Distinct patterns of GABAergic interneuron pathology in autism are associated with intellectual impairment and stereotypic behaviors / Brett D. DUFOUR in Autism, 27-6 (August 2023)  

Public ISBD [article]  inAutism > 27-6 (August 2023) . - p.1730-1745 Titre : Distinct patterns of GABAergic interneuron pathology in autism are associated with intellectual impairment and stereotypic behaviors Type de document : texte imprimé Auteurs : Brett D. DUFOUR, Auteur ; Erin MCBRIDE, Auteur ; Trevor BARTLEY, Auteur ; A. Pablo JUAREZ, Auteur ; Verónica MARTÍNEZ-CERDEÑO, Auteur Article en page(s) : p.1730-1745 Langues : Anglais (eng) Mots-clés : autism;behavior;human;interneuron;postmortem Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. How specific anatomical alterations contribute to the clinical profile of autism spectrum disorder remains largely uncharacterized. We have previously shown that parvalbumin-positive Chandelier cells, a specific type of GABAergic interneuron, are reduced in number in the autism spectrum disorder prefrontal cortex. Here, we assessed the relationship between interneuron pathology with autism spectrum disorder symptom severity and comorbidity. We collected clinical records from autism (n=20) and control (n=19) brain donors, from whom we previously characterized GABAergic interneuron pathology in three regions of the prefrontal cortex (BA9, 46, and 47). We assessed the relationship between the severity of core symptoms, as indicated by Autism Diagnostic Interview-Revised scores, and Chandelier cell pathology in autism spectrum disorder, and also differences in interneuron pathology associated with autism spectrum disorder comorbidities. Total GABAergic interneuron number was significantly reduced in autism spectrum disorder cases with intellectual disability in the prefrontal cortex (PFC )-by 36.6% relative to autism spectrum disorder without intellectual disability and by 38.7% relative to neurotypical controls. The severity of autism spectrum disorder motor stereotypies was correlated with the severity of Chandelier cell loss in BA47, as indicated by reductions in parvalbumin+ interneurons and GABA transporter 1+ cartridges. Chandelier cell loss is associated with the core autism spectrum disorder symptom domain of restricted repetitive behaviors and likely plays a role in stereotypic motor mannerisms. Intellectual impairment in autism spectrum disorder reflects a more severe form of a common underlying neuropathology-cortical GABAergic interneuron loss.Lay AbstractAutism spectrum disorder is a neurodevelopmental condition characterized by deficits in sociability and communication and the presence of repetitive behaviors. How specific pathological alterations of the brain contribute to the clinical profile of autism spectrum disorder remains unknown. We previously found that a specific type of inhibitory interneuron is reduced in number in the autism spectrum disorder prefrontal cortex. Here, we assessed the relationship between interneuron reduction and autism spectrum disorder symptom severity. We collected clinical records from autism spectrum disorder (n=20) and assessed the relationship between the severity of symptoms and interneuron number. We found that the reduced number of inhibitory interneurons that we previously reported is linked to specific symptoms of autism spectrum disorder, particularly stereotypic movements and intellectual impairments. En ligne : http://dx.doi.org/10.1177/13623613231154053 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=509 [article] Distinct patterns of GABAergic interneuron pathology in autism are associated with intellectual impairment and stereotypic behaviors [texte imprimé] / Brett D. DUFOUR, Auteur ; Erin MCBRIDE, Auteur ; Trevor BARTLEY, Auteur ; A. Pablo JUAREZ, Auteur ; Verónica MARTÍNEZ-CERDEÑO, Auteur . - p.1730-1745. Langues : Anglais (eng) in Autism > 27-6 (August 2023) . - p.1730-1745 Mots-clés : autism;behavior;human;interneuron;postmortem Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. How specific anatomical alterations contribute to the clinical profile of autism spectrum disorder remains largely uncharacterized. We have previously shown that parvalbumin-positive Chandelier cells, a specific type of GABAergic interneuron, are reduced in number in the autism spectrum disorder prefrontal cortex. Here, we assessed the relationship between interneuron pathology with autism spectrum disorder symptom severity and comorbidity. We collected clinical records from autism (n=20) and control (n=19) brain donors, from whom we previously characterized