Dépouillements

Immune activation during pregnancy exacerbates ASD-related alterations in Shank3-deficient mice / Andrea Pérez ARÉVALO ; Ines GRAF ; Rong ZHANG ; Juergen BOCKMANN ; Anne-Kathrin LUTZ ; Tobias M. BOECKERS in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 1 p. Titre : Immune activation during pregnancy exacerbates ASD-related alterations in Shank3-deficient mice Type de document : Texte imprimé et/ou numérique Auteurs : Andrea Pérez ARÉVALO, Auteur ; Ines GRAF, Auteur ; Rong ZHANG, Auteur ; Juergen BOCKMANN, Auteur ; Anne-Kathrin LUTZ, Auteur ; Tobias M. BOECKERS, Auteur Article en page(s) : 1 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is mainly characterized by deficits in social interaction and communication and repetitive behaviors. Known causes of ASD are mutations of certain risk genes like the postsynaptic protein SHANK3 and environmental factors including prenatal infections. METHODS: To analyze the gene-environment interplay in ASD, we combined the Shank3?11-/-?ASD mouse model with maternal immune activation (MIA) via an intraperitoneal injection of polyinosinic/polycytidylic acid (Poly I:C) on gestational day 12.5. The offspring of the injected dams was further analyzed for autistic-like behaviors and comorbidities followed by biochemical experiments with a focus on synaptic analysis. RESULTS: We show that the two-hit mice exhibit excessive grooming and deficits in social behavior more prominently than the Shank3?11-/-?mice. Interestingly, these behavioral changes were accompanied by an unexpected upregulation of postsynaptic density (PSD) proteins at excitatory synapses in striatum, hippocampus and prefrontal cortex. LIMITATIONS: We found several PSD proteins to be increased in the two-hit mice; however, we can only speculate about possible pathways behind the worsening of the autistic phenotype in those mice. CONCLUSIONS: With this study, we demonstrate that there is an interplay between genetic susceptibility and environmental factors defining the severity of ASD symptoms. Moreover, we show that a general misbalance of PSD proteins at excitatory synapses is linked to ASD symptoms, making this two-hit model a promising tool for the investigation of the complex pathophysiology of neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/s13229-022-00532-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Immune activation during pregnancy exacerbates ASD-related alterations in Shank3-deficient mice [Texte imprimé et/ou numérique] / Andrea Pérez ARÉVALO, Auteur ; Ines GRAF, Auteur ; Rong ZHANG, Auteur ; Juergen BOCKMANN, Auteur ; Anne-Kathrin LUTZ, Auteur ; Tobias M. BOECKERS, Auteur . - 1 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 1 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is mainly characterized by deficits in social interaction and communication and repetitive behaviors. Known causes of ASD are mutations of certain risk genes like the postsynaptic protein SHANK3 and environmental factors including prenatal infections. METHODS: To analyze the gene-environment interplay in ASD, we combined the Shank3?11-/-?ASD mouse model with maternal immune activation (MIA) via an intraperitoneal injection of polyinosinic/polycytidylic acid (Poly I:C) on gestational day 12.5. The offspring of the injected dams was further analyzed for autistic-like behaviors and comorbidities followed by biochemical experiments with a focus on synaptic analysis. RESULTS: We show that the two-hit mice exhibit excessive grooming and deficits in social behavior more prominently than the Shank3?11-/-?mice. Interestingly, these behavioral changes were accompanied by an unexpected upregulation of postsynaptic density (PSD) proteins at excitatory synapses in striatum, hippocampus and prefrontal cortex. LIMITATIONS: We found several PSD proteins to be increased in the two-hit mice; however, we can only speculate about possible pathways behind the worsening of the autistic phenotype in those mice. CONCLUSIONS: With this study, we demonstrate that there is an interplay between genetic susceptibility and environmental factors defining the severity of ASD symptoms. Moreover, we show that a general misbalance of PSD proteins at excitatory synapses is linked to ASD symptoms, making this two-hit model a promising tool for the investigation of the complex pathophysiology of neurodevelopmental disorders. En ligne : http://dx.doi.org/10.1186/s13229-022-00532-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Brain correlates of declarative memory atypicalities in autism: a systematic review of functional neuroimaging findings / Bérengère GUILLERY ; Edgar MOUSSAOUI ; Francis EUSTACHE ; Dermot M. BOWLER ; Fabian GUENOLE in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 2 p. Titre : Brain correlates of declarative memory atypicalities in autism: a systematic review of functional neuroimaging findings Type de document : Texte imprimé et/ou numérique Auteurs : Bérengère GUILLERY, Auteur ; Edgar MOUSSAOUI, Auteur ; Francis EUSTACHE, Auteur ; Dermot