower development of endogenous visual foraging. This slower development presented as prolonged engagement with a salient stimulus in a static display relative to typically developing infants. In terms of exogenous attention shifting, NF1 infants showed faster saccadic reaction times than typical likelihood infants. However, the NF1 group demonstrated a slower developmental improvement from 5 to 14 months of age. Individual differences in foraging and saccade times were concurrently related to visual reception abilities within the full infant cohort (NF1, typical likelihood and those with a family history of ASD/ADHD). CONCLUSIONS: Our results provide preliminary evidence that alterations in saccadic reaction time and visual foraging may contribute to learning difficulties in infants with NF1. En ligne : https://dx.doi.org/10.1186/s11689-025-09599-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Integrating parent report, observed behavior, and physiological measures to identify biomarkers of sensory over-responsivity in autism Type de document : texte imprimé Auteurs : Apurva CHATURVEDI, Auteur ; Sapna RAMAPPA, Auteur ; Ariana ANDERSON, Auteur ; Megan BANCHIK, Auteur ; Urvi SHAH, Auteur ; Michelle CRASKE, Auteur ; Shulamite GREEN, Auteur Langues : Anglais (eng) Mots-clés : Humans Male Female Adolescent Child Autism Spectrum Disorder/physiopathology/diagnosis Heart Rate/physiology Parents Biomarkers Electrocardiography Inhibition, Psychological Behavior Observation Techniques Autism spectrum disorder Behavioral inhibition Heart rate Masking Physiology Sensory over-responsivity Sensory processing by the UCLA Institutional Review Board, and informed consent and assent were obtained from the participants and their parents. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory over-responsivity (SOR) is a heightened reaction to environmental stimuli commonly seen in autism spectrum disorder (ASD) which impacts daily functioning. Parent-reported and observed behavioral assessments are used to study SOR, but show limited associations with each other, possibly because they measure different aspects of SOR or because children inhibit their responses during standardized assessments. Physiological measures provide an objective measure of sensory reactivity, and atypical heart rate (HR) responses to aversive stimuli have been shown to be related to SOR in ASD youth. This study aimed to compare how reported and observed measures of SOR predict HR and to examine if the level of reported behavioral inhibition in ASD youth affects how observed SOR behaviors correlate with physiological reactivity. METHODS: Participants were 54 typically developing (TD) and 83 ASD youth, ages 8-17, who completed a standardized behavioral assessment of SOR while electrocardiogram recordings were collected. Participants' parents also reported on their child's SOR symptoms and behavioral inhibition. RESULTS: ASD youth showed lower inter-beat-intervals (IBI; higher HR) across all auditory and tactile stimuli. For ASD youth, parent-reported SOR interacted with observed SOR to predict HR changes across the stimulation periods, indicating that ASD participants whose parents reported they had high SOR in their daily life, and showed high observed SOR in the lab assessment, exhibited reduced HR deceleration (orienting) after the onset of the stimulus and subsequent increased HR acceleration. Finally, we found that ASD participants who had lower parent-reported behavioral inhibition had a stronger correlation between observed SOR behavior and atypical HR responses. CONCLUSIONS: Results support prior findings that increased HR responses to aversive stimuli is related to both ASD and SOR. Furthermore, observed and parent-reported SOR interacted to predict HR, suggesting that a multi-method approach may best capture the extent of SOR for an individual. However, observed SOR measures may be most accurate for ASD youth who are less likely to inhibit their behavioral responses. This study illustrates the importance of integrating multiple measures of sensory reactivity to identify SOR. HR measures of sensory reactivity have the potential to serve as a biomarker of SOR across a diverse range of individuals. En ligne : https://dx.doi.org/10.1186/s11689-025-09597-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Integrating parent report, observed behavior, and physiological measures to identify biomarkers of sensory over-responsivity in autism [texte imprimé] / Apurva CHATURVEDI, Auteur ; Sapna RAMAPPA, Auteur ; Ariana ANDERSON, Auteur ; Megan BANCHIK, Auteur ; Urvi SHAH, Auteur ; Michelle CRASKE, Auteur ; Shulamite GREEN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Male Female Adolescent Child Autism Spectrum Disorder/physiopathology/diagnosis Heart Rate/physiology Parents Biomarkers Electrocardiography Inhibition, Psychological Behavior Observation Techniques Autism spectrum disorder Behavioral inhibition Heart rate Masking Physiology Sensory over-responsivity Sensory processing by the UCLA Institutional Review Board, and informed consent and assent were obtained from the participants and their parents. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory over-responsivity (SOR) is a heightened reaction to environmental stimuli commonly seen in autism spectrum disorder (ASD) which impacts daily functioning. Parent-reported and observed behavioral assessments are used to study SOR, but show limited associations with each other, possibly because they measure different aspects of SOR or because children inhibit their responses during standardized assessments. Physiological measures provide an objective measure of sensory reactivity, and atypical heart rate (HR) responses to aversive stimuli have been shown to be related to SOR in ASD youth. This study aimed to compare how reported and observed measures of SOR predict HR and to examine if the level of reported behavioral inhibition in ASD youth affects how observed SOR behaviors correlate with physiological reactivity. METHODS: Participants were 54 typically developing (TD) and 83 ASD youth, ages 8-17, who completed a standardized behavioral assessment of SOR while electrocardiogram recordings were collected. Participants' parents also reported on their child's SOR symptoms and behavioral inhibition. RESULTS: ASD youth showed lower inter-beat-intervals (IBI; higher HR) across all auditory and tactile stimuli. For ASD youth, parent-reported SOR interacted with observed SOR to predict HR changes across the stimulation periods, indicating that ASD participants whose parents reported they had high SOR in their daily life, and showed high observed SOR in the lab assessment, exhibited reduced HR deceleration (orienting) after the onset of the stimulus and subsequent increased HR acceleration. Finally, we found that ASD participants who had lower parent-reported behavioral inhibition had a stronger correlation between observed SOR behavior and atypical HR responses. CONCLUSIONS: Results support prior findings that increased HR responses to aversive stimuli is related to both ASD and SOR. Furthermore, observed and parent-reported SOR interacted to predict HR, suggesting that a multi-method approach may best capture the extent of SOR for an individual. However, observed SOR measures may be most accurate for ASD youth who are less likely to inhibit their behavioral responses. This study illustrates the importance of integrating multiple measures of sensory reactivity to identify SOR. HR measures of sensory reactivity have the potential to serve as a biomarker of SOR across a diverse range of individuals. En ligne : https://dx.doi.org/10.1186/s11689-025-09597-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Pubertal developmental, body mass index, and cardiovascular autonomic function in children and adolescents with and without autism spectrum disorder: a four-time point accelerated longitudinal study Type de document : texte imprimé Auteurs : Rachael A. MUSCATELLO, Auteur ; Meredith COLA, Auteur ; Simon VANDEKAR, Auteur ; Blythe A. CORBETT, Auteur Langues : Anglais (eng) Mots-clés : Humans Adolescent Child Male Female Autism Spectrum Disorder/physiopathology Longitudinal Studies Body Mass Index Autonomic Nervous System/physiopathology Puberty/physiology Heart Rate/physiology Respiratory Sinus Arrhythmia/physiology Autism Autonomic Cardiovascular Health Heart rate Physical Pubertal development Variability out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). The Vanderbilt Institutional Review Board approved all study procedures. In compliance with the Institutional Review Board, informed written consent and verbal assent was obtained from all parent/guardians and children, respectively, prior to inclusion in the study. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Autonomic Nervous System (ANS) regulates 'automatic' functions such as heart rate, and alterations may have significant impacts on health outcomes. Cardiovascular measures of autonomic function such as heart rate variability are of interest as biological markers in autism spectrum disorder (ASD). The interplay between the ANS and physical health establishes a need to examine cardiovascular autonomic functioning in youth with and without ASD over development. The current study aimed to identify change in autonomic function and balance across the parasympathetic and sympathetic branches over time as a function of diagnosis, age, pubertal development, and physical health status. METHODS: The study included 244 ASD (N = 140) or neurotypical (NT) (N = 104) youth, ages 10 to 13 years at enrollment and followed over four years. Resting state autonomic functioning was measured using respiratory sinus arrhythmia (RSA; parasympathetic) and pre-ejection period (PEP; sympathetic). Autonomic balance and regulation were also examined as outcomes. Linear mixed models tested between- and within-group differences in the primary autonomic outcomes as well as the influence of pubertal development, body weight, and medication use. RESULTS: Baseline models showed diagnostic differences, with lower parasympathetic regulation, in youth with ASD, but no differences were observed for the other three outcomes. Adding body mass index (BMI) percentile and medication use removed the statistically significant diagnostic effect, while both variables were significantly related to lower RSA and overall autonomic regulation. Parasympathetic function (RSA) was stable over age and pubertal stage, while a notable decrease in sympathetic control (increased PEP) was found for age and pubertal stage. BMI percentile at enrollment significantly predicted autonomic function, while change in BMI over time did not. CONCLUSIONS: Minimal research to date has explored physical health (e.g., BMI) and autonomic outcomes in ASD. The current study observed few group differences yet demonstrates important effects of physical health on ANS function in both ASD and neurotypical youth. Findings further emphasize a need to focus on individual traits such as BMI and medication use to elucidate the extent to which autonomic differences are related to health status, irrespective of diagnostic category, across the lifespan. En ligne : https://dx.doi.org/10.1186/s11689-025-09602-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Pubertal developmental, body mass index, and cardiovascular autonomic function in children and adolescents with and without autism spectrum disorder: a four-time point accelerated longitudinal study [texte imprimé] / Rachael A. MUSCATELLO, Auteur ; Meredith COLA, Auteur ; Simon VANDEKAR, Auteur ; Blythe A. CORBETT, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Adolescent Child Male Female Autism Spectrum Disorder/physiopathology Longitudinal Studies Body Mass Index Autonomic Nervous System/physiopathology Puberty/physiology Heart Rate/physiology Respiratory Sinus Arrhythmia/physiology Autism Autonomic Cardiovascular Health Heart rate Physical Pubertal development Variability out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). The Vanderbilt Institutional Review Board approved all study procedures. In compliance with the Institutional Review Board, informed written consent and verbal assent was obtained from all parent/guardians and children, respectively, prior to inclusion in the study. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Autonomic Nervous System (ANS) regulates 'automatic' functions such as heart rate, and alterations may have significant impacts on health outcomes. Cardiovascular measures of autonomic function such as heart rate variability are of interest as biological markers in autism spectrum disorder (ASD). The interplay between the ANS and physical health establishes a need to examine cardiovascular autonomic functioning in youth with and without ASD over development. The current study aimed to identify change in autonomic function and balance across the parasympathetic and sympathetic branches over time as a function of diagnosis, age, pubertal development, and physical health status. METHODS: The study included 244 ASD (N = 140) or neurotypical (NT) (N = 104) youth, ages 10 to 13 years at enrollment and followed over four years. Resting state autonomic functioning was measured using respiratory sinus arrhythmia (RSA; parasympathetic) and pre-ejection period (PEP; sympathetic). Autonomic balance and regulation were also examined as outcomes. Linear mixed models tested between- and within-group differences in the primary autonomic outcomes as well as the influence of pubertal development, body weight, and medication use. RESULTS: Baseline models showed diagnostic differences, with lower parasympathetic regulation, in youth with ASD, but no differences were observed for the other three outcomes. Adding body mass index (BMI) percentile and medication use removed the statistically significant diagnostic effect, while both variables were significantly related to lower RSA and overall autonomic regulation. Parasympathetic function (RSA) was stable over age and pubertal stage, while a notable decrease in sympathetic control (increased PEP) was found for age and pubertal stage. BMI percentile at enrollment significantly predicted autonomic function, while change in BMI over time did not. CONCLUSIONS: Minimal research to date has explored physical health (e.g., BMI) and autonomic outcomes in ASD. The current study observed few group differences yet demonstrates important effects of physical health on ANS function in both ASD and neurotypical youth. Findings further emphasize a need to focus on individual traits such as BMI and medication use to elucidate the extent to which autonomic differences are related to health status, irrespective of diagnostic category, across the lifespan. En ligne : https://dx.doi.org/10.1186/s11689-025-09602-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Modifying quantitative sensory testing to investigate tactile sensory function and behavioral reactivity in children with intellectual and developmental disabilities: establishing feasibility and testing sex, autism, and self-injury effects Type de document : texte imprimé Auteurs : Jaclyn GUNDERSON, Auteur ; Emma WORTHLEY, Auteur ; Breanne BYIERS, Auteur ; Alyssa MERBLER, Auteur ; Andrea HUEBNER, Auteur ; Deanna HOFSCHULTE, Auteur ; Jasmine LEE, Auteur ; Catherine RIODIQUE, Auteur ; Frank SYMONS, Auteur Langues : Anglais (eng) Mots-clés : Humans Male Child Female Self-Injurious Behavior/physiopathology/diagnosis Feasibility Studies Child, Preschool Developmental Disabilities/physiopathology/complications Autistic Disorder/physiopathology/complications Intellectual Disability/physiopathology/complications Touch/physiology Touch Perception/physiology Sex Factors Reproducibility of Results Autism Intellectual developmental disability Modified quantitative sensory test Self-injurious behavior Sensory responsivity Tactile reactivity obtained from Mayo Clinic and Fairview Health internal review boards. Written informed consent was obtained for all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory reactivity differences are common across neurodevelopmental disorders (NDDs), however very few studies specifically examine tactile or pain responses in children with NNDs, especially those with communication challenges. The current study aimed to (a) replicate the feasibility of a modified quantitative sensory test (mQST) with a sample of children with NDDs, (b) assess validity evidence based on behavioral reactivity during mQST application and the corresponding behavioral measurement coding system, and (c) explore group differences in behavioral reactivity to mQST stimuli by demographic (sex), clinical (autism status), and behavioral pathology (self-injury) variables. METHODS: The mQST protocol was implemented and blindly coded across 47 participants aged 2-12 years (M age = 6.7 years, SD = 2.6; 70% male) with NDDs. Feasibility was measured by completion of the mQST protocol and interobserver agreement. Validity was assessed using paired t-tests investigating differences between behavioral reactivity to active stimuli compared to a sham trial. Boxplots were used to visually explore differences in group characteristics (sex, autism status, and self-injurious behavior), with two-sample t-tests used to further characterize differences in SIB group characteristics in behavioral reactivity to mQST stimuli. RESULTS: The mQST provided codable data across 91% of stimuli applications with high IOA (84.7% [76.7-95%]). Behavioral reactivity was significantly higher for active vs. sham stimuli. Children reported to engage in self-injurious behavior showed significantly more reactivity to the second half of the repeated von Frey stimulus application compared to children without caregiver-reported self-injurious behavior (M = 6.14, SD = 3.44), t (40)= -2.247, p =.04). CONCLUSION: The mQST is a feasible approach to investigate tactile reactivity in children with NDDs and complex communication needs. The mQST may be useful in understanding sensory variables in relation to developmental and behavioral outcomes such as self-injurious behavior. En ligne : https://dx.doi.org/10.1186/s11689-025-09603-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Modifying quantitative sensory testing to investigate tactile sensory function and behavioral reactivity in children with intellectual and developmental disabilities: establishing feasibility and testing sex, autism, and self-injury effects [texte imprimé] / Jaclyn GUNDERSON, Auteur ; Emma WORTHLEY, Auteur ; Breanne BYIERS, Auteur ; Alyssa MERBLER, Auteur ; Andrea HUEBNER, Auteur ; Deanna HOFSCHULTE, Auteur ; Jasmine LEE, Auteur ; Catherine RIODIQUE, Auteur ; Frank SYMONS, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Male Child Female Self-Injurious Behavior/physiopathology/diagnosis Feasibility Studies Child, Preschool Developmental Disabilities/physiopathology/complications Autistic Disorder/physiopathology/complications Intellectual Disability/physiopathology/complications Touch/physiology Touch Perception/physiology Sex Factors Reproducibility of Results Autism Intellectual developmental disability Modified quantitative sensory test Self-injurious behavior Sensory responsivity Tactile reactivity obtained from Mayo Clinic and Fairview Health internal review boards. Written informed consent was obtained for all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory reactivity differences are common across neurodevelopmental disorders (NDDs), however very few studies specifically examine tactile or pain responses in children with NNDs, especially those with communication challenges. The current study aimed to (a) replicate the feasibility of a modified quantitative sensory test (mQST) with a sample of children with NDDs, (b) assess validity evidence based on behavioral reactivity during mQST application and the corresponding behavioral measurement coding system, and (c) explore group differences in behavioral reactivity to mQST stimuli by demographic (sex), clinical (autism status), and behavioral pathology (self-injury) variables. METHODS: The mQST protocol was implemented and blindly coded across 47 participants aged 2-12 years (M age = 6.7 years, SD = 2.6; 70% male) with NDDs. Feasibility was measured by completion of the mQST protocol and interobserver agreement. Validity was assessed using paired t-tests investigating differences between behavioral reactivity to active stimuli compared to a sham trial. Boxplots were used to visually explore differences in group characteristics (sex, autism status, and self-injurious behavior), with two-sample t-tests used to further characterize differences in SIB group characteristics in behavioral reactivity to mQST stimuli. RESULTS: The mQST provided codable data across 91% of stimuli applications with high IOA (84.7% [76.7-95%]). Behavioral reactivity was significantly higher for active vs. sham stimuli. Children reported to engage in self-injurious behavior showed significantly more reactivity to the second half of the repeated von Frey stimulus application compared to children without caregiver-reported self-injurious behavior (M = 6.14, SD = 3.44), t (40)= -2.247, p =.04). CONCLUSION: The mQST is a feasible approach to investigate tactile reactivity in children with NDDs and complex communication needs. The mQST may be useful in understanding sensory variables in relation to developmental and behavioral outcomes such as self-injurious behavior. En ligne : https://dx.doi.org/10.1186/s11689-025-09603-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder Type de document : texte imprimé Auteurs : Serena B. GUMUSOGLU, Auteur ; Brandon M. SCHICKLING, Auteur ; Donna A. SANTILLAN, Auteur ; Lynn M. TEESCH, Auteur ; Mark K. SANTILLAN, Auteur Langues : Anglais (eng) Mots-clés : Humans Autism Spectrum Disorder/metabolism/blood/diagnosis Female Male Carbohydrate Metabolism/physiology Biomarkers/blood Fetal Blood/metabolism Metabolomics Child Pregnancy Gas Chromatography-Mass Spectrometry Case-Control Studies Autism Carbohydrates Cord blood Monosaccharides Polysaccharides used in this study are derived from a tissue bank which is approved by the University of Iowa Institutional Review Board (IRB #: 200910784). This study was performed in line with the principles of the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Despite the power and promise of early detection and treatment in autism spectrum disorder (ASD), early-life biomarkers are limited. An early-life risk biosignature would advance the field's understanding of ASD pathogenies and targets for early diagnosis and intervention. We therefore sought to add to the growing ASD biomarker literature and evaluate whether fetal metabolomics are altered in idiopathic ASD. METHODS: Banked cord blood plasma samples (N = 36 control, 16 ASD) were analyzed via gas chromatography and mass spectrometry (GC-MS). Samples were from babies later diagnosed with idiopathic ASD (non-familial, non-syndromic) or matched, neurotypical controls. Metabolite set enrichment analysis (MSEA) and biomarker prediction were performed (MetaboAnalyst). RESULTS: We detected 76 metabolites in all samples. Of these, 20 metabolites differed significantly between groups: 10 increased and 10 decreased in ASD samples relative to neurotypical controls (p < 0.05). MSEA revealed significant changes in metabolic pathways related to carbohydrate metabolism and glycemic control. Untargeted principle components analysis of all metabolites did not reveal group differences, while targeted biomarker assessment (using only Fructose 6-phosphate, D-Mannose, and D-Fructose) by a Random Forest algorithm generated an area under the curve (AUC) = 0.766 (95% CI: 0.612-0.896) for ASD prediction. CONCLUSIONS: Despite a high and increasing prevalence, ASD has no definitive biomarkers or available treatments for its core symptoms. ASD's earliest developmental antecedents remain unclear. We find that fetal plasma metabolomics differ with child ASD status, in particular invoking altered carbohydrate metabolism. While prior clinical and preclinical work has linked carbohydrate metabolism to ASD, no prior fetal studies have reported these disruptions in neonates or fetuses who go on to be diagnosed with ASD. Future work will investigate concordance with maternal metabolomics to determine maternal-fetal mechanisms. En ligne : https://dx.doi.org/10.1186/s11689-025-09601-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder [texte imprimé] / Serena B. GUMUSOGLU, Auteur ; Brandon M. SCHICKLING, Auteur ; Donna A. SANTILLAN, Auteur ; Lynn M. TEESCH, Auteur ; Mark K. SANTILLAN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Autism Spectrum Disorder/metabolism/blood/diagnosis Female Male Carbohydrate Metabolism/physiology Biomarkers/blood Fetal Blood/metabolism Metabolomics Child Pregnancy Gas Chromatography-Mass Spectrometry Case-Control Studies Autism Carbohydrates Cord blood Monosaccharides Polysaccharides used in this study are derived from a tissue bank which is approved by the University of Iowa Institutional Review Board (IRB #: 200910784). This study was performed in line with the principles of the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Despite the power and promise of early detection and treatment in autism spectrum disorder (ASD), early-life biomarkers are limited. An early-life risk biosignature would advance the field's understanding of ASD pathogenies and targets for early diagnosis and intervention. We therefore sought to add to the growing ASD biomarker literature and evaluate whether fetal metabolomics are altered in idiopathic ASD. METHODS: Banked cord blood plasma samples (N = 36 control, 16 ASD) were analyzed via gas chromatography and mass spectrometry (GC-MS). Samples were from babies later diagnosed with idiopathic ASD (non-familial, non-syndromic) or matched, neurotypical controls. Metabolite set enrichment analysis (MSEA) and biomarker prediction were performed (MetaboAnalyst). RESULTS: We detected 76 metabolites in all samples. Of these, 20 metabolites differed significantly between groups: 10 increased and 10 decreased in ASD samples relative to neurotypical controls (p < 0.05). MSEA revealed significant changes in metabolic pathways related to carbohydrate metabolism and glycemic control. Untargeted principle components analysis of all metabolites did not reveal group differences, while targeted biomarker assessment (using only Fructose 6-phosphate, D-Mannose, and D-Fructose) by a Random Forest algorithm generated an area under the curve (AUC) = 0.766 (95% CI: 0.612-0.896) for ASD prediction. CONCLUSIONS: Despite a high and increasing prevalence, ASD has no definitive biomarkers or available treatments for its core symptoms. ASD's earliest developmental antecedents remain unclear. We find that fetal plasma metabolomics differ with child ASD status, in particular invoking altered carbohydrate metabolism. While prior clinical and preclinical work has linked carbohydrate metabolism to ASD, no prior fetal studies have reported these disruptions in neonates or fetuses who go on to be diagnosed with ASD. Future work will investigate concordance with maternal metabolomics to determine maternal-fetal mechanisms. En ligne : https://dx.doi.org/10.1186/s11689-025-09601-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Verbal narrative ability and episodic autobiographical memory in adolescents and young adults with 22q11.2 deletion syndrome Type de document : texte imprimé Auteurs : Claire MAYOR, Auteur ; Julie HUSMANN, Auteur ; Selma BENAGHMOUCH, Auteur ; Stephan ELIEZ, Auteur ; Clémence FELLER, Auteur ; Maude SCHNEIDER, Auteur Langues : Anglais (eng) Mots-clés : Humans Memory, Episodic Adolescent Male Female Young Adult Narration DiGeorge Syndrome/psychology/complications/physiopathology Neuropsychological Tests Adult Mental Recall Index. décimale : PER Périodiques Résumé : BACKGROUND: Poor episodic autobiographical future thinking has recently been reported in 22q11.2 carriers. However, whether these impairments are due to poor language skills or indicate a true episodic autobiographical memory deficit remains unclear. Language impairments are the hallmark of the neuropsychological profile of young children with 22q11DS, but language outcomes in adolescence and young adulthood, especially high-level linguistic skills such as narrative, remain largely unexplored. The aims of this study are first to precisely characterize the narrative abilities of a group of adolescents and young adults with a 22q11DS and normal verbal intellectual functioning, in comparison to a control group. Second, to assess their (past) autobiographical episodic memory and their future episodic thinking abilities. Third, to examine the relationship between linguistic and autobiographical memory skills. METHODS: Fifteen adolescents and young adults with 22q11DS were compared with 15 age- and sex-matched controls. Narrative ability was assessed with a storytelling task and included microstructural, macrostructural, and pragmatic linguistic measures. Episodic autobiographical memory was assessed using a paradigm involving recall of past personal memories and future thinking conditions. RESULTS: Adolescents and young adults with 22q11DS still struggled with high-level language skills such as storytelling tasks, and all linguistic levels were impaired, i.e., the microstructural, macrostructural, and pragmatic components of narrative. Second, 22q11DS carriers showed poor episodic autobiographical recall of their personal memories and reduced access to sensory details (visual, auditory…) compared to controls. Their poor autobiographical episodic memory skills were independent of language impairment, and there were no effects of age or intellectual level on their autobiographical (past) memories recollection. On the other hand, age and verbal intellectual functioning significantly contributed to their ability to produce episodic narratives in the future thinking condition, suggesting that the future thinking task relies on more complex and intricate factors than pure episodic memory ability. CONCLUSIONS: Verbal narrative impairments did not account for poor recall of personal memories, suggesting dysfunctional episodic memory networks between hippocampi and posterior cortical areas in 22q11DS, where neuroanatomical and neurofunctional alterations have indeed been reported. En ligne : https://dx.doi.org/10.1186/s11689-025-09606-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Verbal narrative ability and episodic autobiographical memory in adolescents and young adults with 22q11.2 deletion syndrome [texte imprimé] / Claire MAYOR, Auteur ; Julie HUSMANN, Auteur ; Selma BENAGHMOUCH, Auteur ; Stephan ELIEZ, Auteur ; Clémence FELLER, Auteur ; Maude SCHNEIDER, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Memory, Episodic Adolescent Male Female Young Adult Narration DiGeorge Syndrome/psychology/complications/physiopathology Neuropsychological Tests Adult Mental Recall Index. décimale : PER Périodiques Résumé : BACKGROUND: Poor episodic autobiographical future thinking has recently been reported in 22q11.2 carriers. However, whether these impairments are due to poor language skills or indicate a true episodic autobiographical memory deficit remains unclear. Language impairments are the hallmark of the neuropsychological profile of young children with 22q11DS, but language outcomes in adolescence and young adulthood, especially high-level linguistic skills such as narrative, remain largely unexplored. The aims of this study are first to precisely characterize the narrative abilities of a group of adolescents and young adults with a 22q11DS and normal verbal intellectual functioning, in comparison to a control group. Second, to assess their (past) autobiographical episodic memory and their future episodic thinking abilities. Third, to examine the relationship between linguistic and autobiographical memory skills. METHODS: Fifteen adolescents and young adults with 22q11DS were compared with 15 age- and sex-matched controls. Narrative ability was assessed with a storytelling task and included microstructural, macrostructural, and pragmatic linguistic measures. Episodic autobiographical memory was assessed using a paradigm involving recall of past personal memories and future thinking conditions. RESULTS: Adolescents and young adults with 22q11DS still struggled with high-level language skills such as storytelling tasks, and all linguistic levels were impaired, i.e., the microstructural, macrostructural, and pragmatic components of narrative. Second, 22q11DS carriers showed poor episodic autobiographical recall of their personal memories and reduced access to sensory details (visual, auditory…) compared to controls. Their poor autobiographical episodic memory skills were independent of language impairment, and there were no effects of age or intellectual level on their autobiographical (past) memories recollection. On the other hand, age and verbal intellectual functioning significantly contributed to their ability to produce episodic narratives in the future thinking condition, suggesting that the future thinking task relies on more complex and intricate factors than pure episodic memory ability. CONCLUSIONS: Verbal narrative impairments did not account for poor recall of personal memories, suggesting dysfunctional episodic memory networks between hippocampi and posterior cortical areas in 22q11DS, where neuroanatomical and neurofunctional alterations have indeed been reported. En ligne : https://dx.doi.org/10.1186/s11689-025-09606-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Brain structure in triple X syndrome: regional gray matter volume and cortical thickness in adult women with 47,XXX karyotype Type de document : texte imprimé Auteurs : Gregor DOMES, Auteur ; Marie-Anne CROYÉ, Auteur ; Petra FREILINGER, Auteur ; Andreas BOHLSCHEID, Auteur ; Winfried A. WILLINEK, Auteur ; Jobst MEYER, Auteur Langues : Anglais (eng) Mots-clés : Humans Female Adult Gray Matter/pathology/diagnostic imaging Magnetic Resonance Imaging Young Adult Adolescent Middle Aged Sex Chromosome Disorders of Sex Development/pathology/diagnostic imaging Brain/pathology/diagnostic imaging Trisomy/pathology Cerebral Cortex/pathology/diagnostic imaging Organ Size Sex Chromosome Aberrations Sex Chromosome Disorders/pathology/diagnostic imaging Chromosomes, Human, X 47,xxx Amygdala Basal ganglia Cerebellum Hippocampus Morphometry Triple X syndrome Trisomy X authors declare no competing interests. Ethical approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the ethics committee of the state medical association Rhineland-Palatinate (#2022–16572). Participants gave written-informed consent before participation. Index. décimale : PER Périodiques Résumé : BACKGROUND: Changes in the brain structure of women with Triple X syndrome (karyotype 47,XXX) have been described in a few studies to date, including reduced total brain volume and regional reductions in gray substance in cortical and subcortical areas. However, the empirical evidence from adults is very limited and group comparison on a voxel-wise basis for gray matter volume and cortical thickness is still missing. METHODS: Using voxel-based morphometry (VBM) and surface-based morphometry (SBM), we investigated regional gray matter changes in a sample of n = 20 adult women (aged 18-49 years) with 47,XXX karyotype using T1-weighted 3T MRI scans. RESULTS: Compared to an age- and education-matched control group (and controlled for differences in total intracranial volume), the VBM revealed decreased regional gray matter volumes in the hippocampus, amygdala, parts of the basal ganglia, insula, prefrontal areas and cerebellum. To a lesser extent, we also noted specific reductions in cortical thickness in a smaller part of those regions. CONCLUSION: The observed network is significantly involved in the processing of cognitive, affective, and social stimuli and might be a potential neuronal correlate of the autism-like social-cognitive problems described in 47,XXX in the literature. En ligne : https://dx.doi.org/10.1186/s11689-025-09608-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Brain structure in triple X syndrome: regional gray matter volume and cortical thickness in adult women with 47,XXX karyotype [texte imprimé] / Gregor DOMES, Auteur ; Marie-Anne CROYÉ, Auteur ; Petra FREILINGER, Auteur ; Andreas BOHLSCHEID, Auteur ; Winfried A. WILLINEK, Auteur ; Jobst MEYER, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Female Adult Gray Matter/pathology/diagnostic imaging Magnetic Resonance Imaging Young Adult Adolescent Middle Aged Sex Chromosome Disorders of Sex Development/pathology/diagnostic imaging Brain/pathology/diagnostic imaging Trisomy/pathology Cerebral Cortex/pathology/diagnostic imaging Organ Size Sex Chromosome Aberrations Sex Chromosome Disorders/pathology/diagnostic imaging Chromosomes, Human, X 47,xxx Amygdala Basal ganglia Cerebellum Hippocampus Morphometry Triple X syndrome Trisomy X authors declare no competing interests. Ethical approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the ethics committee of the state medical association Rhineland-Palatinate (#2022–16572). Participants gave written-informed consent before participation. Index. décimale : PER Périodiques Résumé : BACKGROUND: Changes in the brain structure of women with Triple X syndrome (karyotype 47,XXX) have been described in a few studies to date, including reduced total brain volume and regional reductions in gray substance in cortical and subcortical areas. However, the empirical evidence from adults is very limited and group comparison on a voxel-wise basis for gray matter volume and cortical thickness is still missing. METHODS: Using voxel-based morphometry (VBM) and surface-based morphometry (SBM), we investigated regional gray matter changes in a sample of n = 20 adult women (aged 18-49 years) with 47,XXX karyotype using T1-weighted 3T MRI scans. RESULTS: Compared to an age- and education-matched control group (and controlled for differences in total intracranial volume), the VBM revealed decreased regional gray matter volumes in the hippocampus, amygdala, parts of the basal ganglia, insula, prefrontal areas and cerebellum. To a lesser extent, we also noted specific reductions in cortical thickness in a smaller part of those regions. CONCLUSION: The observed network is significantly involved in the processing of cognitive, affective, and social stimuli and might be a potential neuronal correlate of the autism-like social-cognitive problems described in 47,XXX in the literature. En ligne : https://dx.doi.org/10.1186/s11689-025-09608-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Behavioral and psychological symptoms of dementia and Alzheimer's disease progression in Down syndrome Type de document : texte imprimé Auteurs : Melissa R. JENKINS, Auteur ; Jamie C. PEVEN, Auteur ; Lauren KUBIC, Auteur ; Benjamin L. HANDEN, Auteur ; Sharon J. KRINSKY-MCHALE, Auteur ; Christy L. HOM, Auteur ; Alice LEE, Auteur ; Dana L. TUDORASCU, Auteur ; Max MCLACHLAN, Auteur ; Matthew ZAMMIT, Auteur ; Davneet MINHAS, Auteur ; Weiquan LUO, Auteur ; Charles LAYMON, Auteur ; Joseph H. LEE, Auteur ; Ira LOTT, Auteur ; Annie COHEN, Auteur ; Beau M. ANCES, Auteur ; H. Diana ROSAS, Auteur ; Florence LAI, Auteur ; Shahid H. ZAMAN, Auteur ; Elizabeth HEAD, Auteur ; Mark MAPSTONE, Auteur ; Bradley T. CHRISTIAN, Auteur ; Sigan L. HARTLEY, Auteur ; ALZHEIMER BIOMARKER CONSORTIUM - DOWN SYNDROME, Auteur Langues : Anglais (eng) Mots-clés : Humans Down Syndrome/complications/psychology/diagnostic imaging Male Female Alzheimer Disease/psychology/diagnostic imaging/complications/metabolism/physiopathology Disease Progression Middle Aged Dementia/psychology/diagnostic imaging/complications/physiopathology Adult Positron-Emission Tomography Cognitive Dysfunction/diagnostic imaging/psychology Amyloid beta-Peptides/metabolism Cohort Studies Aged Alzheimer’s disease Amyloid Down syndrome Psychiatric symptoms Tau was approved by the Internal Review Boards of the University of Pittsburgh, University of Wisconsin Madison, and University of California, Irvine. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Adults with Down syndrome (DS) have a 90% lifetime risk for Alzheimer's disease (AD), with neurobiological pathology present decades prior to dementia onset. The profile and timing of cognitive decline in DS is well-documented. However, there is a small body of research on whether Behavioral and Psychological Symptoms of Dementia (BPSD) occur early on in the progression of AD in DS and are associated with early AD pathology (i.e., amyloid-beta [Aβ] and neurofibrillary tau tangles [NFT]). METHODS: Data were analyzed from 337 adults with DS (M = 45.13 years, SD = 9.53 years) enrolled in a large cohort study. The Reiss Screen for Maladaptive Behavior (RSMB) measured common behaviors reported in BPSD across up to four study cycles (spaced approximately 16 months apart). Linear mixed models estimated change in BPSD as predicted by baseline (a) dementia status (i.e., cognitively stable, mild cognitive impairment [MCI], or dementia), (b) Aβ positron emission tomography (PET) tracer [(11)C] PiB, and (c) NFT PET tracer [(18)F]AV-1451. Models controlled for chronological age, sex, study site, premorbid intellectual disability level, APOE e4 allele carrier status, psychiatric diagnoses, and psychiatric medication use. RESULTS: Compared to cognitively stable participants, participants whose status was MCI or dementia, had significantly higher baseline RSMB subdomain scores. Increases in RSMB Depression-Behavioral, Depression-Physical, and Psychosis were observed for participants with MCI. Higher baseline Aβ and NFT were associated with higher RSMB Avoidant at baseline, and increases in RSMB Depression-Physical and Psychosis over time. CONCLUSIONS: BPSD are an important part of AD in DS, particularly during the prodromal stage. Elevated Aβ and NFT predict higher initial avoidance and change in physical depression behaviors and may indicate MCI in adults with DS. Broader increases in BPSD are observed as adults with DS progress from early to late-stage dementia. Clinicians should rule out other possible causes of BPSD when screening for AD, such as stressful life experiences or co-occurring medical conditions. Caregivers of adults with DS should have resources on BPSD management and self-care strategies. En ligne : https://dx.doi.org/10.1186/s11689-025-09604-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Behavioral and psychological symptoms of dementia and Alzheimer's disease progression in Down syndrome [texte imprimé] / Melissa R. JENKINS, Auteur ; Jamie C. PEVEN, Auteur ; Lauren KUBIC, Auteur ; Benjamin L. HANDEN, Auteur ; Sharon J. KRINSKY-MCHALE, Auteur ; Christy L. HOM, Auteur ; Alice LEE, Auteur ; Dana L. TUDORASCU, Auteur ; Max MCLACHLAN, Auteur ; Matthew ZAMMIT, Auteur ; Davneet MINHAS, Auteur ; Weiquan LUO, Auteur ; Charles LAYMON, Auteur ; Joseph H. LEE, Auteur ; Ira LOTT, Auteur ; Annie COHEN, Auteur ; Beau M. ANCES, Auteur ; H. Diana ROSAS, Auteur ; Florence LAI, Auteur ; Shahid H. ZAMAN, Auteur ; Elizabeth HEAD, Auteur ; Mark MAPSTONE, Auteur ; Bradley T. CHRISTIAN, Auteur ; Sigan L. HARTLEY, Auteur ; ALZHEIMER BIOMARKER CONSORTIUM - DOWN SYNDROME, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Down Syndrome/complications/psychology/diagnostic imaging Male Female Alzheimer Disease/psychology/diagnostic imaging/complications/metabolism/physiopathology Disease Progression Middle Aged Dementia/psychology/diagnostic imaging/complications/physiopathology Adult Positron-Emission Tomography Cognitive Dysfunction/diagnostic imaging/psychology Amyloid beta-Peptides/metabolism Cohort Studies Aged Alzheimer’s disease Amyloid Down syndrome Psychiatric symptoms Tau was approved by the Internal Review Boards of the University of Pittsburgh, University of Wisconsin Madison, and University of California, Irvine. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Adults with Down syndrome (DS) have a 90% lifetime risk for Alzheimer's disease (AD), with neurobiological pathology present decades prior to dementia onset. The profile and timing of cognitive decline in DS is well-documented. However, there is a small body of research on whether Behavioral and Psychological Symptoms of Dementia (BPSD) occur early on in the progression of AD in DS and are associated with early AD pathology (i.e., amyloid-beta [Aβ] and neurofibrillary tau tangles [NFT]). METHODS: Data were analyzed from 337 adults with DS (M = 45.13 years, SD = 9.53 years) enrolled in a large cohort study. The Reiss Screen for Maladaptive Behavior (RSMB) measured common behaviors reported in BPSD across up to four study cycles (spaced approximately 16 months apart). Linear mixed models estimated change in BPSD as predicted by baseline (a) dementia status (i.e., cognitively stable, mild cognitive impairment [MCI], or dementia), (b) Aβ positron emission tomography (PET) tracer [(11)C] PiB, and (c) NFT PET tracer [(18)F]AV-1451. Models controlled for chronological age, sex, study site, premorbid intellectual disability level, APOE e4 allele carrier status, psychiatric diagnoses, and psychiatric medication use. RESULTS: Compared to cognitively stable participants, participants whose status was MCI or dementia, had significantly higher baseline RSMB subdomain scores. Increases in RSMB Depression-Behavioral, Depression-Physical, and Psychosis were observed for participants with MCI. Higher baseline Aβ and NFT were associated with higher RSMB Avoidant at baseline, and increases in RSMB Depression-Physical and Psychosis over time. CONCLUSIONS: BPSD are an important part of AD in DS, particularly during the prodromal stage. Elevated Aβ and NFT predict higher initial avoidance and change in physical depression behaviors and may indicate MCI in adults with DS. Broader increases in BPSD are observed as adults with DS progress from early to late-stage dementia. Clinicians should rule out other possible causes of BPSD when screening for AD, such as stressful life experiences or co-occurring medical conditions. Caregivers of adults with DS should have resources on BPSD management and self-care strategies. En ligne : https://dx.doi.org/10.1186/s11689-025-09604-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Serotonin dysfunction in ADHD Type de document : texte imprimé Auteurs : Eleanor F. JACKSON, Auteur ; Timothy B. RILEY, Auteur ; Paul G. OVERTON, Auteur Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/metabolism/drug therapy/physiopathology Humans Serotonin/metabolism Tryptophan/metabolism Animals Synaptic Transmission/physiology 5-hydroxytryptophan. Attention deficit hyperactivity disorder Kynurenine Serotonin Tryptophan for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : It is well accepted that attention deficit hyperactivity disorder (ADHD) is in part driven by dysfunction in the monoaminergic neurotransmitter system, but both the extent of dysfunction and possible therapeutic avenues presented by serotonergic neurotransmission is frequently overlooked. As such, we present key evidence for dysfunction in serotonergic transmission, as seen from biochemical, genetic and pharmacological perspectives. An overall deficit in serotonin availability is a common theme throughout the literature, thus this review aims to explore possible dysfunctions in the serotonin synthesis pathway which result in this reduced bioavailability, and investigate whether such dysfunctions could be loci of change in ADHD. We have identified several steps in transmission, namely the conversion of tryptophan to 5-hydroxytryptophan and its use of cofactor tetrahydrobiopterin, which could present promising avenues for development of novel clinical interventions for ADHD. En ligne : https://dx.doi.org/10.1186/s11689-025-09610-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Serotonin dysfunction in ADHD [texte imprimé] / Eleanor F. JACKSON, Auteur ; Timothy B. RILEY, Auteur ; Paul G. OVERTON, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Attention Deficit Disorder with Hyperactivity/metabolism/drug therapy/physiopathology Humans Serotonin/metabolism Tryptophan/metabolism Animals Synaptic Transmission/physiology 5-hydroxytryptophan. Attention deficit hyperactivity disorder Kynurenine Serotonin Tryptophan for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : It is well accepted that attention deficit hyperactivity disorder (ADHD) is in part driven by dysfunction in the monoaminergic neurotransmitter system, but both the extent of dysfunction and possible therapeutic avenues presented by serotonergic neurotransmission is frequently overlooked. As such, we present key evidence for dysfunction in serotonergic transmission, as seen from biochemical, genetic and pharmacological perspectives. An overall deficit in serotonin availability is a common theme throughout the literature, thus this review aims to explore possible dysfunctions in the serotonin synthesis pathway which result in this reduced bioavailability, and investigate whether such dysfunctions could be loci of change in ADHD. We have identified several steps in transmission, namely the conversion of tryptophan to 5-hydroxytryptophan and its use of cofactor tetrahydrobiopterin, which could present promising avenues for development of novel clinical interventions for ADHD. En ligne : https://dx.doi.org/10.1186/s11689-025-09610-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Psychopharmacology in children with genetic disorders of epigenetic and chromatin regulation Type de document : texte imprimé Auteurs : Sophia LENZ, Auteur ; Ajilan SIVALOGANATHAN, Auteur ; Sarah J. GOODMAN, Auteur ; Cheryl CYTRYNBAUM, Auteur ; Jesiqua RAPLEY, Auteur ; Emma CANNING, Auteur ; Danielle BARIBEAU, Auteur Langues : Anglais (eng) Mots-clés : Humans Child Female Male Epigenesis, Genetic Psychotropic Drugs/therapeutic use/adverse effects Intellectual Disability/genetics/drug therapy Child, Preschool Adolescent Chromatin/genetics Autistic Disorder/genetics/drug therapy Autism Spectrum Disorder/genetics/drug therapy Autism Behavioural disorders Epigenetic regulation Psychopharmacology Rare genetic neurodevelopmental disorders by the Research Ethics Board at Holland Bloorview Kids Rehabilitation Hospital. Competing interests: DB is the site lead for a clinical trial funded by MapLight Therapeutics. The remaining authors declare no potential competing interests. Index. décimale : PER Périodiques Résumé : OBJECTIVE: Hundreds of rare genetic variants associated with autism or intellectual disability have been identified, and many impact genes known to have a primary epigenetic/chromatin regulatory function. The objective of this study was to examine and compare behavioural profiles and longitudinal psychotropic treatment patterns in children with epigenetic/chromatin variants, other rare variants impacting neurodevelopment, or no known genetic condition. METHODS: Using electronic medical records from a pediatric psychopharmacology program for children with autism or intellectual disability, we compared clinical characteristics, longitudinal psychotropic medication profiles and side effects between those with and without a rare genetic variant, and by variant subtype [epigenetic/chromatin regulation or other variant]. RESULTS: A total of 331 children attended 2724 unique medical visits between 2019 and 2022, with a mean of 8 follow-up visits over 3.4 years. Nine children (3%) had variants in epigenetic/chromatin regulatory genes (EC), twenty-three children (7%) had other rare genetic variants (OTH), and the rest had no reported variant (NR, n = 299, 90%). Those with a rare genetic variant (EC or OTH) were more likely to have an intellectual disability and had a greater number of co-occurring physical health conditions (p < 0.01). Overall, 66% of psychotropic medications were continued for ≥ 3 visits, while 26% were discontinued. Rates of psychotropic polypharmacy, medication patterns, behavioural challenges, and co-occurring developmental diagnoses were similar between genetic groups. Analyses uncorrected for multiple comparisons suggested those with genetic variants were more likely to experience drowsiness/sedation as a side effect (EC 33%, OTH 35%, NR 16%, p < 0.05); weight gain as a side effect was also higher in the epigenetic/chromatin group (EC 50% vs OTH 11%). CONCLUSION: Genetic classification of neurodevelopmental disorders (NDDs) may help anticipate treatment tolerability; additional prescribing considerations may be needed for those with rare variants. Current psychotropic prescribing practices do not differ across rare genetic NDD subgroups. En ligne : https://dx.doi.org/10.1186/s11689-025-09605-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Psychopharmacology in children with genetic disorders of epigenetic and chromatin regulation [texte imprimé] / Sophia LENZ, Auteur ; Ajilan SIVALOGANATHAN, Auteur ; Sarah J. GOODMAN, Auteur ; Cheryl CYTRYNBAUM, Auteur ; Jesiqua RAPLEY, Auteur ; Emma CANNING, Auteur ; Danielle BARIBEAU, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Child Female Male Epigenesis, Genetic Psychotropic Drugs/therapeutic use/adverse effects Intellectual Disability/genetics/drug therapy Child, Preschool Adolescent Chromatin/genetics Autistic Disorder/genetics/drug therapy Autism Spectrum Disorder/genetics/drug therapy Autism Behavioural disorders Epigenetic regulation Psychopharmacology Rare genetic neurodevelopmental disorders by the Research Ethics Board at Holland Bloorview Kids Rehabilitation Hospital. Competing interests: DB is the site lead for a clinical trial funded by MapLight Therapeutics. The remaining authors declare no potential competing interests. Index. décimale : PER Périodiques Résumé : OBJECTIVE: Hundreds of rare genetic variants associated with autism or intellectual disability have been identified, and many impact genes known to have a primary epigenetic/chromatin regulatory function. The objective of this study was to examine and compare behavioural profiles and longitudinal psychotropic treatment patterns in children with epigenetic/chromatin variants, other rare variants impacting neurodevelopment, or no known genetic condition. METHODS: Using electronic medical records from a pediatric psychopharmacology program for children with autism or intellectual disability, we compared clinical characteristics, longitudinal psychotropic medication profiles and side effects between those with and without a rare genetic variant, and by variant subtype [epigenetic/chromatin regulation or other variant]. RESULTS: A total of 331 children attended 2724 unique medical visits between 2019 and 2022, with a mean of 8 follow-up visits over 3.4 years. Nine children (3%) had variants in epigenetic/chromatin regulatory genes (EC), twenty-three children (7%) had other rare genetic variants (OTH), and the rest had no reported variant (NR, n = 299, 90%). Those with a rare genetic variant (EC or OTH) were more likely to have an intellectual disability and had a greater number of co-occurring physical health conditions (p < 0.01). Overall, 66% of psychotropic medications were continued for ≥ 3 visits, while 26% were discontinued. Rates of psychotropic polypharmacy, medication patterns, behavioural challenges, and co-occurring developmental diagnoses were similar between genetic groups. Analyses uncorrected for multiple comparisons suggested those with genetic variants were more likely to experience drowsiness/sedation as a side effect (EC 33%, OTH 35%, NR 16%, p < 0.05); weight gain as a side effect was also higher in the epigenetic/chromatin group (EC 50% vs OTH 11%). CONCLUSION: Genetic classification of neurodevelopmental disorders (NDDs) may help anticipate treatment tolerability; additional prescribing considerations may be needed for those with rare variants. Current psychotropic prescribing practices do not differ across rare genetic NDD subgroups. En ligne : https://dx.doi.org/10.1186/s11689-025-09605-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Transcriptomic profiling of unmethylated full mutation carriers implicates TET3 in FMR1 CGG repeat expansion methylation dynamics in fragile X syndrome Type de document : texte imprimé Auteurs : Grace FARMILOE, Auteur ; Veronika BEJCZY, Auteur ; Elisabetta TABOLACCI, Auteur ; Rob WILLEMSEN, Auteur ; Frank JACOBS, Auteur Langues : Anglais (eng) Mots-clés : Fragile X Mental Retardation Protein/genetics Fragile X Syndrome/genetics/metabolism Humans DNA Methylation/genetics Trinucleotide Repeat Expansion/genetics Male Gene Expression Profiling Fibroblasts/metabolism Female Heterozygote Mutation Promoter Regions, Genetic Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the expansion of a CGG repeat in the 5'UTR of the FMR1 (fragile X messenger ribonucleoprotein 1) gene. Healthy individuals possess a repeat 30-55 CGG units in length. Once the CGG repeat exceeds 200 copies it triggers methylation at the locus. This methylation covers the FMR1 promoter region and silences expression of the gene and the production of FMRP (fragile X messenger ribonucleoprotein). The loss of FMRP is responsible for a number of pathologies including neurodevelopmental delay and autism spectrum disorder. Methylation of the expanded repeat in the FMR1 locus is the causal factor for FXS, however it is not known why the expanded repeat triggers this epigenetic change or how exactly DNA methylation is established. Intriguingly, genetic engineering of expanded CGG repeats of over 300 copies in the FMR1 locus in mice remains unmethylated. Also in humans, in very rare cases, individuals can have an FMR1 CGG expansion > 200 copies but the locus remains unmethylated. These unmethylated full mutation (UFM) individuals give us a rare opportunity to investigate the mechanism of FMR1 promoter methylation. METHODS: Fibroblasts were obtained from a healthy control, an FXS patient and two unmethylated full expansion carriers. RNA was extracted and comparative transcriptomic analysis was performed on all samples. Whole genome sequencing was carried out on DNA from the two UFM carriers and the results analysed to investigate DNA variants that could explain the observed differences in gene expression. RESULTS: Our analyses focused on genes involved in epigenetic modification. We show that Tet methylcytosine dioxygenase 3 (TET3), a gene involved in DNA methylation, is significantly downregulated in UFM carriers compared to healthy controls or FXS patient derived cells. Genomic analyses reveal a number of rare variants present in the TET3 locus in UFM carriers when compared to the reference genome. However, no clear modifying TET3 variants were identified. CONCLUSION: Our results suggest that TET3 is a candidate factor responsible for the lack of methylation of the expanded FMR1 locus. Further analyses are needed to further elucidate this relationship, however given its potential to directly interact with CGG repeats and its ambiguous role in 5-hydroxy-methylation of CG containing sequences, TET3 is a strong candidate for further exploration. En ligne : https://dx.doi.org/10.1186/s11689-025-09609-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Transcriptomic profiling of unmethylated full mutation carriers implicates TET3 in FMR1 CGG repeat expansion methylation dynamics in fragile X syndrome [texte imprimé] / Grace FARMILOE, Auteur ; Veronika BEJCZY, Auteur ; Elisabetta TABOLACCI, Auteur ; Rob WILLEMSEN, Auteur ; Frank JACOBS, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Fragile X Mental Retardation Protein/genetics Fragile X Syndrome/genetics/metabolism Humans DNA Methylation/genetics Trinucleotide Repeat Expansion/genetics Male Gene Expression Profiling Fibroblasts/metabolism Female Heterozygote Mutation Promoter Regions, Genetic Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the expansion of a CGG repeat in the 5'UTR of the FMR1 (fragile X messenger ribonucleoprotein 1) gene. Healthy individuals possess a repeat 30-55 CGG units in length. Once the CGG repeat exceeds 200 copies it triggers methylation at the locus. This methylation covers the FMR1 promoter region and silences expression of the gene and the production of FMRP (fragile X messenger ribonucleoprotein). The loss of FMRP is responsible for a number of pathologies including neurodevelopmental delay and autism spectrum disorder. Methylation of the expanded repeat in the FMR1 locus is the causal factor for FXS, however it is not known why the expanded repeat triggers this epigenetic change or how exactly DNA methylation is established. Intriguingly, genetic engineering of expanded CGG repeats of over 300 copies in the FMR1 locus in mice remains unmethylated. Also in humans, in very rare cases, individuals can have an FMR1 CGG expansion > 200 copies but the locus remains unmethylated. These unmethylated full mutation (UFM) individuals give us a rare opportunity to investigate the mechanism of FMR1 promoter methylation. METHODS: Fibroblasts were obtained from a healthy control, an FXS patient and two unmethylated full expansion carriers. RNA was extracted and comparative transcriptomic analysis was performed on all samples. Whole genome sequencing was carried out on DNA from the two UFM carriers and the results analysed to investigate DNA variants that could explain the observed differences in gene expression. RESULTS: Our analyses focused on genes involved in epigenetic modification. We show that Tet methylcytosine dioxygenase 3 (TET3), a gene involved in DNA methylation, is significantly downregulated in UFM carriers compared to healthy controls or FXS patient derived cells. Genomic analyses reveal a number of rare variants present in the TET3 locus in UFM carriers when compared to the reference genome. However, no clear modifying TET3 variants were identified. CONCLUSION: Our results suggest that TET3 is a candidate factor responsible for the lack of methylation of the expanded FMR1 locus. Further analyses are needed to further elucidate this relationship, however given its potential to directly interact with CGG repeats and its ambiguous role in 5-hydroxy-methylation of CG containing sequences, TET3 is a strong candidate for further exploration. En ligne : https://dx.doi.org/10.1186/s11689-025-09609-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Functional connectivity between the visual and salience networks and autistic social features at school-age Type de document : texte imprimé Auteurs : Jessica B. GIRAULT, Auteur ; Tomoyuki NISHINO, Auteur ; Muhamed TALOVIĆ, Auteur ; Mary Beth NEBEL, Auteur ; Margaret REYNOLDS, Auteur ; Catherine A. BURROWS, Auteur ; Jed T. ELISON, Auteur ; Chimei M. LEE, Auteur ; Abraham Z. SNYDER, Auteur ; Mark D. SHEN, Auteur ; Audrey M. SHEN, Auteur ; Kelly N. BOTTERON, Auteur ; Annette M. ESTES, Auteur ; Stephen R. DAGER, Auteur ; Guido GERIG, Auteur ; Heather C. HAZLETT, Auteur ; Natasha MARRUS, Auteur ; Robert C. MCKINSTRY, Auteur ; Juhi PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Tanya ST JOHN, Auteur ; Martin A. STYNER, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Alexandre A. TODOROV, Auteur ; Joseph PIVEN, Auteur ; John R. Jr PRUETT, Auteur ; IBIS NETWORK, Auteur Langues : Anglais (eng) Mots-clés : Humans Male Child Female Magnetic Resonance Imaging Autism Spectrum Disorder/physiopathology/diagnostic imaging/psychology Longitudinal Studies Brain/physiopathology/diagnostic imaging Social Behavior Neural Pathways/physiopathology/diagnostic imaging Nerve Net/physiopathology/diagnostic imaging Autism Brain networks Functional connectivity Mri Social behavior provided by all participating families. Study procedures were approved by the Institutional Review Boards (IRB) at each research site: University of North Carolina at Chapel Hill, Washington University in St. Louis, University of Washington in Seattle, and the Children’s Hospital of Philadelphia. A single governing IRB at UNC Chapel Hill was in place (IRB #17–1871, PI: Piven). Consent for publication: Not applicable. Competing interests: Dr. Robert McKinstry serves on the medical advisory board and receives stock options for Turing Medical he also receives funding for meals and travel from Siemens Healthineers, Philips Healthcare, RadiAction Medical, and meals from Hyperfine, Inc. Abraham Z. Snyder is a consultant for Sora Neuroscience, LLC. A.M. Shen discloses a familial relationship with M.D. Shen, but their institution’s COI Office has determined there is no scientific or financial conflict of interest. All other authors report no financial relationships with commercial interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD. METHODS: Resting state functional connectivity MRIs (fcMRI) and behavioral data were analyzed from 97 school-age children (8.1-12.0 years, 55 males, 15 ASD) with (n = 63) or without (n = 34) a family history of ASD. fcMRI enrichment analysis (EA) was used to screen for associations between network-level functional connectivity and six behaviors of interest in a data-driven manner: social affect, restricted and repetitive behavior (RRB), generalized anxiety, inattention, motor coordination, and matrix reasoning. RESULTS: Functional connectivity between the visual and salience networks was significantly associated with social affect symptoms at school-age after accounting for all other behaviors. Results indicated that stronger connectivity was associated with higher social affect scores. No other behaviors were robustly associated with functional connectivity, though trends were observed between visual-salience connectivity and RRBs. CONCLUSIONS: Connectivity between the visual and salience networks may play an important role in social affect symptom variability among children with ASD and those with genetic liability for ASD. These findings align with and extend earlier reports in this sample of the central role of the visual system during infancy in ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09613-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Functional connectivity between the visual and salience networks and autistic social features at school-age [texte imprimé] / Jessica B. GIRAULT, Auteur ; Tomoyuki NISHINO, Auteur ; Muhamed TALOVIĆ, Auteur ; Mary Beth NEBEL, Auteur ; Margaret REYNOLDS, Auteur ; Catherine A. BURROWS, Auteur ; Jed T. ELISON, Auteur ; Chimei M. LEE, Auteur ; Abraham Z. SNYDER, Auteur ; Mark D. SHEN, Auteur ; Audrey M. SHEN, Auteur ; Kelly N. BOTTERON, Auteur ; Annette M. ESTES, Auteur ; Stephen R. DAGER, Auteur ; Guido GERIG, Auteur ; Heather C. HAZLETT, Auteur ; Natasha MARRUS, Auteur ; Robert C. MCKINSTRY, Auteur ; Juhi PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; Tanya ST JOHN, Auteur ; Martin A. STYNER, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Alexandre A. TODOROV, Auteur ; Joseph PIVEN, Auteur ; John R. Jr PRUETT, Auteur ; IBIS NETWORK, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Male Child Female Magnetic Resonance Imaging Autism Spectrum Disorder/physiopathology/diagnostic imaging/psychology Longitudinal Studies Brain/physiopathology/diagnostic imaging Social Behavior Neural Pathways/physiopathology/diagnostic imaging Nerve Net/physiopathology/diagnostic imaging Autism Brain networks Functional connectivity Mri Social behavior provided by all participating families. Study procedures were approved by the Institutional Review Boards (IRB) at each research site: University of North Carolina at Chapel Hill, Washington University in St. Louis, University of Washington in Seattle, and the Children’s Hospital of Philadelphia. A single governing IRB at UNC Chapel Hill was in place (IRB #17–1871, PI: Piven). Consent for publication: Not applicable. Competing interests: Dr. Robert McKinstry serves on the medical advisory board and receives stock options for Turing Medical he also receives funding for meals and travel from Siemens Healthineers, Philips Healthcare, RadiAction Medical, and meals from Hyperfine, Inc. Abraham Z. Snyder is a consultant for Sora Neuroscience, LLC. A.M. Shen discloses a familial relationship with M.D. Shen, but their institution’s COI Office has determined there is no scientific or financial conflict of interest. All other authors report no financial relationships with commercial interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD. METHODS: Resting state functional connectivity MRIs (fcMRI) and behavioral data were analyzed from 97 school-age children (8.1-12.0 years, 55 males, 15 ASD) with (n = 63) or without (n = 34) a family history of ASD. fcMRI enrichment analysis (EA) was used to screen for associations between network-level functional connectivity and six behaviors of interest in a data-driven manner: social affect, restricted and repetitive behavior (RRB), generalized anxiety, inattention, motor coordination, and matrix reasoning. RESULTS: Functional connectivity between the visual and salience networks was significantly associated with social affect symptoms at school-age after accounting for all other behaviors. Results indicated that stronger connectivity was associated with higher social affect scores. No other behaviors were robustly associated with functional connectivity, though trends were observed between visual-salience connectivity and RRBs. CONCLUSIONS: Connectivity between the visual and salience networks may play an important role in social affect symptom variability among children with ASD and those with genetic liability for ASD. These findings align with and extend earlier reports in this sample of the central role of the visual system during infancy in ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09613-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Automated extraction of functional biomarkers of verbal and ambulatory ability from multi-institutional clinical notes using large language models Type de document : texte imprimé Auteurs : Levi KASTER, Auteur ; Ethan HILLIS, Auteur ; Inez Y. OH, Auteur ; Bhooma R. ARAVAMUTHAN, Auteur ; Virginia C. LANZOTTI, Auteur ; Casey R. VICKSTROM, Auteur ; BRAIN GENE REGISTRY CONSORTIUM, Auteur ; Christina A. GURNETT, Auteur ; Philip R.O. PAYNE, Auteur ; Aditi GUPTA, Auteur Langues : Anglais (eng) Mots-clés : Adolescent Adult Child Child, Preschool Female Humans Male Young Adult Biomarkers Cerebral Palsy/physiopathology/diagnosis Developmental Disabilities/physiopathology/diagnosis Electronic Health Records Intellectual Disability/physiopathology/diagnosis Large Language Models Natural Language Processing Registries Electronic health records Functional biomarkers Large language models Neurodevelopmental disorders recruited specifically for this study. This work constitutes secondary use of data approved by the Washington University in St. Louis IRB (protocols #202010013 [Brain Gene Registry cohort] and #202309003 [cerebral palsy cohort]). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Functional biomarkers in neurodevelopmental disorders, such as verbal and ambulatory abilities, are essential for clinical care and research activities. Treatment planning, intervention monitoring, and identifying comorbid conditions in individuals with intellectual and developmental disabilities (IDDs) rely on standardized assessments of these abilities. However, traditional assessments impose a burden on patients and providers, often leading to longitudinal inconsistencies and inequities due to evolving guidelines and associated time-cost. Therefore, this study aimed to develop an automated approach to classify verbal and ambulatory abilities from EHR data of IDD and cerebral palsy (CP) patients. Application of large language models (LLMs) to clinical notes, which are rich in longitudinal data, may provide a low-burden pipeline for extracting functional biomarkers efficiently and accurately. METHODS: Data from the multi-institutional National Brain Gene Registry (BGR) and a CP clinic cohort were utilized, comprising 3,245 notes from 125 individuals and 5,462 clinical notes from 260 individuals, respectively. Employing three LLMs-GPT-3.5 Turbo, GPT-4 Turbo, and GPT-4 Omni-we provided the models with a clinical note and utilized a detailed conversational format to prompt the models to answer: "Does the individual use any words?" and "Can the individual walk without aid?" These responses were evaluated against ground-truth abilities, which were established using neurobehavioral assessments collected for each dataset. RESULTS: LLM pipelines demonstrated high accuracy (weighted-F1 scores > .90) in predicting ambulatory ability for both cohorts, likely due to the consistent use of Gross Motor Functional Classification System (GMFCS) as a consistent ground-truth standard. However, verbal ability predictions were more accurate in the BGR cohort, likely due to higher adherence between the prompt and ground-truth assessment questions. While LLMs can be computationally expensive, analysis of our protocol affirmed the cost effectiveness when applied to select notes from the EHR. CONCLUSIONS: LLMs are effective at extracting functional biomarkers from EHR data and broadly generalizable across variable note-taking practices and institutions. Individual verbal and ambulatory ability were accurately extracted, supporting the method's ability to streamline workflows by offering automated, efficient data extraction for patient care and research. Future studies are needed to extend this methodology to additional populations and to demonstrate more granular functional data classification. En ligne : https://dx.doi.org/10.1186/s11689-025-09612-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Automated extraction of functional biomarkers of verbal and ambulatory ability from multi-institutional clinical notes using large language models [texte imprimé] / Levi KASTER, Auteur ; Ethan HILLIS, Auteur ; Inez Y. OH, Auteur ; Bhooma R. ARAVAMUTHAN, Auteur ; Virginia C. LANZOTTI, Auteur ; Casey R. VICKSTROM, Auteur ; BRAIN GENE REGISTRY CONSORTIUM, Auteur ; Christina A. GURNETT, Auteur ; Philip R.O. PAYNE, Auteur ; Aditi GUPTA, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Adolescent Adult Child Child, Preschool Female Humans Male Young Adult Biomarkers Cerebral Palsy/physiopathology/diagnosis Developmental Disabilities/physiopathology/diagnosis Electronic Health Records Intellectual Disability/physiopathology/diagnosis Large Language Models Natural Language Processing Registries Electronic health records Functional biomarkers Large language models Neurodevelopmental disorders recruited specifically for this study. This work constitutes secondary use of data approved by the Washington University in St. Louis IRB (protocols #202010013 [Brain Gene Registry cohort] and #202309003 [cerebral palsy cohort]). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Functional biomarkers in neurodevelopmental disorders, such as verbal and ambulatory abilities, are essential for clinical care and research activities. Treatment planning, intervention monitoring, and identifying comorbid conditions in individuals with intellectual and developmental disabilities (IDDs) rely on standardized assessments of these abilities. However, traditional assessments impose a burden on patients and providers, often leading to longitudinal inconsistencies and inequities due to evolving guidelines and associated time-cost. Therefore, this study aimed to develop an automated approach to classify verbal and ambulatory abilities from EHR data of IDD and cerebral palsy (CP) patients. Application of large language models (LLMs) to clinical notes, which are rich in longitudinal data, may provide a low-burden pipeline for extracting functional biomarkers efficiently and accurately. METHODS: Data from the multi-institutional National Brain Gene Registry (BGR) and a CP clinic cohort were utilized, comprising 3,245 notes from 125 individuals and 5,462 clinical notes from 260 individuals, respectively. Employing three LLMs-GPT-3.5 Turbo, GPT-4 Turbo, and GPT-4 Omni-we provided the models with a clinical note and utilized a detailed conversational format to prompt the models to answer: "Does the individual use any words?" and "Can the individual walk without aid?" These responses were evaluated against ground-truth abilities, which were established using neurobehavioral assessments collected for each dataset. RESULTS: LLM pipelines demonstrated high accuracy (weighted-F1 scores > .90) in predicting ambulatory ability for both cohorts, likely due to the consistent use of Gross Motor Functional Classification System (GMFCS) as a consistent ground-truth standard. However, verbal ability predictions were more accurate in the BGR cohort, likely due to higher adherence between the prompt and ground-truth assessment questions. While LLMs can be computationally expensive, analysis of our protocol affirmed the cost effectiveness when applied to select notes from the EHR. CONCLUSIONS: LLMs are effective at extracting functional biomarkers from EHR data and broadly generalizable across variable note-taking practices and institutions. Individual verbal and ambulatory ability were accurately extracted, supporting the method's ability to streamline workflows by offering automated, efficient data extraction for patient care and research. Future studies are needed to extend this methodology to additional populations and to demonstrate more granular functional data classification. En ligne : https://dx.doi.org/10.1186/s11689-025-09612-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns Type de document : texte imprimé Auteurs : Hailey SILVER, Auteur ; Rori GREENBERG, Auteur ; Paige M. SIPER, Auteur ; Jessica ZWEIFACH, Auteur ; Renee SOUFER, Auteur ; Mustafa SAHIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Alexander KOLEVZON, Auteur ; Dorothy E. GRICE, Auteur ; Joseph D. BUXBAUM, Auteur ; Tess LEVY, Auteur Langues : Anglais (eng) Mots-clés : Humans Autism Spectrum Disorder/genetics/physiopathology Male Female Nerve Tissue Proteins/genetics Child Child, Preschool Chromosome Disorders/genetics/physiopathology Developmental Disabilities/genetics/physiopathology Adolescent Attention Deficit Disorder with Hyperactivity/genetics Intellectual Disability/genetics Chromosomes, Human, Pair 22/genetics Adult Cohort Studies Chromosome Deletion Autism spectrum disorder Developmental delay Intellectual and developmental disability Phenotype SHANK2 Medicine at Mount Sinai’s Institutional Review Board (IRB) approved the study. Caregivers or legal guardians of the participants provided informed consent, and assent was obtained when applicable. Consent for publication: Not applicable. Competing interests: A.K. receives research support from AMO Pharma and consults for Acadia, Alkermes, Neuren, and GW Pharma. He serves on Scientific Advisory Boards for Ovid Therapeutics, Jaguar Therapeutics, and Ritrova Therapeutics. P.M.S. and Mount Sinai licensed the SAND developed by P.M.S. to Stoelting, Co. J.D.B. holds a patent for IGF-1 in Phelan-McDermid syndrome, holds an honorary professorship from Aarhus University Denmark, and is a journal editor for Springer Nature. M.S. reports grant support from Biogen, Astellas, Neurvati Neurosciences, Bridgebio, and Aucta. He has served on scientific advisory boards for Neurogene, Jaguar Gene Therapy and Noema. EBK has received funding from Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin, Ovid, Retrophin, AMO, Yamo, Acadia, Avexis, Ionis, Ultragenyx, Lumos, GeneTx, and Vtesse/Sucampo/Mallinkcrodt Pharmaceuticals to consult on trial design or development strategies and/or conduct clinical trials in FXS or other NDDs or neurodegenerative disorders, and from Asuragen Inc to develop testing standards for FMR1 testing. All funding to EBK is directed to Rush University Medical Center to support rare disease programs. EBK receives no personal funds. The remaining authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK2 disorder is a rare neurodevelopmental disorder caused by a deletion or pathogenic sequence variant of the SHANK2 gene and is associated with autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay. To date, research in SHANK2 has focused on laboratory-based in vivo and in vitro studies with few prospective clinical studies in humans. METHODS: A remote assessment battery was comprised of caregiver interviews with a psychiatrist, psychologists, and a genetic counselor, caregiver-reports, and review of records. Results from this cohort were reported using descriptive statistics. An age-matched sample of participants with SHANK3 haploinsufficiency (Phelan-McDermid syndrome, PMS) was used to compare adaptive behavior between the two groups. RESULTS: All ten participants demonstrated delays in adaptive behavior, with most motor skills preserved and a weakness in communication. According to parent report, 90% of participants carried a formal diagnosis of ASD, 50% of participants carried a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and mild-to-moderate developmental delays were noted. Sensory hyperreactivity and seeking behaviors were more pronounced than sensory hyporeactivity. Medical features included hypotonia, recurrent ear infections, and gastrointestinal abnormalities. No similar facial dysmorphic features were observed. Compared to PMS participants, individuals with SHANK2 disorder had significantly higher adaptive functioning. CONCLUSIONS: Consistent with previous studies of SHANK2 disorder, these results indicate mild to moderate developmental impairment. Overall, SHANK2 disorder is associated with developmental and adaptive functioning delays, high rates of autism, including sensory symptoms and repetitive behaviors, and ADHD. This study was limited by its remote nature, diverse age range, and the homogeneous racial and ethnic sample. Future studies should examine larger, diverse cohorts, add cognitive testing, capture longitudinal data, and include in-person assessments. En ligne : https://dx.doi.org/10.1186/s11689-025-09600-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns [texte imprimé] / Hailey SILVER, Auteur ; Rori GREENBERG, Auteur ; Paige M. SIPER, Auteur ; Jessica ZWEIFACH, Auteur ; Renee SOUFER, Auteur ; Mustafa SAHIN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Latha Valluripalli SOORYA, Auteur ; Audrey THURM, Auteur ; Jonathan A. BERNSTEIN, Auteur ; Alexander KOLEVZON, Auteur ; Dorothy E. GRICE, Auteur ; Joseph D. BUXBAUM, Auteur ; Tess LEVY, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Autism Spectrum Disorder/genetics/physiopathology Male Female Nerve Tissue Proteins/genetics Child Child, Preschool Chromosome Disorders/genetics/physiopathology Developmental Disabilities/genetics/physiopathology Adolescent Attention Deficit Disorder with Hyperactivity/genetics Intellectual Disability/genetics Chromosomes, Human, Pair 22/genetics Adult Cohort Studies Chromosome Deletion Autism spectrum disorder Developmental delay Intellectual and developmental disability Phenotype SHANK2 Medicine at Mount Sinai’s Institutional Review Board (IRB) approved the study. Caregivers or legal guardians of the participants provided informed consent, and assent was obtained when applicable. Consent for publication: Not applicable. Competing interests: A.K. receives research support from AMO Pharma and consults for Acadia, Alkermes, Neuren, and GW Pharma. He serves on Scientific Advisory Boards for Ovid Therapeutics, Jaguar Therapeutics, and Ritrova Therapeutics. P.M.S. and Mount Sinai licensed the SAND developed by P.M.S. to Stoelting, Co. J.D.B. holds a patent for IGF-1 in Phelan-McDermid syndrome, holds an honorary professorship from Aarhus University Denmark, and is a journal editor for Springer Nature. M.S. reports grant support from Biogen, Astellas, Neurvati Neurosciences, Bridgebio, and Aucta. He has served on scientific advisory boards for Neurogene, Jaguar Gene Therapy and Noema. EBK has received funding from Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin, Ovid, Retrophin, AMO, Yamo, Acadia, Avexis, Ionis, Ultragenyx, Lumos, GeneTx, and Vtesse/Sucampo/Mallinkcrodt Pharmaceuticals to consult on trial design or development strategies and/or conduct clinical trials in FXS or other NDDs or neurodegenerative disorders, and from Asuragen Inc to develop testing standards for FMR1 testing. All funding to EBK is directed to Rush University Medical Center to support rare disease programs. EBK receives no personal funds. The remaining authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK2 disorder is a rare neurodevelopmental disorder caused by a deletion or pathogenic sequence variant of the SHANK2 gene and is associated with autism spectrum disorder (ASD), intellectual disability (ID), and developmental delay. To date, research in SHANK2 has focused on laboratory-based in vivo and in vitro studies with few prospective clinical studies in humans. METHODS: A remote assessment battery was comprised of caregiver interviews with a psychiatrist, psychologists, and a genetic counselor, caregiver-reports, and review of records. Results from this cohort were reported using descriptive statistics. An age-matched sample of participants with SHANK3 haploinsufficiency (Phelan-McDermid syndrome, PMS) was used to compare adaptive behavior between the two groups. RESULTS: All ten participants demonstrated delays in adaptive behavior, with most motor skills preserved and a weakness in communication. According to parent report, 90% of participants carried a formal diagnosis of ASD, 50% of participants carried a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and mild-to-moderate developmental delays were noted. Sensory hyperreactivity and seeking behaviors were more pronounced than sensory hyporeactivity. Medical features included hypotonia, recurrent ear infections, and gastrointestinal abnormalities. No similar facial dysmorphic features were observed. Compared to PMS participants, individuals with SHANK2 disorder had significantly higher adaptive functioning. CONCLUSIONS: Consistent with previous studies of SHANK2 disorder, these results indicate mild to moderate developmental impairment. Overall, SHANK2 disorder is associated with developmental and adaptive functioning delays, high rates of autism, including sensory symptoms and repetitive behaviors, and ADHD. This study was limited by its remote nature, diverse age range, and the homogeneous racial and ethnic sample. Future studies should examine larger, diverse cohorts, add cognitive testing, capture longitudinal data, and include in-person assessments. En ligne : https://dx.doi.org/10.1186/s11689-025-09600-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Visual feedback and motor memory contributions to sustained motor control deficits in autism spectrum disorder across childhood and into adulthood Type de document : texte imprimé Auteurs : Robin L. SHAFER, Auteur ; James BARTOLOTTI, Auteur ; Abigail DRIGGERS, Auteur ; Erin BOJANEK, Auteur ; Zheng WANG, Auteur ; Matthew W. MOSCONI, Auteur Langues : Anglais (eng) Mots-clés : Humans Adolescent Child Autism Spectrum Disorder/physiopathology/complications Male Young Adult Feedback, Sensory/physiology Adult Female Psychomotor Performance/physiology Memory/physiology Motor Skills/physiology Hand Strength/physiology Autism spectrum disorders Entropy Fine motor control Grip force Motor memory Sensorimotor Sensory integration Visual feedback Visuomotor provided written informed consent after a complete description of the study, in accordance with the Declaration of Helsinki. For participants under the age of 18 and adults who were under legal guardianship, a parent or legal guardian provided written informed consent on behalf of the participant, and the participant provided written assent. All study procedures were approved by the University of Kansas Medical Center Institutional Review Board (IRB#: STUDY00140269). Consent for publication: Not applicable. Competing interests: MWM is PI on an investigator initiated clinical trial of behavioral inflexibility in autism funded by Acadia Pharmaceuticals. MWM and ZW received funding from Novartis Pharmaceuticals Corporation for an investigator-initiated study of Phelan McDermid Syndrome. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic individuals show deficits in sustained fine motor control which are associated with an over-reliance on visual feedback. Motor memory deficits also have been reported during sustained fine motor control in autism spectrum disorders (ASD). The development of motor memory and visuomotor feedback processes contributing to sustained motor control issues in ASD are not known. The present study aimed to characterize age-related changes in visual feedback and motor memory processes contributing to sustained fine motor control issues in ASD. METHODS: Fifty-four autistic participants and 31 neurotypical (NT) controls ages 10-25 years completed visually guided and memory guided sustained precision gripping tests by pressing on force sensors with their dominant hand index finger and thumb. For visually guided trials, participants viewed a stationary target bar and a force bar that moved upwards with increased force for 15s. During memory guided trials, the force bar was visible for 3s, after which participants attempted to maintain their force output without visual feedback for another 12s. To assess visual feedback processing, force accuracy, variability (standard deviation), and regularity (sample entropy) were examined. To assess motor memory, force decay latency, slope, and magnitude were examined during epochs without visual feedback. RESULTS: Relative to NT controls, autistic individuals showed a greater magnitude and a trend for a steeper slope of force decay during memory guided trials. Across conditions, the ASD group showed reduced force accuracy (β = 0.41, R(2) = 0.043, t(79.3)=2.36, p = .021) and greater force variability (β=-2.16, R(2) = 0.143, t(77.1)=-4.04, p = .0001) and regularity (β=-0.52, R(2) = 0.021, t(77.4)=-2.21, p = .030) relative to NT controls at younger ages, but these differences normalized by adolescence (age x group interactions). Lower force accuracy and greater force variability during visually guided trials and steeper decay slope during memory guided trials were associated with overall autism severity. CONCLUSIONS: Our findings that autistic individuals show a greater magnitude and tendency for a greater rate of force decay than NT individuals following the removal of visual feedback indicate that motor memory deficits contribute to fine motor control issues in ASD. Findings that sensorimotor differences in ASD were specific to younger ages suggest delayed development across multiple motor control processes. En ligne : https://dx.doi.org/10.1186/s11689-025-09607-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Visual feedback and motor memory contributions to sustained motor control deficits in autism spectrum disorder across childhood and into adulthood [texte imprimé] / Robin L. SHAFER, Auteur ; James BARTOLOTTI, Auteur ; Abigail DRIGGERS, Auteur ; Erin BOJANEK, Auteur ; Zheng WANG, Auteur ; Matthew W. MOSCONI, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Adolescent Child Autism Spectrum Disorder/physiopathology/complications Male Young Adult Feedback, Sensory/physiology Adult Female Psychomotor Performance/physiology Memory/physiology Motor Skills/physiology Hand Strength/physiology Autism spectrum disorders Entropy Fine motor control Grip force Motor memory Sensorimotor Sensory integration Visual feedback Visuomotor provided written informed consent after a complete description of the study, in accordance with the Declaration of Helsinki. For participants under the age of 18 and adults who were under legal guardianship, a parent or legal guardian provided written informed consent on behalf of the participant, and the participant provided written assent. All study procedures were approved by the University of Kansas Medical Center Institutional Review Board (IRB#: STUDY00140269). Consent for publication: Not applicable. Competing interests: MWM is PI on an investigator initiated clinical trial of behavioral inflexibility in autism funded by Acadia Pharmaceuticals. MWM and ZW received funding from Novartis Pharmaceuticals Corporation for an investigator-initiated study of Phelan McDermid Syndrome. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic individuals show deficits in sustained fine motor control which are associated with an over-reliance on visual feedback. Motor memory deficits also have been reported during sustained fine motor control in autism spectrum disorders (ASD). The development of motor memory and visuomotor feedback processes contributing to sustained motor control issues in ASD are not known. The present study aimed to characterize age-related changes in visual feedback and motor memory processes contributing to sustained fine motor control issues in ASD. METHODS: Fifty-four autistic participants and 31 neurotypical (NT) controls ages 10-25 years completed visually guided and memory guided sustained precision gripping tests by pressing on force sensors with their dominant hand index finger and thumb. For visually guided trials, participants viewed a stationary target bar and a force bar that moved upwards with increased force for 15s. During memory guided trials, the force bar was visible for 3s, after which participants attempted to maintain their force output without visual feedback for another 12s. To assess visual feedback processing, force accuracy, variability (standard deviation), and regularity (sample entropy) were examined. To assess motor memory, force decay latency, slope, and magnitude were examined during epochs without visual feedback. RESULTS: Relative to NT controls, autistic individuals showed a greater magnitude and a trend for a steeper slope of force decay during memory guided trials. Across conditions, the ASD group showed reduced force accuracy (β = 0.41, R(2) = 0.043, t(79.3)=2.36, p = .021) and greater force variability (β=-2.16, R(2) = 0.143, t(77.1)=-4.04, p = .0001) and regularity (β=-0.52, R(2) = 0.021, t(77.4)=-2.21, p = .030) relative to NT controls at younger ages, but these differences normalized by adolescence (age x group interactions). Lower force accuracy and greater force variability during visually guided trials and steeper decay slope during memory guided trials were associated with overall autism severity. CONCLUSIONS: Our findings that autistic individuals show a greater magnitude and tendency for a greater rate of force decay than NT individuals following the removal of visual feedback indicate that motor memory deficits contribute to fine motor control issues in ASD. Findings that sensorimotor differences in ASD were specific to younger ages suggest delayed development across multiple motor control processes. En ligne : https://dx.doi.org/10.1186/s11689-025-09607-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Acute administration of lovastatin had no pronounced effect on motor abilities, motor coordination, gait nor simple cognition in a mouse model of Angelman syndrome Type de document : texte imprimé Auteurs : Timothy A. FENTON, Auteur ; Stela P. PETKOVA, Auteur ; Anna ADHIKARI, Auteur ; Jill L. SILVERMAN, Auteur Langues : Anglais (eng) Mots-clés : Animals Lovastatin/pharmacology/administration & dosage Angelman Syndrome/drug therapy/physiopathology/genetics Disease Models, Animal Mice Gait/drug effects Male Cognition/drug effects Female Behavior, Animal/drug effects Mice, Inbred C57BL Ubiquitin-Protein Ligases/genetics Motor Activity/drug effects Angelman syndrome Behavior Gait Lovastatin Neurodevelopmental disorder UBE3A reviewed and approved by the UC Davis IACUC on April 20, 2023. Active protocols are reviewed annually. Title: Novel Testing of Therapeutics for Angelman Syndrome. Principal Investigator: Jill L. Silverman Protocol #: 23384 Institution: University of California, Davis This institution is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care, International (AAALAC). This institution has an Animal Welfare Assurance on file with the Office of Laboratory Animal Welfare (OLAW). The Assurance Number is D16-00272 (A3433-01). The IACUC is constituted in accordance with U.S. Public Health Service (PHS) Animal Welfare Policy and includes a member of the public and a non-scientist. Consent for publication: FAST, the MIND Institute and the NIH/NICHD IDDRC consent for the data presented herein to be publishable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : Translational research is needed to discover pharmacological targets and treatments for the diagnostic behavioral domains of neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASDs) and intellectual disabilities (IDs). One NDD, associated with ASD and ID, is Angelman Syndrome (AS). AS is a rare genetic NDD for which there is currently no cure nor effective therapeutics. The genetic cause is known to be the loss of expression from the maternal allele of ubiquitin protein ligase E3A (UBE3A). The Ube3a maternal deletion mouse model of AS reliably demonstrates behavioral phenotypes of relevance to AS and therefore offers a suitable in vivo system in which to test potential therapeutics, with construct and face validity. Successes in reducing hyperexcitability and epileptogenesis have been reported in an AS model following acute treatment with lovastatin, an ERK inhibitor by reducing seizure threshold and percentage of mice exhibiting seizures. Since there has been literature reporting disruption of the ERK signaling pathway in AS, we chose to evaluate the effects of acute lovastatin administration in a tailored set of translationally relevant behavioral assays in a mouse model of AS. Unexpectedly, deleterious effects of sedation were observed in wildtype (WT), age matched littermate control mice and despite a baseline hypolocomotive phenotype in AS mice, even further reductions in exploratory activity, were observed post-acute lovastatin treatment. Limitations of this work include that chronic lower dose regimens, more akin to drug administration in humans were beyond the scope of this work, and may have produced a more favorable impact of lovastatin administration over single acute high doses. In addition, lovastatin's effects were not assessed in younger subjects, since our study focused exclusively on adult functional outcomes. Metrics of gait, as well as motor coordination and motor learning in rotarod, previously observed to be impaired in AS mice, were not improved by lovastatin treatment. Finally, cognition by novel object recognition task was worsened in WT controls and not improved in AS, following lovastatin administration. In conclusion, lovastatin did not indicate any major improvement to AS symptoms, and in fact, worsened behavioral outcomes in the WT control groups. Therefore, despite its attractive low toxicity, immediate availability, and low cost of the drug, further investigation for clinical study is unwarranted given the results presented herein. En ligne : https://dx.doi.org/10.1186/s11689-025-09616-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Acute administration of lovastatin had no pronounced effect on motor abilities, motor coordination, gait nor simple cognition in a mouse model of Angelman syndrome [texte imprimé] / Timothy A. FENTON, Auteur ; Stela P. PETKOVA, Auteur ; Anna ADHIKARI, Auteur ; Jill L. SILVERMAN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Animals Lovastatin/pharmacology/administration & dosage Angelman Syndrome/drug therapy/physiopathology/genetics Disease Models, Animal Mice Gait/drug effects Male Cognition/drug effects Female Behavior, Animal/drug effects Mice, Inbred C57BL Ubiquitin-Protein Ligases/genetics Motor Activity/drug effects Angelman syndrome Behavior Gait Lovastatin Neurodevelopmental disorder UBE3A reviewed and approved by the UC Davis IACUC on April 20, 2023. Active protocols are reviewed annually. Title: Novel Testing of Therapeutics for Angelman Syndrome. Principal Investigator: Jill L. Silverman Protocol #: 23384 Institution: University of California, Davis This institution is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care, International (AAALAC). This institution has an Animal Welfare Assurance on file with the Office of Laboratory Animal Welfare (OLAW). The Assurance Number is D16-00272 (A3433-01). The IACUC is constituted in accordance with U.S. Public Health Service (PHS) Animal Welfare Policy and includes a member of the public and a non-scientist. Consent for publication: FAST, the MIND Institute and the NIH/NICHD IDDRC consent for the data presented herein to be publishable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : Translational research is needed to discover pharmacological targets and treatments for the diagnostic behavioral domains of neurodevelopmental disorders (NDDs), including autism spectrum disorders (ASDs) and intellectual disabilities (IDs). One NDD, associated with ASD and ID, is Angelman Syndrome (AS). AS is a rare genetic NDD for which there is currently no cure nor effective therapeutics. The genetic cause is known to be the loss of expression from the maternal allele of ubiquitin protein ligase E3A (UBE3A). The Ube3a maternal deletion mouse model of AS reliably demonstrates behavioral phenotypes of relevance to AS and therefore offers a suitable in vivo system in which to test potential therapeutics, with construct and face validity. Successes in reducing hyperexcitability and epileptogenesis have been reported in an AS model following acute treatment with lovastatin, an ERK inhibitor by reducing seizure threshold and percentage of mice exhibiting seizures. Since there has been literature reporting disruption of the ERK signaling pathway in AS, we chose to evaluate the effects of acute lovastatin administration in a tailored set of translationally relevant behavioral assays in a mouse model of AS. Unexpectedly, deleterious effects of sedation were observed in wildtype (WT), age matched littermate control mice and despite a baseline hypolocomotive phenotype in AS mice, even further reductions in exploratory activity, were observed post-acute lovastatin treatment. Limitations of this work include that chronic lower dose regimens, more akin to drug administration in humans were beyond the scope of this work, and may have produced a more favorable impact of lovastatin administration over single acute high doses. In addition, lovastatin's effects were not assessed in younger subjects, since our study focused exclusively on adult functional outcomes. Metrics of gait, as well as motor coordination and motor learning in rotarod, previously observed to be impaired in AS mice, were not improved by lovastatin treatment. Finally, cognition by novel object recognition task was worsened in WT controls and not improved in AS, following lovastatin administration. In conclusion, lovastatin did not indicate any major improvement to AS symptoms, and in fact, worsened behavioral outcomes in the WT control groups. Therefore, despite its attractive low toxicity, immediate availability, and low cost of the drug, further investigation for clinical study is unwarranted given the results presented herein. En ligne : https://dx.doi.org/10.1186/s11689-025-09616-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Contribution of families using the GenIDA database to the description of MED13L syndrome and literature review Type de document : texte imprimé Auteurs : Roseline CAUMES, Auteur ; Pauline BURGER, Auteur ; Jean-Louis MANDEL, Auteur ; Hélène BÉHAL, Auteur ; Jamal GHOUMID, Auteur ; Thomas SMOL, Auteur Langues : Anglais (eng) Mots-clés : Humans Intellectual Disability/genetics/epidemiology/physiopathology Male Female Child Developmental Disabilities/genetics Mediator Complex/genetics Child, Preschool Phenotype Adolescent Databases, Factual Family Infant Intellectual disability Med13l Patient registry collected and informed consent was obtained for genetic studies. Analyses were performed on a diagnostic basis in accordance with the bioethical rules of French law. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : The GenIDA project aims to improve the understanding and management of rare genetic forms of intellectual disability by fostering collaboration among patients, caregivers, healthcare professionals, and research professionals. Clinical data is provided by patients' families via a structured questionnaire to identify medically relevant insights and better understand the natural history of rare diseases. This study focused on MED13L syndrome, analyzing data from 41 patients in the GenIDA database and comparing it with 102 cases from the scientific literature and 6 new descriptions of patients from our medical center.The GenIDA series confirmed the key features of MED13L syndrome, including global developmental delay, poor speech, intellectual disability, and cardiac defects (OMIM #616789), at frequencies similar to those reported in the literature. The GenIDA series identified a higher prevalence of visual impairment (76%) and highlighted under-recognized musculoskeletal issues, such as foot deformities, which had previously received little attention. This study highlights the value of family-reported data in describing the full phenotype of rare syndromes. A comprehensive review of published cases showed that patients with missense variants have more severe impairments, including increased cardiac defects, global developmental delay, and a higher incidence of epilepsy, than patients with premature truncated variants.These findings highlight the importance of family involvement in rare disease research and the need for further studies to explore genotype-phenotype correlations to improve patient care and outcomes. En ligne : https://dx.doi.org/10.1186/s11689-025-09618-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Contribution of families using the GenIDA database to the description of MED13L syndrome and literature review [texte imprimé] / Roseline CAUMES, Auteur ; Pauline BURGER, Auteur ; Jean-Louis MANDEL, Auteur ; Hélène BÉHAL, Auteur ; Jamal GHOUMID, Auteur ; Thomas SMOL, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Intellectual Disability/genetics/epidemiology/physiopathology Male Female Child Developmental Disabilities/genetics Mediator Complex/genetics Child, Preschool Phenotype Adolescent Databases, Factual Family Infant Intellectual disability Med13l Patient registry collected and informed consent was obtained for genetic studies. Analyses were performed on a diagnostic basis in accordance with the bioethical rules of French law. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : The GenIDA project aims to improve the understanding and management of rare genetic forms of intellectual disability by fostering collaboration among patients, caregivers, healthcare professionals, and research professionals. Clinical data is provided by patients' families via a structured questionnaire to identify medically relevant insights and better understand the natural history of rare diseases. This study focused on MED13L syndrome, analyzing data from 41 patients in the GenIDA database and comparing it with 102 cases from the scientific literature and 6 new descriptions of patients from our medical center.The GenIDA series confirmed the key features of MED13L syndrome, including global developmental delay, poor speech, intellectual disability, and cardiac defects (OMIM #616789), at frequencies similar to those reported in the literature. The GenIDA series identified a higher prevalence of visual impairment (76%) and highlighted under-recognized musculoskeletal issues, such as foot deformities, which had previously received little attention. This study highlights the value of family-reported data in describing the full phenotype of rare syndromes. A comprehensive review of published cases showed that patients with missense variants have more severe impairments, including increased cardiac defects, global developmental delay, and a higher incidence of epilepsy, than patients with premature truncated variants.These findings highlight the importance of family involvement in rare disease research and the need for further studies to explore genotype-phenotype correlations to improve patient care and outcomes. En ligne : https://dx.doi.org/10.1186/s11689-025-09618-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Remote EEG acquisition in Angelman syndrome using PANDABox-EEG Type de document : texte imprimé Auteurs : Kimberly GÁLVEZ-ORTEGA, Auteur ; Roslyn HAROLD, Auteur ; Wei Siong NEO, Auteur ; Orlando S. HOILETT, Auteur ; Amanda M. BOROSH, Auteur ; Alexa FRIESEN-HAARER, Auteur ; Stephanie GOMBAS, Auteur ; Dan FOTI, Auteur ; Bridgette KELLEHER, Auteur Langues : Anglais (eng) Mots-clés : Humans Angelman Syndrome/physiopathology/diagnosis Electroencephalography/methods/instrumentation Male Child Female Child, Preschool Telemedicine Adolescent Caregivers Adult Reproducibility of Results Angelman syndrome Assessment Delta Eeg Reliability Telehealth Index. décimale : PER Périodiques Résumé : OBJECTIVE: We describe the development and validation of PANDABox-EEG, a novel protocol for remote EEG assessment with no on-site technician, tailored for Angelman syndrome (AS). We argue that this protocol is reliable, valid, and widely acceptable for use in families affected by Angelman syndrome. BACKGROUND: AS is a rare neurogenetic condition characterized by developmental delays, sleep problems, seizures, and a happy demeanor. People with AS are frequently monitored via EEG to inform clinical care, and EEG-measured delta activity has been proposed as a reliable biomarker to monitor treatment effectiveness. Traditional EEG assessments pose logistical and financial burdens for families due to the need to travel to a medical center to complete assessments. Telehealth methods, however, offer a pathway forward. METHODS: PANDABox-EEG was developed through multidisciplinary collaboration with psychologists, psychophysiologists, engineers, and special-education scholars, incorporating caregiver feedback and user-centered design principles. It pairs PANDABox, a telehealth platform for biobehavioral assessment in rare disorders, with a dry electrode EEG system. Twenty-eight participants (7 AS, 7 siblings, 14 caregivers) completed three 5-min EEG sessions each over the course of a week. Caregivers were asked to provide feedback on acceptability of the design, and EEG data was quantified and assessed for metrics of reliability and validity. RESULTS: PANDABox-EEG demonstrated high feasibility and acceptability, with 91% of caregivers reporting strong satisfaction assessment comfort. EEG data quality was promising, with high internal consistency (split-half reliability range for children with AS: r = .96-.98) and test-retest reliability for delta power among (test-retest reliability range for children with AS: ρ = .88-.96). Finally, we successfully detected the characteristic increased delta power in AS (effect size between AS and non-AS siblings: d = 1.56-2.85) and its association with age (effect size between non-AS siblings and caregivers: d = 2.19-2.72). CONCLUSION: PANDABox-EEG provides a feasible, cost-effective, and reliable method for remote EEG assessment in AS. Its high caregiver satisfaction and ability to capture relevant neurophysiological markers suggest potential for broader application. With further validation, PANDABox-EEG can enhance accessibility and inclusivity, benefiting clinical management and research in AS and other clinical populations in need of frequent EEG monitoring by eliminating the need to travel. En ligne : https://dx.doi.org/10.1186/s11689-025-09611-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Remote EEG acquisition in Angelman syndrome using PANDABox-EEG [texte imprimé] / Kimberly GÁLVEZ-ORTEGA, Auteur ; Roslyn HAROLD, Auteur ; Wei Siong NEO, Auteur ; Orlando S. HOILETT, Auteur ; Amanda M. BOROSH, Auteur ; Alexa FRIESEN-HAARER, Auteur ; Stephanie GOMBAS, Auteur ; Dan FOTI, Auteur ; Bridgette KELLEHER, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Angelman Syndrome/physiopathology/diagnosis Electroencephalography/methods/instrumentation Male Child Female Child, Preschool Telemedicine Adolescent Caregivers Adult Reproducibility of Results Angelman syndrome Assessment Delta Eeg Reliability Telehealth Index. décimale : PER Périodiques Résumé : OBJECTIVE: We describe the development and validation of PANDABox-EEG, a novel protocol for remote EEG assessment with no on-site technician, tailored for Angelman syndrome (AS). We argue that this protocol is reliable, valid, and widely acceptable for use in families affected by Angelman syndrome. BACKGROUND: AS is a rare neurogenetic condition characterized by developmental delays, sleep problems, seizures, and a happy demeanor. People with AS are frequently monitored via EEG to inform clinical care, and EEG-measured delta activity has been proposed as a reliable biomarker to monitor treatment effectiveness. Traditional EEG assessments pose logistical and financial burdens for families due to the need to travel to a medical center to complete assessments. Telehealth methods, however, offer a pathway forward. METHODS: PANDABox-EEG was developed through multidisciplinary collaboration with psychologists, psychophysiologists, engineers, and special-education scholars, incorporating caregiver feedback and user-centered design principles. It pairs PANDABox, a telehealth platform for biobehavioral assessment in rare disorders, with a dry electrode EEG system. Twenty-eight participants (7 AS, 7 siblings, 14 caregivers) completed three 5-min EEG sessions each over the course of a week. Caregivers were asked to provide feedback on acceptability of the design, and EEG data was quantified and assessed for metrics of reliability and validity. RESULTS: PANDABox-EEG demonstrated high feasibility and acceptability, with 91% of caregivers reporting strong satisfaction assessment comfort. EEG data quality was promising, with high internal consistency (split-half reliability range for children with AS: r = .96-.98) and test-retest reliability for delta power among (test-retest reliability range for children with AS: ρ = .88-.96). Finally, we successfully detected the characteristic increased delta power in AS (effect size between AS and non-AS siblings: d = 1.56-2.85) and its association with age (effect size between non-AS siblings and caregivers: d = 2.19-2.72). CONCLUSION: PANDABox-EEG provides a feasible, cost-effective, and reliable method for remote EEG assessment in AS. Its high caregiver satisfaction and ability to capture relevant neurophysiological markers suggest potential for broader application. With further validation, PANDABox-EEG can enhance accessibility and inclusivity, benefiting clinical management and research in AS and other clinical populations in need of frequent EEG monitoring by eliminating the need to travel. En ligne : https://dx.doi.org/10.1186/s11689-025-09611-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Acceptability and safety of a probiotic beverage supplementation (Bio-K +) and feasibility of the proposed protocol in children with a diagnosis of autism spectrum disorder Type de document : texte imprimé Auteurs : Ghizlane GAOUGAOU, Auteur ; Riham ZAHRA, Auteur ; Sophia MOREL, Auteur ; Véronique BÉLANGER, Auteur ; Inga Sophia KNOTH, Auteur ; Dominique COUSINEAU, Auteur ; Baudouin Forgeot D'ARC, Auteur ; Kelly GRZYWACZ, Auteur ; Guy ROUSSEAU, Auteur ; Eric DÉZIEL, Auteur ; Roger GODBOUT, Auteur ; Sarah LIPPE, Auteur ; Mathieu MILLETTE, Auteur ; Valérie MARCIL, Auteur Langues : Anglais (eng) Mots-clés : Humans Autism Spectrum Disorder/diet therapy/complications Probiotics/administration & dosage/adverse effects/therapeutic use Male Child Female Child, Preschool Feasibility Studies Gastrointestinal Diseases Sleep Wake Disorders Dietary Supplements Beverages Patient Acceptance of Health Care Acceptability Autism spectrum disorders Autistic symptoms Children Feasibility Gastrointestinal symptoms Probiotics Safety Sleep disorder by the ethics review board of the CHU Sainte-Justine (#2021–3412). Informed consent was obtained from all participants and parents involved in the study. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders defined by stereotyped behavior and challenges in social communication and social interaction. ASD is associated with various comorbidities, including anxiety, gastrointestinal (GI) symptoms and sleep disorders. Evidence supports an association between intestinal dysbiosis and the severity of ASD-related symptoms. Probiotic intake was suggested to restore microbial homeostasis and decrease neurobehavioral, GI and sleep symptoms in individuals diagnosed with autism. METHODS: This study aims to evaluate the acceptability and safety of a Bio-K + probiotics beverage in autistic children aged 4 to 11 years and the feasibility of the proposed research protocol to measure its impact on behaviors and comorbidities. The 30-week study consisted of daily supplementation with Bio-K + probiotics for 14 weeks. Acceptability and safety were monitored throughout the study. Feasibility was assessed by comparing recruitment and completion rates to pre-established thresholds. Preliminary impact of supplementation on behaviors (Autism Treatment Evaluation Checklist (ATEC) score), GI symptoms and sleep disorders was evaluated. RESULTS: Of the 23 children recruited (mean age 6.7 ± 2.2 years, 70% males), 65% had GI problems and 91% had sleep disorders. Probiotic supplementation was accepted by all participants and no product-related adverse event was reported. Feasibility rates exceeded pre-established thresholds for almost all study outcomes including recruitment rate, compliance, electroencephalography, actigraphy and completion of questionnaires. Preliminary data suggest an improvement in behaviors associated with autism assessed with the total ATEC score, and in GI symptoms and sleep disorders. CONCLUSION: This study demonstrates probiotic beverage acceptability and safety and protocol feasibility in autistic children. To further support our data, a double-blinded placebo-controlled study is needed to determine its efficacy. En ligne : https://dx.doi.org/10.1186/s11689-025-09617-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Acceptability and safety of a probiotic beverage supplementation (Bio-K +) and feasibility of the proposed protocol in children with a diagnosis of autism spectrum disorder [texte imprimé] / Ghizlane GAOUGAOU, Auteur ; Riham ZAHRA, Auteur ; Sophia MOREL, Auteur ; Véronique BÉLANGER, Auteur ; Inga Sophia KNOTH, Auteur ; Dominique COUSINEAU, Auteur ; Baudouin Forgeot D'ARC, Auteur ; Kelly GRZYWACZ, Auteur ; Guy ROUSSEAU, Auteur ; Eric DÉZIEL, Auteur ; Roger GODBOUT, Auteur ; Sarah LIPPE, Auteur ; Mathieu MILLETTE, Auteur ; Valérie MARCIL, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Autism Spectrum Disorder/diet therapy/complications Probiotics/administration & dosage/adverse effects/therapeutic use Male Child Female Child, Preschool Feasibility Studies Gastrointestinal Diseases Sleep Wake Disorders Dietary Supplements Beverages Patient Acceptance of Health Care Acceptability Autism spectrum disorders Autistic symptoms Children Feasibility Gastrointestinal symptoms Probiotics Safety Sleep disorder by the ethics review board of the CHU Sainte-Justine (#2021–3412). Informed consent was obtained from all participants and parents involved in the study. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders defined by stereotyped behavior and challenges in social communication and social interaction. ASD is associated with various comorbidities, including anxiety, gastrointestinal (GI) symptoms and sleep disorders. Evidence supports an association between intestinal dysbiosis and the severity of ASD-related symptoms. Probiotic intake was suggested to restore microbial homeostasis and decrease neurobehavioral, GI and sleep symptoms in individuals diagnosed with autism. METHODS: This study aims to evaluate the acceptability and safety of a Bio-K + probiotics beverage in autistic children aged 4 to 11 years and the feasibility of the proposed research protocol to measure its impact on behaviors and comorbidities. The 30-week study consisted of daily supplementation with Bio-K + probiotics for 14 weeks. Acceptability and safety were monitored throughout the study. Feasibility was assessed by comparing recruitment and completion rates to pre-established thresholds. Preliminary impact of supplementation on behaviors (Autism Treatment Evaluation Checklist (ATEC) score), GI symptoms and sleep disorders was evaluated. RESULTS: Of the 23 children recruited (mean age 6.7 ± 2.2 years, 70% males), 65% had GI problems and 91% had sleep disorders. Probiotic supplementation was accepted by all participants and no product-related adverse event was reported. Feasibility rates exceeded pre-established thresholds for almost all study outcomes including recruitment rate, compliance, electroencephalography, actigraphy and completion of questionnaires. Preliminary data suggest an improvement in behaviors associated with autism assessed with the total ATEC score, and in GI symptoms and sleep disorders. CONCLUSION: This study demonstrates probiotic beverage acceptability and safety and protocol feasibility in autistic children. To further support our data, a double-blinded placebo-controlled study is needed to determine its efficacy. En ligne : https://dx.doi.org/10.1186/s11689-025-09617-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Enhancing the discriminatory power of polygenic scores for ADHD and autism in clinical and non-clinical samples Type de document : texte imprimé Auteurs : James J. LI, Auteur ; Quanfa HE, Auteur ; Stephen DORN, Auteur ; Zihang WANG, Auteur ; Qiongshi LU, Auteur Langues : Anglais (eng) Mots-clés : Humans Attention Deficit Disorder with Hyperactivity/genetics/diagnosis/epidemiology Multifactorial Inheritance/genetics Autism Spectrum Disorder/genetics/diagnosis/epidemiology Male Female Child Adolescent Cohort Studies Autistic Disorder/genetics Adhd Asd GenomicSEM Neurodevelopment Polygenic scores Neurodevelopmental Cohort (PNC) and the Simons Foundation Powering Autism Research for Knowledge (SPARK) datasets are both publicly available, de-identified datasets. This study was exempt from requiring approval from the University of Wisconsin-Madison Health Sciences Institutional Review Board (see "Category 4" exemption: https://kb.wisc.edu/gsadminkb/page.php?id=29465 ). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Polygenic scores (PGS) are widely used in psychiatric genetic associations studies due to their predictive power for focal outcomes. However, they lack discriminatory power, in part due to the high degree of genetic overlap between psychiatric disorders. The lack of prediction specificity limits the clinical utility of psychiatric PGS, particularly for diagnostic applications. The goal of the study was to enhance the discriminatory power of psychiatric PGS for two highly comorbid and genetically correlated neurodevelopmental disorders in ADHD and autism spectrum disorder (ASD). METHODS: Genomic structural equation modeling (GenomicSEM) was used to generate novel PGS for ADHD and ASD by accounting for the genetic overlap between these disorders (and eight others) to achieve greater discriminatory power in non-focal outcome predictions. PGS associations were tested in two large independent samples - the Philadelphia Neurodevelopmental Cohort (N = 4,789) and the Simons Foundation Powering Autism Research for Knowledge (SPARK) ASD and sibling controls (N = 5,045) cohort. RESULTS: PGS from GenomicSEM achieved superior discriminatory power in terms of showing significantly attenuated associations with non-focal outcomes relative to traditionally computed PGS for these disorders. Additionally, genetic correlations between GenomicSEM PGS for ASD and ADHD were significantly attenuated in cross-trait associations with other psychiatric disorders and outcomes. CONCLUSIONS: Psychiatric PGS associations are likely inflated by the high degree of genetic overlap between the psychiatric disorders. Methods such as GenomicSEM can be used to refine PGS signals to be more disorder-specific, thereby enhancing their discriminatory power for future diagnostic applications. En ligne : https://dx.doi.org/10.1186/s11689-025-09620-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Enhancing the discriminatory power of polygenic scores for ADHD and autism in clinical and non-clinical samples [texte imprimé] / James J. LI, Auteur ; Quanfa HE, Auteur ; Stephen DORN, Auteur ; Zihang WANG, Auteur ; Qiongshi LU, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Attention Deficit Disorder with Hyperactivity/genetics/diagnosis/epidemiology Multifactorial Inheritance/genetics Autism Spectrum Disorder/genetics/diagnosis/epidemiology Male Female Child Adolescent Cohort Studies Autistic Disorder/genetics Adhd Asd GenomicSEM Neurodevelopment Polygenic scores Neurodevelopmental Cohort (PNC) and the Simons Foundation Powering Autism Research for Knowledge (SPARK) datasets are both publicly available, de-identified datasets. This study was exempt from requiring approval from the University of Wisconsin-Madison Health Sciences Institutional Review Board (see "Category 4" exemption: https://kb.wisc.edu/gsadminkb/page.php?id=29465 ). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Polygenic scores (PGS) are widely used in psychiatric genetic associations studies due to their predictive power for focal outcomes. However, they lack discriminatory power, in part due to the high degree of genetic overlap between psychiatric disorders. The lack of prediction specificity limits the clinical utility of psychiatric PGS, particularly for diagnostic applications. The goal of the study was to enhance the discriminatory power of psychiatric PGS for two highly comorbid and genetically correlated neurodevelopmental disorders in ADHD and autism spectrum disorder (ASD). METHODS: Genomic structural equation modeling (GenomicSEM) was used to generate novel PGS for ADHD and ASD by accounting for the genetic overlap between these disorders (and eight others) to achieve greater discriminatory power in non-focal outcome predictions. PGS associations were tested in two large independent samples - the Philadelphia Neurodevelopmental Cohort (N = 4,789) and the Simons Foundation Powering Autism Research for Knowledge (SPARK) ASD and sibling controls (N = 5,045) cohort. RESULTS: PGS from GenomicSEM achieved superior discriminatory power in terms of showing significantly attenuated associations with non-focal outcomes relative to traditionally computed PGS for these disorders. Additionally, genetic correlations between GenomicSEM PGS for ASD and ADHD were significantly attenuated in cross-trait associations with other psychiatric disorders and outcomes. CONCLUSIONS: Psychiatric PGS associations are likely inflated by the high degree of genetic overlap between the psychiatric disorders. Methods such as GenomicSEM can be used to refine PGS signals to be more disorder-specific, thereby enhancing their discriminatory power for future diagnostic applications. En ligne : https://dx.doi.org/10.1186/s11689-025-09620-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review Type de document : texte imprimé Auteurs : Amy L. SYLVESTER, Auteur ; Eva HENSENNE, Auteur ; Dimo IVANOV, Auteur ; Benedikt A. POSER, Auteur ; David E.J. LINDEN, Auteur ; Thérèse VAN AMELSVOORT, Auteur ; Claudia VINGERHOETS, Auteur Langues : Anglais (eng) Mots-clés : Humans DNA Copy Number Variations/genetics Neurodevelopmental Disorders/genetics/physiopathology Neural Inhibition/physiology Copy number variation Excitation Glutamate Inhibition Neurodevelopmental disorders γ-aminobutyric acid for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : Cumulative evidence suggests neurodevelopmental disorders are closely related. The risk of these disorders is increased by a series of copy number variant syndromes - phenotypically heterogeneous genetic disorders, present in a minority of the population. Recent models suggest that a disruption in the balance between excitatory and inhibitory neural activity may contribute to the aetiology of neurodevelopmental disorders, and may be additionally disturbed in copy number variant syndromes. In this systematic review, the databases PubMed, Embase, and Scopus were searched for studies of excitation/inhibition imbalance in relation to neurodevelopmental disorders in human copy number variant samples. A total of 53 studies were included, representing a variety of copy number variants and research methodologies. The resulting data suggests excitation/inhibition balance is indeed disrupted in different copy number variant populations, providing insight into a putative mechanism of both idiopathic and genetic neurodevelopmental disorders. However, the high level of heterogeneity in the data set, alongside emerging techniques for excitation/inhibition assessment, prompts further investigation of this field. En ligne : https://dx.doi.org/10.1186/s11689-025-09614-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review [texte imprimé] / Amy L. SYLVESTER, Auteur ; Eva HENSENNE, Auteur ; Dimo IVANOV, Auteur ; Benedikt A. POSER, Auteur ; David E.J. LINDEN, Auteur ; Thérèse VAN AMELSVOORT, Auteur ; Claudia VINGERHOETS, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans DNA Copy Number Variations/genetics Neurodevelopmental Disorders/genetics/physiopathology Neural Inhibition/physiology Copy number variation Excitation Glutamate Inhibition Neurodevelopmental disorders γ-aminobutyric acid for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : Cumulative evidence suggests neurodevelopmental disorders are closely related. The risk of these disorders is increased by a series of copy number variant syndromes - phenotypically heterogeneous genetic disorders, present in a minority of the population. Recent models suggest that a disruption in the balance between excitatory and inhibitory neural activity may contribute to the aetiology of neurodevelopmental disorders, and may be additionally disturbed in copy number variant syndromes. In this systematic review, the databases PubMed, Embase, and Scopus were searched for studies of excitation/inhibition imbalance in relation to neurodevelopmental disorders in human copy number variant samples. A total of 53 studies were included, representing a variety of copy number variants and research methodologies. The resulting data suggests excitation/inhibition balance is indeed disrupted in different copy number variant populations, providing insight into a putative mechanism of both idiopathic and genetic neurodevelopmental disorders. However, the high level of heterogeneity in the data set, alongside emerging techniques for excitation/inhibition assessment, prompts further investigation of this field. En ligne : https://dx.doi.org/10.1186/s11689-025-09614-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Developmental milestones and cognitive trajectories in school-aged children with 16p11.2 deletion Type de document : texte imprimé Auteurs : Jente VERBESSELT, Auteur ; Jeroen BRECKPOT, Auteur ; Inge ZINK, Auteur ; Ann SWILLEN, Auteur Langues : Anglais (eng) Mots-clés : Humans Child Adolescent Female Male Chromosomes, Human, Pair 16/genetics Child, Preschool Intellectual Disability/physiopathology/genetics Longitudinal Studies Chromosome Deletion Chromosome Disorders/physiopathology/complications/genetics Intelligence Cognition/physiology Child Development/physiology Developmental Disabilities/genetics/physiopathology Fecal Incontinence/physiopathology Intelligence Tests Autistic Disorder 16p11.2 deletion syndrome Cognition Copy number variants Deep phenotyping Developmental trajectories Early development in accordance with the Declaration of Helsinki and approved by the Ethics Committee Research of University Hospitals Leuven (protocol code S54485, 6 December 2012 and 26 March 2021). Patients and their parents were directly informed about the aims of the research project, and all participants signed informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: 16p11.2 deletion syndrome (16p11.2DS) is a recurrent CNV that occurs de novo in approximately 70% of cases and confers risk for neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorders (ASD). The current study focusses on developmental milestones, cognitive profiles and longitudinal cognitive trajectories. METHODS: In-person assessments, digital medical records and parental interviews on developmental history of 24 children (5-16 years) with a confirmed BP4-BP5 16p11.2DS were reviewed and analysed for developmental milestones (motor, language, continence). Standardised intelligence tests were administered in all children, and longitudinal IQ-data were available for a subgroup (79%, 19/24). RESULTS: Motor, language, and continence milestones were delayed. Average IQ was in the borderline range (IQ 71) with 46% (11/24) having borderline IQ (IQ 70-84). Both intra- and interindividual variability were found across the five cognitive domains with significant discrepancies between verbal and non-verbal skills in 55% (11/20). Longitudinal IQ-data indicate that school-aged children with 16p11.2DS perform statistically significantly lower at the second time point (p < 0.001) with 58% showing a growing into deficit trajectory. CONCLUSION: Delayed motor, language and continence milestones are common in 16p11.2DS carriers. School-aged children with 16p11.2DS show increasing cognitive impairments over time, pointing to the need for early diagnosis, regular cognitive follow-up and individualised intervention. The high prevalence of disharmonic IQ-profiles highlights the importance of expanding the focus beyond full-scale IQ (FSIQ) outcomes. Future studies in larger cohorts including carrier relatives are needed to gain more insight into the penetrance and phenotypic variability of 16p11.2DS. En ligne : https://dx.doi.org/10.1186/s11689-025-09615-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Developmental milestones and cognitive trajectories in school-aged children with 16p11.2 deletion [texte imprimé] / Jente VERBESSELT, Auteur ; Jeroen BRECKPOT, Auteur ; Inge ZINK, Auteur ; Ann SWILLEN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Child Adolescent Female Male Chromosomes, Human, Pair 16/genetics Child, Preschool Intellectual Disability/physiopathology/genetics Longitudinal Studies Chromosome Deletion Chromosome Disorders/physiopathology/complications/genetics Intelligence Cognition/physiology Child Development/physiology Developmental Disabilities/genetics/physiopathology Fecal Incontinence/physiopathology Intelligence Tests Autistic Disorder 16p11.2 deletion syndrome Cognition Copy number variants Deep phenotyping Developmental trajectories Early development in accordance with the Declaration of Helsinki and approved by the Ethics Committee Research of University Hospitals Leuven (protocol code S54485, 6 December 2012 and 26 March 2021). Patients and their parents were directly informed about the aims of the research project, and all participants signed informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: 16p11.2 deletion syndrome (16p11.2DS) is a recurrent CNV that occurs de novo in approximately 70% of cases and confers risk for neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorders (ASD). The current study focusses on developmental milestones, cognitive profiles and longitudinal cognitive trajectories. METHODS: In-person assessments, digital medical records and parental interviews on developmental history of 24 children (5-16 years) with a confirmed BP4-BP5 16p11.2DS were reviewed and analysed for developmental milestones (motor, language, continence). Standardised intelligence tests were administered in all children, and longitudinal IQ-data were available for a subgroup (79%, 19/24). RESULTS: Motor, language, and continence milestones were delayed. Average IQ was in the borderline range (IQ 71) with 46% (11/24) having borderline IQ (IQ 70-84). Both intra- and interindividual variability were found across the five cognitive domains with significant discrepancies between verbal and non-verbal skills in 55% (11/20). Longitudinal IQ-data indicate that school-aged children with 16p11.2DS perform statistically significantly lower at the second time point (p < 0.001) with 58% showing a growing into deficit trajectory. CONCLUSION: Delayed motor, language and continence milestones are common in 16p11.2DS carriers. School-aged children with 16p11.2DS show increasing cognitive impairments over time, pointing to the need for early diagnosis, regular cognitive follow-up and individualised intervention. The high prevalence of disharmonic IQ-profiles highlights the importance of expanding the focus beyond full-scale IQ (FSIQ) outcomes. Future studies in larger cohorts including carrier relatives are needed to gain more insight into the penetrance and phenotypic variability of 16p11.2DS. En ligne : https://dx.doi.org/10.1186/s11689-025-09615-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Common and rare variant analyses implicate late-infancy cerebellar development and immune genes in ADHD Type de document : texte imprimé Auteurs : Yuanxin ZHONG, Auteur ; Larry W. BAUM, Auteur ; Justin D. TUBBS, Auteur ; Rui YE, Auteur ; Lu Hua CHEN, Auteur ; Tian WU, Auteur ; Se-fong HUNG, Auteur ; Chun-pan TANG, Auteur ; Ting-pong HO, Auteur ; Robert MOYZIS, Auteur ; James SWANSON, Auteur ; Chi-chiu LEE, Auteur ; Pak