GABAergic interneuron pathology in three regions of the prefrontal cortex (BA9, 46, and 47). We assessed the relationship between the severity of core symptoms, as indicated by Autism Diagnostic Interview-Revised scores, and Chandelier cell pathology in autism spectrum disorder, and also differences in interneuron pathology associated with autism spectrum disorder comorbidities. Total GABAergic interneuron number was significantly reduced in autism spectrum disorder cases with intellectual disability in the prefrontal cortex (PFC )-by 36.6% relative to autism spectrum disorder without intellectual disability and by 38.7% relative to neurotypical controls. The severity of autism spectrum disorder motor stereotypies was correlated with the severity of Chandelier cell loss in BA47, as indicated by reductions in parvalbumin+ interneurons and GABA transporter 1+ cartridges. Chandelier cell loss is associated with the core autism spectrum disorder symptom domain of restricted repetitive behaviors and likely plays a role in stereotypic motor mannerisms. Intellectual impairment in autism spectrum disorder reflects a more severe form of a common underlying neuropathology-cortical GABAergic interneuron loss.Lay AbstractAutism spectrum disorder is a neurodevelopmental condition characterized by deficits in sociability and communication and the presence of repetitive behaviors. How specific pathological alterations of the brain contribute to the clinical profile of autism spectrum disorder remains unknown. We previously found that a specific type of inhibitory interneuron is reduced in number in the autism spectrum disorder prefrontal cortex. Here, we assessed the relationship between interneuron reduction and autism spectrum disorder symptom severity. We collected clinical records from autism spectrum disorder (n=20) and assessed the relationship between the severity of symptoms and interneuron number. We found that the reduced number of inhibitory interneurons that we previously reported is linked to specific symptoms of autism spectrum disorder, particularly stereotypic movements and intellectual impairments. En ligne : http://dx.doi.org/10.1177/13623613231154053 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=509

Hypothalamic volume is associated with dysregulated sleep in autistic and non-autistic young children / Burt HATCH in Autism, 29-11 (November 2025)  

Public ISBD [article]  inAutism > 29-11 (November 2025) . - p.2885-2897 Titre : Hypothalamic volume is associated with dysregulated sleep in autistic and non-autistic young children Type de document : texte imprimé Auteurs : Burt HATCH, Auteur ; Derek S. ANDREWS, Auteur ; Brett D. DUFOUR, Auteur ; Shayan M. ALAVYNEJAD, Auteur ; Joshua K. LEE, Auteur ; Sally J. ROGERS, Auteur ; Marjorie SOLOMON, Auteur ; Meghan MILLER, Auteur ; Christine W. NORDAHL, Auteur Article en page(s) : p.2885-2897 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  externalizing  hypothalamus  internalizing  MRI  sleep Index. décimale : PER Périodiques Résumé : Difficulty initiating or maintaining sleep is common among autistic individuals and co-occurs with internalizing and externalizing symptoms. This study tested associations between subcortical regions implicated in sleep processes and measures of dysregulated sleep initiation/maintenance in autistic and non-autistic 2- to 4-year-olds. The role of co-occurring externalizing and internalizing symptoms in these associations was also evaluated. Participants included 203 autistic (131 males, 72 females) and 92 non-autistic (49 males, 43 females) 2- to 4-year-olds who completed magnetic resonance imaging. A subscale of items from the Children’s Sleep Habits Questionnaire, previously shown to be reliable across both autistic and non-autistic children, was used to measure dysregulated sleep initiation/maintenance. Externalizing and internalizing symptoms were evaluated using the Child Behavior Checklist–Preschool. Associations between volumes for nine subcortical structures known to be implicated in sleep were separately modeled. Mediation analyses explored whether such associations could be accounted for by externalizing or internalizing symptoms. Smaller right hypothalamus volume was associated with dysregulated sleep initiation/maintenance in both autistic and non-autistic children. Externalizing (but not internalizing) problems partially mediated this association. Findings implicate the right hypothalamus in sleep initiation and maintenance issues for both autistic and non-autistic young children, supporting prior evidence of its central role in sleep