M. BOWLER, Auteur ; Fabian GUENOLE, Auteur Article en page(s) : 2 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The long-described atypicalities of memory functioning experienced by people with autism have major implications for daily living, academic learning, as well as cognitive remediation. Though behavioral studies have identified a robust profile of memory strengths and weaknesses in autism spectrum disorder (ASD), few works have attempted to establish a synthesis concerning their neural bases. In this systematic review of functional neuroimaging studies, we highlight functional brain asymmetries in three anatomical planes during memory processing between individuals with ASD and typical development. These asymmetries consist of greater activity of the left hemisphere than the right in ASD participants, of posterior brain regions-including hippocampus-rather than anterior ones, and presumably of the ventral (occipito-temporal) streams rather than the dorsal (occipito-parietal) ones. These functional alterations may be linked to atypical memory processes in ASD, including the pre-eminence of verbal over spatial information, impaired active maintenance in working memory, and preserved relational memory despite poor context processing in episodic memory. En ligne : http://dx.doi.org/10.1186/s13229-022-00525-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Brain correlates of declarative memory atypicalities in autism: a systematic review of functional neuroimaging findings [Texte imprimé et/ou numérique] / Bérengère GUILLERY, Auteur ; Edgar MOUSSAOUI, Auteur ; Francis EUSTACHE, Auteur ; Dermot M. BOWLER, Auteur ; Fabian GUENOLE, Auteur . - 2 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 2 p. Index. décimale : PER Périodiques Résumé : The long-described atypicalities of memory functioning experienced by people with autism have major implications for daily living, academic learning, as well as cognitive remediation. Though behavioral studies have identified a robust profile of memory strengths and weaknesses in autism spectrum disorder (ASD), few works have attempted to establish a synthesis concerning their neural bases. In this systematic review of functional neuroimaging studies, we highlight functional brain asymmetries in three anatomical planes during memory processing between individuals with ASD and typical development. These asymmetries consist of greater activity of the left hemisphere than the right in ASD participants, of posterior brain regions-including hippocampus-rather than anterior ones, and presumably of the ventral (occipito-temporal) streams rather than the dorsal (occipito-parietal) ones. These functional alterations may be linked to atypical memory processes in ASD, including the pre-eminence of verbal over spatial information, impaired active maintenance in working memory, and preserved relational memory despite poor context processing in episodic memory. En ligne : http://dx.doi.org/10.1186/s13229-022-00525-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Profiles of autism characteristics in thirteen genetic syndromes: a machine learning approach / Alice WELHAM ; Dawn ADAMS ; Stacey BISSELL ; Hilgo BRUINING ; Hayley CRAWFORD ; Kate EDEN ; Lisa NELSON ; Christopher OLIVER ; Laurie POWIS ; Caroline RICHARDS ; Jane WAITE ; Peter WATSON ; Hefin RHYS ; Lucy WILDE ; Kate WOODCOCK ; Joanna MOSS in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 3 p. Titre : Profiles of autism characteristics in thirteen genetic syndromes: a machine learning approach Type de document : Texte imprimé et/ou numérique Auteurs : Alice WELHAM, Auteur ; Dawn ADAMS, Auteur ; Stacey BISSELL, Auteur ; Hilgo BRUINING, Auteur ; Hayley CRAWFORD, Auteur ; Kate EDEN, Auteur ; Lisa NELSON, Auteur ; Christopher OLIVER, Auteur ; Laurie POWIS, Auteur ; Caroline RICHARDS, Auteur ; Jane WAITE, Auteur ; Peter WATSON, Auteur ; Hefin RHYS, Auteur ; Lucy WILDE, Auteur ; Kate WOODCOCK, Auteur ; Joanna MOSS, Auteur Article en page(s) : 3 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Phenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of>1500 individuals with rare genetic syndromes. METHODS: Profiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n=154, Cri du Chat n=75, Cornelia de Lange n=199, fragile X n=297, Prader-Willi n=278, Lowe n=89, Smith-Magenis n=54, Down n=135, Sotos n=40, Rubinstein-Taybi n=102, 1p36 deletion n=41, tuberous sclerosis complex n=83 and Phelan-McDermid n=35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n=254). Self-help skills were included as an additional predictor. RESULTS: Genetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader-Willi, Rubinstein-Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith-Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy. LIMITATIONS: The key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups. CONCLUSIONS: These findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID. En ligne : http://dx.doi.org/10.1186/s13229-022-00530-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Profiles