C. SHAM, Auteur ; Patrick W.L. LEUNG, Auteur Langues : Anglais (eng) Mots-clés : Humans Attention Deficit Disorder with Hyperactivity/genetics/immunology/physiopathology Cerebellum/growth & development/diagnostic imaging/physiopathology Male Female Genome-Wide Association Study Genetic Predisposition to Disease Child Magnetic Resonance Imaging Hong Kong Polymorphism, Single Nucleotide Infant Adhd Cerebellum Common variant Immune response Late-infancy Low-frequency / rare variant University of Hong Kong-New Territories East Cluster, the Hospital Authority Kowloon Central and Kowloon West Cluster Clinical Research Ethics Committee provided ethical approval for this study, which complies with the most recent Declaration of Helsinki. All participants provided informed consent for the current study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder with a significant genetic component. The latest genome-wide association study (GWAS) meta-analysis of ADHD identified 27 whole-genome significant risk loci in the European population. However, genetic risk factors for ADHD are less well-characterized in the Asian population, especially for low-frequency / rare variants. METHODS: In this study, we aimed to investigate the contributions of both common and low-frequency / rare variants to ADHD in a Hong Kong sample. Our sample comprised 279 cases and 432 controls who underwent genotyping using the Illumina Infinium Global Screening Array. We employed various analytical methods at different levels, while also leveraging multi-omics data and large-scale summary statistics to comprehensively analyze the genetic basis of ADHD. RESULTS: We identified 41 potential genomic risk loci with a suggestive association (p < 1e(-4)), pointing to 111 candidate risk genes, which were enriched for genes differentially expressed during late infancy brain development. Furthermore, tissue enrichment analysis implicated the involvement of the cerebellum. At the polygenic level, we also discovered a strong genetic correlation with resting-state functional MRI connectivity of the cerebellum involved in the attention/central executive and subcortical-cerebellum networks. In addition, an accumulation of ADHD common-variant risks found in European ancestry samples was found to be significantly associated with ADHD in the current study. In low-frequency / rare variant analyses, we discovered the correlations between ADHD and collapsing effects of rare damaging variants in TEP1, MTMR10, DBH, TBCC, and ANO1. Based on biological and functional profiles of the potential risk genes and gene sets, both common and low-frequency / rare variant analyses demonstrated that ADHD genetic risk was associated with immune processes. CONCLUSIONS: These findings re-validate the abnormal development of the neural system in ADHD and extend the existing neuro-dysfunction hypothesis to a multi-system perspective. The current study identified convergent risk factors from common and low-frequency / rare variants, which implicates vulnerability in late-infancy brain development, affecting especially the cerebellum, and the involvement of immune processes. En ligne : https://dx.doi.org/10.1186/s11689-025-09626-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Common and rare variant analyses implicate late-infancy cerebellar development and immune genes in ADHD [texte imprimé] / Yuanxin ZHONG, Auteur ; Larry W. BAUM, Auteur ; Justin D. TUBBS, Auteur ; Rui YE, Auteur ; Lu Hua CHEN, Auteur ; Tian WU, Auteur ; Se-fong HUNG, Auteur ; Chun-pan TANG, Auteur ; Ting-pong HO, Auteur ; Robert MOYZIS, Auteur ; James SWANSON, Auteur ; Chi-chiu LEE, Auteur ; Pak C. SHAM, Auteur ; Patrick W.L. LEUNG, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Attention Deficit Disorder with Hyperactivity/genetics/immunology/physiopathology Cerebellum/growth & development/diagnostic imaging/physiopathology Male Female Genome-Wide Association Study Genetic Predisposition to Disease Child Magnetic Resonance Imaging Hong Kong Polymorphism, Single Nucleotide Infant Adhd Cerebellum Common variant Immune response Late-infancy Low-frequency / rare variant University of Hong Kong-New Territories East Cluster, the Hospital Authority Kowloon Central and Kowloon West Cluster Clinical Research Ethics Committee provided ethical approval for this study, which complies with the most recent Declaration of Helsinki. All participants provided informed consent for the current study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder with a significant genetic component. The latest genome-wide association study (GWAS) meta-analysis of ADHD identified 27 whole-genome significant risk loci in the European population. However, genetic risk factors for ADHD are less well-characterized in the Asian population, especially for low-frequency / rare variants. METHODS: In this study, we aimed to investigate the contributions of both common and low-frequency / rare variants to ADHD in a Hong Kong sample. Our sample comprised 279 cases and 432 controls who underwent genotyping using the Illumina Infinium Global Screening Array. We employed various analytical methods at different levels, while also leveraging multi-omics data and large-scale summary statistics to comprehensively analyze the genetic basis of ADHD. RESULTS: We identified 41 potential genomic risk loci with a suggestive association (p < 1e(-4)), pointing to 111 candidate risk genes, which were enriched for genes differentially expressed during late infancy brain development. Furthermore, tissue enrichment analysis implicated the involvement of the cerebellum. At the polygenic level, we also discovered a strong genetic correlation with resting-state functional MRI connectivity of the cerebellum involved in the attention/central executive and subcortical-cerebellum networks. In addition, an accumulation of ADHD common-variant risks found in European ancestry samples was found to be significantly associated with ADHD in the current study. In low-frequency / rare variant analyses, we discovered the correlations between ADHD and collapsing effects of rare damaging variants in TEP1, MTMR10, DBH, TBCC, and ANO1. Based on biological and functional profiles of the potential risk genes and gene sets, both common and low-frequency / rare variant analyses demonstrated that ADHD genetic risk was associated with immune processes. CONCLUSIONS: These findings re-validate the abnormal development of the neural system in ADHD and extend the existing neuro-dysfunction hypothesis to a multi-system perspective. The current study identified convergent risk factors from common and low-frequency / rare variants, which implicates vulnerability in late-infancy brain development, affecting especially the cerebellum, and the involvement of immune processes. En ligne : https://dx.doi.org/10.1186/s11689-025-09626-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Pathways to autism diagnosis in adulthood Type de document : texte imprimé Auteurs : Isabelle DUFOUR, Auteur ; Yohann CHIU, Auteur ; Sébastien BRODEUR, Auteur ; Mireille COURTEAU, Auteur ; Josiane COURTEAU, Auteur ; Émilie DUBÉ, Auteur ; Alain LESAGE, Auteur ; Eric FOMBONNE, Auteur ; Mélanie COUTURE, Auteur Langues : Anglais (eng) Mots-clés : Humans Adult Male Female Retrospective Studies Quebec/epidemiology Middle Aged Autistic Disorder/diagnosis/epidemiology Young Adult Adolescent Neurodevelopmental Disorders/epidemiology/diagnosis Attention Deficit Disorder with Hyperactivity/epidemiology Aged Autism spectrum disorder Healthcare use Mental healthcare Neurodevelopmental disorder Psychiatric disorder State sequence analysis by the Research Ethics Board Committee of the Université de Sherbrooke and by the Commission d'accès à l'information of Quebec. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: This study explored Trajectories of Diagnoses (TDs) preceding a first diagnosis of autism in adulthood. METHODS: This retrospective cohort study used health administrative data from Quebec, Canada, and included all adults with a first recorded diagnosis of autism between 2012 and 2017. A TDs was defined as a succession of medical records of psychiatric and/or neurodevelopmental conditions over time. These TDs were retrospectively analyzed from 2002 to 2017, using a state sequence analysis of diagnoses, in order: Autism, Intellectual or developmental disabilities (IDDs), Schizophrenia spectrum disorder (SSD), Bipolar Disorder (BD), Depressive Disorder (DD), Anxiety Disorder (AD), Attention-deficit/hyperactivity disorder (ADHD), and Other psychiatric and/or neurodevelopmental conditions. RESULTS: The cohort included 2799 adults with a first recorded diagnosis of autism between 2012 and 2017. Several psychiatric and/or neurodevelopmental conditions were recorded since 2002, including AD (77.5%), DD (58.0%), SSD (49.4%), BD (48.3%), and IDDs (33.2%). Results revealed 5 distinct types of TDs. Types 1 (63.8%), 2 (17.6%) and 3 (6%) represented individuals in younger age groups with similar characteristics but with very different sequences of diagnoses, characterized by mixed diagnoses in type 1, SSD and AD in Type 2, and IDDs, DD, AD, and ADHD in type 3. Types 4 and 5 (9.0% and 3.6%), representing middle-aged/older groups, displayed distinctive TDs associated with high healthcare use, almost entirely associated with SSD (Type 4) and BD (Type 5). CONCLUSION: This study proposes a complementary examination of the multiple pathways to diagnosis experienced by adults, highlighting the need to address differential diagnosis and co-occurring psychiatric and neurodevelopmental conditions. En ligne : https://dx.doi.org/10.1186/s11689-025-09627-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Pathways to autism diagnosis in adulthood [texte imprimé] / Isabelle DUFOUR, Auteur ; Yohann CHIU, Auteur ; Sébastien BRODEUR, Auteur ; Mireille COURTEAU, Auteur ; Josiane COURTEAU, Auteur ; Émilie DUBÉ, Auteur ; Alain LESAGE, Auteur ; Eric FOMBONNE, Auteur ; Mélanie COUTURE, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Adult Male Female Retrospective Studies Quebec/epidemiology Middle Aged Autistic Disorder/diagnosis/epidemiology Young Adult Adolescent Neurodevelopmental Disorders/epidemiology/diagnosis Attention Deficit Disorder with Hyperactivity/epidemiology Aged Autism spectrum disorder Healthcare use Mental healthcare Neurodevelopmental disorder Psychiatric disorder State sequence analysis by the Research Ethics Board Committee of the Université de Sherbrooke and by the Commission d'accès à l'information of Quebec. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: This study explored Trajectories of Diagnoses (TDs) preceding a first diagnosis of autism in adulthood. METHODS: This retrospective cohort study used health administrative data from Quebec, Canada, and included all adults with a first recorded diagnosis of autism between 2012 and 2017. A TDs was defined as a succession of medical records of psychiatric and/or neurodevelopmental conditions over time. These TDs were retrospectively analyzed from 2002 to 2017, using a state sequence analysis of diagnoses, in order: Autism, Intellectual or developmental disabilities (IDDs), Schizophrenia spectrum disorder (SSD), Bipolar Disorder (BD), Depressive Disorder (DD), Anxiety Disorder (AD), Attention-deficit/hyperactivity disorder (ADHD), and Other psychiatric and/or neurodevelopmental conditions. RESULTS: The cohort included 2799 adults with a first recorded diagnosis of autism between 2012 and 2017. Several psychiatric and/or neurodevelopmental conditions were recorded since 2002, including AD (77.5%), DD (58.0%), SSD (49.4%), BD (48.3%), and IDDs (33.2%). Results revealed 5 distinct types of TDs. Types 1 (63.8%), 2 (17.6%) and 3 (6%) represented individuals in younger age groups with similar characteristics but with very different sequences of diagnoses, characterized by mixed diagnoses in type 1, SSD and AD in Type 2, and IDDs, DD, AD, and ADHD in type 3. Types 4 and 5 (9.0% and 3.6%), representing middle-aged/older groups, displayed distinctive TDs associated with high healthcare use, almost entirely associated with SSD (Type 4) and BD (Type 5). CONCLUSION: This study proposes a complementary examination of the multiple pathways to diagnosis experienced by adults, highlighting the need to address differential diagnosis and co-occurring psychiatric and neurodevelopmental conditions. En ligne : https://dx.doi.org/10.1186/s11689-025-09627-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria Type de document : texte imprimé Auteurs : Jèssica PARDO, Auteur ; Clara CAPDEVILA-LACASA, Auteur ; Bàrbara SEGURA, Auteur ; Adriana PANÉ, Auteur ; Pedro J. MORENO, Auteur ; Glòria GARRABOU, Auteur ; Josep M. GRAU-JUNYENT, Auteur ; Carme JUNQUÉ, Auteur Langues : Anglais (eng) Mots-clés : Humans Phenylketonurias/blood/diagnostic imaging/psychology/diet therapy/pathology/complications Phenylalanine/blood Adult Male Female Diffusion Tensor Imaging White Matter/diagnostic imaging/pathology Cognition/physiology Young Adult Brain/diagnostic imaging Neuropsychological Tests Cerebral white matter Dietary control Neuropsychological performance Phenylketonuria by the Bioethics Committee of the University of Barcelona (IRB00003099) and Hospital Clínic of Barcelona (HCB/2020/0552) and was conducted in accordance with the basic principles of the Declaration of Helsinki. This study was conducted following the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. All the participants of this study provided signed written informed consent, after a complete explanation of the procedures involved, and are available from the corresponding author upon reasonable request. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Altered white matter (WM) is consistently reported in patients with phenylketonuria (PKU). However, the knowledge about WM microstructural integrity in early-treated adults with classical PKU and its relationship with cognition and metabolic parameters is inconclusive. This study aims to explore the cerebral WM microstructural alterations in adult patients with early-treated classical PKU and their association with blood phenylalanine (Phe) levels and neuropsychological performance using whole-brain diffusion tensor imaging (DTI). METHODS: Twenty-nine patients with early-treated classical PKU (mean age = 30.86, SD = 7.74) and 31 healthy controls (mean age = 32.45, SD = 9.40) underwent neuropsychological assessment and MRI. Phe dry blood spot (DBS-Phe) samples, along with venous Phe levels, were collected from the PKU sample to calculate the index of dietary control (IDC). Tract-based spatial statistics (TBSS) of the mean diffusivity (MD), and fractional anisotropy (FA), were carried out with FSL v6.0.4 to assess between-group differences and to explore associations with both cognitive and clinical data. RESULTS: Patients exhibited a widespread white matter tract involvement, with lower MD and higher FA values compared to controls. The most affected tracts were the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus for MD, and the anterior corona radiata, uncinate fasciculus and forceps minor for FA. MD negatively correlated with IDC and venous Phe levels, whereas FA negatively correlated with full-scale intelligence quotient (FSIQ) (p-value ≤0.05 FWE-corrected). CONCLUSIONS: Microstructural WM alterations were present in adults with early-treated classical PKU, and these abnormalities were related to global intelligence and metabolic control markers. Although our results suggest the importance of proper disease management, further studies are needed to determine its long-term relevance. En ligne : https://dx.doi.org/10.1186/s11689-025-09622-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria [texte imprimé] / Jèssica PARDO, Auteur ; Clara CAPDEVILA-LACASA, Auteur ; Bàrbara SEGURA, Auteur ; Adriana PANÉ, Auteur ; Pedro J. MORENO, Auteur ; Glòria GARRABOU, Auteur ; Josep M. GRAU-JUNYENT, Auteur ; Carme JUNQUÉ, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Phenylketonurias/blood/diagnostic imaging/psychology/diet therapy/pathology/complications Phenylalanine/blood Adult Male Female Diffusion Tensor Imaging White Matter/diagnostic imaging/pathology Cognition/physiology Young Adult Brain/diagnostic imaging Neuropsychological Tests Cerebral white matter Dietary control Neuropsychological performance Phenylketonuria by the Bioethics Committee of the University of Barcelona (IRB00003099) and Hospital Clínic of Barcelona (HCB/2020/0552) and was conducted in accordance with the basic principles of the Declaration of Helsinki. This study was conducted following the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. All the participants of this study provided signed written informed consent, after a complete explanation of the procedures involved, and are available from the corresponding author upon reasonable request. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Altered white matter (WM) is consistently reported in patients with phenylketonuria (PKU). However, the knowledge about WM microstructural integrity in early-treated adults with classical PKU and its relationship with cognition and metabolic parameters is inconclusive. This study aims to explore the cerebral WM microstructural alterations in adult patients with early-treated classical PKU and their association with blood phenylalanine (Phe) levels and neuropsychological performance using whole-brain diffusion tensor imaging (DTI). METHODS: Twenty-nine patients with early-treated classical PKU (mean age = 30.86, SD = 7.74) and 31 healthy controls (mean age = 32.45, SD = 9.40) underwent neuropsychological assessment and MRI. Phe dry blood spot (DBS-Phe) samples, along with venous Phe levels, were collected from the PKU sample to calculate the index of dietary control (IDC). Tract-based spatial statistics (TBSS) of the mean diffusivity (MD), and fractional anisotropy (FA), were carried out with FSL v6.0.4 to assess between-group differences and to explore associations with both cognitive and clinical data. RESULTS: Patients exhibited a widespread white matter tract involvement, with lower MD and higher FA values compared to controls. The most affected tracts were the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus for MD, and the anterior corona radiata, uncinate fasciculus and forceps minor for FA. MD negatively correlated with IDC and venous Phe levels, whereas FA negatively correlated with full-scale intelligence quotient (FSIQ) (p-value ≤0.05 FWE-corrected). CONCLUSIONS: Microstructural WM alterations were present in adults with early-treated classical PKU, and these abnormalities were related to global intelligence and metabolic control markers. Although our results suggest the importance of proper disease management, further studies are needed to determine its long-term relevance. En ligne : https://dx.doi.org/10.1186/s11689-025-09622-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Novel ANKRD17 variants implicate synaptic and mitochondrial disruptions in intellectual disability and autism spectrum disorder Type de document : texte imprimé Auteurs : Dan XIA, Auteur ; Yuanyuan XU, Auteur ; Zhanwen HE, Auteur ; Rui CHEN, Auteur ; Xiaoqin XIAO, Auteur ; Xiaojuan LI, Auteur ; Kewen DENG, Auteur ; Shuyun DENG, Auteur ; Lina ZHANG, Auteur ; Jieming ZHANG, Auteur ; Xiaofang PENG, Auteur ; Zhe MENG, Auteur ; Ruohao WU, Auteur ; Dilong WANG, Auteur ; Zulin LIU, Auteur ; Hui CHEN, Auteur ; Lu LI, Auteur ; Liyang LIANG, Auteur Langues : Anglais (eng) Mots-clés : Child Humans Male Autism Spectrum Disorder/genetics Intellectual Disability/genetics Mitochondria/genetics/metabolism Synapses ANKRD17 haploinsufficiency Autism Spectrum Disorder (ASD) Intellectual Disability (ID) Mitochondrial inhibition Synaptic protein abnormalities reviewed and approved by the Ethics Committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University (Ethical code: SYSEC-KY-KS-2023–153 and BAP20230154). Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : ANKRD17 has recently been implicated in intellectual disability (ID) and autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. Using trio whole-exome sequencing (Trio-WES) and chromosomal microarray analysis (CMA), we identified two unrelated cases with novel de novo heterozygous ANKRD17 variants. Case 1 describes a fetus with multiple congenital anomalies, where genetic analysis revealed a microdeletion at 4q13.3 truncating the ANKRD17 gene. Case 2 involves a 12-year-old male presenting with mild ID and progressive social impairments, associated with a NM_032217.5: c.1252 C > T (p.Arg418*) variation in ANKRD17. Our study highlighted in mouse models an association between Ankrd17 haploinsufficiency and deficits in social behavior, spatial learning and memory, as well as elevated anxiety. Furthermore, our studies suggest dysregulation of synaptic proteins and mitochondrial function, along with impaired neural circuits following Ankrd17 knockdown. These results expand the genetic and phenotypic spectrum of ANKRD17-related disorders, underscore the critical role of mitochondrial dysfunction in the pathophysiology of ANKRD17-related ID and ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09619-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Novel ANKRD17 variants implicate synaptic and mitochondrial disruptions in intellectual disability and autism spectrum disorder [texte imprimé] / Dan XIA, Auteur ; Yuanyuan XU, Auteur ; Zhanwen HE, Auteur ; Rui CHEN, Auteur ; Xiaoqin XIAO, Auteur ; Xiaojuan LI, Auteur ; Kewen DENG, Auteur ; Shuyun DENG, Auteur ; Lina ZHANG, Auteur ; Jieming ZHANG, Auteur ; Xiaofang PENG, Auteur ; Zhe MENG, Auteur ; Ruohao WU, Auteur ; Dilong WANG, Auteur ; Zulin LIU, Auteur ; Hui CHEN, Auteur ; Lu LI, Auteur ; Liyang LIANG, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Child Humans Male Autism Spectrum Disorder/genetics Intellectual Disability/genetics Mitochondria/genetics/metabolism Synapses ANKRD17 haploinsufficiency Autism Spectrum Disorder (ASD) Intellectual Disability (ID) Mitochondrial inhibition Synaptic protein abnormalities reviewed and approved by the Ethics Committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University (Ethical code: SYSEC-KY-KS-2023–153 and BAP20230154). Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : ANKRD17 has recently been implicated in intellectual disability (ID) and autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. Using trio whole-exome sequencing (Trio-WES) and chromosomal microarray analysis (CMA), we identified two unrelated cases with novel de novo heterozygous ANKRD17 variants. Case 1 describes a fetus with multiple congenital anomalies, where genetic analysis revealed a microdeletion at 4q13.3 truncating the ANKRD17 gene. Case 2 involves a 12-year-old male presenting with mild ID and progressive social impairments, associated with a NM_032217.5: c.1252 C > T (p.Arg418*) variation in ANKRD17. Our study highlighted in mouse models an association between Ankrd17 haploinsufficiency and deficits in social behavior, spatial learning and memory, as well as elevated anxiety. Furthermore, our studies suggest dysregulation of synaptic proteins and mitochondrial function, along with impaired neural circuits following Ankrd17 knockdown. These results expand the genetic and phenotypic spectrum of ANKRD17-related disorders, underscore the critical role of mitochondrial dysfunction in the pathophysiology of ANKRD17-related ID and ASD. En ligne : https://dx.doi.org/10.1186/s11689-025-09619-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Charting the future: current and future directions in translational research for individuals with Down syndrome Type de document : texte imprimé Auteurs : Katherine A. WAUGH, Auteur ; Heather M. WILKINS, Auteur ; Keith P. SMITH, Auteur ; Lauren T. PTOMEY, Auteur Langues : Anglais (eng) Mots-clés : Down Syndrome/therapy/metabolism Humans Translational Research, Biomedical/trends Precision Medicine Biomarkers Brain Health Down syndrome Intellectual and Developmental Disability Precision Medicine Trisomy 21 for publication: We give consent for the publication of all text, figures, and tables in this review. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : The most common genetic cause of intellectual and developmental disability is trisomy of human chromosome 21 (trisomy 21) or Down syndrome. Relative to the general population, individuals with Down syndrome heterogeneously experience atypical morphogenesis, a distinct neurocognitive profile, and a unique spectrum of diverse medical conditions that impact every major organ system. How trisomy 21 results in the highly variable manifestations of Down syndrome remains largely unknown and an active area of heavy investigation with therapeutic implications. For example, common inflammatory and metabolic signatures have begun to emerge across various co-occurring conditions in Down syndrome with assorted impacts on diverse yet intertwined organ systems that could directly or indirectly impact brain health. Here, we review current progress, resources, knowledge gaps, and bottlenecks for precision medicine approaches to promote brain health across the lifespan among individuals with Down syndrome within the larger context of research efforts geared towards our other distinct yet intertwined organ systems. Within this framework, we advocate for interdisciplinary pursuit of systems-level biomarkers to facilitate holistic intervention strategies that precisely benefit individuals with trisomy 21 each experiencing Down syndrome in their own unique way. To this end, we quantitatively assess clinical studies that are actively recruiting participants with Down syndrome and provide historical context through summary figures sourced to user-friendly tables that have been curated from federal websites to empower efficient exploration of research opportunities for interdisciplinary collaborations. En ligne : https://dx.doi.org/10.1186/s11689-025-09630-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Charting the future: current and future directions in translational research for individuals with Down syndrome [texte imprimé] / Katherine A. WAUGH, Auteur ; Heather M. WILKINS, Auteur ; Keith P. SMITH, Auteur ; Lauren T. PTOMEY, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Down Syndrome/therapy/metabolism Humans Translational Research, Biomedical/trends Precision Medicine Biomarkers Brain Health Down syndrome Intellectual and Developmental Disability Precision Medicine Trisomy 21 for publication: We give consent for the publication of all text, figures, and tables in this review. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : The most common genetic cause of intellectual and developmental disability is trisomy of human chromosome 21 (trisomy 21) or Down syndrome. Relative to the general population, individuals with Down syndrome heterogeneously experience atypical morphogenesis, a distinct neurocognitive profile, and a unique spectrum of diverse medical conditions that impact every major organ system. How trisomy 21 results in the highly variable manifestations of Down syndrome remains largely unknown and an active area of heavy investigation with therapeutic implications. For example, common inflammatory and metabolic signatures have begun to emerge across various co-occurring conditions in Down syndrome with assorted impacts on diverse yet intertwined organ systems that could directly or indirectly impact brain health. Here, we review current progress, resources, knowledge gaps, and bottlenecks for precision medicine approaches to promote brain health across the lifespan among individuals with Down syndrome within the larger context of research efforts geared towards our other distinct yet intertwined organ systems. Within this framework, we advocate for interdisciplinary pursuit of systems-level biomarkers to facilitate holistic intervention strategies that precisely benefit individuals with trisomy 21 each experiencing Down syndrome in their own unique way. To this end, we quantitatively assess clinical studies that are actively recruiting participants with Down syndrome and provide historical context through summary figures sourced to user-friendly tables that have been curated from federal websites to empower efficient exploration of research opportunities for interdisciplinary collaborations. En ligne : https://dx.doi.org/10.1186/s11689-025-09630-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Identifying compound heterozygous variants in the EEFSEC gene linked to progressive cerebellar atrophy Type de document : texte imprimé Auteurs : Zhen LIU, Auteur ; Mei HE, Auteur ; Xuan LUO, Auteur ; Hu PAN, Auteur ; Juanli HU, Auteur ; Zhengqing WAN, Auteur ; Yin PENG, Auteur ; Yixiao LUO, Auteur ; Hua WANG, Auteur ; Xiao MAO, Auteur Langues : Anglais (eng) Mots-clés : Humans Female Child, Preschool Atrophy/genetics Cerebellum/pathology/diagnostic imaging Heterozygote Cerebellar Diseases/genetics EEFSEC gene Developmental delay Oxidized lipids Progressive cerebellar atrophy Selenium Selenoproteins conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (IRB) of Hunan Provincial Maternal and Child Health Care Hospital. Written informed consent was obtained from the legal guardians of all participants involved in the study. The consent covered all facets of participation and data utilization. To ensure the protection of our patient’s and control subjects' privacy, all personal identifiers were removed from the study data. Consent for publication: We hereby clarify that written informed consent for the publication of their personal or clinical details, along with any identifying images, has been obtained from all participants involved in the study. For minor patient, written informed consent has been obtained from his parents. This consent encompasses the use of these details and images in this study and any potential publication in scientific journals. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : Selenium, an essential micronutrient integrated into selenoproteins as selenocysteine, is fundamental to human health. These selenoproteins are vital for several physiological functions, including maintaining redox balance, safeguarding DNA, and metabolizing thyroid hormones, and are produced via complex pathways involving Sec-tRNA([Ser]Sec), the SECIS element, and specific proteins such as eEFSec. This study investigates a 4-year-old girl with global developmental delay and cerebellar atrophy, revealing compound heterozygous variants in the EEFSEC gene (p.V488Dfs*113 and p.R443P) through extensive genetic analysis and whole exome sequencing. Both functional prediction tools and structural analysis underscored the detrimental impact of the p.R443P variant. Notably, the patient's plasma exhibited elevated levels of oxidized fatty acid metabolites compared to those in healthy controls, suggesting an impairment in antioxidant mechanisms. This case link a human disease directly to variants in the EEFSEC gene, emphasizing its vital role in cerebellar atrophy and the broader implications for genetic disorders related to defects in selenoprotein synthesis. The results highlight the significance of genetic screening for EEFSEC variants in similar cases, potentially broadening the spectrum of known genetic subtypes associated with selenoprotein translation abnormalities. En ligne : https://dx.doi.org/10.1186/s11689-025-09632-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Identifying compound heterozygous variants in the EEFSEC gene linked to progressive cerebellar atrophy [texte imprimé] / Zhen LIU, Auteur ; Mei HE, Auteur ; Xuan LUO, Auteur ; Hu PAN, Auteur ; Juanli HU, Auteur ; Zhengqing WAN, Auteur ; Yin PENG, Auteur ; Yixiao LUO, Auteur ; Hua WANG, Auteur ; Xiao MAO, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Female Child, Preschool Atrophy/genetics Cerebellum/pathology/diagnostic imaging Heterozygote Cerebellar Diseases/genetics EEFSEC gene Developmental delay Oxidized lipids Progressive cerebellar atrophy Selenium Selenoproteins conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (IRB) of Hunan Provincial Maternal and Child Health Care Hospital. Written informed consent was obtained from the legal guardians of all participants involved in the study. The consent covered all facets of participation and data utilization. To ensure the protection of our patient’s and control subjects' privacy, all personal identifiers were removed from the study data. Consent for publication: We hereby clarify that written informed consent for the publication of their personal or clinical details, along with any identifying images, has been obtained from all participants involved in the study. For minor patient, written informed consent has been obtained from his parents. This consent encompasses the use of these details and images in this study and any potential publication in scientific journals. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : Selenium, an essential micronutrient integrated into selenoproteins as selenocysteine, is fundamental to human health. These selenoproteins are vital for several physiological functions, including maintaining redox balance, safeguarding DNA, and metabolizing thyroid hormones, and are produced via complex pathways involving Sec-tRNA([Ser]Sec), the SECIS element, and specific proteins such as eEFSec. This study investigates a 4-year-old girl with global developmental delay and cerebellar atrophy, revealing compound heterozygous variants in the EEFSEC gene (p.V488Dfs*113 and p.R443P) through extensive genetic analysis and whole exome sequencing. Both functional prediction tools and structural analysis underscored the detrimental impact of the p.R443P variant. Notably, the patient's plasma exhibited elevated levels of oxidized fatty acid metabolites compared to those in healthy controls, suggesting an impairment in antioxidant mechanisms. This case link a human disease directly to variants in the EEFSEC gene, emphasizing its vital role in cerebellar atrophy and the broader implications for genetic disorders related to defects in selenoprotein synthesis. The results highlight the significance of genetic screening for EEFSEC variants in similar cases, potentially broadening the spectrum of known genetic subtypes associated with selenoprotein translation abnormalities. En ligne : https://dx.doi.org/10.1186/s11689-025-09632-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Brain functional connectivity correlates of autism diagnosis and familial liability in 24-month-olds Type de document : texte imprimé Auteurs : John R. Jr PRUETT, Auteur ; Alexandre A. TODOROV, Auteur ; Zoë W. HAWKS, Auteur ; Muhamed TALOVIĆ, Auteur ; Tomoyuki NISHINO, Auteur ; Steven E. PETERSEN, Auteur ; Savannah DAVIS, Auteur ; Lyn STAHL, Auteur ; Kelly N. BOTTERON, Auteur ; John N. CONSTANTINO, Auteur ; Stephen R. DAGER, Auteur ; Jed T. ELISON, Auteur ; Annette M. ESTES, Auteur ; Alan C. EVANS, Auteur ; Guido GERIG, Auteur ; Jessica B. GIRAULT, Auteur ; Heather HAZLETT, Auteur ; Leigh MACINTYRE, Auteur ; Natasha MARRUS, Auteur ; Robert C. MCKINSTRY, Auteur ; Juhi PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; William D. SHANNON, Auteur ; Mark D. SHEN, Auteur ; Abraham Z. SNYDER, Auteur ; Martin STYNER, Auteur ; Jason J. WOLFF, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Joseph PIVEN, Auteur ; THE IBIS NETWORK, Auteur Langues : Anglais (eng) Mots-clés : Humans Male Female Magnetic Resonance Imaging Autism Spectrum Disorder/physiopathology/diagnostic imaging Child, Preschool Brain/physiopathology/diagnostic imaging Support Vector Machine Connectome Nerve Net/physiopathology/diagnostic imaging Infant Siblings Default mode network Familial Functional connectivity MRI reviewed and approved by the internal review boards of Washington University School of Medicine, IRB IDs 201103140 and 201301110, the University of Washington, IRB IDs 12317 and STUDY00012991, The Children’s Hospital of Philadelphia, IRB ID 07-005689, and the University of North Carolina at Chapel Hill, IRB ID 05-2293. Informed consent was signed by all study participants. Competing interests: Dr. Robert McKinstry serves on the advisory board of Nous Imaging, Inc. and receives funding for meals and travel from Siemens Healthineers and Philips Healthcare. Abraham Z. Snyder is a consultant for Sora Neuroscience, LLC. All other authors report no financial relationships with commercial interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD. METHODS: fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses. RESULTS: OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP versus HLN (p = 0.047) nor HLN versus LLN (p = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)- temporal default mode network (tDMN) pair (p = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (p = 0.0461 and 0.0004). HLP did not differ from HLN (p = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (p = 0.0036). CONCLUSIONS: 24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis. En ligne : https://dx.doi.org/10.1186/s11689-025-09621-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Brain functional connectivity correlates of autism diagnosis and familial liability in 24-month-olds [texte imprimé] / John R. Jr PRUETT, Auteur ; Alexandre A. TODOROV, Auteur ; Zoë W. HAWKS, Auteur ; Muhamed TALOVIĆ, Auteur ; Tomoyuki NISHINO, Auteur ; Steven E. PETERSEN, Auteur ; Savannah DAVIS, Auteur ; Lyn STAHL, Auteur ; Kelly N. BOTTERON, Auteur ; John N. CONSTANTINO, Auteur ; Stephen R. DAGER, Auteur ; Jed T. ELISON, Auteur ; Annette M. ESTES, Auteur ; Alan C. EVANS, Auteur ; Guido GERIG, Auteur ; Jessica B. GIRAULT, Auteur ; Heather HAZLETT, Auteur ; Leigh MACINTYRE, Auteur ; Natasha MARRUS, Auteur ; Robert C. MCKINSTRY, Auteur ; Juhi PANDEY, Auteur ; Robert T. SCHULTZ, Auteur ; William D. SHANNON, Auteur ; Mark D. SHEN, Auteur ; Abraham Z. SNYDER, Auteur ; Martin STYNER, Auteur ; Jason J. WOLFF, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Joseph PIVEN, Auteur ; THE IBIS NETWORK, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Male Female Magnetic Resonance Imaging Autism Spectrum Disorder/physiopathology/diagnostic imaging Child, Preschool Brain/physiopathology/diagnostic imaging Support Vector Machine Connectome Nerve Net/physiopathology/diagnostic imaging Infant Siblings Default mode network Familial Functional connectivity MRI reviewed and approved by the internal review boards of Washington University School of Medicine, IRB IDs 201103140 and 201301110, the University of Washington, IRB IDs 12317 and STUDY00012991, The Children’s Hospital of Philadelphia, IRB ID 07-005689, and the University of North Carolina at Chapel Hill, IRB ID 05-2293. Informed consent was signed by all study participants. Competing interests: Dr. Robert McKinstry serves on the advisory board of Nous Imaging, Inc. and receives funding for meals and travel from Siemens Healthineers and Philips Healthcare. Abraham Z. Snyder is a consultant for Sora Neuroscience, LLC. All other authors report no financial relationships with commercial interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD. METHODS: fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses. RESULTS: OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP versus HLN (p = 0.047) nor HLN versus LLN (p = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)- temporal default mode network (tDMN) pair (p = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (p = 0.0461 and 0.0004). HLP did not differ from HLN (p = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (p = 0.0036). CONCLUSIONS: 24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis. En ligne : https://dx.doi.org/10.1186/s11689-025-09621-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Elevated autistic traits and social anxiety, and reduced empathy in adult women with triple X syndrome Type de document : texte imprimé Auteurs : Marie-Anne CROYÉ, Auteur ; Petra FREILINGER, Auteur ; Hendrik JÜRGENLIMKE, Auteur ; Gregor DOMES, Auteur ; Jobst MEYER, Auteur Langues : Anglais (eng) Mots-clés : Humans Female Adult Empathy/physiology Anxiety/psychology Young Adult Autistic Disorder/psychology Chromosomes, Human, X Adaptation, Psychological Case-Control Studies Sex Chromosome Aberrations Trisomy Sex Chromosome Disorders of Sex Development 47,xxx Autistic traits Chronic stress Sex chromosome aneuploidy Social anxiety Social functioning Somatization Stress coping mechanisms Triple X syndrome Trisomy X conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of the University of Trier (Ref. No. 30/2021). All participants provided written informed consent prior to their participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Triple X syndrome (TXS, 47,XXX) is a sex chromosome aneuploidy affecting females. The condition is associated with cognitive, emotional, and social challenges. While prior research has primarily focused on children, the social and psychological profile of adult women with TXS remains understudied. This study aims to provide a comprehensive assessment of these aspects in adult women with TXS compared to matched controls. METHODS: A cohort of 44 women with TXS (mean age 30.5 years) was compared to 50 age- and education-matched controls (mean age 29.7 years). Standardized assessments measured verbal IQ, psychological distress, chronic stress, emotion regulation, coping mechanisms, social anxiety, empathy, autistic traits, and personality traits. Group comparisons were conducted using ANOVAs and MANOVAs, with additional χ² tests for categorical variables. RESULTS: Depression and trait anxiety did not significantly differ between groups, though both groups exhibited notably high scores. However, a greater number of individuals in the TXS group reported elevated social anxiety and autistic traits, and reduced empathy. Moreover, there were indications of increased self-reported social tensions, personal distress, and somatization within the TXS group. No significant differences were found in personality traits, verbal IQ, chronic stress levels, and emotion regulation. Additionally, TXS participants tended to rely less on the maladaptive coping strategy of alcohol and cigarette consumption. CONCLUSION: Our findings underscore autistic traits, social anxiety, and reduced empathy as significant challenges for adult women with TXS. While cognitive and emotional characteristics were largely comparable to those of age- and education-matched controls, the heightened social difficulties suggest a potential benefit of targeted interventions, such as social skills training, to support affected individuals. Longitudinal studies are essential to understand the long-term progression of these challenges and to develop effective therapeutic strategies. En ligne : https://dx.doi.org/10.1186/s11689-025-09631-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Elevated autistic traits and social anxiety, and reduced empathy in adult women with triple X syndrome [texte imprimé] / Marie-Anne CROYÉ, Auteur ; Petra FREILINGER, Auteur ; Hendrik JÜRGENLIMKE, Auteur ; Gregor DOMES, Auteur ; Jobst MEYER, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Female Adult Empathy/physiology Anxiety/psychology Young Adult Autistic Disorder/psychology Chromosomes, Human, X Adaptation, Psychological Case-Control Studies Sex Chromosome Aberrations Trisomy Sex Chromosome Disorders of Sex Development 47,xxx Autistic traits Chronic stress Sex chromosome aneuploidy Social anxiety Social functioning Somatization Stress coping mechanisms Triple X syndrome Trisomy X conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of the University of Trier (Ref. No. 30/2021). All participants provided written informed consent prior to their participation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Triple X syndrome (TXS, 47,XXX) is a sex chromosome aneuploidy affecting females. The condition is associated with cognitive, emotional, and social challenges. While prior research has primarily focused on children, the social and psychological profile of adult women with TXS remains understudied. This study aims to provide a comprehensive assessment of these aspects in adult women with TXS compared to matched controls. METHODS: A cohort of 44 women with TXS (mean age 30.5 years) was compared to 50 age- and education-matched controls (mean age 29.7 years). Standardized assessments measured verbal IQ, psychological distress, chronic stress, emotion regulation, coping mechanisms, social anxiety, empathy, autistic traits, and personality traits. Group comparisons were conducted using ANOVAs and MANOVAs, with additional χ² tests for categorical variables. RESULTS: Depression and trait anxiety did not significantly differ between groups, though both groups exhibited notably high scores. However, a greater number of individuals in the TXS group reported elevated social anxiety and autistic traits, and reduced empathy. Moreover, there were indications of increased self-reported social tensions, personal distress, and somatization within the TXS group. No significant differences were found in personality traits, verbal IQ, chronic stress levels, and emotion regulation. Additionally, TXS participants tended to rely less on the maladaptive coping strategy of alcohol and cigarette consumption. CONCLUSION: Our findings underscore autistic traits, social anxiety, and reduced empathy as significant challenges for adult women with TXS. While cognitive and emotional characteristics were largely comparable to those of age- and education-matched controls, the heightened social difficulties suggest a potential benefit of targeted interventions, such as social skills training, to support affected individuals. Longitudinal studies are essential to understand the long-term progression of these challenges and to develop effective therapeutic strategies. En ligne : https://dx.doi.org/10.1186/s11689-025-09631-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Distinct early development trajectories in Nf1(±) and Tsc2(±) mouse models of autism Type de document : texte imprimé Auteurs : Helena FERREIRA, Auteur ; Sofia SANTOS, Auteur ; João MARTINS, Auteur ; Miguel CASTELO-BRANCO, Auteur ; Joana GONÇALVES, Auteur Langues : Anglais (eng) Mots-clés : Animals Disease Models, Animal Tuberous Sclerosis Complex 2 Protein/genetics Male Female Mice Vocalization, Animal/physiology Autism Spectrum Disorder/genetics/physiopathology Neurofibromatosis 1/genetics/physiopathology Neurofibromin 1/genetics Animals, Newborn Tuberous Sclerosis/genetics Sex Characteristics Maternal Deprivation Mice, Inbred C57BL Asd Developmental milestones Neurofibromatosis type 1 Tuberous sclerosis complex 2 Ultrasonic vocalizations following the European Union Council Directive (2010/63/EU), National Regulations, and ORBEA board of ICNAS (1/2017). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, and repetitive behaviors. Males are three times more likely to be diagnosed with ASD than females, and sex-dependent alterations in behavior and communication have been reported both in clinical and animal research. Animal models are useful for understanding ASD-related manifestations and their associated neurobiological mechanisms. However, even though ASD is diagnosed during childhood, relatively few animal studies have focused on neonatal development. METHODS: Here, we performed a detailed analysis of neonatal developmental milestones and maternal separation-induced ultrasonic vocalizations (USVs) in two genetic animal models of ASD, neurofibromatosis type 1 (Nf1(±)) and tuberous sclerosis complex 2 (Tsc2(±)). RESULTS: Nf1(±) and Tsc2(±) mice display strikingly distinct developmental profiles regarding motor, strength, and coordination skills. Nf1(±) mouse pups mostly show genotype-related differences, whereas Tsc2(±) mouse pups mainly present sexual dimorphisms. Furthermore, we found several differences regarding the number of USVs, frequency modulation, and temporal and spectral profile. Importantly, Nf1(±) animals tend to present sex- and genotype-dependent differences earlier than the Tsc2(±) mouse pups, suggesting distinct developmental curves between these two animal models. CONCLUSIONS: This study provides a nuanced understanding of how these two ASD models differ in their developmental trajectories. It underscores the importance of studying sex differences and early-life developmental markers, as these could offer crucial insights into ASD's progression and neurobiology. The distinct profiles of these models may help guide more targeted therapeutic strategies in the future. En ligne : https://dx.doi.org/10.1186/s11689-025-09624-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Distinct early development trajectories in Nf1(±) and Tsc2(±) mouse models of autism [texte imprimé] / Helena FERREIRA, Auteur ; Sofia SANTOS, Auteur ; João MARTINS, Auteur ; Miguel CASTELO-BRANCO, Auteur ; Joana GONÇALVES, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Animals Disease Models, Animal Tuberous Sclerosis Complex 2 Protein/genetics Male Female Mice Vocalization, Animal/physiology Autism Spectrum Disorder/genetics/physiopathology Neurofibromatosis 1/genetics/physiopathology Neurofibromin 1/genetics Animals, Newborn Tuberous Sclerosis/genetics Sex Characteristics Maternal Deprivation Mice, Inbred C57BL Asd Developmental milestones Neurofibromatosis type 1 Tuberous sclerosis complex 2 Ultrasonic vocalizations following the European Union Council Directive (2010/63/EU), National Regulations, and ORBEA board of ICNAS (1/2017). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, and repetitive behaviors. Males are three times more likely to be diagnosed with ASD than females, and sex-dependent alterations in behavior and communication have been reported both in clinical and animal research. Animal models are useful for understanding ASD-related manifestations and their associated neurobiological mechanisms. However, even though ASD is diagnosed during childhood, relatively few animal studies have focused on neonatal development. METHODS: Here, we performed a detailed analysis of neonatal developmental milestones and maternal separation-induced ultrasonic vocalizations (USVs) in two genetic animal models of ASD, neurofibromatosis type 1 (Nf1(±)) and tuberous sclerosis complex 2 (Tsc2(±)). RESULTS: Nf1(±) and Tsc2(±) mice display strikingly distinct developmental profiles regarding motor, strength, and coordination skills. Nf1(±) mouse pups mostly show genotype-related differences, whereas Tsc2(±) mouse pups mainly present sexual dimorphisms. Furthermore, we found several differences regarding the number of USVs, frequency modulation, and temporal and spectral profile. Importantly, Nf1(±) animals tend to present sex- and genotype-dependent differences earlier than the Tsc2(±) mouse pups, suggesting distinct developmental curves between these two animal models. CONCLUSIONS: This study provides a nuanced understanding of how these two ASD models differ in their developmental trajectories. It underscores the importance of studying sex differences and early-life developmental markers, as these could offer crucial insights into ASD's progression and neurobiology. The distinct profiles of these models may help guide more targeted therapeutic strategies in the future. En ligne : https://dx.doi.org/10.1186/s11689-025-09624-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Patient reported outcomes used in clinical trials and core outcome sets for individuals with genetic intellectual disability: a scoping review Type de document : texte imprimé Auteurs : Nadia Y. VAN SILFHOUT, Auteur ; Maud M. VAN MUILEKOM, Auteur ; Clara D. VAN KARNEBEEK, Auteur ; Joost G. DAAMS, Auteur ; Lotte HAVERMAN, Auteur ; Agnies M. VAN EEGHEN, Auteur Langues : Anglais (eng) Mots-clés : Humans Clinical Trials as Topic Intellectual Disability/therapy/psychology/genetics Patient Reported Outcome Measures Quality of Life Genetic intellectual disability Patient reported outcome measures Patient reported outcomes for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The impact of genetic intellectual disability (GID) on daily life is significant. To better understand the impact of GID, it is essential to measure relevant patient reported outcomes (PROs). The aim of this study is to provide an overview of PROs used for individuals with GID, laying the groundwork for a future generic core PRO set for GID. METHODS: To identify PROs used for individuals with GID, results of two literature reviews were integrated; (1) PROs extracted from a scoping review on outcomes in clinical trials, and (2) PROs identified from a scoping review on core outcome sets (COSs) for specific GIDs through a search in MEDLINE (Ovid), PsycINFO, Embase, and the COMET database. Descriptive analyses were performed. RESULTS: In the first scoping review, 66 different PROs were identified. In the second scoping review, 22 different PROs were identified. After integrating PROs, 18 unique PROs remained, which were classified into a conceptual framework. Most frequently reported PROs were quality of life, perceived health, cognitive functioning, anxiety/stress, and depressive symptoms. CONCLUSION: This study provides an overview of PROs used for individuals with GID. These results will assist in developing a generic core PRO set for GID, to harmonize PROs used in care and research. En ligne : https://dx.doi.org/10.1186/s11689-025-09633-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Patient reported outcomes used in clinical trials and core outcome sets for individuals with genetic intellectual disability: a scoping review [texte imprimé] / Nadia Y. VAN SILFHOUT, Auteur ; Maud M. VAN MUILEKOM, Auteur ; Clara D. VAN KARNEBEEK, Auteur ; Joost G. DAAMS, Auteur ; Lotte HAVERMAN, Auteur ; Agnies M. VAN EEGHEN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Clinical Trials as Topic Intellectual Disability/therapy/psychology/genetics Patient Reported Outcome Measures Quality of Life Genetic intellectual disability Patient reported outcome measures Patient reported outcomes for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The impact of genetic intellectual disability (GID) on daily life is significant. To better understand the impact of GID, it is essential to measure relevant patient reported outcomes (PROs). The aim of this study is to provide an overview of PROs used for individuals with GID, laying the groundwork for a future generic core PRO set for GID. METHODS: To identify PROs used for individuals with GID, results of two literature reviews were integrated; (1) PROs extracted from a scoping review on outcomes in clinical trials, and (2) PROs identified from a scoping review on core outcome sets (COSs) for specific GIDs through a search in MEDLINE (Ovid), PsycINFO, Embase, and the COMET database. Descriptive analyses were performed. RESULTS: In the first scoping review, 66 different PROs were identified. In the second scoping review, 22 different PROs were identified. After integrating PROs, 18 unique PROs remained, which were classified into a conceptual framework. Most frequently reported PROs were quality of life, perceived health, cognitive functioning, anxiety/stress, and depressive symptoms. CONCLUSION: This study provides an overview of PROs used for individuals with GID. These results will assist in developing a generic core PRO set for GID, to harmonize PROs used in care and research. En ligne : https://dx.doi.org/10.1186/s11689-025-09633-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Pupil responses to social stimuli are associated with adaptive behaviors across the first 24 months of life Type de document : texte imprimé Auteurs : Rebecca GRZADZINSKI, Auteur ; Raymond S. 3rd CARPENTER, Auteur ; Josh RUTSOHN, Auteur ; Alapika JATKAR, Auteur ; Kattia MATA, Auteur ; Ambika BHATT, Auteur ; Maria M. ORTIZ-JUZA, Auteur ; Madison R. DENNEHEY, Auteur ; Donna GILLESKIE, Auteur ; Jed T. ELISON, Auteur ; Nicolas PÉGARD, Auteur ; Jose RODRIGUEZ-ROMAGUERA, Auteur Langues : Anglais (eng) Mots-clés : Autism Autism-spectrum disorder Eye-tracking Pupil change Pupil dynamics Pupillometry Social arousal Social attention approved by the Institutional Review Board at the University of North Carolina at Chapel Hill (IRB #21-1704). A parent or legal guardian provided written informed consent. Consent for publication: All authors have approved the manuscript for publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Pupil changes in response to well-controlled stimuli can be used to understand processes that regulate attention, learning, and arousal. This study investigates whether pupil dynamics to social stimuli are associated with concurrent adaptive behavior in typically developing infants. To accomplish this, we developed and assessed pupillary responses to Stimuli for Early Social Arousal and Motivation in Infants (SESAMI). METHODS: A sample of forty-six typically developing children aged six to twenty-four months were exposed to SESAMI. Infants were presented with either dynamic social faces or non-social stimuli that controlled for luminance, motion, and auditory exposure. A multi-level mixed effects model was used to fit pupillary response functions (PRFs) that measure the change in pupil size over time as the infants fixate on either a socially dynamic face or a non-social control. This model produces separate social and non-social PRFs for both the population and each individual. An average individual deviation score from the population PRF was calculated separately for social and non-social trials yielding the pupil response index (PRI). Vineland Adaptive Behavior Scales (VABS) were regressed on social and non-social individual PRIs while controlling for age and average fixation time. We tested whether the social PRI was a statistically significant predictor of adaptive behavior by comparing the model predicted VABS scores with observed scores. RESULTS: An increase in PRI to social stimuli was significantly associated with better adaptive behaviors in typically developing children between 6 and 24 months of age. CONCLUSIONS: SESAMI combined with pupillometry and multi-level mixed effects modeling, provides a novel and scalable framework for quantifying individual differences in pupil changes in response to social stimuli relative to a population-level baseline. By demonstrating that pupil response indices during social fixations predict adaptive behaviors, we lay the foundation to test how these measures may help identify infants with intellectual and developmental disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09628-2. En ligne : https://dx.doi.org/10.1186/s11689-025-09628-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Pupil responses to social stimuli are associated with adaptive behaviors across the first 24 months of life [texte imprimé] / Rebecca GRZADZINSKI, Auteur ; Raymond S. 3rd CARPENTER, Auteur ; Josh RUTSOHN, Auteur ; Alapika JATKAR, Auteur ; Kattia MATA, Auteur ; Ambika BHATT, Auteur ; Maria M. ORTIZ-JUZA, Auteur ; Madison R. DENNEHEY, Auteur ; Donna GILLESKIE, Auteur ; Jed T. ELISON, Auteur ; Nicolas PÉGARD, Auteur ; Jose RODRIGUEZ-ROMAGUERA, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Autism Autism-spectrum disorder Eye-tracking Pupil change Pupil dynamics Pupillometry Social arousal Social attention approved by the Institutional Review Board at the University of North Carolina at Chapel Hill (IRB #21-1704). A parent or legal guardian provided written informed consent. Consent for publication: All authors have approved the manuscript for publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Pupil changes in response to well-controlled stimuli can be used to understand processes that regulate attention, learning, and arousal. This study investigates whether pupil dynamics to social stimuli are associated with concurrent adaptive behavior in typically developing infants. To accomplish this, we developed and assessed pupillary responses to Stimuli for Early Social Arousal and Motivation in Infants (SESAMI). METHODS: A sample of forty-six typically developing children aged six to twenty-four months were exposed to SESAMI. Infants were presented with either dynamic social faces or non-social stimuli that controlled for luminance, motion, and auditory exposure. A multi-level mixed effects model was used to fit pupillary response functions (PRFs) that measure the change in pupil size over time as the infants fixate on either a socially dynamic face or a non-social control. This model produces separate social and non-social PRFs for both the population and each individual. An average individual deviation score from the population PRF was calculated separately for social and non-social trials yielding the pupil response index (PRI). Vineland Adaptive Behavior Scales (VABS) were regressed on social and non-social individual PRIs while controlling for age and average fixation time. We tested whether the social PRI was a statistically significant predictor of adaptive behavior by comparing the model predicted VABS scores with observed scores. RESULTS: An increase in PRI to social stimuli was significantly associated with better adaptive behaviors in typically developing children between 6 and 24 months of age. CONCLUSIONS: SESAMI combined with pupillometry and multi-level mixed effects modeling, provides a novel and scalable framework for quantifying individual differences in pupil changes in response to social stimuli relative to a population-level baseline. By demonstrating that pupil response indices during social fixations predict adaptive behaviors, we lay the foundation to test how these measures may help identify infants with intellectual and developmental disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09628-2. En ligne : https://dx.doi.org/10.1186/s11689-025-09628-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Autism-like phenotype across the lifespan of Shank3B-mutant mice of both sexes Type de document : texte imprimé Auteurs : Jakub SZABÓ, Auteur ; Johan FILO, Auteur ; Rebeka DÉMUTHOVÁ, Auteur ; Emese RENCZÉS, Auteur ; Veronika BORBÉLYOVÁ, Auteur ; Daniela OSTATNIKOVA, Auteur ; Peter CELEC, Auteur Langues : Anglais (eng) Mots-clés : Animals Male Female Mice Nerve Tissue Proteins/genetics Behavior, Animal/physiology Phenotype Disease Models, Animal Mice, Inbred C57BL Autism Spectrum Disorder/genetics/physiopathology Anxiety/genetics/physiopathology Aging/physiology Social Behavior Mice, Knockout Sex Factors Microfilament Proteins Animal model Phelan-McDermid syndrome Phenotyping Symptom development conducted in accordance with the Slovak national laws and approved by the ethics committee of the Institute of Molecular Biomedicine. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: High heritability (80-90%) of the autism spectrum disorder (ASD) and sex-biased incidence (3-4 times more boys than girls) suggest the roles of genetic predisposition and sex in the etiopathogenesis of the disorder. As ASD is commonly diagnosed in early childhood, most of the research is focused on children, yet animal research predominantly uses adult-aged animals. The effect of aging on the core and secondary ASD symptomatology is understudied, both in patients and animal models of ASD. METHODS: To investigate the effect of aging on sociability, repetitive behavior, exploration, locomotor activity, anxiety-like behavior, and object-avoidance behavior, behavioral phenotyping was conducted in Shank3B(-/-) (n = 67) and C57BL/6J wild-type (WT, n = 68) mice of both sexes (female n = 70, male n = 65) in adolescence (1-2 months of age, n = 42), adulthood (3-6 months of age, n = 40), and old age (12-18 months of age, n = 53). RESULTS: Social deficits were observed only in old Shank3B(-/-) males. Anxiety-like behavior peaked in adulthood with Shank3B(-/-) mice roughly 20% more anxious than controls. Repetitive grooming and object-induced avoidance behavior were twice more prevalent in Shank3B(-/-) mice consistently across the lifespan. Hypoactivity (20% less distance moved) and reduced exploration (30% less rearing behavior) were recorded in Shank3B(-/-) mice and were more prevalent in female animals (30% less rearing behavior). Data were analyzed using the Three-way ANOVA (genotype, sex, age), followed by a posthoc Bonferroni correction to compare respective subgroups. CONCLUSIONS: Present study shows that aging affects ASD-like phenotype in the Shank3B-mutant mouse model, even though the effect size seems to be small. The mechanisms underlying these partially sex-specific effects should be the subject of further research with potential translational implications. En ligne : https://dx.doi.org/10.1186/s11689-025-09635-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Autism-like phenotype across the lifespan of Shank3B-mutant mice of both sexes [texte imprimé] / Jakub SZABÓ, Auteur ; Johan FILO, Auteur ; Rebeka DÉMUTHOVÁ, Auteur ; Emese RENCZÉS, Auteur ; Veronika BORBÉLYOVÁ, Auteur ; Daniela OSTATNIKOVA, Auteur ; Peter CELEC, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Animals Male Female Mice Nerve Tissue Proteins/genetics Behavior, Animal/physiology Phenotype Disease Models, Animal Mice, Inbred C57BL Autism Spectrum Disorder/genetics/physiopathology Anxiety/genetics/physiopathology Aging/physiology Social Behavior Mice, Knockout Sex Factors Microfilament Proteins Animal model Phelan-McDermid syndrome Phenotyping Symptom development conducted in accordance with the Slovak national laws and approved by the ethics committee of the Institute of Molecular Biomedicine. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: High heritability (80-90%) of the autism spectrum disorder (ASD) and sex-biased incidence (3-4 times more boys than girls) suggest the roles of genetic predisposition and sex in the etiopathogenesis of the disorder. As ASD is commonly diagnosed in early childhood, most of the research is focused on children, yet animal research predominantly uses adult-aged animals. The effect of aging on the core and secondary ASD symptomatology is understudied, both in patients and animal models of ASD. METHODS: To investigate the effect of aging on sociability, repetitive behavior, exploration, locomotor activity, anxiety-like behavior, and object-avoidance behavior, behavioral phenotyping was conducted in Shank3B(-/-) (n = 67) and C57BL/6J wild-type (WT, n = 68) mice of both sexes (female n = 70, male n = 65) in adolescence (1-2 months of age, n = 42), adulthood (3-6 months of age, n = 40), and old age (12-18 months of age, n = 53). RESULTS: Social deficits were observed only in old Shank3B(-/-) males. Anxiety-like behavior peaked in adulthood with Shank3B(-/-) mice roughly 20% more anxious than controls. Repetitive grooming and object-induced avoidance behavior were twice more prevalent in Shank3B(-/-) mice consistently across the lifespan. Hypoactivity (20% less distance moved) and reduced exploration (30% less rearing behavior) were recorded in Shank3B(-/-) mice and were more prevalent in female animals (30% less rearing behavior). Data were analyzed using the Three-way ANOVA (genotype, sex, age), followed by a posthoc Bonferroni correction to compare respective subgroups. CONCLUSIONS: Present study shows that aging affects ASD-like phenotype in the Shank3B-mutant mouse model, even though the effect size seems to be small. The mechanisms underlying these partially sex-specific effects should be the subject of further research with potential translational implications. En ligne : https://dx.doi.org/10.1186/s11689-025-09635-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Objective diagnosis of attention-deficit/hyperactivity disorder by using load cell movement analysis under a smart chair in a simulated classroom: influence of sex and age Type de document : texte imprimé Auteurs : Chen-Sen OUYANG, Auteur ; Rong-Ching WU, Auteur ; Yi-Hung CHIU, Auteur ; Rei-Cheng YANG, Auteur ; Lung-Chang LIN, Auteur Langues : Anglais (eng) Mots-clés : Humans Attention Deficit Disorder with Hyperactivity/diagnosis/physiopathology Male Female Child Sex Factors Age Factors Movement/physiology Attention-deficit/hyperactivity disorder Average trajectory length Load cells Smart chair consent was obtained by a participant’s family member or legal guardian after the procedure had been explained. In addition, informed consent was also obtained from them for the publication of their children’s images. This study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUIRB-SV(I)- 20190060) in accordance with the Declaration of Helsinki. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children, typically characterized by persistent patterns of inattention or hyperactivity-impulsivity. Its diagnosis relies on criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and is primarily based on subjective observations and information provided by parents and teachers. Despite the availability of assessment tools such as the Swanson, Nolan, and Pelham questionnaire, diagnosing ADHD in children remains challenging. Such scales predominantly offer subjective insights into the disorder. Therefore, in this study, we developed an objective method that employs load cells for the objective diagnosis of ADHD. METHODS: A simulated classroom environment was constructed to replicate a real-world setting. The setup included a desk, chair, and large screen. Load cells, which deform under applied force, were integrated into the four legs of the chair to capture movement data. This study involved 30 children with ADHD (14 boys and 16 girls; mean age: 8 years and 1 month ± 1 year and 10 months) and 30 age- and sex-matched children without ADHD (mean age: 8 years and 3 months ± 1 year and 10 months). Participants were instructed to sit on the chair and watch an age-appropriate educational video on mathematics. Movement data, captured through the load cells, were analyzed to calculate the average trajectory length (ATL) as a measure of activity. For participants with ADHD, SNAP-IV questionnaires were completed by parents and teachers. RESULTS: The ATL values for the ADHD and non-ADHD groups were 0.0378 ± 0.0191 and 0.0157 ± 0.0119 (p < 0.0001), respectively. In the ADHD group, boys exhibited a higher ATL (0.0443 ± 0.0100) than girls (0.0303 ± 0.0228; p = 0.0432). The SNAP-IV scores assigned by parents and teachers for participants with ADHD were 33.14 ± 13.75 and 30.95 ± 14.32, respectively. Decision tree classifiers incorporating sex as a variable demonstrated robust performance, achieving an accuracy of 90.67%, sensitivity of 92.33%, specificity of 89.00%, and area under the curve of 91.06%. CONCLUSION: The smart chair equipped with load cells is an interesting development in progress tool for the objective diagnosis of ADHD and can aid clinical physicians in making decisions regarding ADHD evaluation. En ligne : https://dx.doi.org/10.1186/s11689-025-09641-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Objective diagnosis of attention-deficit/hyperactivity disorder by using load cell movement analysis under a smart chair in a simulated classroom: influence of sex and age [texte imprimé] / Chen-Sen OUYANG, Auteur ; Rong-Ching WU, Auteur ; Yi-Hung CHIU, Auteur ; Rei-Cheng YANG, Auteur ; Lung-Chang LIN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Attention Deficit Disorder with Hyperactivity/diagnosis/physiopathology Male Female Child Sex Factors Age Factors Movement/physiology Attention-deficit/hyperactivity disorder Average trajectory length Load cells Smart chair consent was obtained by a participant’s family member or legal guardian after the procedure had been explained. In addition, informed consent was also obtained from them for the publication of their children’s images. This study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUIRB-SV(I)- 20190060) in accordance with the Declaration of Helsinki. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children, typically characterized by persistent patterns of inattention or hyperactivity-impulsivity. Its diagnosis relies on criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and is primarily based on subjective observations and information provided by parents and teachers. Despite the availability of assessment tools such as the Swanson, Nolan, and Pelham questionnaire, diagnosing ADHD in children remains challenging. Such scales predominantly offer subjective insights into the disorder. Therefore, in this study, we developed an objective method that employs load cells for the objective diagnosis of ADHD. METHODS: A simulated classroom environment was constructed to replicate a real-world setting. The setup included a desk, chair, and large screen. Load cells, which deform under applied force, were integrated into the four legs of the chair to capture movement data. This study involved 30 children with ADHD (14 boys and 16 girls; mean age: 8 years and 1 month ± 1 year and 10 months) and 30 age- and sex-matched children without ADHD (mean age: 8 years and 3 months ± 1 year and 10 months). Participants were instructed to sit on the chair and watch an age-appropriate educational video on mathematics. Movement data, captured through the load cells, were analyzed to calculate the average trajectory length (ATL) as a measure of activity. For participants with ADHD, SNAP-IV questionnaires were completed by parents and teachers. RESULTS: The ATL values for the ADHD and non-ADHD groups were 0.0378 ± 0.0191 and 0.0157 ± 0.0119 (p < 0.0001), respectively. In the ADHD group, boys exhibited a higher ATL (0.0443 ± 0.0100) than girls (0.0303 ± 0.0228; p = 0.0432). The SNAP-IV scores assigned by parents and teachers for participants with ADHD were 33.14 ± 13.75 and 30.95 ± 14.32, respectively. Decision tree classifiers incorporating sex as a variable demonstrated robust performance, achieving an accuracy of 90.67%, sensitivity of 92.33%, specificity of 89.00%, and area under the curve of 91.06%. CONCLUSION: The smart chair equipped with load cells is an interesting development in progress tool for the objective diagnosis of ADHD and can aid clinical physicians in making decisions regarding ADHD evaluation. En ligne : https://dx.doi.org/10.1186/s11689-025-09641-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Current situation and influencing factors of Chinese children's diagnosis delay in autism Type de document : texte imprimé Auteurs : Feng-Lei ZHU, Auteur ; Yue JI, Auteur ; Lu WANG, Auteur ; Min XU, Auteur ; Xiao-Bing ZOU, Auteur Langues : Anglais (eng) Mots-clés : Child Child, Preschool Female Humans Infant Male Autistic Disorder/diagnosis China/epidemiology Delayed Diagnosis/statistics & numerical data Risk Factors Adolescent East Asian People Age of diagnosis (AOD) Age of first concern (AOC) Autism Children Diagnostic delay The Cox proportional hazard model methods were carried out in accordance with the Declaration of Helsinki. Ethical approval for this study was obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. The ethical approval number: [2019] 02-013-01. All participants provided informed consent and were fully informed that their participation was voluntary and confidential. Informed consent was obtained from the guardians. Competing interests: The authors declare no competing interests. Clinical trial: Not applicable. Index. décimale : PER Périodiques Résumé : BACKGROUND: Although experienced clinicians are capable of diagnosing autism in children before they reach the age of 2, the average age of diagnosis reported internationally is between 4 and 5 years, indicating a significant delay. This study aimed to determine the factors influencing the diagnostic delay time (DDT) in Chinese autistic children. METHODS: We employed the Cox proportional hazard model to examine the effects of individual, family, sociodemographic, and healthcare system indicators on DDT in 480 Chinese autistic children (age range: 16.10-190.16 months; male-to-female ratio: 5.67:1) recruited from a tertiary hospital between 2021 and 2023. RESULTS: The median DDT was 9.58 months (IQR = 15.01). Independent risk factors for delayed diagnosis included normal language competence (RR = 1.747, p < 0.001), non-core symptoms as first concerns (RR = 1.642, p = 0.013), school attendance (RR = 1.941, p < 0.001), irregular well-child visits (RR = 1.264, p = 0.028), and misdiagnosis history (RR = 0.648, p = 0.001). CONCLUSIONS: Diagnosis delay in Chinese autistic children is heterogeneous. Early monitoring for children with normal language skills and school-aged children, alongside improved healthcare system practices, is critical. En ligne : https://dx.doi.org/10.1186/s11689-025-09636-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Current situation and influencing factors of Chinese children's diagnosis delay in autism [texte imprimé] / Feng-Lei ZHU, Auteur ; Yue JI, Auteur ; Lu WANG, Auteur ; Min XU, Auteur ; Xiao-Bing ZOU, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Child Child, Preschool Female Humans Infant Male Autistic Disorder/diagnosis China/epidemiology Delayed Diagnosis/statistics & numerical data Risk Factors Adolescent East Asian People Age of diagnosis (AOD) Age of first concern (AOC) Autism Children Diagnostic delay The Cox proportional hazard model methods were carried out in accordance with the Declaration of Helsinki. Ethical approval for this study was obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. The ethical approval number: [2019] 02-013-01. All participants provided informed consent and were fully informed that their participation was voluntary and confidential. Informed consent was obtained from the guardians. Competing interests: The authors declare no competing interests. Clinical trial: Not applicable. Index. décimale : PER Périodiques Résumé : BACKGROUND: Although experienced clinicians are capable of diagnosing autism in children before they reach the age of 2, the average age of diagnosis reported internationally is between 4 and 5 years, indicating a significant delay. This study aimed to determine the factors influencing the diagnostic delay time (DDT) in Chinese autistic children. METHODS: We employed the Cox proportional hazard model to examine the effects of individual, family, sociodemographic, and healthcare system indicators on DDT in 480 Chinese autistic children (age range: 16.10-190.16 months; male-to-female ratio: 5.67:1) recruited from a tertiary hospital between 2021 and 2023. RESULTS: The median DDT was 9.58 months (IQR = 15.01). Independent risk factors for delayed diagnosis included normal language competence (RR = 1.747, p < 0.001), non-core symptoms as first concerns (RR = 1.642, p = 0.013), school attendance (RR = 1.941, p < 0.001), irregular well-child visits (RR = 1.264, p = 0.028), and misdiagnosis history (RR = 0.648, p = 0.001). CONCLUSIONS: Diagnosis delay in Chinese autistic children is heterogeneous. Early monitoring for children with normal language skills and school-aged children, alongside improved healthcare system practices, is critical. En ligne : https://dx.doi.org/10.1186/s11689-025-09636-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Challenges with shifting, regardless of disengagement: attention mechanisms and eye movements in Williams syndrome Type de document : texte imprimé Auteurs : Astrid HALLMAN, Auteur ; Charlotte WILLFORS, Auteur ; Christine FAWCETT, Auteur ; Matilda A. FRICK, Auteur ; Ann NORDGREN, Auteur ; Johan Lundin KLEBERG, Auteur Langues : Anglais (eng) Mots-clés : Eye tracking Intellectual disability Orienting attention Phasic alerting effect Pupil dilation Shifting attention Visual disengagement Williams syndrome in accordance with the Declaration of Helsinki and received approval from the Regional Ethics Committee of Stockholm, Sweden (dnr 2018/1218-31 with subsequent amendments). Informed consents were collected from the participants and/or their legal guardians. Informed assent was obtained from all participants who were able to assent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: People with Williams syndrome (WS) face challenges in various areas of cognitive processing, including attention. Previous studies suggest that these challenges are particularly pronounced when disengagement of attention from a previously attended stimulus is required, as compared to shifting attention without the need to disengage. Difficulties with attention could in turn be implicated in several of the behavioral characteristics of WS. Here, disengagement and shifting of visual attention, together with pupil dilation, were independently assessed in one of the largest eye-tracking studies of WS to date. METHODS: We investigated shifting, disengagement, and the effects of auditory alerting cues on pupil dilation in WS individuals (n = 45, age range = 9–58 years), non-WS individuals with intellectual disability (ID) (n = 36, age range = 6–59 years), and typically developed (TD) infants (n = 32, age range = 6–7 months), children and adults (n = 31, age range = 9–60 years), using a modified gap-overlap task. Data were analyzed using linear mixed-effect models (LMMs). RESULTS: Individuals with WS were less likely to shift their attention to upcoming targets than TD individuals (all ages), but more likely than the ID group to do so. When they did shift attention, participants with WS and ID were slower to initiate a gaze shift than TD participants regardless of whether disengagement was needed. In the WS group, failure to shift attention was strongly predicted by higher arousal (pupil dilation), which was induced by auditory alerting cues. CONCLUSIONS: Contrasting with previous theories of attention in WS, we found no evidence for a specific challenge in disengaging attention. Instead, our results point to a more general challenge in shifting attention. Reduced attention shifting in WS may be partly explained by atypical arousal regulation. These results contribute to our understanding of the WS phenotype. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09639-z. En ligne : https://dx.doi.org/10.1186/s11689-025-09639-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Challenges with shifting, regardless of disengagement: attention mechanisms and eye movements in Williams syndrome [texte imprimé] / Astrid HALLMAN, Auteur ; Charlotte WILLFORS, Auteur ; Christine FAWCETT, Auteur ; Matilda A. FRICK, Auteur ; Ann NORDGREN, Auteur ; Johan Lundin KLEBERG, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Eye tracking Intellectual disability Orienting attention Phasic alerting effect Pupil dilation Shifting attention Visual disengagement Williams syndrome in accordance with the Declaration of Helsinki and received approval from the Regional Ethics Committee of Stockholm, Sweden (dnr 2018/1218-31 with subsequent amendments). Informed consents were collected from the participants and/or their legal guardians. Informed assent was obtained from all participants who were able to assent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: People with Williams syndrome (WS) face challenges in various areas of cognitive processing, including attention. Previous studies suggest that these challenges are particularly pronounced when disengagement of attention from a previously attended stimulus is required, as compared to shifting attention without the need to disengage. Difficulties with attention could in turn be implicated in several of the behavioral characteristics of WS. Here, disengagement and shifting of visual attention, together with pupil dilation, were independently assessed in one of the largest eye-tracking studies of WS to date. METHODS: We investigated shifting, disengagement, and the effects of auditory alerting cues on pupil dilation in WS individuals (n = 45, age range = 9–58 years), non-WS individuals with intellectual disability (ID) (n = 36, age range = 6–59 years), and typically developed (TD) infants (n = 32, age range = 6–7 months), children and adults (n = 31, age range = 9–60 years), using a modified gap-overlap task. Data were analyzed using linear mixed-effect models (LMMs). RESULTS: Individuals with WS were less likely to shift their attention to upcoming targets than TD individuals (all ages), but more likely than the ID group to do so. When they did shift attention, participants with WS and ID were slower to initiate a gaze shift than TD participants regardless of whether disengagement was needed. In the WS group, failure to shift attention was strongly predicted by higher arousal (pupil dilation), which was induced by auditory alerting cues. CONCLUSIONS: Contrasting with previous theories of attention in WS, we found no evidence for a specific challenge in disengaging attention. Instead, our results point to a more general challenge in shifting attention. Reduced attention shifting in WS may be partly explained by atypical arousal regulation. These results contribute to our understanding of the WS phenotype. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09639-z. En ligne : https://dx.doi.org/10.1186/s11689-025-09639-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : An epigenome-wide association study in the case-control study to explore early development identifies differential DNA methylation near ZFP57 as associated with autistic traits Type de document : texte imprimé Auteurs : Ellen M. HOWERTON, Auteur ; Valerie MORRILL, Auteur ; Rose SCHROTT, Auteur ; Jason DANIELS, Auteur ; Ashley Y. SONG, Auteur ; Kelly BENKE, Auteur ; Heather VOLK, Auteur ; Homayoon FARZADEGAN, Auteur ; Aimee ANIDO ALEXANDER, Auteur ; Amanda L. TAPIA, Auteur ; Gabriel S. DICHTER, Auteur ; Lisa A. CROEN, Auteur ; Lisa WIGGINS, Auteur ; Genevieve WOJCIK, Auteur ; M. Daniele FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur Langues : Anglais (eng) Mots-clés : Humans DNA Methylation/genetics Male Female Case-Control Studies Genome-Wide Association Study Autism Spectrum Disorder/genetics Child, Preschool DNA-Binding Proteins/genetics Transcription Factors/genetics Epigenome Quantitative Trait Loci Repressor Proteins Autism DNA methylation Quantitative trait Social Responsiveness Scale by the institutional review boards (IRBs) at each SEED site. SEED 1 recruitment was approved by the IRB of each recruitment site: IRB-C, CDC Human Research Protection Office Kaiser Foundation Research Institute (KFRI) Kaiser Permanente Northern California IRB, Colorado Multiple IRB, Emory University IRB, Georgia Department of Public Health IRB, Maryland Department of Health and Mental Hygiene IRB, Johns Hopkins Bloomberg School of Public Health IRB, University of North Carolina IRB and Office of Human Research Ethics, IRB of The Children’s Hospital of Philadelphia, and IRB of the University of Pennsylvania. All enrolled families provided written consent for participation. Consent for publication: Not applicable. Competing interests: CLA reports receiving consulting fees from the University of Iowa for providing expertise on epigenetics outside of this work. All other authors declare that they have no conflict of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative measures of autism spectrum disorder (ASD)-related traits can provide insight into trait presentation across the population. Previous studies have identified epigenomic variation associated with ASD diagnosis, but few have evaluated quantitative traits. We sought to identify DNA methylation patterns in child blood associated with Social Responsiveness Scale score, Second Edition (SRS). METHODS: We conducted an epigenome-wide association study of SRS in child blood at approximately age 5 in the Study to Explore Early Development, a case-control study of ASD in the United States. We measured DNA methylation using the Illumina 450K array with 857 samples in our analysis after quality control. We performed regression of the M-value to identify single sites or differentially methylated regions (DMRs) associated with SRS scores, adjusting for sources of biological and technical variation. We examined methylation quantitative trait loci and conducted gene-ontology-term pathway analyses for regions of interest. RESULTS: We identified a region about 3.5 kb upstream of ZFP57 on chromosome 6 as differentially methylated (family-wise error rate [fwer] < 0.1) by continuous SRS T-score in the full sample (N = 857; fwer = 0.074) and among ASD cases only (N = 390; fwer = 0.021). ZFP57 encodes a transcription factor involved in imprinting regulation and maintenance, and this DMR has been previously associated with ASD in brain and buccal samples. CONCLUSIONS: Blood DNA methylation near ZFP57 was associated (fwer < 0.1) with SRS in the full population sample and appears to be largely driven by trait heterogeneity within the autism case group. Our results indicate DNA methylation associations with ASD quantitative traits are observable in a population and provide insights into specific biologic changes related to autism trait heterogeneity. En ligne : https://dx.doi.org/10.1186/s11689-025-09637-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] An epigenome-wide association study in the case-control study to explore early development identifies differential DNA methylation near ZFP57 as associated with autistic traits [texte imprimé] / Ellen M. HOWERTON, Auteur ; Valerie MORRILL, Auteur ; Rose SCHROTT, Auteur ; Jason DANIELS, Auteur ; Ashley Y. SONG, Auteur ; Kelly BENKE, Auteur ; Heather VOLK, Auteur ; Homayoon FARZADEGAN, Auteur ; Aimee ANIDO ALEXANDER, Auteur ; Amanda L. TAPIA, Auteur ; Gabriel S. DICHTER, Auteur ; Lisa A. CROEN, Auteur ; Lisa WIGGINS, Auteur ; Genevieve WOJCIK, Auteur ; M. Daniele FALLIN, Auteur ; Christine LADD-ACOSTA, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans DNA Methylation/genetics Male Female Case-Control Studies Genome-Wide Association Study Autism Spectrum Disorder/genetics Child, Preschool DNA-Binding Proteins/genetics Transcription Factors/genetics Epigenome Quantitative Trait Loci Repressor Proteins Autism DNA methylation Quantitative trait Social Responsiveness Scale by the institutional review boards (IRBs) at each SEED site. SEED 1 recruitment was approved by the IRB of each recruitment site: IRB-C, CDC Human Research Protection Office Kaiser Foundation Research Institute (KFRI) Kaiser Permanente Northern California IRB, Colorado Multiple IRB, Emory University IRB, Georgia Department of Public Health IRB, Maryland Department of Health and Mental Hygiene IRB, Johns Hopkins Bloomberg School of Public Health IRB, University of North Carolina IRB and Office of Human Research Ethics, IRB of The Children’s Hospital of Philadelphia, and IRB of the University of Pennsylvania. All enrolled families provided written consent for participation. Consent for publication: Not applicable. Competing interests: CLA reports receiving consulting fees from the University of Iowa for providing expertise on epigenetics outside of this work. All other authors declare that they have no conflict of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative measures of autism spectrum disorder (ASD)-related traits can provide insight into trait presentation across the population. Previous studies have identified epigenomic variation associated with ASD diagnosis, but few have evaluated quantitative traits. We sought to identify DNA methylation patterns in child blood associated with Social Responsiveness Scale score, Second Edition (SRS). METHODS: We conducted an epigenome-wide association study of SRS in child blood at approximately age 5 in the Study to Explore Early Development, a case-control study of ASD in the United States. We measured DNA methylation using the Illumina 450K array with 857 samples in our analysis after quality control. We performed regression of the M-value to identify single sites or differentially methylated regions (DMRs) associated with SRS scores, adjusting for sources of biological and technical variation. We examined methylation quantitative trait loci and conducted gene-ontology-term pathway analyses for regions of interest. RESULTS: We identified a region about 3.5 kb upstream of ZFP57 on chromosome 6 as differentially methylated (family-wise error rate [fwer] < 0.1) by continuous SRS T-score in the full sample (N = 857; fwer = 0.074) and among ASD cases only (N = 390; fwer = 0.021). ZFP57 encodes a transcription factor involved in imprinting regulation and maintenance, and this DMR has been previously associated with ASD in brain and buccal samples. CONCLUSIONS: Blood DNA methylation near ZFP57 was associated (fwer < 0.1) with SRS in the full population sample and appears to be largely driven by trait heterogeneity within the autism case group. Our results indicate DNA methylation associations with ASD quantitative traits are observable in a population and provide insights into specific biologic changes related to autism trait heterogeneity. En ligne : https://dx.doi.org/10.1186/s11689-025-09637-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Biomarker development in Sturge-Weber syndrome Type de document : texte imprimé Auteurs : Siddharth S. GUPTA, Auteur ; Katharine E. JOSLYN, Auteur ; Kieran D. MCKENNEY, Auteur ; Anne M. COMI, Auteur Langues : Anglais (eng) Mots-clés : Humans Sturge-Weber Syndrome/diagnosis/genetics/metabolism Biomarkers/metabolism Biomarker EEG biomarkers Gnaq Mri Neurocutaneous syndrome Neuroimaging biomarkers Qeeg Sturge-Weber syndrome Urine angiogenic factor Vascular biomarkers for publication: Not applicable. Competing interests: A.M.C. is an inventor on patents related to the R183Q GNAQ mutation in SWS and to the use of cannabidiol for the treatment of SWS no funding has been received by her from these patents. The remaining authors have no conflicts of interest to disclose. Index. décimale : PER Périodiques Résumé : Sturge-Weber Syndrome (SWS) is a congenital neurovascular disorder caused by a somatic mosaic mutation in the R183Q GNAQ gene and characterized by capillary-venous malformations of the brain, skin, and eyes. Clinical manifestations include facial port-wine birthmark, glaucoma, seizures, headache or migraine, hemiparesis, stroke or stroke-like episodes, developmental delay, behavioral problems, and hormonal deficiencies. SWS requires careful monitoring, management, and early identification to improve outcome and prevent neurological deterioration. Over the last 25 years, biomarkers have been developed to improve early diagnosis and prognosis and allow for the monitoring of clinical status and treatment response. Importantly, advancements in biomarker research may enable presymptomatic treatment for infants with SWS. This review summarizes current, ongoing, and potential future SWS biomarker studies. These biomarkers, in combination with clinical data, offer a rich source of data for rare disease research leveraging machine learning in future research. En ligne : https://dx.doi.org/10.1186/s11689-025-09640-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Biomarker development in Sturge-Weber syndrome [texte imprimé] / Siddharth S. GUPTA, Auteur ; Katharine E. JOSLYN, Auteur ; Kieran D. MCKENNEY, Auteur ; Anne M. COMI, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Sturge-Weber Syndrome/diagnosis/genetics/metabolism Biomarkers/metabolism Biomarker EEG biomarkers Gnaq Mri Neurocutaneous syndrome Neuroimaging biomarkers Qeeg Sturge-Weber syndrome Urine angiogenic factor Vascular biomarkers for publication: Not applicable. Competing interests: A.M.C. is an inventor on patents related to the R183Q GNAQ mutation in SWS and to the use of cannabidiol for the treatment of SWS no funding has been received by her from these patents. The remaining authors have no conflicts of interest to disclose. Index. décimale : PER Périodiques Résumé : Sturge-Weber Syndrome (SWS) is a congenital neurovascular disorder caused by a somatic mosaic mutation in the R183Q GNAQ gene and characterized by capillary-venous malformations of the brain, skin, and eyes. Clinical manifestations include facial port-wine birthmark, glaucoma, seizures, headache or migraine, hemiparesis, stroke or stroke-like episodes, developmental delay, behavioral problems, and hormonal deficiencies. SWS requires careful monitoring, management, and early identification to improve outcome and prevent neurological deterioration. Over the last 25 years, biomarkers have been developed to improve early diagnosis and prognosis and allow for the monitoring of clinical status and treatment response. Importantly, advancements in biomarker research may enable presymptomatic treatment for infants with SWS. This review summarizes current, ongoing, and potential future SWS biomarker studies. These biomarkers, in combination with clinical data, offer a rich source of data for rare disease research leveraging machine learning in future research. En ligne : https://dx.doi.org/10.1186/s11689-025-09640-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Phenotypic variation in neural sensory processing by deletion size, age, and sex in Phelan-McDermid syndrome Type de document : texte imprimé Auteurs : Melody Reese SMITH, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Andrew THALIATH, Auteur ; Emily L. ISENSTEIN, Auteur ; Allison R. DURKIN, Auteur ; Jennifer FOSS-FEIG, Auteur ; Paige M. SIPER, Auteur ; Charles A. NELSON, Auteur ; Lauren BACZEWSKI, Auteur ; April R. LEVIN, Auteur ; Craig M. POWELL, Auteur ; Stormi L. PULVER, Auteur ; Matthew W. MOSCONI, Auteur ; Alexander KOLEVZON, Auteur ; Lauren E. ETHRIDGE, Auteur Langues : Anglais (eng) Mots-clés : Humans Female Male Adolescent Child Electroencephalography Chromosomes, Human, Pair 22/genetics Chromosome Disorders/physiopathology/genetics Chromosome Deletion Phenotype Evoked Potentials/physiology Age Factors Sensory Gating/physiology Acoustic Stimulation Brain/physiopathology Evoked Potentials, Auditory/physiology Auditory Perception/physiology Sex Factors Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare genetic condition characterized by deletion or mutation of region 22q13.3, which includes the SHANK3 gene. Clinical descriptions of this population include severely impaired or absent expressive language, mildly dysmorphic features, neonatal hypotonia, developmental delays, intellectual impairments, and autistic-like traits including abnormal reactivity to sensory stimuli. Electroencephalography (EEG) has shown promise as a tool for identifying neurophysiological abnormalities in neurodevelopmental disorders. However, few EEG studies focused on sensory processing have been performed on this population. Thus, this study focuses on comparisons of event-related potential (ERP), event-related spectral perturbation (ERSP), and inter-trial coherence (ITC) between PMS and typically developing (TD) individuals in a standard auditory gating task measuring attenuation of neural activity to repetitive auditory stimuli. METHODS: A total of 37 participants, 21 PMS (12 females, age range 8-18.6 years) and 16 TD individuals (8 females, age range 8.2-15.3 years) were included. Analysis consisted of a series of general linear models using a regional (frontal) and global (whole-head) approach to characterize neural activity between PMS and TD participants by age, sex, and group. RESULTS: Most notably, individuals with PMS had delayed or low amplitude P50, N1, and P2 responses in frontal and whole-head analyses as well as poor frontal phase-locking to auditory stimuli for alpha, beta and gamma ITC, indicating impaired processing of stimulus properties. Additionally, individuals with PMS differed from TD by age in delta, theta, and alpha power, as well as frontal beta-gamma ITC, suggesting different developmental trajectories for individuals with PMS. Within PMS, larger deletion sizes were associated with increased auditory processing abnormalities for frontal P50 as well as whole-head P50 and N1. LIMITATIONS: This is one of the largest EEG studies of PMS. However, PMS is a rare genetic condition, and our small sample has limited statistical power for subgroup comparisons. Findings should be considered exploratory. CONCLUSIONS: Results suggest that participants with PMS exhibit auditory processing abnormalities with complex variation by deletion-size, age, and sex with congruency to impaired early recognition (P50), feature processing (N1), information integration (delta, theta), sensory processing and auditory inhibition (alpha), and inhibitory modulation of repeated auditory stimuli (beta, gamma). Findings may provide valuable insight into clinical characterization of sensory and speech behaviors in future studies. En ligne : https://dx.doi.org/10.1186/s11689-025-09642-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Phenotypic variation in neural sensory processing by deletion size, age, and sex in Phelan-McDermid syndrome [texte imprimé] / Melody Reese SMITH, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Andrew THALIATH, Auteur ; Emily L. ISENSTEIN, Auteur ; Allison R. DURKIN, Auteur ; Jennifer FOSS-FEIG, Auteur ; Paige M. SIPER, Auteur ; Charles A. NELSON, Auteur ; Lauren BACZEWSKI, Auteur ; April R. LEVIN, Auteur ; Craig M. POWELL, Auteur ; Stormi L. PULVER, Auteur ; Matthew W. MOSCONI, Auteur ; Alexander KOLEVZON, Auteur ; Lauren E. ETHRIDGE, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Female Male Adolescent Child Electroencephalography Chromosomes, Human, Pair 22/genetics Chromosome Disorders/physiopathology/genetics Chromosome Deletion Phenotype Evoked Potentials/physiology Age Factors Sensory Gating/physiology Acoustic Stimulation Brain/physiopathology Evoked Potentials, Auditory/physiology Auditory Perception/physiology Sex Factors Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare genetic condition characterized by deletion or mutation of region 22q13.3, which includes the SHANK3 gene. Clinical descriptions of this population include severely impaired or absent expressive language, mildly dysmorphic features, neonatal hypotonia, developmental delays, intellectual impairments, and autistic-like traits including abnormal reactivity to sensory stimuli. Electroencephalography (EEG) has shown promise as a tool for identifying neurophysiological abnormalities in neurodevelopmental disorders. However, few EEG studies focused on sensory processing have been performed on this population. Thus, this study focuses on comparisons of event-related potential (ERP), event-related spectral perturbation (ERSP), and inter-trial coherence (ITC) between PMS and typically developing (TD) individuals in a standard auditory gating task measuring attenuation of neural activity to repetitive auditory stimuli. METHODS: A total of 37 participants, 21 PMS (12 females, age range 8-18.6 years) and 16 TD individuals (8 females, age range 8.2-15.3 years) were included. Analysis consisted of a series of general linear models using a regional (frontal) and global (whole-head) approach to characterize neural activity between PMS and TD participants by age, sex, and group. RESULTS: Most notably, individuals with PMS had delayed or low amplitude P50, N1, and P2 responses in frontal and whole-head analyses as well as poor frontal phase-locking to auditory stimuli for alpha, beta and gamma ITC, indicating impaired processing of stimulus properties. Additionally, individuals with PMS differed from TD by age in delta, theta, and alpha power, as well as frontal beta-gamma ITC, suggesting different developmental trajectories for individuals with PMS. Within PMS, larger deletion sizes were associated with increased auditory processing abnormalities for frontal P50 as well as whole-head P50 and N1. LIMITATIONS: This is one of the largest EEG studies of PMS. However, PMS is a rare genetic condition, and our small sample has limited statistical power for subgroup comparisons. Findings should be considered exploratory. CONCLUSIONS: Results suggest that participants with PMS exhibit auditory processing abnormalities with complex variation by deletion-size, age, and sex with congruency to impaired early recognition (P50), feature processing (N1), information integration (delta, theta), sensory processing and auditory inhibition (alpha), and inhibitory modulation of repeated auditory stimuli (beta, gamma). Findings may provide valuable insight into clinical characterization of sensory and speech behaviors in future studies. En ligne : https://dx.doi.org/10.1186/s11689-025-09642-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Face perception, attention, and memory as predictors of social change in autistic children Type de document : texte imprimé Auteurs : Sara Jane WEBB, Auteur ; Brian KWAN, Auteur ; Raphael BERNIER, Auteur ; Katarzyna CHARWARSKA, Auteur ; Geraldine DAWSON, Auteur ; James DZIURA, Auteur ; Susan FAJA, Auteur ; Gerhard HELLMANN, Auteur ; Shafali JESTE, Auteur ; Natalia KLEINHANS, Auteur ; April LEVIN, Auteur ; Adam NAPLES, Auteur ; Maura SABATOS-DEVITO, Auteur ; Damla SENTURK, Auteur ; Frederick SHIC, Auteur ; Catherine SUGAR, Auteur ; James C. MCPARTLAND, Auteur ; AUTISM BIOMARKERS CONSORTIUM FOR CLINICAL TRIALS, Auteur Langues : Anglais (eng) Mots-clés : Asd Biomarkers Erp Eye tracking Face memory Social attention Social cognition Social perception the Declaration of Helsinki, the study was reviewed and approved by the Yale Institutional Review Board which served as Central Institutional Review Board for the study. Written informed consent was provided by the participants' legal guardian assent was provided by the child participant. While not a clinical trial, the study was registered with ClinicalTrials.gov (NCT02996669). Consent for publication: Not applicable. Competing interests: Geraldine Dawson is on the Scientific Advisory Boards of Tris Pharma and the Nonverbal Learning Disability Project, a consultant for Apple, Inc, and receives book royalties from Guilford Press, Springer, and Oxford University Press. Shafali Jeste is a consultant for Roche Pharmaceutical Company. James C. McPartland consults or has consulted with Customer Value Partners, Bridgebio, Determined Health, Apple, and BlackThorn Therapeutics, has received research funding from Janssen Research and Development, serves on the Scientific Advisory Boards of Pastorus and Modern Clinics, and receives royalties from Guilford Press, Lambert, Oxford, and Springer. Frederick Shic is a consultant for Roche Pharmaceutical Company and Janssen Research. All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential competing interest. Index. décimale : PER Périodiques Résumé : OBJECTIVE: Social perception and attention markers have been identified that, on average, differentiate autistic from non-autistic children. However, little is known about how these markers predict behavior over time at both short and long time intervals. METHODS: We conducted a large multisite, naturalistic study of 6- to 11-year-old children diagnosed with ASD (n = 214). We evaluated three markers of social processing: social perception via the ERP N170 Latency to Upright Faces; social attention via the Eye Tracking (ET) OMI (Oculomotor Index of Gaze to Human Faces) that captures percent looking to faces from three tasks; and social cognition via the NEPSY Face Memory task. Each was evaluated in predicting social ability and autistic social behaviors derived from parental interviews and questionnaires about child behavior at + 6 months (T3) and + 4 years (T4). RESULTS: Adjusting for baseline performance, time between measurements, age, and sex, our results suggest differential prognostic relations for each of the markers. The ERP N170 Latency to Upright Faces showed limited prognostic relations, with a significant relation to short term changes in face memory. The ET OMI was related to face memory over both short and long term. Both the ET OMI and Face Memory predicted long-term autistic social behavior scores. CONCLUSIONS: In the context of a large-scale, rigorous evaluation of candidate markers for use in future clinical trials, our primary markers had significant but small-effect prognostic capability. The ET OMI and Face Memory showed significant long-term predictive relations, with increased visual attention to faces and better face memory at baseline related to increased social approach and decreased autistic social behaviors 4 years later. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09646-0. En ligne : https://dx.doi.org/10.1186/s11689-025-09646-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Face perception, attention, and memory as predictors of social change in autistic children [texte imprimé] / Sara Jane WEBB, Auteur ; Brian KWAN, Auteur ; Raphael BERNIER, Auteur ; Katarzyna CHARWARSKA, Auteur ; Geraldine DAWSON, Auteur ; James DZIURA, Auteur ; Susan FAJA, Auteur ; Gerhard HELLMANN, Auteur ; Shafali JESTE, Auteur ; Natalia KLEINHANS, Auteur ; April LEVIN, Auteur ; Adam NAPLES, Auteur ; Maura SABATOS-DEVITO, Auteur ; Damla SENTURK, Auteur ; Frederick SHIC, Auteur ; Catherine SUGAR, Auteur ; James C. MCPARTLAND, Auteur ; AUTISM BIOMARKERS CONSORTIUM FOR CLINICAL TRIALS, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Asd Biomarkers Erp Eye tracking Face memory Social attention Social cognition Social perception the Declaration of Helsinki, the study was reviewed and approved by the Yale Institutional Review Board which served as Central Institutional Review Board for the study. Written informed consent was provided by the participants' legal guardian assent was provided by the child participant. While not a clinical trial, the study was registered with ClinicalTrials.gov (NCT02996669). Consent for publication: Not applicable. Competing interests: Geraldine Dawson is on the Scientific Advisory Boards of Tris Pharma and the Nonverbal Learning Disability Project, a consultant for Apple, Inc, and receives book royalties from Guilford Press, Springer, and Oxford University Press. Shafali Jeste is a consultant for Roche Pharmaceutical Company. James C. McPartland consults or has consulted with Customer Value Partners, Bridgebio, Determined Health, Apple, and BlackThorn Therapeutics, has received research funding from Janssen Research and Development, serves on the Scientific Advisory Boards of Pastorus and Modern Clinics, and receives royalties from Guilford Press, Lambert, Oxford, and Springer. Frederick Shic is a consultant for Roche Pharmaceutical Company and Janssen Research. All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential competing interest. Index. décimale : PER Périodiques Résumé : OBJECTIVE: Social perception and attention markers have been identified that, on average, differentiate autistic from non-autistic children. However, little is known about how these markers predict behavior over time at both short and long time intervals. METHODS: We conducted a large multisite, naturalistic study of 6- to 11-year-old children diagnosed with ASD (n = 214). We evaluated three markers of social processing: social perception via the ERP N170 Latency to Upright Faces; social attention via the Eye Tracking (ET) OMI (Oculomotor Index of Gaze to Human Faces) that captures percent looking to faces from three tasks; and social cognition via the NEPSY Face Memory task. Each was evaluated in predicting social ability and autistic social behaviors derived from parental interviews and questionnaires about child behavior at + 6 months (T3) and + 4 years (T4). RESULTS: Adjusting for baseline performance, time between measurements, age, and sex, our results suggest differential prognostic relations for each of the markers. The ERP N170 Latency to Upright Faces showed limited prognostic relations, with a significant relation to short term changes in face memory. The ET OMI was related to face memory over both short and long term. Both the ET OMI and Face Memory predicted long-term autistic social behavior scores. CONCLUSIONS: In the context of a large-scale, rigorous evaluation of candidate markers for use in future clinical trials, our primary markers had significant but small-effect prognostic capability. The ET OMI and Face Memory showed significant long-term predictive relations, with increased visual attention to faces and better face memory at baseline related to increased social approach and decreased autistic social behaviors 4 years later. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09646-0. En ligne : https://dx.doi.org/10.1186/s11689-025-09646-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy Type de document : texte imprimé Auteurs : Álvaro BELTRÁN-CORBELLINI, Auteur ; Adrián VALLS-CARBÓ, Auteur ; Rafael TOLEDANO, Auteur ; Irene GARCÍA-MORALES, Auteur ; Irene SÁNCHEZ-MIRANDA ROMÁN, Auteur ; Antonio GIL-NAGEL, Auteur Langues : Anglais (eng) Mots-clés : Humans Eukaryotic Translation Initiation Factor 5A Peptide Initiation Factors/genetics Male RNA-Binding Proteins/genetics Mixed Function Oxygenases/genetics Oxidoreductases Acting on CH-NH Group Donors/genetics Female Brain Diseases/genetics Child, Preschool Lysine/analogs & derivatives Dhps Dohh Developmental and epileptic encephalopathy Dravet syndrome Eif5a Eukaryotic translation factors Febrile seizures Fenfluramine Refractory epilepsy committee waived the need for approval regarding this case report. Consent for publication: Written consent for publication was obtained from the parents of the patient. Competing interests: ABC, RT, IGM, ISMR and AGN have received support from, and served as paid consultants for UCB Pharma. AVC has no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Eukaryotic initiation factor 5 A (eIF5A) and hypusination-related disorders (eIF5A-HRD) are recently described diseases caused by pathogenic heterozygous variants in the translation factor EIF5A or biallelic variants in the two enzymes involved in the post-translational synthesis of hypusine in the eIF5A precursor, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), necessary for its activation. We review the current knowledge regarding eIF5A-HRD, and report the case of the sixth and oldest known patient with DOHH-related disorder (DOHH-D), aiming to expand and discuss the molecular basis and the general and epilepsy phenotypes of this group of diseases. RESULTS: Literature review yielded one paper describing 7 individuals with eIF5A-related disorders (eIF5A-D), one reporting 5 subjects with DHPS-related disorders (DHPS-D) and one characterizing 5 individuals with DOHH-D. Main phenotypic features consisted of prenatal issues, hypotonia, dysmorphisms, microcephaly, moderate-severe neurodevelopmental disorders/intellectual disability and behavioral disorders. We report the case of a 24-years-old male with DOHH-D manifesting as Dravet-like syndrome. He displays microcephaly and neurodevelopmental delay with attention deficit with hyperactivity disorder, along with a happy demeanor. Basic language skills and ambulation capacity with crouch gait are preserved. Onset of epilepsy was at 8 months with refractory temperature-triggered hemiclonic seizures and status epilepticus, followed by nocturnal tonic-clonic seizures from adolescence. Fenfluramine was the most effective approach, reducing seizure intensity, duration and frequency, and contributing to cognitive and behavior improvements. No patient with eIF5A-D presented seizures. Taking our patient into account, 4/5 and 4/6 reported individuals with DHPS-D and DOHH-D, respectively, presented epilepsy. Seven out of 8 epilepsy patients debuted between 2 and 5 years, most of them presented developmental and epileptic encephalopathies or generalized epilepsies (5/8 with temperature or infection-triggered seizures), and 4/8 were refractory. We hypothesize that dysregulation of IQSEC2 and SHANK3, among other genes, might contribute to the eIF5A-HRD phenotype. CONCLUSIONS: eIF5A-HRD are recently described entities displaying neurodevelopmental disorders and microcephaly, and reported patients are scarce. More than 70% of DHPS-D and DOHH-D patients present epilepsy, 63% of them with temperature-triggered seizures. Valproic acid or fenfluramine may be effective. Rare homozygous or compound heterozygous missense variants in these genes should be screened in patients with encephalopathy and temperature-triggered seizures. En ligne : https://dx.doi.org/10.1186/s11689-025-09649-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy [texte imprimé] / Álvaro BELTRÁN-CORBELLINI, Auteur ; Adrián VALLS-CARBÓ, Auteur ; Rafael TOLEDANO, Auteur ; Irene GARCÍA-MORALES, Auteur ; Irene SÁNCHEZ-MIRANDA ROMÁN, Auteur ; Antonio GIL-NAGEL, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Eukaryotic Translation Initiation Factor 5A Peptide Initiation Factors/genetics Male RNA-Binding Proteins/genetics Mixed Function Oxygenases/genetics Oxidoreductases Acting on CH-NH Group Donors/genetics Female Brain Diseases/genetics Child, Preschool Lysine/analogs & derivatives Dhps Dohh Developmental and epileptic encephalopathy Dravet syndrome Eif5a Eukaryotic translation factors Febrile seizures Fenfluramine Refractory epilepsy committee waived the need for approval regarding this case report. Consent for publication: Written consent for publication was obtained from the parents of the patient. Competing interests: ABC, RT, IGM, ISMR and AGN have received support from, and served as paid consultants for UCB Pharma. AVC has no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Eukaryotic initiation factor 5 A (eIF5A) and hypusination-related disorders (eIF5A-HRD) are recently described diseases caused by pathogenic heterozygous variants in the translation factor EIF5A or biallelic variants in the two enzymes involved in the post-translational synthesis of hypusine in the eIF5A precursor, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), necessary for its activation. We review the current knowledge regarding eIF5A-HRD, and report the case of the sixth and oldest known patient with DOHH-related disorder (DOHH-D), aiming to expand and discuss the molecular basis and the general and epilepsy phenotypes of this group of diseases. RESULTS: Literature review yielded one paper describing 7 individuals with eIF5A-related disorders (eIF5A-D), one reporting 5 subjects with DHPS-related disorders (DHPS-D) and one characterizing 5 individuals with DOHH-D. Main phenotypic features consisted of prenatal issues, hypotonia, dysmorphisms, microcephaly, moderate-severe neurodevelopmental disorders/intellectual disability and behavioral disorders. We report the case of a 24-years-old male with DOHH-D manifesting as Dravet-like syndrome. He displays microcephaly and neurodevelopmental delay with attention deficit with hyperactivity disorder, along with a happy demeanor. Basic language skills and ambulation capacity with crouch gait are preserved. Onset of epilepsy was at 8 months with refractory temperature-triggered hemiclonic seizures and status epilepticus, followed by nocturnal tonic-clonic seizures from adolescence. Fenfluramine was the most effective approach, reducing seizure intensity, duration and frequency, and contributing to cognitive and behavior improvements. No patient with eIF5A-D presented seizures. Taking our patient into account, 4/5 and 4/6 reported individuals with DHPS-D and DOHH-D, respectively, presented epilepsy. Seven out of 8 epilepsy patients debuted between 2 and 5 years, most of them presented developmental and epileptic encephalopathies or generalized epilepsies (5/8 with temperature or infection-triggered seizures), and 4/8 were refractory. We hypothesize that dysregulation of IQSEC2 and SHANK3, among other genes, might contribute to the eIF5A-HRD phenotype. CONCLUSIONS: eIF5A-HRD are recently described entities displaying neurodevelopmental disorders and microcephaly, and reported patients are scarce. More than 70% of DHPS-D and DOHH-D patients present epilepsy, 63% of them with temperature-triggered seizures. Valproic acid or fenfluramine may be effective. Rare homozygous or compound heterozygous missense variants in these genes should be screened in patients with encephalopathy and temperature-triggered seizures. En ligne : https://dx.doi.org/10.1186/s11689-025-09649-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Learning impairments in Fmr1(-/-)mice on an audio-visual temporal pattern discrimination task Type de document : texte imprimé Auteurs : William MOL, Auteur ; Sam POST, Auteur ; Megan LEE, Auteur ; Ritika THAPA, Auteur ; Michael ERICKSON, Auteur ; Anubhuti GOEL, Auteur Langues : Anglais (eng) Mots-clés : Animals Fragile X Mental Retardation Protein/genetics Mice Male Fragile X Syndrome/genetics/physiopathology Disease Models, Animal Mice, Knockout Auditory Perception/physiology Mice, Inbred C57BL Learning Disabilities/genetics/physiopathology Discrimination Learning/physiology Time Perception/physiology Acoustic Stimulation Discrimination, Psychological/physiology Visual Perception/physiology Photic Stimulation Index. décimale : PER Périodiques Résumé : Estimating time and making predictions is integral to our experience of the world. Given the importance of timing to most behaviors, disruptions in temporal processing and timed performance are reported in a number of neuropsychiatric disorders such as Schizophrenia, Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), and Attention-deficit Hyperactivity Disorder (ADHD). Symptoms that implicitly include disruption in timing are atypical turn-taking during social interactions, unusual verbal intonations, poor reading, speech and language skills, inattention, delays in learning, and difficulties making predictions. Currently, there are no viable treatments for these symptoms, the reason being the underlying neural dysfunction that contributes to timing deficits in neuropsychiatric disorders is unknown. To address this unknown, we have designed a novel Temporal Pattern Sensory Discrimination Task (TPSD) for awake-behaving mice. Stimuli consist of paired audiovisual stimuli that differ in duration. Compared to Wild-Type (WT) mice, Fmr1(-/-) mice, a well-established mouse model of FXS, showed significant impairment in learning the TPSD task, as evidenced by reduced discriminability indices and atypical licking patterns. Often sensory information is multimodal and, indeed, studies show that learning in humans and rodents improves with multimodal stimuli than with unimodal stimuli. To test how the multimodal nature of stimuli impacted performance of Fmr1(-/-) mice, following training on the audiovisual stimuli, we tested mice on audio-only or visual-only stimuli. While WT mice showed significant disruption in performance when tested on unimodal stimuli, Fmr1(-/-) mice displayed equivalent performance on visual-only stimuli when compared to the multimodal task. Our novel task captures timing difficulties and multisensory integration issues in Fmr1(-/-) mice and provides an assay to examine the associated neural dysfunction. En ligne : https://dx.doi.org/10.1186/s11689-025-09638-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Learning impairments in Fmr1(-/-)mice on an audio-visual temporal pattern discrimination task [texte imprimé] / William MOL, Auteur ; Sam POST, Auteur ; Megan LEE, Auteur ; Ritika THAPA, Auteur ; Michael ERICKSON, Auteur ; Anubhuti GOEL, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Animals Fragile X Mental Retardation Protein/genetics Mice Male Fragile X Syndrome/genetics/physiopathology Disease Models, Animal Mice, Knockout Auditory Perception/physiology Mice, Inbred C57BL Learning Disabilities/genetics/physiopathology Discrimination Learning/physiology Time Perception/physiology Acoustic Stimulation Discrimination, Psychological/physiology Visual Perception/physiology Photic Stimulation Index. décimale : PER Périodiques Résumé : Estimating time and making predictions is integral to our experience of the world. Given the importance of timing to most behaviors, disruptions in temporal processing and timed performance are reported in a number of neuropsychiatric disorders such as Schizophrenia, Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), and Attention-deficit Hyperactivity Disorder (ADHD). Symptoms that implicitly include disruption in timing are atypical turn-taking during social interactions, unusual verbal intonations, poor reading, speech and language skills, inattention, delays in learning, and difficulties making predictions. Currently, there are no viable treatments for these symptoms, the reason being the underlying neural dysfunction that contributes to timing deficits in neuropsychiatric disorders is unknown. To address this unknown, we have designed a novel Temporal Pattern Sensory Discrimination Task (TPSD) for awake-behaving mice. Stimuli consist of paired audiovisual stimuli that differ in duration. Compared to Wild-Type (WT) mice, Fmr1(-/-) mice, a well-established mouse model of FXS, showed significant impairment in learning the TPSD task, as evidenced by reduced discriminability indices and atypical licking patterns. Often sensory information is multimodal and, indeed, studies show that learning in humans and rodents improves with multimodal stimuli than with unimodal stimuli. To test how the multimodal nature of stimuli impacted performance of Fmr1(-/-) mice, following training on the audiovisual stimuli, we tested mice on audio-only or visual-only stimuli. While WT mice showed significant disruption in performance when tested on unimodal stimuli, Fmr1(-/-) mice displayed equivalent performance on visual-only stimuli when compared to the multimodal task. Our novel task captures timing difficulties and multisensory integration issues in Fmr1(-/-) mice and provides an assay to examine the associated neural dysfunction. En ligne : https://dx.doi.org/10.1186/s11689-025-09638-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Preliminary perspectives on gene therapy in fragile X syndrome: a caregiver view Type de document : texte imprimé Auteurs : Sarah E.A. ELEY, Auteur ; Sydni WEISSGOLD, Auteur ; Andrew C. STANFIELD, Auteur Langues : Anglais (eng) Mots-clés : Humans Fragile X Syndrome/therapy/genetics Genetic Therapy/psychology Caregivers/psychology Male Surveys and Questionnaires Female Adult Parents/psychology Child Middle Aged Health Knowledge, Attitudes, Practice Adolescent Fragile X syndrome Gene therapy Qualitative Questionnaire Treatment Views by Edinburgh medical school research ethics committee (EMREC) with favourable opinion granted on 25th April 2024 (REC Reference: 24-EMREC-011). Study participation was voluntary and confidential. Data collection occurred between May and July 2024. Competing interests: ACS has received grants and consultancy fees paid to the University of Edinburgh from Novartis, Roche, Shionogi, Enthorin Therapuetics and Zynerba. Index. décimale : PER Périodiques Résumé : BACKGROUND: There have been increasing numbers of clinical trials of medications for fragile X syndrome (FXS) in recent years, many targeted at proposed underlying cellular or circuit based mechanisms. As yet none of these have led to widespread changes in clinical practice. Genetic therapies represent a different therapeutic approach, which aim to address the genetic mechanisms by which FXS arises. Although not yet moving into human studies in FXS, this is an area of increasing research importance in neurodevelopmental conditions more broadly. It is important that families affected by FXS get the chance to give their views about future genetic therapies, given the potential controversies around genetic therapies. METHODS: We developed a questionnaire to capture caregiver views around gene therapy in FXS. The questionnaire was developed alongside a group of parents / caregivers of a child with FXS to ensure the language used was appropriate and that it would allow a variety of views to be captured. The questionnaire contained questions around current knowledge of gene therapy, what families think of gene therapy and their views on gene therapy trials taking place. Responses were analysed by thematic analysis carried out by two of the authors with data from the questionnaires being grouped into themes and subthemes. RESULTS: The questionnaire was completed by 195 individuals who are parents of, or who care for, someone with FXS. Respondents were primarily from the UK (60.5%) and the Americas (22.1%). The majority of dependants were male (86%). Responses showed a strong interest from the Fragile X community in gene therapy trials taking place, with themes emerging around quality of life, outcomes and feelings. Hope for positive change was balanced against caution about unintended consequences, the newness of the treatment and tolerability. CONCLUSION: Overall, caregivers felt hopeful, excited and interested in the prospect of gene therapy potentially providing a new treatment option, but there was some trepidation about the potential effects. Taking caregiver views into account will help inform decisions around the development and testing of any future genetic interventions. En ligne : https://dx.doi.org/10.1186/s11689-025-09629-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Preliminary perspectives on gene therapy in fragile X syndrome: a caregiver view [texte imprimé] / Sarah E.A. ELEY, Auteur ; Sydni WEISSGOLD, Auteur ; Andrew C. STANFIELD, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Fragile X Syndrome/therapy/genetics Genetic Therapy/psychology Caregivers/psychology Male Surveys and Questionnaires Female Adult Parents/psychology Child Middle Aged Health Knowledge, Attitudes, Practice Adolescent Fragile X syndrome Gene therapy Qualitative Questionnaire Treatment Views by Edinburgh medical school research ethics committee (EMREC) with favourable opinion granted on 25th April 2024 (REC Reference: 24-EMREC-011). Study participation was voluntary and confidential. Data collection occurred between May and July 2024. Competing interests: ACS has received grants and consultancy fees paid to the University of Edinburgh from Novartis, Roche, Shionogi, Enthorin Therapuetics and Zynerba. Index. décimale : PER Périodiques Résumé : BACKGROUND: There have been increasing numbers of clinical trials of medications for fragile X syndrome (FXS) in recent years, many targeted at proposed underlying cellular or circuit based mechanisms. As yet none of these have led to widespread changes in clinical practice. Genetic therapies represent a different therapeutic approach, which aim to address the genetic mechanisms by which FXS arises. Although not yet moving into human studies in FXS, this is an area of increasing research importance in neurodevelopmental conditions more broadly. It is important that families affected by FXS get the chance to give their views about future genetic therapies, given the potential controversies around genetic therapies. METHODS: We developed a questionnaire to capture caregiver views around gene therapy in FXS. The questionnaire was developed alongside a group of parents / caregivers of a child with FXS to ensure the language used was appropriate and that it would allow a variety of views to be captured. The questionnaire contained questions around current knowledge of gene therapy, what families think of gene therapy and their views on gene therapy trials taking place. Responses were analysed by thematic analysis carried out by two of the authors with data from the questionnaires being grouped into themes and subthemes. RESULTS: The questionnaire was completed by 195 individuals who are parents of, or who care for, someone with FXS. Respondents were primarily from the UK (60.5%) and the Americas (22.1%). The majority of dependants were male (86%). Responses showed a strong interest from the Fragile X community in gene therapy trials taking place, with themes emerging around quality of life, outcomes and feelings. Hope for positive change was balanced against caution about unintended consequences, the newness of the treatment and tolerability. CONCLUSION: Overall, caregivers felt hopeful, excited and interested in the prospect of gene therapy potentially providing a new treatment option, but there was some trepidation about the potential effects. Taking caregiver views into account will help inform decisions around the development and testing of any future genetic interventions. En ligne : https://dx.doi.org/10.1186/s11689-025-09629-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : MED13L-related disorder characterized by severe motor speech impairment Type de document : texte imprimé Auteurs : Marissa W. MITCHEL, Auteur ; Stefanie TURNER, Auteur ; Lauren K. WALSH, Auteur ; Rebecca I. TORENE, Auteur ; Scott M. MYERS, Auteur ; Cora M. TAYLOR, Auteur Langues : Anglais (eng) Mots-clés : Humans Child Male Female Adolescent Cross-Sectional Studies Child, Preschool Young Adult Mediator Complex/genetics Intellectual Disability/genetics/physiopathology Speech Disorders/genetics/physiopathology Dysarthria/physiopathology/genetics Med13l Apraxia of speech Dysarthria Motor impairment Speech disorders consent for study participation was obtained from all participants or their legal representatives. Ethics approval for this study was obtained from the Geisinger Institutional Review Board (#00008345) under protocol #2013–0446. This research was conducted in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: MED13L-related disorder is associated with intellectual disability, motor delay, and speech deficits. Previous studies have focused on broad clinical descriptions of individuals, but limited information regarding specific speech diagnoses and results of direct testing has been published to date. We conducted deep phenotyping to characterize the speech, language, motor, cognitive, and adaptive phenotypes of individuals with MED13L-related disorder. METHODS: In this cross-sectional study, we administered standardized articulation, language, motor, and cognitive testing to 17 children and adolescents (mean age 9y 9m; SD 4y 5m; range 4y 2m to 19y 7m). In-person testing was supplemented with broad developmental, medical, and behavioral information collected virtually from a cohort of 67 individuals. RESULTS: All individuals who completed in-person articulation testing met diagnostic criteria for speech apraxia, dysarthria, or both. Language impairment was present in all of the in-person cohort and reported for almost all (97%) of the virtual cohort. Those who were able to complete motor testing demonstrated significant deficits in visual motor integration (mean 57.08, SD 9.26). Full scale IQs fell in the borderline to intellectual disability range, consistent with reported cognitive impairment in 97% of the virtual cohort. Notable medical features included hypotonia (83%), vision problems (72%), recurrent otitis media (58%), gastrointestinal problems (57%), and seizures (31%). CONCLUSIONS: MED13L-related disorder is characterized by a high rate of motor speech disorders that occur in the context of globally impaired motor, language, and cognitive skills. Children would benefit from early referrals to speech therapy to assess their speech, language, and support needs. En ligne : https://dx.doi.org/10.1186/s11689-025-09645-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] MED13L-related disorder characterized by severe motor speech impairment [texte imprimé] / Marissa W. MITCHEL, Auteur ; Stefanie TURNER, Auteur ; Lauren K. WALSH, Auteur ; Rebecca I. TORENE, Auteur ; Scott M. MYERS, Auteur ; Cora M. TAYLOR, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Child Male Female Adolescent Cross-Sectional Studies Child, Preschool Young Adult Mediator Complex/genetics Intellectual Disability/genetics/physiopathology Speech Disorders/genetics/physiopathology Dysarthria/physiopathology/genetics Med13l Apraxia of speech Dysarthria Motor impairment Speech disorders consent for study participation was obtained from all participants or their legal representatives. Ethics approval for this study was obtained from the Geisinger Institutional Review Board (#00008345) under protocol #2013–0446. This research was conducted in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: MED13L-related disorder is associated with intellectual disability, motor delay, and speech deficits. Previous studies have focused on broad clinical descriptions of individuals, but limited information regarding specific speech diagnoses and results of direct testing has been published to date. We conducted deep phenotyping to characterize the speech, language, motor, cognitive, and adaptive phenotypes of individuals with MED13L-related disorder. METHODS: In this cross-sectional study, we administered standardized articulation, language, motor, and cognitive testing to 17 children and adolescents (mean age 9y 9m; SD 4y 5m; range 4y 2m to 19y 7m). In-person testing was supplemented with broad developmental, medical, and behavioral information collected virtually from a cohort of 67 individuals. RESULTS: All individuals who completed in-person articulation testing met diagnostic criteria for speech apraxia, dysarthria, or both. Language impairment was present in all of the in-person cohort and reported for almost all (97%) of the virtual cohort. Those who were able to complete motor testing demonstrated significant deficits in visual motor integration (mean 57.08, SD 9.26). Full scale IQs fell in the borderline to intellectual disability range, consistent with reported cognitive impairment in 97% of the virtual cohort. Notable medical features included hypotonia (83%), vision problems (72%), recurrent otitis media (58%), gastrointestinal problems (57%), and seizures (31%). CONCLUSIONS: MED13L-related disorder is characterized by a high rate of motor speech disorders that occur in the context of globally impaired motor, language, and cognitive skills. Children would benefit from early referrals to speech therapy to assess their speech, language, and support needs. En ligne : https://dx.doi.org/10.1186/s11689-025-09645-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : The association between infant EEG aperiodic exponent and the trajectory of restricted and repetitive behaviors for toddlers with and without autism Type de document : texte imprimé Auteurs : Haerin CHUNG, Auteur ; Alex JOB SAID, Auteur ; Helen TAGER-FLUSBERG, Auteur ; Charles A. NELSON, Auteur ; Carol L. WILKINSON, Auteur Langues : Anglais (eng) Mots-clés : Humans Infant Electroencephalography Male Female Child, Preschool Autism Spectrum Disorder/physiopathology Stereotyped Behavior/physiology Autistic Disorder/physiopathology Aperiodic exponent Autism Eeg Early development Restricted and repetitive behaviors provided by all participating families. Study procedures were approved by the Institutional Review Boards (IRB) at Boston Children’s Hospital (IRB- #P00018377, PI: Nelson & Tager-Flusberg). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviors (RRB) are core features of autism but are also observed in typical development. Our understanding of the neural underpinnings of RRBs is limited. Given that excitation-inhibition (E/I) balance may underlie RRBs, we aimed to evaluate the relationship between aperiodic exponent (as a proxy of E/I balance) and changes in RRBs over time in infants with and without elevated likelihood of autism. METHODS: Resting-state EEG data were collected from 12-to-14-month-old infants and aperiodic exponent was calculated. Parent-reported RRBs were obtained using the Repetitive Behavior Scale-Revised questionnaire to measure the severity and change in RRBs from 12-to-36 months. Multiple linear regressions were conducted to assess relationships between aperiodic and change in RRBs. RESULTS: Marginal effects analysis of linear regressions revealed significant associations such that lower aperiodic exponent was associated with elevated RRBs reported over time across the whole sample ([Formula: see text]=0.31, β= -0.21, p = 0.01), which was more prominently observed in the infants who later received an autism diagnosis (δy/δx = -15.57, p < .001). CONCLUSIONS: Results suggest that early EEG aperiodic activity may serve as a potential correlate of increased manifestation of RRBs. Longitudinal studies are needed to elucidate whether the early trajectory of aperiodic activity in development influences the severity of RRBs in childhood. En ligne : https://dx.doi.org/10.1186/s11689-025-09651-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] The association between infant EEG aperiodic exponent and the trajectory of restricted and repetitive behaviors for toddlers with and without autism [texte imprimé] / Haerin CHUNG, Auteur ; Alex JOB SAID, Auteur ; Helen TAGER-FLUSBERG, Auteur ; Charles A. NELSON, Auteur ; Carol L. WILKINSON, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Infant Electroencephalography Male Female Child, Preschool Autism Spectrum Disorder/physiopathology Stereotyped Behavior/physiology Autistic Disorder/physiopathology Aperiodic exponent Autism Eeg Early development Restricted and repetitive behaviors provided by all participating families. Study procedures were approved by the Institutional Review Boards (IRB) at Boston Children’s Hospital (IRB- #P00018377, PI: Nelson & Tager-Flusberg). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviors (RRB) are core features of autism but are also observed in typical development. Our understanding of the neural underpinnings of RRBs is limited. Given that excitation-inhibition (E/I) balance may underlie RRBs, we aimed to evaluate the relationship between aperiodic exponent (as a proxy of E/I balance) and changes in RRBs over time in infants with and without elevated likelihood of autism. METHODS: Resting-state EEG data were collected from 12-to-14-month-old infants and aperiodic exponent was calculated. Parent-reported RRBs were obtained using the Repetitive Behavior Scale-Revised questionnaire to measure the severity and change in RRBs from 12-to-36 months. Multiple linear regressions were conducted to assess relationships between aperiodic and change in RRBs. RESULTS: Marginal effects analysis of linear regressions revealed significant associations such that lower aperiodic exponent was associated with elevated RRBs reported over time across the whole sample ([Formula: see text]=0.31, β= -0.21, p = 0.01), which was more prominently observed in the infants who later received an autism diagnosis (δy/δx = -15.57, p < .001). CONCLUSIONS: Results suggest that early EEG aperiodic activity may serve as a potential correlate of increased manifestation of RRBs. Longitudinal studies are needed to elucidate whether the early trajectory of aperiodic activity in development influences the severity of RRBs in childhood. En ligne : https://dx.doi.org/10.1186/s11689-025-09651-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Patient reported outcomes that matter to individuals with (genetic) intellectual disabilities: a qualitative study Type de document : texte imprimé Auteurs : Nadia Y. VAN SILFHOUT, Auteur ; Maud M. VAN MUILEKOM, Auteur ; Clara D. VAN KARNEBEEK, Auteur ; Lotte HAVERMAN, Auteur ; Agnies M. VAN EEGHEN, Auteur Langues : Anglais (eng) Mots-clés : Genetic syndromes Intellectual disabilities Patient reported outcome measures Patient reported outcomes Review Committee of the Amsterdam UMC declared that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study and that a formal ethical approval was not necessary (W22_345 # 22.413). All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: To improve the quality of care and the impact of interventions for individuals with (genetic) intellectual disabilities ((G)ID), it is essential to identify and measure relevant patient reported outcomes (PROs), which represent patient perspective on their health and functioning. Currently, various, and potentially irrelevant PROs are being measured for individuals with (G)ID. The aim of this study is to identify relevant PROs from the perspective of different stakeholders, as one of the first steps towards development of a meaningful PRO set for children and adults with (G)ID. METHODS: A qualitative study was performed using focus groups and interviews with individuals with (G)ID, caregivers, healthcare professionals (HCPs) and European patient representatives. A focus group- and interview guide was developed including two themes: the impact of (G)ID on daily life and important topics to discuss with HCPs. Data collection took place until data sufficiency was reached. All sessions were recorded and transcribed verbatim. Transcripts were analysed by three researchers using a thematic analysis approach. PROs were classified and conceptualized (i.e., describing the content of each PRO in detail) within a conceptual framework. RESULTS: Ten focus groups and 13 interviews were conducted with a total of 51 participants. In total, seven adolescents and 10 adults with (G)ID, 12 caregivers, 13 multidisciplinary HCPs and nine European patient representatives participated. Data sufficiency was reached. PROs reported by participants were related to all health domains including physical, mental, and social functioning. Themes related to the negative impact of (G)ID were prioritized for discussion during consultations. CONCLUSIONS: This study sheds light on relevant PROs for individuals with (G)ID, marking one of the first steps in developing a meaningful PRO set for (G)ID. Once established, this set will inform care, research agendas, policymaking, and the development of a generic patient reported outcome measure (PROM) set for (G)ID, improving care quality and research impact for this complex and vulnerable population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09647-z. En ligne : https://dx.doi.org/10.1186/s11689-025-09647-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Patient reported outcomes that matter to individuals with (genetic) intellectual disabilities: a qualitative study [texte imprimé] / Nadia Y. VAN SILFHOUT, Auteur ; Maud M. VAN MUILEKOM, Auteur ; Clara D. VAN KARNEBEEK, Auteur ; Lotte HAVERMAN, Auteur ; Agnies M. VAN EEGHEN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Genetic syndromes Intellectual disabilities Patient reported outcome measures Patient reported outcomes Review Committee of the Amsterdam UMC declared that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study and that a formal ethical approval was not necessary (W22_345 # 22.413). All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: To improve the quality of care and the impact of interventions for individuals with (genetic) intellectual disabilities ((G)ID), it is essential to identify and measure relevant patient reported outcomes (PROs), which represent patient perspective on their health and functioning. Currently, various, and potentially irrelevant PROs are being measured for individuals with (G)ID. The aim of this study is to identify relevant PROs from the perspective of different stakeholders, as one of the first steps towards development of a meaningful PRO set for children and adults with (G)ID. METHODS: A qualitative study was performed using focus groups and interviews with individuals with (G)ID, caregivers, healthcare professionals (HCPs) and European patient representatives. A focus group- and interview guide was developed including two themes: the impact of (G)ID on daily life and important topics to discuss with HCPs. Data collection took place until data sufficiency was reached. All sessions were recorded and transcribed verbatim. Transcripts were analysed by three researchers using a thematic analysis approach. PROs were classified and conceptualized (i.e., describing the content of each PRO in detail) within a conceptual framework. RESULTS: Ten focus groups and 13 interviews were conducted with a total of 51 participants. In total, seven adolescents and 10 adults with (G)ID, 12 caregivers, 13 multidisciplinary HCPs and nine European patient representatives participated. Data sufficiency was reached. PROs reported by participants were related to all health domains including physical, mental, and social functioning. Themes related to the negative impact of (G)ID were prioritized for discussion during consultations. CONCLUSIONS: This study sheds light on relevant PROs for individuals with (G)ID, marking one of the first steps in developing a meaningful PRO set for (G)ID. Once established, this set will inform care, research agendas, policymaking, and the development of a generic patient reported outcome measure (PROM) set for (G)ID, improving care quality and research impact for this complex and vulnerable population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09647-z. En ligne : https://dx.doi.org/10.1186/s11689-025-09647-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Courtship and distress ultrasonic vocalizations are altered in a mouse model of Angelman syndrome Type de document : texte imprimé Auteurs : Caleigh D. GUOYNES, Auteur ; Grace PAVALKO, Auteur ; Michael S. SIDOROV, Auteur Langues : Anglais (eng) Mots-clés : Angelman syndrome Behavior Ube3a Ultrasonic vocalizations protocols were approved by and performed in accordance with the relevant guidelines and regulations of the Institutional Animal Care and Use Committee of Children’s National Hospital and were in compliance with the US National Research Council’s Guide for the Care and Use of Laboratory Animals, the US Public Health Service’s Policy on Humane Care and Use of Laboratory Animals, and Guide for the Care and Use of Laboratory Animals. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS) is a single-gene neurodevelopmental disorder caused by loss of function of the maternal copy of the UBE3A gene. Nearly all individuals with AS lack speech, resulting in major impacts on daily life for patients and caregivers. To evaluate new therapies for AS, it is crucial to have a mouse model that characterizes meaningful clinical features. Vocalizations are used in many contexts in mice, including pup retrieval, social interactions, courtship, and distress. Previous work in the Ube3a(m−/p+) mouse model of AS found abnormalities in the number of ultrasonic vocalizations (USVs) mice produced during pup isolation and same-sex social interactions. Here, we evaluated Ube3a(m−/p+) vocalizations during courtship and distress. Quantifying USVs in these contexts enables comparison of USVs in social (courtship) and non-social (distress) settings. In addition, we assessed the utility of incorporating USV testing into existing Ube3a(m−/p+) mouse behavioral assessments used to evaluate potential AS treatments. METHODS: We used multiple behavioral paradigms to evaluate courtship vocalizations and tail suspension tests to evaluate distress vocalizations in adult wild-type (WT) and Ube3a(m−/p+) littermates, and quantified USV properties using the program DeepSqueak. A subset of mice also performed an established Ube3a(m−/p+) behavioral battery that included rotarod, open field, marble burying, and nest building. We used principal component analysis to evaluate the value of USV testing in this cohort in the context of other behaviors. RESULTS: In both social courtship and nonsocial distress behavioral paradigms, Ube3a(m−/p+) mice made fewer USVs compared to WT mice. Spectral properties of USVs were abnormal in Ube3a(m−/p+) mice on courtship tests but mostly typical on distress tests. Including USVs in the Ube3a(m−/p+) mouse behavior battery increased the distance between Ube3a(m−/p+) and WT clusters in principal component space. CONCLUSIONS: Ube3a(m−/p+) mice have disrupted USV production in social and nonsocial contexts. Spectral properties of USVs are most impacted in the social courtship context. Adding USVs to the Ube3a(m−/p+) behavior battery may improve sensitivity to detect group differences and changes in communication. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09648-y. En ligne : https://dx.doi.org/10.1186/s11689-025-09648-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Courtship and distress ultrasonic vocalizations are altered in a mouse model of Angelman syndrome [texte imprimé] / Caleigh D. GUOYNES, Auteur ; Grace PAVALKO, Auteur ; Michael S. SIDOROV, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Angelman syndrome Behavior Ube3a Ultrasonic vocalizations protocols were approved by and performed in accordance with the relevant guidelines and regulations of the Institutional Animal Care and Use Committee of Children’s National Hospital and were in compliance with the US National Research Council’s Guide for the Care and Use of Laboratory Animals, the US Public Health Service’s Policy on Humane Care and Use of Laboratory Animals, and Guide for the Care and Use of Laboratory Animals. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS) is a single-gene neurodevelopmental disorder caused by loss of function of the maternal copy of the UBE3A gene. Nearly all individuals with AS lack speech, resulting in major impacts on daily life for patients and caregivers. To evaluate new therapies for AS, it is crucial to have a mouse model that characterizes meaningful clinical features. Vocalizations are used in many contexts in mice, including pup retrieval, social interactions, courtship, and distress. Previous work in the Ube3a(m−/p+) mouse model of AS found abnormalities in the number of ultrasonic vocalizations (USVs) mice produced during pup isolation and same-sex social interactions. Here, we evaluated Ube3a(m−/p+) vocalizations during courtship and distress. Quantifying USVs in these contexts enables comparison of USVs in social (courtship) and non-social (distress) settings. In addition, we assessed the utility of incorporating USV testing into existing Ube3a(m−/p+) mouse behavioral assessments used to evaluate potential AS treatments. METHODS: We used multiple behavioral paradigms to evaluate courtship vocalizations and tail suspension tests to evaluate distress vocalizations in adult wild-type (WT) and Ube3a(m−/p+) littermates, and quantified USV properties using the program DeepSqueak. A subset of mice also performed an established Ube3a(m−/p+) behavioral battery that included rotarod, open field, marble burying, and nest building. We used principal component analysis to evaluate the value of USV testing in this cohort in the context of other behaviors. RESULTS: In both social courtship and nonsocial distress behavioral paradigms, Ube3a(m−/p+) mice made fewer USVs compared to WT mice. Spectral properties of USVs were abnormal in Ube3a(m−/p+) mice on courtship tests but mostly typical on distress tests. Including USVs in the Ube3a(m−/p+) mouse behavior battery increased the distance between Ube3a(m−/p+) and WT clusters in principal component space. CONCLUSIONS: Ube3a(m−/p+) mice have disrupted USV production in social and nonsocial contexts. Spectral properties of USVs are most impacted in the social courtship context. Adding USVs to the Ube3a(m−/p+) behavior battery may improve sensitivity to detect group differences and changes in communication. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09648-y. En ligne : https://dx.doi.org/10.1186/s11689-025-09648-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : The neurodevelopmental spectrum of CASK-related disorder Type de document : texte imprimé Auteurs : Jessica MARTIN, Auteur ; Alkistis MAVROGALOU-FOTI, Auteur ; Josefine ECK, Auteur ; Laura HATTERSLEY, Auteur ; Kate BAKER, Auteur Langues : Anglais (eng) Mots-clés : Humans Child Guanylate Kinases/genetics Neurodevelopmental Disorders/genetics/physiopathology/epidemiology Male Female Adolescent Child, Preschool CASK-related disorder Adaptive function Autism characteristics Cerebral visual impairment Epilepsy Genetic Micpch Sleep difficulties X-linked intellectual disability approved by the Cambridge Central Research Ethics Committee (IRAS reference: 11/EE/0330, 'Phenotypes in Intellectual Disability'), and written informed consent was obtained from each participant’s parent/caregiver prior to inclusion. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Pathogenic CASK variants are associated with neurodevelopmental disorders of variable severity including X-linked intellectual disability (XLID) and microcephaly with pontocerebellar hypoplasia (MICPCH). Although the number of diagnosed cases is rising, current understanding of the CASK-related neurodevelopmental spectrum is limited. Here, we systematically review the published characteristics of individuals with CASK-related disorder, and compare these to a more recently-diagnosed group. We provide quantitative information about the ranges of adaptive abilities, motor function, visual function and social-emotional-behavioural characteristics, and explore within-group associations. METHODS: One hundred and fifty-one individuals with CASK variants were identified in published literature. Thirty-one children and young people with CASK variants were recruited to the UK-based Brain and Behaviour in Neurodevelopmental disorders of Genetic Origin (BINGO) project. BINGO-participating caregivers completed a bespoke medical history questionnaire and battery of standardised neurodevelopmental measures. RESULTS: Comparing the recently diagnosed BINGO CASK-related disorder group to previously reported individuals, we found consistent prevalence of tone abnormalities, sensorineural hearing loss and epilepsy, but lower prevalence of severe/profound ID, MICPCH, optic atrophy and nystagmus. Areas of frequent difficulty not highlighted in previous reports include sleep difficulties and cerebral visual impairment (CVI). Neurodevelopmental characteristics were highly variable within the BINGO CASK-related disorder group, and group-wide patterns were similar to those observed in other rare genetic conditions. Within the BINGO CASK-related group, epilepsy is significantly associated with ID severity, after controlling for age. Sub-groups with MICPCH or microcephaly only have equivalent ranges of adaptive function, but MICPCH may be associated with more severe motor difficulties. CONCLUSION: The spectrum of neurodevelopmental characteristics associated with CASK-related disorder appears to be broadening with increased access to genome-wide diagnostic testing. Further studies are needed to elucidate the relationships between CASK variants, structural brain development, epilepsy, and neurodevelopmental characteristics. En ligne : https://dx.doi.org/10.1186/s11689-025-09643-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] The neurodevelopmental spectrum of CASK-related disorder [texte imprimé] / Jessica MARTIN, Auteur ; Alkistis MAVROGALOU-FOTI, Auteur ; Josefine ECK, Auteur ; Laura HATTERSLEY, Auteur ; Kate BAKER, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Child Guanylate Kinases/genetics Neurodevelopmental Disorders/genetics/physiopathology/epidemiology Male Female Adolescent Child, Preschool CASK-related disorder Adaptive function Autism characteristics Cerebral visual impairment Epilepsy Genetic Micpch Sleep difficulties X-linked intellectual disability approved by the Cambridge Central Research Ethics Committee (IRAS reference: 11/EE/0330, 'Phenotypes in Intellectual Disability'), and written informed consent was obtained from each participant’s parent/caregiver prior to inclusion. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Pathogenic CASK variants are associated with neurodevelopmental disorders of variable severity including X-linked intellectual disability (XLID) and microcephaly with pontocerebellar hypoplasia (MICPCH). Although the number of diagnosed cases is rising, current understanding of the CASK-related neurodevelopmental spectrum is limited. Here, we systematically review the published characteristics of individuals with CASK-related disorder, and compare these to a more recently-diagnosed group. We provide quantitative information about the ranges of adaptive abilities, motor function, visual function and social-emotional-behavioural characteristics, and explore within-group associations. METHODS: One hundred and fifty-one individuals with CASK variants were identified in published literature. Thirty-one children and young people with CASK variants were recruited to the UK-based Brain and Behaviour in Neurodevelopmental disorders of Genetic Origin (BINGO) project. BINGO-participating caregivers completed a bespoke medical history questionnaire and battery of standardised neurodevelopmental measures. RESULTS: Comparing the recently diagnosed BINGO CASK-related disorder group to previously reported individuals, we found consistent prevalence of tone abnormalities, sensorineural hearing loss and epilepsy, but lower prevalence of severe/profound ID, MICPCH, optic atrophy and nystagmus. Areas of frequent difficulty not highlighted in previous reports include sleep difficulties and cerebral visual impairment (CVI). Neurodevelopmental characteristics were highly variable within the BINGO CASK-related disorder group, and group-wide patterns were similar to those observed in other rare genetic conditions. Within the BINGO CASK-related group, epilepsy is significantly associated with ID severity, after controlling for age. Sub-groups with MICPCH or microcephaly only have equivalent ranges of adaptive function, but MICPCH may be associated with more severe motor difficulties. CONCLUSION: The spectrum of neurodevelopmental characteristics associated with CASK-related disorder appears to be broadening with increased access to genome-wide diagnostic testing. Further studies are needed to elucidate the relationships between CASK variants, structural brain development, epilepsy, and neurodevelopmental characteristics. En ligne : https://dx.doi.org/10.1186/s11689-025-09643-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Clinical determinants of psychiatric care in genetic neurodevelopmental disorders: a cross-sectional analysis Type de document : texte imprimé Auteurs : David J. ADAMS, Auteur ; Alexandra M. KLOMHAUS, Auteur ; Nicole R. WONG, Auteur ; Benjamin N. SCHNEIDER, Auteur ; Charlotte DISTEFANO, Auteur ; Sunil MEHTA, Auteur ; Rujuta B. WILSON, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Shafali S. JESTE, Auteur ; Aaron D. BESTERMAN, Auteur Langues : Anglais (eng) Mots-clés : Genetic testing Multidisciplinary care Neurodevelopmental disorders Neuropsychiatry Precision medicine granted by the UCLA Medical Institutional Review Board 3. One-hundred-ten patients and/or their legal guardians provided informed consent for prospective collection of clinical data (UCLA IRB#: 14-001908). With an IRB-approved waiver of consent, the charts of an additional 206 patients were retrospectively reviewed (UCLA IRB#: 19–000121). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: This study aims to identify clinical and developmental factors associated with psychotropic medication exposure and subspecialty psychiatric service utilization among patients with genetic neurodevelopmental disorders (GNDDs). METHODS: We conducted a retrospective analysis of 316 patients from the Care and Research in Neurogenetics (CARING) Clinic at the University of California, Los Angeles (UCLA). We assessed the association between neurodevelopmental and psychiatric diagnoses, behavioral histories, family history, and service utilization with two outcomes: (1) the number of psychotropic medication classes trialed before clinic intake and (2) whether the patient was evaluated by a CARING psychiatrist. Poisson and logistic regression models were used to evaluate associations while adjusting for demographic and clinical covariates. RESULTS: Individuals with more severe behavioral disturbances had higher psychiatric service needs, while intellectual disability was associated with greater psychotropic medication exposure but not increased psychiatric consultation, possibly due to prior community-based care. The presence of a pathogenic/likely pathogenic genetic variant was not associated with either outcome, suggesting that genetic diagnosis alone does not predict psychiatric needs. Instead, behavioral comorbidities, not genetic status, were the primary drivers of psychotropic use and psychiatric referrals. A history of developmental delay was negatively associated with psychiatric consultation, and mediation analyses indicated that early intervention services partly explained this relationship. Additionally, patients receiving behavioral therapies had higher psychotropic exposure, reflecting greater clinical complexity and frequent use of multimodal treatment strategies. CONCLUSIONS: Our findings suggest that psychiatric needs in GNDDs are more closely tied to behavioral comorbidities than to genetic diagnosis status, reinforcing the importance of symptom-driven psychiatric evaluation. The observed relationship between early developmental interventions and psychiatric service utilization warrants further longitudinal investigation. These results highlight opportunities to optimize psychiatric care pathways through early screening, integrated behavioral and pharmacologic interventions, and targeted resource allocation for individuals with neurodevelopmental disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09654-0. En ligne : https://dx.doi.org/10.1186/s11689-025-09654-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Clinical determinants of psychiatric care in genetic neurodevelopmental disorders: a cross-sectional analysis [texte imprimé] / David J. ADAMS, Auteur ; Alexandra M. KLOMHAUS, Auteur ; Nicole R. WONG, Auteur ; Benjamin N. SCHNEIDER, Auteur ; Charlotte DISTEFANO, Auteur ; Sunil MEHTA, Auteur ; Rujuta B. WILSON, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Shafali S. JESTE, Auteur ; Aaron D. BESTERMAN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Genetic testing Multidisciplinary care Neurodevelopmental disorders Neuropsychiatry Precision medicine granted by the UCLA Medical Institutional Review Board 3. One-hundred-ten patients and/or their legal guardians provided informed consent for prospective collection of clinical data (UCLA IRB#: 14-001908). With an IRB-approved waiver of consent, the charts of an additional 206 patients were retrospectively reviewed (UCLA IRB#: 19–000121). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: This study aims to identify clinical and developmental factors associated with psychotropic medication exposure and subspecialty psychiatric service utilization among patients with genetic neurodevelopmental disorders (GNDDs). METHODS: We conducted a retrospective analysis of 316 patients from the Care and Research in Neurogenetics (CARING) Clinic at the University of California, Los Angeles (UCLA). We assessed the association between neurodevelopmental and psychiatric diagnoses, behavioral histories, family history, and service utilization with two outcomes: (1) the number of psychotropic medication classes trialed before clinic intake and (2) whether the patient was evaluated by a CARING psychiatrist. Poisson and logistic regression models were used to evaluate associations while adjusting for demographic and clinical covariates. RESULTS: Individuals with more severe behavioral disturbances had higher psychiatric service needs, while intellectual disability was associated with greater psychotropic medication exposure but not increased psychiatric consultation, possibly due to prior community-based care. The presence of a pathogenic/likely pathogenic genetic variant was not associated with either outcome, suggesting that genetic diagnosis alone does not predict psychiatric needs. Instead, behavioral comorbidities, not genetic status, were the primary drivers of psychotropic use and psychiatric referrals. A history of developmental delay was negatively associated with psychiatric consultation, and mediation analyses indicated that early intervention services partly explained this relationship. Additionally, patients receiving behavioral therapies had higher psychotropic exposure, reflecting greater clinical complexity and frequent use of multimodal treatment strategies. CONCLUSIONS: Our findings suggest that psychiatric needs in GNDDs are more closely tied to behavioral comorbidities than to genetic diagnosis status, reinforcing the importance of symptom-driven psychiatric evaluation. The observed relationship between early developmental interventions and psychiatric service utilization warrants further longitudinal investigation. These results highlight opportunities to optimize psychiatric care pathways through early screening, integrated behavioral and pharmacologic interventions, and targeted resource allocation for individuals with neurodevelopmental disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09654-0. En ligne : https://dx.doi.org/10.1186/s11689-025-09654-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions Type de document : texte imprimé Auteurs : Jacqueline FITZGERALD, Auteur ; Ciara J. MOLLOY, Auteur ; Thomas DINNEEN, Auteur ; Niamh E. FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Richard O'CONAILL, Auteur ; Maryam AL-SHEHHI, Auteur ; Richard REILLY, Auteur ; Sally Ann LYNCH, Auteur ; Eleisa A. HERON, Auteur ; Clare KELLY, Auteur ; Sanbing SHEN, Auteur ; Louise GALLAGHER, Auteur Langues : Anglais (eng) Mots-clés : Humans Female Male Magnetic Resonance Imaging Adult Young Adult Calcium-Binding Proteins/genetics Diffusion Tensor Imaging Brain/diagnostic imaging/physiopathology Neural Cell Adhesion Molecules/genetics Adolescent Cell Adhesion Molecules, Neuronal/genetics Cognition/physiology Neuropsychological Tests Gene Deletion Neural Pathways/diagnostic imaging/physiopathology Executive Function/physiology Cognition Copy number variant NRXN1 deletion Neuroimaging the study was obtained from St. James’s Hospital/Tallaght University Hospital Research Ethics Committee (REC reference: 2015/03/01). Participants over 18 years provided written consent and parental written consent was provided for those under 18 years. Consent for publication: All authors who contributed to the article have approved the submitted version. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: NRXN1 deletion (NRXN1 del) is a rare copy number variant associated with several neurodevelopmental, neuropsychiatric, and cognitive outcomes. The NRXN1 gene encodes for a pre-synaptic cell adhesion molecule that is important for synapse formation, regulation and neurotransmission. We used a gene-first approach to investigate neurocognitive and brain phenotypes in NRXN1 del carriers. METHODS: Forty-two participants (21 NRXN1 del carriers and 21 neurotypical age and sex-matched comparisons) completed IQ assessments, and a neurocognitive battery, including, executive function, attention, and social cognition tasks. Magnetic resonance imaging (MRI) data, including T1-weighted anatomical scans, resting state functional MRI and diffusion tensor imaging, were acquired in 36 participants (17 NRXN1 del carriers and 19 comparisons). RESULTS: NRXN1 del carriers had lower mean IQ and poorer spatial working memory performance compared to comparisons (p ≤ 0.05). Neuroimaging results revealed group differences in visual and ventral attention resting state networks (p < 0.05). Network-based statistical analysis showed a significant effect of group status for 28/115 connections, with poorer segregation between visual and default networks in NRXN1 del carriers relative to comparisons. No differences in brain structural volume or cortical thickness, or diffusion measures of white matter structural architecture were observed between groups. CONCLUSIONS: This exploratory study provides evidence for neurocognitive impacts and brain functional differences related to underlying synaptic mechanisms. Brain functional differences in NRXN1 del carriers may support altered excitation/inhibition dynamics within the brain. Gene-first approaches may establish brain-based translational markers to identify neurobiologically informed subgroups within neurodevelopmental and neuropsychiatric conditions, and ultimately transdiagnostic therapeutic strategies. En ligne : https://dx.doi.org/10.1186/s11689-025-09625-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions [texte imprimé] / Jacqueline FITZGERALD, Auteur ; Ciara J. MOLLOY, Auteur ; Thomas DINNEEN, Auteur ; Niamh E. FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Richard O'CONAILL, Auteur ; Maryam AL-SHEHHI, Auteur ; Richard REILLY, Auteur ; Sally Ann LYNCH, Auteur ; Eleisa A. HERON, Auteur ; Clare KELLY, Auteur ; Sanbing SHEN, Auteur ; Louise GALLAGHER, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Female Male Magnetic Resonance Imaging Adult Young Adult Calcium-Binding Proteins/genetics Diffusion Tensor Imaging Brain/diagnostic imaging/physiopathology Neural Cell Adhesion Molecules/genetics Adolescent Cell Adhesion Molecules, Neuronal/genetics Cognition/physiology Neuropsychological Tests Gene Deletion Neural Pathways/diagnostic imaging/physiopathology Executive Function/physiology Cognition Copy number variant NRXN1 deletion Neuroimaging the study was obtained from St. James’s Hospital/Tallaght University Hospital Research Ethics Committee (REC reference: 2015/03/01). Participants over 18 years provided written consent and parental written consent was provided for those under 18 years. Consent for publication: All authors who contributed to the article have approved the submitted version. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: NRXN1 deletion (NRXN1 del) is a rare copy number variant associated with several neurodevelopmental, neuropsychiatric, and cognitive outcomes. The NRXN1 gene encodes for a pre-synaptic cell adhesion molecule that is important for synapse formation, regulation and neurotransmission. We used a gene-first approach to investigate neurocognitive and brain phenotypes in NRXN1 del carriers. METHODS: Forty-two participants (21 NRXN1 del carriers and 21 neurotypical age and sex-matched comparisons) completed IQ assessments, and a neurocognitive battery, including, executive function, attention, and social cognition tasks. Magnetic resonance imaging (MRI) data, including T1-weighted anatomical scans, resting state functional MRI and diffusion tensor imaging, were acquired in 36 participants (17 NRXN1 del carriers and 19 comparisons). RESULTS: NRXN1 del carriers had lower mean IQ and poorer spatial working memory performance compared to comparisons (p ≤ 0.05). Neuroimaging results revealed group differences in visual and ventral attention resting state networks (p < 0.05). Network-based statistical analysis showed a significant effect of group status for 28/115 connections, with poorer segregation between visual and default networks in NRXN1 del carriers relative to comparisons. No differences in brain structural volume or cortical thickness, or diffusion measures of white matter structural architecture were observed between groups. CONCLUSIONS: This exploratory study provides evidence for neurocognitive impacts and brain functional differences related to underlying synaptic mechanisms. Brain functional differences in NRXN1 del carriers may support altered excitation/inhibition dynamics within the brain. Gene-first approaches may establish brain-based translational markers to identify neurobiologically informed subgroups within neurodevelopmental and neuropsychiatric conditions, and ultimately transdiagnostic therapeutic strategies. En ligne : https://dx.doi.org/10.1186/s11689-025-09625-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Functional connectivity patterns differ as a function of co-occurring attentional problems in preschoolers with autism Type de document : texte imprimé Auteurs : Alex BOXBERGER, Auteur ; Bosi CHEN, Auteur ; Lindsay OLSON, Auteur ; Michaela CORDOVA, Auteur ; Judy MAHMALJI, Auteur ; Adriana RIOS, Auteur ; Annika C. LINKE, Auteur ; Inna FISHMAN, Auteur Langues : Anglais (eng) Mots-clés : Humans Child, Preschool Male Female Autism Spectrum Disorder/physiopathology/diagnostic imaging/complications Attention Deficit Disorder with Hyperactivity/physiopathology/diagnostic imaging/complications/epidemiology Magnetic Resonance Imaging Infant Connectome Brain/physiopathology/diagnostic imaging Nerve Net/physiopathology/diagnostic imaging Child Development/physiology Attention Autism spectrum Early development Functional MRI Network connectivity was approved by the institutional review boards of the University of California San Diego and San Diego State University (Joint Review IRB #151091). Informed consent was obtained from caregivers of all children included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Symptoms of attention-deficit/hyperactivity disorder (ADHD) are common in children with autism spectrum disorder (ASD), and are associated with greater developmental challenges, poorer clinical outcomes, and alterations in functional connectivity (FC) of the brain. However, despite the consensus that ASD and other neurodevelopmental conditions emerge early in life, little is known about the trajectories of brain and behavioral development during the first years of life in children with ASD and co-occurring attention problems (AP). METHODS: In a sample of 122 young children (ages 1.5-5 years) with and without ASD, we examined whether toddlers and preschoolers with ASD and co-occurring AP already differ from peers with ASD without co-occurring AP on adaptive and developmental skills, ASD symptoms, and FC of the frontoparietal and salience networks, which have been previously linked to ADHD symptoms in older children with ASD and ADHD. RESULTS: Results of general linear model analyses revealed lower developmental and adaptive skills across multiple domains in children with ASD and elevated AP compared with their peers with lower AP, despite equivalent levels of ASD symptoms. Further, children with ASD and elevated AP showed reduced FC within the frontoparietal network (p = .027), between the frontoparietal and language networks (p = .004), and the frontoparietal and default mode networks (p = .046) in comparison to their peers with lower AP. No group differences in FC of the salience network were observed (all p > .05). CONCLUSIONS: These findings provide evidence that neurodevelopmental and behavioral differences in children with ASD and co-occurring AP emerge very early in life, before a reliable diagnosis of ADHD is typically made. Specifically, these results demonstrate that early inattention symptoms are associated with unique connectivity patterns in executive circuitry as early as the first years of life in toddlers and preschoolers with ASD, likely contributing to the phenotypic and neural heterogeneity recognized in autism. Thus, our results underscore the importance of considering co-occurring conditions early in developmental research and clinical care, as further understanding these trajectories can inform early interventions during the critical time period when they have the greatest potential for positive impact. En ligne : https://dx.doi.org/10.1186/s11689-025-09650-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Functional connectivity patterns differ as a function of co-occurring attentional problems in preschoolers with autism [texte imprimé] / Alex BOXBERGER, Auteur ; Bosi CHEN, Auteur ; Lindsay OLSON, Auteur ; Michaela CORDOVA, Auteur ; Judy MAHMALJI, Auteur ; Adriana RIOS, Auteur ; Annika C. LINKE, Auteur ; Inna FISHMAN, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Child, Preschool Male Female Autism Spectrum Disorder/physiopathology/diagnostic imaging/complications Attention Deficit Disorder with Hyperactivity/physiopathology/diagnostic imaging/complications/epidemiology Magnetic Resonance Imaging Infant Connectome Brain/physiopathology/diagnostic imaging Nerve Net/physiopathology/diagnostic imaging Child Development/physiology Attention Autism spectrum Early development Functional MRI Network connectivity was approved by the institutional review boards of the University of California San Diego and San Diego State University (Joint Review IRB #151091). Informed consent was obtained from caregivers of all children included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Symptoms of attention-deficit/hyperactivity disorder (ADHD) are common in children with autism spectrum disorder (ASD), and are associated with greater developmental challenges, poorer clinical outcomes, and alterations in functional connectivity (FC) of the brain. However, despite the consensus that ASD and other neurodevelopmental conditions emerge early in life, little is known about the trajectories of brain and behavioral development during the first years of life in children with ASD and co-occurring attention problems (AP). METHODS: In a sample of 122 young children (ages 1.5-5 years) with and without ASD, we examined whether toddlers and preschoolers with ASD and co-occurring AP already differ from peers with ASD without co-occurring AP on adaptive and developmental skills, ASD symptoms, and FC of the frontoparietal and salience networks, which have been previously linked to ADHD symptoms in older children with ASD and ADHD. RESULTS: Results of general linear model analyses revealed lower developmental and adaptive skills across multiple domains in children with ASD and elevated AP compared with their peers with lower AP, despite equivalent levels of ASD symptoms. Further, children with ASD and elevated AP showed reduced FC within the frontoparietal network (p = .027), between the frontoparietal and language networks (p = .004), and the frontoparietal and default mode networks (p = .046) in comparison to their peers with lower AP. No group differences in FC of the salience network were observed (all p > .05). CONCLUSIONS: These findings provide evidence that neurodevelopmental and behavioral differences in children with ASD and co-occurring AP emerge very early in life, before a reliable diagnosis of ADHD is typically made. Specifically, these results demonstrate that early inattention symptoms are associated with unique connectivity patterns in executive circuitry as early as the first years of life in toddlers and preschoolers with ASD, likely contributing to the phenotypic and neural heterogeneity recognized in autism. Thus, our results underscore the importance of considering co-occurring conditions early in developmental research and clinical care, as further understanding these trajectories can inform early interventions during the critical time period when they have the greatest potential for positive impact. En ligne : https://dx.doi.org/10.1186/s11689-025-09650-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Longitudinal characterization of clinical, developmental, and behavioral phenotypes in 101 children and adults with FOXG1 syndrome Type de document : texte imprimé Auteurs : Elise BRIMBLE, Auteur ; Pam VENTOLA, Auteur ; Elizabeth BLOMENBERG, Auteur ; Kelsey FRAHLICH, Auteur ; Kopika KUHATHAAS, Auteur ; Christopher E. HART, Auteur ; Nadia BAHI-BUISSON, Auteur ; Heather E. OLSON, Auteur ; Eric D. MARSH, Auteur ; Gai AYALON, Auteur Langues : Anglais (eng) Mots-clés : Clinical trial readiness FOXG1 syndrome Genotype-phenotype correlations Natural history studies Neurodevelopmental disorders Rare disorders Real-world data Real-world evidence guardians of study participants provided broad consent to share de-identified data for research. This study received determinations of exemption through a central institutional review board via exemption categories 2, 7, and 8 of the revised Common Rule. Consent for publication: Not applicable. Competing interests: Elise Brimble, Elizabeth Blomenberg, and Kelsey Frahlich are current employees of Citizen Health with vested and unvested stock options. Kopika Kuhathaas and Gai Ayalon are current employees of FOXG1 Research Foundation. Index. décimale : PER Périodiques Résumé : BACKGROUND: FOXG1 syndrome is a severe