regulation.Lay Abstract Difficulty initiating or maintaining sleep is common among autistic individuals and often goes alongside difficulties regulating emotions and behavior during the day. Although there is a body of research suggesting that subcortical brain regions, including a brain region known as the hypothalamus, play important roles regulating sleep, few studies have examined whether this extends to young autistic children. Using data from a sample of 203 autistic (131 males, 72 females) and 92 non-autistic (49 males, 43 females) 2- to 4-year-olds, we examined whether size of subcortical brain regions implicated in sleep processes is associated with difficulties initiating and/or maintaining sleep. In addition, we examined whether daytime behaviors and emotions were also implicated in these associations. We found that smaller right hypothalamus volume was associated with dysregulated sleep initiation/maintenance in both autistic and non-autistic children. This relationship remained evident even after accounting for externalizing behaviors and emotions like anger that were also associated with both the hypothalamus and dysregulated sleep initiation/maintenance. The strength of association between right hypothalamus volumes and dysregulated sleep initiation/maintenance was similar for autistic and non-autistic children. These findings suggest that for both young autistic and non-autistic children, the hypothalamus plays unique roles in regulating both sleep and externalizing behaviors. For managing sleep initiation and maintenance difficulties in clinical practice, the findings underscore the importance of considering environmental (e.g. not having a regular bedtime routine) and neurobiological factors, for both autistic and non-autistic young children. En ligne : https://dx.doi.org/10.1177/13623613251352249 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=570 [article] Hypothalamic volume is associated with dysregulated sleep in autistic and non-autistic young children [texte imprimé] / Burt HATCH, Auteur ; Derek S. ANDREWS, Auteur ; Brett D. DUFOUR, Auteur ; Shayan M. ALAVYNEJAD, Auteur ; Joshua K. LEE, Auteur ; Sally J. ROGERS, Auteur ; Marjorie SOLOMON, Auteur ; Meghan MILLER, Auteur ; Christine W. NORDAHL, Auteur . - p.2885-2897. Langues : Anglais (eng) in Autism > 29-11 (November 2025) . - p.2885-2897 Mots-clés : autism spectrum disorder  externalizing  hypothalamus  internalizing  MRI  sleep Index. décimale : PER Périodiques Résumé : Difficulty initiating or maintaining sleep is common among autistic individuals and co-occurs with internalizing and externalizing symptoms. This study tested associations between subcortical regions implicated in sleep processes and measures of dysregulated sleep initiation/maintenance in autistic and non-autistic 2- to 4-year-olds. The role of co-occurring externalizing and internalizing symptoms in these associations was also evaluated. Participants included 203 autistic (131 males, 72 females) and 92 non-autistic (49 males, 43 females) 2- to 4-year-olds who completed magnetic resonance imaging. A subscale of items from the Children’s Sleep Habits Questionnaire, previously shown to be reliable across both autistic and non-autistic children, was used to measure dysregulated sleep initiation/maintenance. Externalizing and internalizing symptoms were evaluated using the Child Behavior Checklist–Preschool. Associations between volumes for nine subcortical structures known to be implicated in sleep were separately modeled. Mediation analyses explored whether such associations could be accounted for by externalizing or internalizing symptoms. Smaller right hypothalamus volume was associated with dysregulated sleep initiation/maintenance in both autistic and non-autistic children. Externalizing (but not internalizing) problems partially mediated this association. Findings implicate the right hypothalamus in sleep initiation and maintenance issues for both autistic and non-autistic young children, supporting prior evidence of its central role in sleep regulation.Lay Abstract Difficulty initiating or maintaining sleep is common among autistic individuals and often goes alongside difficulties regulating emotions and behavior during the day. Although there is a body of research suggesting that subcortical brain regions, including a brain region known as the hypothalamus, play important roles regulating sleep, few studies have examined whether this extends to young autistic children. Using data from a sample of 203 autistic (131 males, 72 females) and 92 non-autistic (49 males, 43 females) 