of autism characteristics in thirteen genetic syndromes: a machine learning approach [Texte imprimé et/ou numérique] / Alice WELHAM, Auteur ; Dawn ADAMS, Auteur ; Stacey BISSELL, Auteur ; Hilgo BRUINING, Auteur ; Hayley CRAWFORD, Auteur ; Kate EDEN, Auteur ; Lisa NELSON, Auteur ; Christopher OLIVER, Auteur ; Laurie POWIS, Auteur ; Caroline RICHARDS, Auteur ; Jane WAITE, Auteur ; Peter WATSON, Auteur ; Hefin RHYS, Auteur ; Lucy WILDE, Auteur ; Kate WOODCOCK, Auteur ; Joanna MOSS, Auteur . - 3 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 3 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of>1500 individuals with rare genetic syndromes. METHODS: Profiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n=154, Cri du Chat n=75, Cornelia de Lange n=199, fragile X n=297, Prader-Willi n=278, Lowe n=89, Smith-Magenis n=54, Down n=135, Sotos n=40, Rubinstein-Taybi n=102, 1p36 deletion n=41, tuberous sclerosis complex n=83 and Phelan-McDermid n=35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n=254). Self-help skills were included as an additional predictor. RESULTS: Genetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader-Willi, Rubinstein-Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith-Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy. LIMITATIONS: The key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups. CONCLUSIONS: These findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID. En ligne : http://dx.doi.org/10.1186/s13229-022-00530-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Correction: WDFY3 mutation alters laminar position and morphology of cortical neurons / Lyvin TAT ; Noemi CANNIZZARO ; Alexios A. PANOUTSOPOULOS ; Ralph GREEN ; Thomas RULICKE ; Simon HIPPENMEYER ; Konstantinos S. ZARBALIS in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 4 p. Titre : Correction: WDFY3 mutation alters laminar position and morphology of cortical neurons Type de document : Texte imprimé et/ou numérique Auteurs : Lyvin TAT, Auteur ; Noemi CANNIZZARO, Auteur ; Alexios A. PANOUTSOPOULOS, Auteur ; Ralph GREEN, Auteur ; Thomas RULICKE, Auteur ; Simon HIPPENMEYER, Auteur ; Konstantinos S. ZARBALIS, Auteur Article en page(s) : 4 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-023-00539-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Correction: WDFY3 mutation alters laminar position and morphology of cortical neurons [Texte imprimé et/ou numérique] / Lyvin TAT, Auteur ; Noemi CANNIZZARO, Auteur ; Alexios A. PANOUTSOPOULOS, Auteur ; Ralph GREEN, Auteur ; Thomas RULICKE, Auteur ; Simon HIPPENMEYER, Auteur ; Konstantinos S. ZARBALIS, Auteur . - 4 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 4 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-023-00539-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Sensory salience processing moderates attenuated gazes on faces in autism spectrum disorder: a case-control study / Luke MASON ; Christine ECKER ; Sarah BAUMEISTER ; Tobias BANASCHEWSKI ; Emily J. H. JONES ; Declan G. M. MURPHY ; Jan K. BUITELAAR ; Eva LOTH ; Gahan PANDINA ; Christine M. FREITAG in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 5 p. Titre : Sensory salience processing moderates attenuated gazes on faces in autism spectrum disorder: a case-control study Type de document : Texte imprimé et/ou numérique Auteurs : Luke MASON, Auteur ; Christine ECKER, Auteur ; Sarah BAUMEISTER, Auteur ; Tobias BANASCHEWSKI, Auteur ; Emily J. H. JONES, Auteur ; Declan G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Eva LOTH, Auteur ; Gahan PANDINA, Auteur ; Christine M. FREITAG, Auteur Article en page(s) : 5 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Attenuated social attention is a key marker of autism spectrum disorder (ASD). Recent neuroimaging findings also emphasize an altered processing of sensory salience in ASD. The locus coeruleus-norepinephrine system (LC-NE) has been established as a modulator of this sensory salience processing (SSP). We tested the hypothesis that altered LC-NE functioning contributes to different SSP and results in diverging social attention in ASD. METHODS: We analyzed the baseline eye-tracking data of the EU-AIMS Longitudinal European Autism Project (LEAP) for subgroups of autistic participants (n=166, age=6-30 years, IQ=61-138, gender [female/male]=41/125) or neurotypical development (TD; n=166, age=6-30 years, IQ=63-138, gender [female/male]=49/117) that were matched for demographic variables and data quality. Participants watched brief movie scenes (k=85) depicting humans in social situations (human) or without humans (non-human). SSP was estimated by gazes on physical and motion salience and a corresponding pupillary response that indexes phasic activity of the LC-NE. Social attention is estimated by gazes on faces via manual areas of interest definition. SSP is compared between groups and related to social attention by linear mixed models that consider temporal dynamics within scenes. Models are controlled for comorbid