genetic neurodevelopmental disorder characterized by intellectual and developmental disabilities (IDD), postnatal microcephaly, epilepsy, and movement disorder. With the advent of molecular therapies, establishing the natural history of FOXG1 syndrome is critical to enable clinical trial readiness. However, traditional study designs are challenging to implement for rare disorders without significant burden to participants. METHODS: The study population included 101 children and adults with (likely) pathogenic variants in or involving FOXG1 (ages 0.4 - 34.8 years). Participant medical records underwent systematic annotation and harmonization of recorded clinical phenotypes, interventions, and outcomes through use of a patient-centric real-world data (RWD) platform. Retrospective medical record data were paired with prospective administration of validated measures of development and behavior, including the Vineland-3, the Aberrant Behavior Checklist, and the Children’s Sleep Habits Questionnaire. Descriptive and inferential statistics were employed to characterize longitudinal phenotypes and to explore genotype-phenotype correlations. RESULTS: Through systematic evaluation of 101 people with FOXG1 syndrome, we generated a robust dataset encompassing >40,000 annotated clinical terminology concepts that represent >770 cumulative patient data years. Core clinical phenotypes include IDD, gastrointestinal disorders, strabismus, epilepsy, movement disorders, and sleep problems. The FOXG1 syndrome behavioral phenotype is characterized by irritability, including aggressive behaviors, stereotypies, social withdrawal, and lethargy; in those with missense variants, features of autism spectrum disorders are also reported. Data derived from both medical records and validated measures confirm and expand upon previously described genotype-phenotype correlations, whereby truncating variants are associated with greater limitations across motor and communication domains, as well as increased frequency of core FOXG1 syndrome phenotypes. Further, individuals with truncating variants had higher scores on a composite measure of FOXG1 syndrome severity, which persists when modeled longitudinally. Employing the same composite measure, we demonstrate that FOXG1 syndrome is a static encephalopathy without evidence of neurodegeneration. CONCLUSIONS: By combining retrospective RWD with prospective survey administration in a large sample population, we establish the natural history of FOXG1 syndrome and highlight candidate clinical endpoints for use in clinical trials, including quantitative evaluations of communication and movement disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09653-1. En ligne : https://dx.doi.org/10.1186/s11689-025-09653-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Longitudinal characterization of clinical, developmental, and behavioral phenotypes in 101 children and adults with FOXG1 syndrome [texte imprimé] / Elise BRIMBLE, Auteur ; Pam VENTOLA, Auteur ; Elizabeth BLOMENBERG, Auteur ; Kelsey FRAHLICH, Auteur ; Kopika KUHATHAAS, Auteur ; Christopher E. HART, Auteur ; Nadia BAHI-BUISSON, Auteur ; Heather E. OLSON, Auteur ; Eric D. MARSH, Auteur ; Gai AYALON, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Clinical trial readiness FOXG1 syndrome Genotype-phenotype correlations Natural history studies Neurodevelopmental disorders Rare disorders Real-world data Real-world evidence guardians of study participants provided broad consent to share de-identified data for research. This study received determinations of exemption through a central institutional review board via exemption categories 2, 7, and 8 of the revised Common Rule. Consent for publication: Not applicable. Competing interests: Elise Brimble, Elizabeth Blomenberg, and Kelsey Frahlich are current employees of Citizen Health with vested and unvested stock options. Kopika Kuhathaas and Gai Ayalon are current employees of FOXG1 Research Foundation. Index. décimale : PER Périodiques Résumé : BACKGROUND: FOXG1 syndrome is a severe genetic neurodevelopmental disorder characterized by intellectual and developmental disabilities (IDD), postnatal microcephaly, epilepsy, and movement disorder. With the advent of molecular therapies, establishing the natural history of FOXG1 syndrome is critical to enable clinical trial readiness. However, traditional study designs are challenging to implement for rare disorders without significant burden to participants. METHODS: The study population included 101 children and adults with (likely) pathogenic variants in or involving FOXG1 (ages 0.4 - 34.8 years). Participant medical records underwent systematic annotation and harmonization of recorded clinical phenotypes, interventions, and outcomes through use of a patient-centric real-world data (RWD) platform. Retrospective medical record data were paired with prospective administration of validated measures of development and behavior, including the Vineland-3, the Aberrant Behavior Checklist, and the Children’s Sleep Habits Questionnaire. Descriptive and inferential statistics were employed to characterize longitudinal phenotypes and to explore genotype-phenotype correlations. RESULTS: Through systematic evaluation of 101 people with FOXG1 syndrome, we generated a robust dataset encompassing >40,000 annotated clinical terminology concepts that represent >770 cumulative patient data years. Core clinical phenotypes include IDD, gastrointestinal disorders, strabismus, epilepsy, movement disorders, and sleep problems. The FOXG1 syndrome behavioral phenotype is characterized by irritability, including aggressive behaviors, stereotypies, social withdrawal, and lethargy; in those with missense variants, features of autism spectrum disorders are also reported. Data derived from both medical records and validated measures confirm and expand upon previously described genotype-phenotype correlations, whereby truncating variants are associated with greater limitations across motor and communication domains, as well as increased frequency of core FOXG1 syndrome phenotypes. Further, individuals with truncating variants had higher scores on a composite measure of FOXG1 syndrome severity, which persists when modeled longitudinally. Employing the same composite measure, we demonstrate that FOXG1 syndrome is a static encephalopathy without evidence of neurodegeneration. CONCLUSIONS: By combining retrospective RWD with prospective survey administration in a large sample population, we establish the natural history of FOXG1 syndrome and highlight candidate clinical endpoints for use in clinical trials, including quantitative evaluations of communication and movement disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09653-1. En ligne : https://dx.doi.org/10.1186/s11689-025-09653-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Development of the Angelman syndrome video assessment: quantifying meaningful change Type de document : texte imprimé Auteurs : Kriszha A. SHEEHY, Auteur ; Mindy G. LEFFLER, Auteur ; Rebecca J. WOODS, Auteur ; Robert KOMOROWSKI, Auteur ; Rebecca CREAN, Auteur ; Christina K. ZIGLER, Auteur ; Jessica DUIS, Auteur ; Olivia BOOROM, Auteur ; Nancy BRADY, Auteur ; Lauren DEVALK, Auteur ; Nicole HARRIS, Auteur ; Amber SAPP, Auteur ; Caroline WOEBER, Auteur ; Anjali SADHWANI, Auteur ; Wen-Hann TAN, Auteur ; ASVA DELPHI PANELISTS, Auteur Langues : Anglais (eng) Mots-clés : Humans Angelman Syndrome/diagnosis/physiopathology Activities of Daily Living Video Recording Male Female Delphi Technique Child Caregivers Communication Adult Adolescent Activities of daily living Angelman syndrome Meaningful clinical outcome Neurodevelopmental Outcome measure Patient outcome assessment Patient-focused drug development Video assessment during the ASVA Pilot study, approved by the central Institutional Review Board IntegReview (Austin, TX) and the ASVA source material study (NCT05637697), approved by Advarra IRB (Pro00057202). All caregivers were legal guardians who provided written consent for themselves and subjects and received compensation for their participation. All participating Delphi panelists signed written agreements to provide consultant services for the purposes of Delphi panel, and they were provided with an honorarium for their time. Since panelists provided expert opinion through consultant services, this was not considered human subjects research. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Angelman Syndrome Video Assessment (ASVA) is a clinician-reported outcome measure that was developed to assess the functional ability of individuals with Angelman Syndrome (AS) in a familiar environment. Through standardized tasks and associated scorecards, clinicians assess four meaningful domains of functioning: communication, activities of daily living (ADLs, which include fine motor skills), gross motor, and external direction (i.e., the ability to follow directions) via scorecards with pre-established criteria. The aim of this project was to develop and refine the scorecards using a rigorous process in partnership with caregivers, clinicians, and researchers in the AS community. METHODS: The Scorecard development process included four phases: (1) video source material study, (2) identification of initial scoring criteria, (3) scorecard drafts, and (4) two (Caregiver and Clinician panel and PT panel) two-round modified Delphi processes to reach consensus. All phases were conducted remotely except for Round 2 of the Caregiver and Clinician Delphi Panel, which was conducted in person. Votes were held for each scoring criterion and consensus was defined as ≥ 70% agreement. RESULTS: In the communication, ADLs, and external direction domains, scorecard criteria reached 80 to 100% agreement among caregivers (n = 8) and clinicians (n = 2), resulting in a total of 218 scoring criteria and levels across 10 tasks. In the gross motor domain, scorecard criteria reached 100% agreement among physical therapists (n = 8) with a total of 347 scoring criteria and levels across 8 tasks. CONCLUSIONS: The ASVA was developed with insights from the AS community, including caregivers of individuals with AS, clinicians, and researchers. The ASVA is a novel, disease-specific, clinician-reported outcome measure that uses standardized video capture and scorecards that were developed through a rigorous process, resulting in well-developed criteria to quantify meaningful changes of function in individuals with AS in communication, ADLs, gross motor function, and external direction. En ligne : https://dx.doi.org/10.1186/s11689-025-09655-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Development of the Angelman syndrome video assessment: quantifying meaningful change [texte imprimé] / Kriszha A. SHEEHY, Auteur ; Mindy G. LEFFLER, Auteur ; Rebecca J. WOODS, Auteur ; Robert KOMOROWSKI, Auteur ; Rebecca CREAN, Auteur ; Christina K. ZIGLER, Auteur ; Jessica DUIS, Auteur ; Olivia BOOROM, Auteur ; Nancy BRADY, Auteur ; Lauren DEVALK, Auteur ; Nicole HARRIS, Auteur ; Amber SAPP, Auteur ; Caroline WOEBER, Auteur ; Anjali SADHWANI, Auteur ; Wen-Hann TAN, Auteur ; ASVA DELPHI PANELISTS, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Angelman Syndrome/diagnosis/physiopathology Activities of Daily Living Video Recording Male Female Delphi Technique Child Caregivers Communication Adult Adolescent Activities of daily living Angelman syndrome Meaningful clinical outcome Neurodevelopmental Outcome measure Patient outcome assessment Patient-focused drug development Video assessment during the ASVA Pilot study, approved by the central Institutional Review Board IntegReview (Austin, TX) and the ASVA source material study (NCT05637697), approved by Advarra IRB (Pro00057202). All caregivers were legal guardians who provided written consent for themselves and subjects and received compensation for their participation. All participating Delphi panelists signed written agreements to provide consultant services for the purposes of Delphi panel, and they were provided with an honorarium for their time. Since panelists provided expert opinion through consultant services, this was not considered human subjects research. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Angelman Syndrome Video Assessment (ASVA) is a clinician-reported outcome measure that was developed to assess the functional ability of individuals with Angelman Syndrome (AS) in a familiar environment. Through standardized tasks and associated scorecards, clinicians assess four meaningful domains of functioning: communication, activities of daily living (ADLs, which include fine motor skills), gross motor, and external direction (i.e., the ability to follow directions) via scorecards with pre-established criteria. The aim of this project was to develop and refine the scorecards using a rigorous process in partnership with caregivers, clinicians, and researchers in the AS community. METHODS: The Scorecard development process included four phases: (1) video source material study, (2) identification of initial scoring criteria, (3) scorecard drafts, and (4) two (Caregiver and Clinician panel and PT panel) two-round modified Delphi processes to reach consensus. All phases were conducted remotely except for Round 2 of the Caregiver and Clinician Delphi Panel, which was conducted in person. Votes were held for each scoring criterion and consensus was defined as ≥ 70% agreement. RESULTS: In the communication, ADLs, and external direction domains, scorecard criteria reached 80 to 100% agreement among caregivers (n = 8) and clinicians (n = 2), resulting in a total of 218 scoring criteria and levels across 10 tasks. In the gross motor domain, scorecard criteria reached 100% agreement among physical therapists (n = 8) with a total of 347 scoring criteria and levels across 8 tasks. CONCLUSIONS: The ASVA was developed with insights from the AS community, including caregivers of individuals with AS, clinicians, and researchers. The ASVA is a novel, disease-specific, clinician-reported outcome measure that uses standardized video capture and scorecards that were developed through a rigorous process, resulting in well-developed criteria to quantify meaningful changes of function in individuals with AS in communication, ADLs, gross motor function, and external direction. En ligne : https://dx.doi.org/10.1186/s11689-025-09655-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : The effectiveness of transcranial electrical stimulation in individuals with specific learning disorder (SLD): systematic review and transfer analysis Type de document : texte imprimé Auteurs : Vahid NEJATI, Auteur ; Fateme GHAFURI, Auteur ; Katayoon HOSSEINI, Auteur ; Roozbeh BEHROOZMAND, Auteur Langues : Anglais (eng) Mots-clés : Humans Transcranial Direct Current Stimulation/methods Learning Disabilities/therapy Transfer, Psychology/physiology Treatment Outcome Effectiveness Meta-analysis Review Specific learning disabilities (SLD) Transcranial electrical stimulation (tES) Transferability meta-analysis study do not involve human subjects hence, ethical approval and consent to participate are not applicable. Consent for publication: All authors consent to the publication of this study. Competing interests: The authors declare that there is no conflict of interest. Index. décimale : PER Périodiques Résumé : This comprehensive review aimed to investigate the transferability of transcranial electrical Stimulation (tES) interventions in individuals with specific learning disabilities (SLD) based on the FIELD model, encompassing function, implements, ecology, level, and durability. A systematic search of electronic databases yielded a total of 13 eligible studies, 11 transcranial direct current stimulation (tDCS), 1 transcranial random noise stimulation (tRNS), and 1 transcranial alternating current stimulation (tACS), encompass 286 individuals with SLD, for inclusion. The overall effect size analysis revealed positive transfer effects in all domains of FIELD, indicating the potential effectiveness of non-invasive brain stimulations (NIBS) interventions in enhancing various aspects of learning and behavior in individuals with SLD. The subgroup analysis further underscored the positive impact of age, dose, and concurrent intervention on transferability. In conclusion, this study contributes valuable insights into the transferability of tES interventions and holds promise for improving learning and behavioral outcomes in individuals with SLD. En ligne : https://dx.doi.org/10.1186/s11689-025-09623-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] The effectiveness of transcranial electrical stimulation in individuals with specific learning disorder (SLD): systematic review and transfer analysis [texte imprimé] / Vahid NEJATI, Auteur ; Fateme GHAFURI, Auteur ; Katayoon HOSSEINI, Auteur ; Roozbeh BEHROOZMAND, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Transcranial Direct Current Stimulation/methods Learning Disabilities/therapy Transfer, Psychology/physiology Treatment Outcome Effectiveness Meta-analysis Review Specific learning disabilities (SLD) Transcranial electrical stimulation (tES) Transferability meta-analysis study do not involve human subjects hence, ethical approval and consent to participate are not applicable. Consent for publication: All authors consent to the publication of this study. Competing interests: The authors declare that there is no conflict of interest. Index. décimale : PER Périodiques Résumé : This comprehensive review aimed to investigate the transferability of transcranial electrical Stimulation (tES) interventions in individuals with specific learning disabilities (SLD) based on the FIELD model, encompassing function, implements, ecology, level, and durability. A systematic search of electronic databases yielded a total of 13 eligible studies, 11 transcranial direct current stimulation (tDCS), 1 transcranial random noise stimulation (tRNS), and 1 transcranial alternating current stimulation (tACS), encompass 286 individuals with SLD, for inclusion. The overall effect size analysis revealed positive transfer effects in all domains of FIELD, indicating the potential effectiveness of non-invasive brain stimulations (NIBS) interventions in enhancing various aspects of learning and behavior in individuals with SLD. The subgroup analysis further underscored the positive impact of age, dose, and concurrent intervention on transferability. In conclusion, this study contributes valuable insights into the transferability of tES interventions and holds promise for improving learning and behavioral outcomes in individuals with SLD. En ligne : https://dx.doi.org/10.1186/s11689-025-09623-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Sex-specific and age-related progression of auditory neurophysiological deficits in the Cln3 mouse model of Batten disease Type de document : texte imprimé Auteurs : Yanya DING, Auteur ; Jingyu FENG, Auteur ; Viollandi PRIFTI, Auteur ; Grace A. RICO, Auteur ; Alexander G. SOLORZANO, Auteur ; Hayley E. CHANG, Auteur ; Edward G. FREEDMAN, Auteur ; John J. FOXE, Auteur ; Kuan Hong WANG, Auteur Langues : Anglais (eng) Mots-clés : Animals Neuronal Ceroid-Lipofuscinoses/physiopathology/genetics Disease Models, Animal Female Mice Male Disease Progression Mice, Knockout Membrane Glycoproteins/genetics Molecular Chaperones/genetics Evoked Potentials, Auditory, Brain Stem/physiology Electroencephalography Age Factors Sex Characteristics Sex Factors Auditory brainstem response (ABR) Auditory evoked potential (AEP) Duration mismatch negativity (MMN) Eeg Translational biomarker conducted in accordance with ethical standards for the care and use of animals of the University Committee on Animal Resource (UCAR) at the University of Rochester Medical Center (URMC, NY). Consent for publication: All authors are consent for publication. Competing interests: The authors declare no competing financial interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: CLN3 disease, also known as juvenile Batten disease, is a recessively inherited neurodevelopmental disorder caused by mutations in the CLN3 gene. It represents the most common form of Neuronal Ceroid Lipofuscinoses (NCLs), a group of lysosomal storage disorders that impair brain function. Clinical features include progressive vision loss, language impairment, and cognitive decline. The early onset of visual deficits complicates the neurological assessment of cognitive dysfunction, while the rarity of CLN3 cases limits the study of sex-specific disease trajectories in humans. Therefore, there is a critical need for objective, translational biomarkers to monitor disease progression and support therapeutic development in preclinical animal models. METHODS: Building on our recent studies in individuals with CLN3 disease, we developed a parallel experimental paradigm using high-density electroencephalography (EEG) in Cln3 knockout (Cln3-/-) mice to longitudinally assess auditory neurophysiological changes. We applied a duration-based mismatch negativity (MMN) paradigm, similar to that used in our human studies, to evaluate automatic detection of auditory pattern changes in male and female mice between 3 and 9 months of age. RESULTS: Wild-type (WT) mice of both sexes showed robust and stable duration MMN responses across this age range. In contrast, Cln3-/- mice showed marked sex- and age-dependent deficits: female mutants displayed persistent MMN deficits, whereas male mutants exhibited early MMN abnormalities that unexpectedly improved with age. Auditory brainstem responses confirmed intact peripheral hearing in Cln3-/- mice, indicating a central origin for the observed abnormalities. Further analyses revealed that MMN impairments were driven by age- and sex-specific alterations in auditory evoked potentials to both standard and deviant stimuli. CONCLUSIONS: These findings demonstrate sex- and age-dependent disruptions in central auditory processing in Cln3-/- mice and support auditory duration MMN as a sensitive, translational biomarker of brain dysfunction in CLN3 disease. This approach offers a functional, cross-species measure for tracking disease progression and evaluating therapeutic interventions in Batten disease. En ligne : https://dx.doi.org/10.1186/s11689-025-09652-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Sex-specific and age-related progression of auditory neurophysiological deficits in the Cln3 mouse model of Batten disease [texte imprimé] / Yanya DING, Auteur ; Jingyu FENG, Auteur ; Viollandi PRIFTI, Auteur ; Grace A. RICO, Auteur ; Alexander G. SOLORZANO, Auteur ; Hayley E. CHANG, Auteur ; Edward G. FREEDMAN, Auteur ; John J. FOXE, Auteur ; Kuan Hong WANG, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Animals Neuronal Ceroid-Lipofuscinoses/physiopathology/genetics Disease Models, Animal Female Mice Male Disease Progression Mice, Knockout Membrane Glycoproteins/genetics Molecular Chaperones/genetics Evoked Potentials, Auditory, Brain Stem/physiology Electroencephalography Age Factors Sex Characteristics Sex Factors Auditory brainstem response (ABR) Auditory evoked potential (AEP) Duration mismatch negativity (MMN) Eeg Translational biomarker conducted in accordance with ethical standards for the care and use of animals of the University Committee on Animal Resource (UCAR) at the University of Rochester Medical Center (URMC, NY). Consent for publication: All authors are consent for publication. Competing interests: The authors declare no competing financial interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: CLN3 disease, also known as juvenile Batten disease, is a recessively inherited neurodevelopmental disorder caused by mutations in the CLN3 gene. It represents the most common form of Neuronal Ceroid Lipofuscinoses (NCLs), a group of lysosomal storage disorders that impair brain function. Clinical features include progressive vision loss, language impairment, and cognitive decline. The early onset of visual deficits complicates the neurological assessment of cognitive dysfunction, while the rarity of CLN3 cases limits the study of sex-specific disease trajectories in humans. Therefore, there is a critical need for objective, translational biomarkers to monitor disease progression and support therapeutic development in preclinical animal models. METHODS: Building on our recent studies in individuals with CLN3 disease, we developed a parallel experimental paradigm using high-density electroencephalography (EEG) in Cln3 knockout (Cln3-/-) mice to longitudinally assess auditory neurophysiological changes. We applied a duration-based mismatch negativity (MMN) paradigm, similar to that used in our human studies, to evaluate automatic detection of auditory pattern changes in male and female mice between 3 and 9 months of age. RESULTS: Wild-type (WT) mice of both sexes showed robust and stable duration MMN responses across this age range. In contrast, Cln3-/- mice showed marked sex- and age-dependent deficits: female mutants displayed persistent MMN deficits, whereas male mutants exhibited early MMN abnormalities that unexpectedly improved with age. Auditory brainstem responses confirmed intact peripheral hearing in Cln3-/- mice, indicating a central origin for the observed abnormalities. Further analyses revealed that MMN impairments were driven by age- and sex-specific alterations in auditory evoked potentials to both standard and deviant stimuli. CONCLUSIONS: These findings demonstrate sex- and age-dependent disruptions in central auditory processing in Cln3-/- mice and support auditory duration MMN as a sensitive, translational biomarker of brain dysfunction in CLN3 disease. This approach offers a functional, cross-species measure for tracking disease progression and evaluating therapeutic interventions in Batten disease. En ligne : https://dx.doi.org/10.1186/s11689-025-09652-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study Type de document : texte imprimé Auteurs : Elizabeth BERRY-KRAVIS, Auteur ; Randi HAGERMAN, Auteur ; Jonathan COHEN, Auteur ; Dejan BUDIMIROVIC, Auteur ; Caroline B. BUCHANAN, Auteur ; Natalie SILOVE, Auteur ; Nancy TICH, Auteur ; Anthony THIBODEAU, Auteur ; Thomas DOBBINS, Auteur ; Terri SEBREE, Auteur ; Stephen O'QUINN, Auteur ; David S. ALBERS, Auteur ; Kristen G. BZDEK, Auteur ; George NOMIKOS, Auteur ; Kumar BUDUR, Auteur Langues : Anglais (eng) Mots-clés : Humans Fragile X Syndrome/drug therapy Adolescent Child Male Administration, Cutaneous Cannabidiol/administration & dosage/adverse effects Female Gels Child, Preschool Endocannabinoid system Fragile x syndrome Irritability Social avoidance Transdermal cannabidiol conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and was approved by Advarra, Inc. Institutional Review Board (IRB Approval Number: Pro00060799. Consent for publication: Not applicable. Competing interests: EB-K, RH, JC, DB, CBB, and NS have received funding from Harmony Biosciences for the conduct of this trial as investigators. TD, TS, and SOQ are paid consultants of Harmony Biosciences. CBB is a paid consultant of Acadia Pharmaceuticals. NT, AT, DSA, KGB, GN, and KB are employees of Harmony Biosciences. Index. décimale : PER Périodiques Résumé : BACKGROUND: Dysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS. DESIGN: ZYN2-CL-017 is an ongoing, long-term, open-label extension (OLE) safety trial of ZYN002 in patients with FXS. We are enrolling patients from past and current ZYN002 clinical trials to evaluate the safety and tolerability of ZYN002 in patients with FXS. METHODS: Primary safety assessments were conducted in patients who enrolled into the OLE from 2 completed ZYN002 trials. Secondary analyses, conducted in a subgroup enrolled from a completed placebo-controlled trial of ZYN002, included the FXS-specific Aberrant Behavior Checklist-Community Social Avoidance and Irritability subscales (ABC-C(FXS) SA and ABC-C(FXS) Irr, examined change from baseline of the randomized study) and the Caregiver Global Impression of Change (CaGI-C, examined change from baseline of the OLE), in which caregivers were asked to rate the change in their child's overall behavior. RESULTS: At the time of this interim analysis data cut (January 31, 2024), 240 patients had been enrolled from 2 completed ZYN002 trials. Mean age at entry to the OLE was 9.7 years (range 3-17 years), and the majority were male (76.3%) and White (80.4%). Mean exposure to ZYN002 during the initial trials and OLE was 28 months. Treatment-related adverse events (AEs) were reported in 12.9% of patients; the most common (6.7% of patients) was short-term application site pain. The highest degree of skin irritation reported by investigators was moderate erythema in 7 patients (2.9%). In the secondary analysis cohort (n=196 evaluable patients), patients demonstrated clinically meaningful changes in ABC-C(FXS) SA, ABC-C(FXS) Irr, and CaGI-C scores. CONCLUSIONS: Interim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS. TRIAL REGISTRATION: ZYN2-CL-017 is registered on Clinicaltrials.gov (NCT03802799) on December 26, 2018. En ligne : https://dx.doi.org/10.1186/s11689-025-09657-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study [texte imprimé] / Elizabeth BERRY-KRAVIS, Auteur ; Randi HAGERMAN, Auteur ; Jonathan COHEN, Auteur ; Dejan BUDIMIROVIC, Auteur ; Caroline B. BUCHANAN, Auteur ; Natalie SILOVE, Auteur ; Nancy TICH, Auteur ; Anthony THIBODEAU, Auteur ; Thomas DOBBINS, Auteur ; Terri SEBREE, Auteur ; Stephen O'QUINN, Auteur ; David S. ALBERS, Auteur ; Kristen G. BZDEK, Auteur ; George NOMIKOS, Auteur ; Kumar BUDUR, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Fragile X Syndrome/drug therapy Adolescent Child Male Administration, Cutaneous Cannabidiol/administration & dosage/adverse effects Female Gels Child, Preschool Endocannabinoid system Fragile x syndrome Irritability Social avoidance Transdermal cannabidiol conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and was approved by Advarra, Inc. Institutional Review Board (IRB Approval Number: Pro00060799. Consent for publication: Not applicable. Competing interests: EB-K, RH, JC, DB, CBB, and NS have received funding from Harmony Biosciences for the conduct of this trial as investigators. TD, TS, and SOQ are paid consultants of Harmony Biosciences. CBB is a paid consultant of Acadia Pharmaceuticals. NT, AT, DSA, KGB, GN, and KB are employees of Harmony Biosciences. Index. décimale : PER Périodiques Résumé : BACKGROUND: Dysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS. DESIGN: ZYN2-CL-017 is an ongoing, long-term, open-label extension (OLE) safety trial of ZYN002 in patients with FXS. We are enrolling patients from past and current ZYN002 clinical trials to evaluate the safety and tolerability of ZYN002 in patients with FXS. METHODS: Primary safety assessments were conducted in patients who enrolled into the OLE from 2 completed ZYN002 trials. Secondary analyses, conducted in a subgroup enrolled from a completed placebo-controlled trial of ZYN002, included the FXS-specific Aberrant Behavior Checklist-Community Social Avoidance and Irritability subscales (ABC-C(FXS) SA and ABC-C(FXS) Irr, examined change from baseline of the randomized study) and the Caregiver Global Impression of Change (CaGI-C, examined change from baseline of the OLE), in which caregivers were asked to rate the change in their child's overall behavior. RESULTS: At the time of this interim analysis data cut (January 31, 2024), 240 patients had been enrolled from 2 completed ZYN002 trials. Mean age at entry to the OLE was 9.7 years (range 3-17 years), and the majority were male (76.3%) and White (80.4%). Mean exposure to ZYN002 during the initial trials and OLE was 28 months. Treatment-related adverse events (AEs) were reported in 12.9% of patients; the most common (6.7% of patients) was short-term application site pain. The highest degree of skin irritation reported by investigators was moderate erythema in 7 patients (2.9%). In the secondary analysis cohort (n=196 evaluable patients), patients demonstrated clinically meaningful changes in ABC-C(FXS) SA, ABC-C(FXS) Irr, and CaGI-C scores. CONCLUSIONS: Interim analysis results of the ongoing OLE in children, adolescents, and young adults with FXS demonstrated that ZYN002 has a favorable long-term safety profile and is generally well tolerated. Clinically meaningful changes in behaviors from baseline continued to be observed during the OLE. These findings support further study of ZYN002 in patients with FXS. TRIAL REGISTRATION: ZYN2-CL-017 is registered on Clinicaltrials.gov (NCT03802799) on December 26, 2018. En ligne : https://dx.doi.org/10.1186/s11689-025-09657-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : A neural substrate for sensory over-responsivity defined by exogenous and endogenous brain systems Type de document : texte imprimé Auteurs : Hannah L. CHOI, Auteur ; Maia C. LAZERWITZ, Auteur ; Rachel POWERS, Auteur ; Mikaela ROWE, Auteur ; Jamie WREN-JARVIS, Auteur ; Amir SADIKOV, Auteur ; Lanya T. CAI, Auteur ; Robyn CHU, Auteur ; LaShelle RULLAN, Auteur ; Kaitlyn J. TRIMARCHI, Auteur ; Rafael D. GARCIA, Auteur ; Elysa J. MARCO, Auteur ; Pratik MUKHERJEE, Auteur Langues : Anglais (eng) Mots-clés : Emotional regulation Functional MRI connectivity Multimodal neuroimaging Neurodevelopment Resilience Sensory over-responsivity Sensory processing disorder involving behavioral and neuroimaging data collection of human participants between ages 8–12 years old was approved by the UCSF institutional review board. Written informed consent from the parent or caregiver and assent from the participant were collected. Consent for publication: All authors have provided approval of the manuscript. This work was made publicly available as a preprint uploaded to PsyArXiv at this link: https://osf.io/preprints/psyarxiv/ajs9w_v1 prior to publishing. It has not been published elsewhere. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Exogenous (outward-directed) and endogenous (inward-directed) neural systems are essential for cognition and behavior. However, how they are altered in neurodiverse (ND) children remains unanswered in part due to heterogeneity. Sensory over-responsivity (SOR), the most prevalent form of sensory processing disorder (SPD), serves as a quintessential paradigm for investigating the interaction between exogenous and endogenous brain networks given that both basic and higher-order sensory processing are substantially implicated in this condition. METHODS: Neurodiverse children ages 8–12 years old (n = 83; 30 females and 53 males) were directly assessed for SOR using a structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment (SP3D:A), and underwent 3 Tesla MRI. 39 ND children presented with SOR (ND/SOR) and 44 ND children presented without SOR (ND/NO-SOR). Exogenous and endogenous functional connectivity networks (FCNs) were generated through independent component analysis and investigated with two local functional connectivity (FC) measures, fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo), as well as a long-range FC measure, dual regression (DR). Moreover, we examined FC in the context of behavioral regulation as assessed through the Behavioral Assessment System for Children, 3rd edition (BASC-3), categorizing children as "resilient" or "dysregulated" through latent profile analysis. RESULTS: In general, ND/SOR children exhibit reduced long-range exogenous FC. However, in terms of local FC, we find that ND/SOR children have reduced exogenous and elevated endogenous FC which is diametrically opposed to ND/NO-SOR children. Furthermore, this double dissociation is specific to ND children who are behaviorally resilient, while emotionally dysregulated ND children possess a distinct pattern. CONCLUSION: Achieving optimal brain system connectivity—a balanced contrast—is influenced by sensory over-responsivity and essential for resilience. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09656-y. En ligne : https://dx.doi.org/10.1186/s11689-025-09656-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] A neural substrate for sensory over-responsivity defined by exogenous and endogenous brain systems [texte imprimé] / Hannah L. CHOI, Auteur ; Maia C. LAZERWITZ, Auteur ; Rachel POWERS, Auteur ; Mikaela ROWE, Auteur ; Jamie WREN-JARVIS, Auteur ; Amir SADIKOV, Auteur ; Lanya T. CAI, Auteur ; Robyn CHU, Auteur ; LaShelle RULLAN, Auteur ; Kaitlyn J. TRIMARCHI, Auteur ; Rafael D. GARCIA, Auteur ; Elysa J. MARCO, Auteur ; Pratik MUKHERJEE, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Emotional regulation Functional MRI connectivity Multimodal neuroimaging Neurodevelopment Resilience Sensory over-responsivity Sensory processing disorder involving behavioral and neuroimaging data collection of human participants between ages 8–12 years old was approved by the UCSF institutional review board. Written informed consent from the parent or caregiver and assent from the participant were collected. Consent for publication: All authors have provided approval of the manuscript. This work was made publicly available as a preprint uploaded to PsyArXiv at this link: https://osf.io/preprints/psyarxiv/ajs9w_v1 prior to publishing. It has not been published elsewhere. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Exogenous (outward-directed) and endogenous (inward-directed) neural systems are essential for cognition and behavior. However, how they are altered in neurodiverse (ND) children remains unanswered in part due to heterogeneity. Sensory over-responsivity (SOR), the most prevalent form of sensory processing disorder (SPD), serves as a quintessential paradigm for investigating the interaction between exogenous and endogenous brain networks given that both basic and higher-order sensory processing are substantially implicated in this condition. METHODS: Neurodiverse children ages 8–12 years old (n = 83; 30 females and 53 males) were directly assessed for SOR using a structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment (SP3D:A), and underwent 3 Tesla MRI. 39 ND children presented with SOR (ND/SOR) and 44 ND children presented without SOR (ND/NO-SOR). Exogenous and endogenous functional connectivity networks (FCNs) were generated through independent component analysis and investigated with two local functional connectivity (FC) measures, fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo), as well as a long-range FC measure, dual regression (DR). Moreover, we examined FC in the context of behavioral regulation as assessed through the Behavioral Assessment System for Children, 3rd edition (BASC-3), categorizing children as "resilient" or "dysregulated" through latent profile analysis. RESULTS: In general, ND/SOR children exhibit reduced long-range exogenous FC. However, in terms of local FC, we find that ND/SOR children have reduced exogenous and elevated endogenous FC which is diametrically opposed to ND/NO-SOR children. Furthermore, this double dissociation is specific to ND children who are behaviorally resilient, while emotionally dysregulated ND children possess a distinct pattern. CONCLUSION: Achieving optimal brain system connectivity—a balanced contrast—is influenced by sensory over-responsivity and essential for resilience. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-025-09656-y. En ligne : https://dx.doi.org/10.1186/s11689-025-09656-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
Titre : Neurodevelopmental delays in children born after medically assisted reproduction: a national population cohort study Type de document : texte imprimé Auteurs : Seung-Ah CHOE, Auteur ; Eunseon GWAK, Auteur ; Juyoung LEE, Auteur ; Jung Hye BYEON, Auteur ; Ju-Young SHIN, Auteur ; Seungbong HAN, Auteur ; Jee Hyun KIM, Auteur Langues : Anglais (eng) Mots-clés : Humans Female Adult Retrospective Studies Republic of Korea/epidemiology Fertilization in Vitro/statistics & numerical data/adverse effects Neurodevelopmental Disorders/epidemiology/etiology Male Young Adult Incidence Child, Preschool Reproductive Techniques, Assisted/statistics & numerical data/adverse effects Infertility, Female/therapy/epidemiology Middle Aged Cohort Studies Infant, Newborn Developmental Disabilities/epidemiology Child Assisted reproduction Developmental screening test Neurodevelopment was anonymous, the protocol of this study was reviewed and exempted from ethical approval (exemption No. KUIRB-2024-0053-01). Consent to participate was not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Importance: The neurodevelopmental outcomes of children born after medically assisted reproduction remain incompletely characterized on a population level. We were to assess the incidence and relative risk of neurodevelopmental delay in the children of infertile women born after unassisted conception, intrauterine insemination (IUI), and in vitro fertilization (IVF). METHOD: We conducted a retrospective cohort study using the National Health Insurance Service database of South Korea from October 2017 through December 2023. The study included 115 839 singleton, full-term, non-low-birthweight children born to women aged 20-49 years with a diagnosis of female infertility. The exposure was mode of conception-spontaneous, IUI, or IVF-balanced by propensity score matching on preconceptional maternal factors. Outcome measure was neurodevelopmental delay, defined as scoring below the cutoff in any of six functional domains on the Korean Developmental Screening Test across six consecutive rounds. Crude incidence rate ratios (IRRs) and adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models. RESULTS: Among 115 839 children, 6 575 (5.7%) exhibited delay in at least one domain. Crude IRRs for any delay were 1.19 (95% confidence interval [CI]: 1.07, 1.61) for IUI and 1.10 (95% CI: 1.03, 1.17) for IVF versus unassisted conception. In the survival models, higher risks persisted for both IUI (aHR = 1.19; 95% CI: 1.06, 1.34) and IVF (1.09, 95% CI: 1.02, 1.06) compared with unassisted conception. When comparing IVF and IUI, IVF conferred a lower risk of fine motor delay than IUI (0.84, 95% CI: 0.72, 0.99). Among IVF births, risk of developmental delay was similar across all six domains for frozen and fresh embryo transfers. CONCLUSIONS: Children conceived via IUI or IVF demonstrated a modest but significant increase in screen-positive neurodevelopmental delay compared with those conceived spontaneously. These findings highlight the need for neurodevelopmental monitoring in this population. En ligne : https://dx.doi.org/10.1186/s11689-025-09658-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
in Journal of Neurodevelopmental Disorders > 17 (2025)[article] Neurodevelopmental delays in children born after medically assisted reproduction: a national population cohort study [texte imprimé] / Seung-Ah CHOE, Auteur ; Eunseon GWAK, Auteur ; Juyoung LEE, Auteur ; Jung Hye BYEON, Auteur ; Ju-Young SHIN, Auteur ; Seungbong HAN, Auteur ; Jee Hyun KIM, Auteur.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 17 (2025)
Mots-clés : Humans Female Adult Retrospective Studies Republic of Korea/epidemiology Fertilization in Vitro/statistics & numerical data/adverse effects Neurodevelopmental Disorders/epidemiology/etiology Male Young Adult Incidence Child, Preschool Reproductive Techniques, Assisted/statistics & numerical data/adverse effects Infertility, Female/therapy/epidemiology Middle Aged Cohort Studies Infant, Newborn Developmental Disabilities/epidemiology Child Assisted reproduction Developmental screening test Neurodevelopment was anonymous, the protocol of this study was reviewed and exempted from ethical approval (exemption No. KUIRB-2024-0053-01). Consent to participate was not applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Importance: The neurodevelopmental outcomes of children born after medically assisted reproduction remain incompletely characterized on a population level. We were to assess the incidence and relative risk of neurodevelopmental delay in the children of infertile women born after unassisted conception, intrauterine insemination (IUI), and in vitro fertilization (IVF). METHOD: We conducted a retrospective cohort study using the National Health Insurance Service database of South Korea from October 2017 through December 2023. The study included 115 839 singleton, full-term, non-low-birthweight children born to women aged 20-49 years with a diagnosis of female infertility. The exposure was mode of conception-spontaneous, IUI, or IVF-balanced by propensity score matching on preconceptional maternal factors. Outcome measure was neurodevelopmental delay, defined as scoring below the cutoff in any of six functional domains on the Korean Developmental Screening Test across six consecutive rounds. Crude incidence rate ratios (IRRs) and adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models. RESULTS: Among 115 839 children, 6 575 (5.7%) exhibited delay in at least one domain. Crude IRRs for any delay were 1.19 (95% confidence interval [CI]: 1.07, 1.61) for IUI and 1.10 (95% CI: 1.03, 1.17) for IVF versus unassisted conception. In the survival models, higher risks persisted for both IUI (aHR = 1.19; 95% CI: 1.06, 1.34) and IVF (1.09, 95% CI: 1.02, 1.06) compared with unassisted conception. When comparing IVF and IUI, IVF conferred a lower risk of fine motor delay than IUI (0.84, 95% CI: 0.72, 0.99). Among IVF births, risk of developmental delay was similar across all six domains for frozen and fresh embryo transfers. CONCLUSIONS: Children conceived via IUI or IVF demonstrated a modest but significant increase in screen-positive neurodevelopmental delay compared with those conceived spontaneously. These findings highlight the need for neurodevelopmental monitoring in this population. En ligne : https://dx.doi.org/10.1186/s11689-025-09658-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576