2- to 4-year-olds, we examined whether size of subcortical brain regions implicated in sleep processes is associated with difficulties initiating and/or maintaining sleep. In addition, we examined whether daytime behaviors and emotions were also implicated in these associations. We found that smaller right hypothalamus volume was associated with dysregulated sleep initiation/maintenance in both autistic and non-autistic children. This relationship remained evident even after accounting for externalizing behaviors and emotions like anger that were also associated with both the hypothalamus and dysregulated sleep initiation/maintenance. The strength of association between right hypothalamus volumes and dysregulated sleep initiation/maintenance was similar for autistic and non-autistic children. These findings suggest that for both young autistic and non-autistic children, the hypothalamus plays unique roles in regulating both sleep and externalizing behaviors. For managing sleep initiation and maintenance difficulties in clinical practice, the findings underscore the importance of considering environmental (e.g. not having a regular bedtime routine) and neurobiological factors, for both autistic and non-autistic young children. En ligne : https://dx.doi.org/10.1177/13623613251352249 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=570

Neuronal and glial cell number is altered in a cortical layer-specific manner in autism / Carmen FALCONE in Autism, 25-8 (November 2021)  

Public ISBD [article]  inAutism > 25-8 (November 2021) . - p.2238-2253 Titre : Neuronal and glial cell number is altered in a cortical layer-specific manner in autism Type de document : texte imprimé Auteurs : Carmen FALCONE, Auteur ; Natalie-Ya MEVISES, Auteur ; Tiffany HONG, Auteur ; Brett DUFOUR, Auteur ; Xiaohui CHEN, Auteur ; Stephen C. NOCTOR, Auteur ; Verónica MARTÍNEZ-CERDEÑO, Auteur Année de publication : 2021 Article en page(s) : p.2238-2253 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder  Autistic Disorder  Cell Count  Cerebral Cortex  Humans  Neuroglia  Neurons  anatomy  autism  cerebral cortex  postmortem Index. décimale : PER Périodiques Résumé : The cerebral cortex affected with autism spectrum disorder presents changes in the number of neurons and glia cells, possibly leading to a dysregulation of brain circuits and affecting behavior. However, little is known about cell number alteration in specific layers of the cortex in autism spectrum disorder. We found an increase in the number of neurons and a decrease in the number of astrocytes in specific layers of the prefrontal cortex in postmortem human brains from autism spectrum disorder cases. We hypothesize that this may be due to a failure in neural stem cells to shift differentiation from neurons to glial cells during prenatal brain development. These data provide key anatomical findings that contribute to the bases of autism spectrum disorder pathogenesis. En ligne : http://dx.doi.org/10.1177/13623613211014408 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=451 [article] Neuronal and glial cell number is altered in a cortical layer-specific manner in autism [texte imprimé] / Carmen FALCONE, Auteur ; Natalie-Ya MEVISES, Auteur ; Tiffany HONG, Auteur ; Brett DUFOUR, Auteur ; Xiaohui CHEN, Auteur ; Stephen C. NOCTOR, Auteur ; Verónica MARTÍNEZ-CERDEÑO, Auteur . - 2021 . - p.2238-2253. Langues : Anglais (eng) in Autism > 25-8 (November 2021) . - p.2238-2253 Mots-clés : Autism Spectrum Disorder  Autistic Disorder  Cell Count  Cerebral Cortex  Humans  Neuroglia  Neurons  anatomy  autism  cerebral cortex  postmortem Index. décimale : PER Périodiques Résumé : The cerebral cortex affected with autism spectrum disorder presents changes in the number of neurons and glia cells, possibly leading to a dysregulation of brain circuits and affecting behavior. However, little is known about cell number alteration in specific layers of the cortex in autism spectrum disorder. We found an increase in the number of neurons and a decrease in the number of astrocytes in specific layers of the prefrontal cortex in postmortem human brains from autism spectrum disorder cases. We hypothesize that this may be due to a failure in neural stem cells to shift differentiation from neurons to glial cells during prenatal brain development. These data provide key anatomical findings that contribute to the bases of autism spectrum disorder pathogenesis. En ligne : http://dx.doi.org/10.1177/13623613211014408 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=451

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