psychopathology, gaze behavior, and luminance. RESULTS: We found no group differences in gazes on salience, whereas pupillary responses were associated with altered gazes on physical and motion salience. In ASD compared to TD, we observed pupillary responses that were higher for non-human scenes and lower for human scenes. In ASD, we observed lower gazes on faces across the duration of the scenes. Crucially, this different social attention was influenced by gazes on physical salience and moderated by pupillary responses. LIMITATIONS: The naturalistic study design precluded experimental manipulations and stimulus control, while effect sizes were small to moderate. Covariate effects of age and IQ indicate that the findings differ between age and developmental subgroups. CONCLUSIONS: Pupillary responses as a proxy of LC-NE phasic activity during visual attention are suggested to modulate sensory salience processing and contribute to attenuated social attention in ASD. En ligne : http://dx.doi.org/10.1186/s13229-023-00537-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Sensory salience processing moderates attenuated gazes on faces in autism spectrum disorder: a case-control study [Texte imprimé et/ou numérique] / Luke MASON, Auteur ; Christine ECKER, Auteur ; Sarah BAUMEISTER, Auteur ; Tobias BANASCHEWSKI, Auteur ; Emily J. H. JONES, Auteur ; Declan G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Eva LOTH, Auteur ; Gahan PANDINA, Auteur ; Christine M. FREITAG, Auteur . - 5 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 5 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Attenuated social attention is a key marker of autism spectrum disorder (ASD). Recent neuroimaging findings also emphasize an altered processing of sensory salience in ASD. The locus coeruleus-norepinephrine system (LC-NE) has been established as a modulator of this sensory salience processing (SSP). We tested the hypothesis that altered LC-NE functioning contributes to different SSP and results in diverging social attention in ASD. METHODS: We analyzed the baseline eye-tracking data of the EU-AIMS Longitudinal European Autism Project (LEAP) for subgroups of autistic participants (n=166, age=6-30 years, IQ=61-138, gender [female/male]=41/125) or neurotypical development (TD; n=166, age=6-30 years, IQ=63-138, gender [female/male]=49/117) that were matched for demographic variables and data quality. Participants watched brief movie scenes (k=85) depicting humans in social situations (human) or without humans (non-human). SSP was estimated by gazes on physical and motion salience and a corresponding pupillary response that indexes phasic activity of the LC-NE. Social attention is estimated by gazes on faces via manual areas of interest definition. SSP is compared between groups and related to social attention by linear mixed models that consider temporal dynamics within scenes. Models are controlled for comorbid psychopathology, gaze behavior, and luminance. RESULTS: We found no group differences in gazes on salience, whereas pupillary responses were associated with altered gazes on physical and motion salience. In ASD compared to TD, we observed pupillary responses that were higher for non-human scenes and lower for human scenes. In ASD, we observed lower gazes on faces across the duration of the scenes. Crucially, this different social attention was influenced by gazes on physical salience and moderated by pupillary responses. LIMITATIONS: The naturalistic study design precluded experimental manipulations and stimulus control, while effect sizes were small to moderate. Covariate effects of age and IQ indicate that the findings differ between age and developmental subgroups. CONCLUSIONS: Pupillary responses as a proxy of LC-NE phasic activity during visual attention are suggested to modulate sensory salience processing and contribute to attenuated social attention in ASD. En ligne : http://dx.doi.org/10.1186/s13229-023-00537-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

The subcortical correlates of autistic traits in school-age children: a population-based neuroimaging study / M. ELSABBAGH ; A. PICKLES ; R. BEDFORD in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 6 p. Titre : The subcortical correlates of autistic traits in school-age children: a population-based neuroimaging study Type de document : Texte imprimé et/ou numérique Auteurs : M. ELSABBAGH, Auteur ; A. PICKLES, Auteur ; R. BEDFORD, Auteur Article en page(s) : 6 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: There is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms. METHODS: Our analyses included data from 7005 children aged 9-10 years (female: 47.19%) participating in the Adolescent Brain Cognitive Development Study. Autistic traits were assessed using scores from the Social Responsiveness Scale (SRS). Volumes of subcortical regions of interest were derived from structural magnetic resonance imaging data. RESULTS: Overall, we did not find strong evidence for an association of autistic traits with differences in subcortical morphology in this sample of school-aged children. Whilst lower absolute volumes of the nucleus accumbens and putamen were associated with higher scores of autistic traits, these differences did not persist once a global measure of brain size was accounted for. LIMITATIONS: It is important to note that autistic traits were assessed using the SRS, of which higher scores are associated with general behavioural problems, and therefore may not be wholly indicative of autism-specific symptoms. In addition, individuals with a moderate or severe autism diagnosis were excluded from the ABCD study, and thus, the average level of autistic traits will be lower than in the general population which may bias findings towards the null. CONCLUSIONS: These findings from our well-powered study suggest that other metrics of brain morphology, such as cortical morphology or shape-based phenotypes, may be stronger candidates to prioritise when attempting to identify robust neuromarkers of autistic traits. En ligne : http://dx.doi.org/10.1186/s13229-023-00538-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] The subcortical correlates of autistic traits in school-age children: a population-based neuroimaging study [Texte imprimé et/ou numérique] / M. ELSABBAGH, Auteur ; A. PICKLES, Auteur ; R. BEDFORD, Auteur . - 6 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 6 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: There is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms. METHODS: Our analyses included data from 7005 children aged 9-10 years (female: 47.19%) participating in the Adolescent Brain Cognitive Development Study. Autistic traits were assessed using scores from the Social Responsiveness Scale (SRS). Volumes of subcortical regions of interest were derived from structural magnetic resonance imaging data. RESULTS: Overall, we did not find strong evidence for an association of autistic traits with differences in subcortical morphology in this sample of school-aged children. Whilst lower absolute volumes of the nucleus accumbens and putamen were associated with higher scores of autistic traits, these differences did not persist once a global measure of brain size was accounted for. LIMITATIONS: It is important to note that autistic traits were assessed using the SRS, of which higher scores are associated with general behavioural problems, and therefore may not be wholly indicative of autism-specific symptoms. In addition, individuals with a moderate or severe autism diagnosis were excluded from the ABCD study, and thus, the average level of autistic traits will be lower than in the general population which may bias findings towards the null. CONCLUSIONS: These findings from our well-powered study suggest that other metrics of brain morphology, such as cortical morphology or shape-based phenotypes, may be stronger candidates to prioritise when attempting to identify robust neuromarkers of autistic traits. En ligne : http://dx.doi.org/10.1186/s13229-023-00538-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions / Patricia SEGURA ; Louise GALLAGHER ; Stelios GEORGIADES ; Panagiota PERVANIDOU ; Audrey THURM ; Lindsay ALEXANDER ; Evdokia ANAGNOSTOU ; Yuta AOKI ; Catherine S. BIRKEN ; Somer L. BISHOP ; Jessica BOI ; Carmela BRAVACCIO ; Helena BRENTANI ; Paola CANEVINI ; Alessandra CARTA ; Alice CHARACH ; Antonella COSTANTINO ; Katherine T. COST ; Elaine A. CRAVO ; Jennifer CROSBIE ; Chiara DAVICO ; Federica DONNO ; Junya FUJINO ; Alessandra GABELLONE ; Cristiane T. GEYER ; Tomoya HIROTA ; Stephen KANNE ; Makiko KAWASHIMA ; Elizabeth KELLEY ; Hosanna KIM ; Young Shin KIM ; So Hyun KIM ; Daphne J. KORCZAK ; Meng-Chuan LAI ; Lucia MARGARI ; Lucia MARZULLI ; Gabriele MASI ; Luigi MAZZONE ; Jane MCGRATH ; Suneeta MONGA ; Paola MOROSINI ; Shinichiro NAKAJIMA ; Antonio NARZISI ; Rob NICOLSON ; Aki NIKOLAIDIS ; Yoshihiro NODA ; Kerri NOWELL ; Miriam POLIZZI ; Joana PORTOLESE ; Maria Pia RICCIO ; Manabu SAITO ; Ida SCHWARTZ ; Anish K. SIMHAL ; Martina SIRACUSANO ; Stefano SOTGIU ; Jacob STROUD ; Fernando SUMIYA ; Yoshiyuki TACHIBANA ; Nicole TAKAHASHI ; Riina TAKAHASHI ; Hiroki TAMON ; Raffaella TANCREDI ; Benedetto VITIELLO ; Alessandro ZUDDAS ; Bennett LEVENTHAL ; Kathleen MERIKANGAS ; Michael P. MILHAM ; Adriana DI MARTINO in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 7 p. Titre : CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions Type de document : Texte imprimé et/ou numérique Auteurs : Patricia SEGURA, Auteur ; Louise GALLAGHER, Auteur ; Stelios GEORGIADES, Auteur ; Panagiota PERVANIDOU, Auteur ; Audrey THURM, Auteur ; Lindsay ALEXANDER, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Yuta AOKI, Auteur ; Catherine S. BIRKEN, Auteur ; Somer L. BISHOP, Auteur ; Jessica BOI, Auteur ; Carmela BRAVACCIO, Auteur ; Helena BRENTANI, Auteur ; Paola CANEVINI, Auteur ; Alessandra CARTA, Auteur ; Alice CHARACH, Auteur ; Antonella COSTANTINO, Auteur ; Katherine T. COST, Auteur ; Elaine A. CRAVO, Auteur ; Jennifer CROSBIE, Auteur ; Chiara DAVICO, Auteur ; Federica DONNO, Auteur ; Junya FUJINO, Auteur ; Alessandra GABELLONE, Auteur ; Cristiane T. GEYER, Auteur ; Tomoya HIROTA, Auteur ; Stephen KANNE, Auteur ; Makiko KAWASHIMA, Auteur ; Elizabeth KELLEY, Auteur ; Hosanna KIM, Auteur ; Young Shin KIM, Auteur ; So Hyun KIM, Auteur ; Daphne J. KORCZAK, Auteur ; Meng-Chuan LAI, Auteur ; Lucia MARGARI, Auteur ; Lucia MARZULLI, Auteur ; Gabriele MASI, Auteur ; Luigi MAZZONE, Auteur ; Jane MCGRATH, Auteur ; Suneeta MONGA, Auteur ; Paola MOROSINI, Auteur ; Shinichiro NAKAJIMA, Auteur ; Antonio NARZISI, Auteur ; Rob NICOLSON, Auteur ; Aki NIKOLAIDIS, Auteur ; Yoshihiro NODA, Auteur ; Kerri NOWELL, Auteur ; Miriam POLIZZI, Auteur ; Joana PORTOLESE, Auteur ; Maria Pia RICCIO, Auteur ; Manabu SAITO, Auteur ; Ida SCHWARTZ, Auteur ; Anish K. SIMHAL, Auteur ; Martina SIRACUSANO, Auteur ; Stefano SOTGIU, Auteur ; Jacob STROUD, Auteur ; Fernando SUMIYA, Auteur ; Yoshiyuki TACHIBANA, Auteur ; Nicole TAKAHASHI, Auteur ; Riina TAKAHASHI, Auteur ; Hiroki TAMON, Auteur ; Raffaella TANCREDI, Auteur ; Benedetto VITIELLO, Auteur ; Alessandro ZUDDAS, Auteur ; Bennett LEVENTHAL, Auteur ; Kathleen MERIKANGAS, Auteur ; Michael P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur Article en page(s) : 7 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. METHODS: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N=1275 individuals with ASD/NDD (age=11.0?+?3.6 years; n females=277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. RESULTS: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. LIMITATIONS: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. CONCLUSIONS: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis. En ligne : http://dx.doi.org/10.1186/s13229-022-00536-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions [Texte imprimé et/ou numérique] / Patricia SEGURA, Auteur ; Louise GALLAGHER, Auteur ; Stelios GEORGIADES, Auteur ; Panagiota PERVANIDOU, Auteur ; Audrey THURM, Auteur ; Lindsay ALEXANDER, Auteur ; Evdokia ANAGNOSTOU, Auteur ; Yuta AOKI, Auteur ; Catherine S. BIRKEN, Auteur ; Somer L. BISHOP, Auteur ; Jessica BOI, Auteur ; Carmela BRAVACCIO, Auteur ; Helena BRENTANI, Auteur ; Paola CANEVINI, Auteur ; Alessandra CARTA, Auteur ; Alice CHARACH, Auteur ; Antonella COSTANTINO, Auteur ; Katherine T. COST, Auteur ; Elaine A. CRAVO, Auteur ; Jennifer CROSBIE, Auteur ; Chiara DAVICO, Auteur ; Federica DONNO, Auteur ; Junya FUJINO, Auteur ; Alessandra GABELLONE, Auteur ; Cristiane T. GEYER, Auteur ; Tomoya HIROTA, Auteur ; Stephen KANNE, Auteur ; Makiko KAWASHIMA, Auteur ; Elizabeth KELLEY, Auteur ; Hosanna KIM, Auteur ; Young Shin KIM, Auteur ; So Hyun KIM, Auteur ; Daphne J. KORCZAK, Auteur ; Meng-Chuan LAI, Auteur ; Lucia MARGARI, Auteur ; Lucia MARZULLI, Auteur ; Gabriele MASI, Auteur ; Luigi MAZZONE, Auteur ; Jane MCGRATH, Auteur ; Suneeta MONGA, Auteur ; Paola MOROSINI, Auteur ; Shinichiro NAKAJIMA, Auteur ; Antonio NARZISI, Auteur ; Rob NICOLSON, Auteur ; Aki NIKOLAIDIS, Auteur ; Yoshihiro NODA, Auteur ; Kerri NOWELL, Auteur ; Miriam POLIZZI, Auteur ; Joana PORTOLESE, Auteur ; Maria Pia RICCIO, Auteur ; Manabu SAITO, Auteur ; Ida SCHWARTZ, Auteur ; Anish K. SIMHAL, Auteur ; Martina SIRACUSANO, Auteur ; Stefano SOTGIU, Auteur ; Jacob STROUD, Auteur ; Fernando SUMIYA, Auteur ; Yoshiyuki TACHIBANA, Auteur ; Nicole TAKAHASHI, Auteur ; Riina TAKAHASHI, Auteur ; Hiroki TAMON, Auteur ; Raffaella TANCREDI, Auteur ; Benedetto VITIELLO, Auteur ; Alessandro ZUDDAS, Auteur ; Bennett LEVENTHAL, Auteur ; Kathleen MERIKANGAS, Auteur ; Michael P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur . - 7 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 7 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. METHODS: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N=1275 individuals with ASD/NDD (age=11.0?+?3.6 years; n females=277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. RESULTS: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. LIMITATIONS: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. CONCLUSIONS: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis. En ligne : http://dx.doi.org/10.1186/s13229-022-00536-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder / Daniel C. DE LA FUENTE ; Meng LI in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 8 p. Titre : Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder Type de document : Texte imprimé et/ou numérique Auteurs : Daniel C. DE LA FUENTE, Auteur ; Meng LI, Auteur Article en page(s) : 8 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Disruptions of SETBP1 (SET binding protein 1) on 18q12.3 by heterozygous gene deletion or loss-of-function variants cause SETBP1 disorder. Clinical features are frequently associated with moderate to severe intellectual disability, autistic traits and speech and motor delays. Despite the association of SETBP1 with neurodevelopmental disorders, little is known about its role in brain development. METHODS: Using CRISPR/Cas9 genome editing technology, we generated a SETBP1 deletion model in human embryonic stem cells (hESCs) and examined the effects of SETBP1-deficiency in neural progenitors (NPCs) and neurons derived from these stem cells using a battery of cellular assays, genome-wide transcriptomic profiling and drug-based phenotypic rescue. RESULTS: Neural induction occurred efficiently in all SETBP1 deletion models as indicated by uniform transition into neural rosettes. However, SETBP1-deficient NPCs exhibited an extended proliferative window and a decrease in neurogenesis coupled with a deficiency in their ability to acquire ventral forebrain fate. Genome-wide transcriptome profiling and protein biochemical analysis revealed enhanced activation of Wnt/?-catenin signaling in SETBP1 deleted cells. Crucially, treatment of the SETBP1-deficient NPCs with a small molecule Wnt inhibitor XAV939 restored hyper canonical ?-catenin activity and restored both cortical and MGE neuronal differentiation. LIMITATIONS: The current study is based on analysis of isogenic hESC lines with genome-edited SETBP1 deletion and further studies would benefit from the use of patient-derived iPSC lines that may harbor additional genetic risk that aggravate brain pathology of SETBP1 disorder. CONCLUSIONS: We identified an important role for SETBP1 in controlling forebrain progenitor expansion and neurogenic differentiation. Our study establishes a novel regulatory link between SETBP1 and Wnt/?-catenin signaling during human cortical neurogenesis and provides mechanistic insights into structural abnormalities and potential therapeutic avenues for SETBP1 disorder. En ligne : http://dx.doi.org/10.1186/s13229-023-00540-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder [Texte imprimé et/ou numérique] / Daniel C. DE LA FUENTE, Auteur ; Meng LI, Auteur . - 8 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 8 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Disruptions of SETBP1 (SET binding protein 1) on 18q12.3 by heterozygous gene deletion or loss-of-function variants cause SETBP1 disorder. Clinical features are frequently associated with moderate to severe intellectual disability, autistic traits and speech and motor delays. Despite the association of SETBP1 with neurodevelopmental disorders, little is known about its role in brain development. METHODS: Using CRISPR/Cas9 genome editing technology, we generated a SETBP1 deletion model in human embryonic stem cells (hESCs) and examined the effects of SETBP1-deficiency in neural progenitors (NPCs) and neurons derived from these stem cells using a battery of cellular assays, genome-wide transcriptomic profiling and drug-based phenotypic rescue. RESULTS: Neural induction occurred efficiently in all SETBP1 deletion models as indicated by uniform transition into neural rosettes. However, SETBP1-deficient NPCs exhibited an extended proliferative window and a decrease in neurogenesis coupled with a deficiency in their ability to acquire ventral forebrain fate. Genome-wide transcriptome profiling and protein biochemical analysis revealed enhanced activation of Wnt/?-catenin signaling in SETBP1 deleted cells. Crucially, treatment of the SETBP1-deficient NPCs with a small molecule Wnt inhibitor XAV939 restored hyper canonical ?-catenin activity and restored both cortical and MGE neuronal differentiation. LIMITATIONS: The current study is based on analysis of isogenic hESC lines with genome-edited SETBP1 deletion and further studies would benefit from the use of patient-derived iPSC lines that may harbor additional genetic risk that aggravate brain pathology of SETBP1 disorder. CONCLUSIONS: We identified an important role for SETBP1 in controlling forebrain progenitor expansion and neurogenic differentiation. Our study establishes a novel regulatory link between SETBP1 and Wnt/?-catenin signaling during human cortical neurogenesis and provides mechanistic insights into structural abnormalities and potential therapeutic avenues for SETBP1 disorder. En ligne : http://dx.doi.org/10.1186/s13229-023-00540-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Sex differences in friendships and loneliness in autistic and non-autistic children across development / Azia KNOX ; Selin ENGIN ; Daniel GESCHWIND ; Julia PARISH-MORRIS ; Connie KASARI in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 9 p. Titre : Sex differences in friendships and loneliness in autistic and non-autistic children across development Type de document : Texte imprimé et/ou numérique Auteurs : Azia KNOX, Auteur ; Selin ENGIN, Auteur ; Daniel GESCHWIND, Auteur ; Julia PARISH-MORRIS, Auteur ; Connie KASARI, Auteur Article en page(s) : 9 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic children have been shown to have less complete definitions of friendships and higher levels of loneliness than their non-autistic peers. However, no known studies have explored sex differences in autistic children's understanding of friendships and reported loneliness across development. Autistic girls demonstrate higher levels of social motivation than autistic boys and appear to "fit in" with their peers, but they often have difficulty recognizing reciprocal friendships during middle childhood. As autistic girls develop a more complex understanding of friendship during adolescence, they may begin to redefine their friendships and experience heightened loneliness. Here, we explored how autistic and non-autistic boys and girls define the meaning of friendship and report feelings of loneliness across development. We also examined their perceptions of friendships and loneliness. METHODS: This mixed-methods study analyzed the transcribed clinical evaluations of 58 autistic children (29 girls) matched to 42 non-autistic children (21 girls) on age and IQ. Transcripts were coded for four categories that children used to define friendships-personality, companionship, dependability, and intimacy-and for reported loneliness. We then compared these codes across diagnosis, sex, and age. Content analyses were further implemented to gain a more holistic understanding of children's perceptions of friendships and loneliness. RESULTS: Girls, regardless of diagnosis, were more likely than boys to refer to personality when defining the meaning of friendship, and the likelihood of referring to dependability and intimacy increased with age. Most children reported having at least one friend, though some autistic adolescents reported not having friends or were uncertain whether they had friends. While autistic and non-autistic boys and girls were equally likely to report feeling lonely at times, several autistic girls and boys reported being frequently lonely. LIMITATIONS: This study was a secondary data analysis. The standardized set of questions on the ADOS limited the amount of information that children provided about their friendships and perceptions of loneliness. CONCLUSION: As with non-autistic children, autistic children acquire a more complex understanding of friendship throughout development. However, as children begin to prioritize dependability and intimacy in friendships, autistic adolescents may have difficulty developing friendships characterized by these constructs. Furthermore, the quantity and/or quality of autistic children's friendships may not be sufficient to alleviate loneliness. En ligne : http://dx.doi.org/10.1186/s13229-023-00542-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Sex differences in friendships and loneliness in autistic and non-autistic children across development [Texte imprimé et/ou numérique] / Azia KNOX, Auteur ; Selin ENGIN, Auteur ; Daniel GESCHWIND, Auteur ; Julia PARISH-MORRIS, Auteur ; Connie KASARI, Auteur . - 9 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 9 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic children have been shown to have less complete definitions of friendships and higher levels of loneliness than their non-autistic peers. However, no known studies have explored sex differences in autistic children's understanding of friendships and reported loneliness across development. Autistic girls demonstrate higher levels of social motivation than autistic boys and appear to "fit in" with their peers, but they often have difficulty recognizing reciprocal friendships during middle childhood. As autistic girls develop a more complex understanding of friendship during adolescence, they may begin to redefine their friendships and experience heightened loneliness. Here, we explored how autistic and non-autistic boys and girls define the meaning of friendship and report feelings of loneliness across development. We also examined their perceptions of friendships and loneliness. METHODS: This mixed-methods study analyzed the transcribed clinical evaluations of 58 autistic children (29 girls) matched to 42 non-autistic children (21 girls) on age and IQ. Transcripts were coded for four categories that children used to define friendships-personality, companionship, dependability, and intimacy-and for reported loneliness. We then compared these codes across diagnosis, sex, and age. Content analyses were further implemented to gain a more holistic understanding of children's perceptions of friendships and loneliness. RESULTS: Girls, regardless of diagnosis, were more likely than boys to refer to personality when defining the meaning of friendship, and the likelihood of referring to dependability and intimacy increased with age. Most children reported having at least one friend, though some autistic adolescents reported not having friends or were uncertain whether they had friends. While autistic and non-autistic boys and girls were equally likely to report feeling lonely at times, several autistic girls and boys reported being frequently lonely. LIMITATIONS: This study was a secondary data analysis. The standardized set of questions on the ADOS limited the amount of information that children provided about their friendships and perceptions of loneliness. CONCLUSION: As with non-autistic children, autistic children acquire a more complex understanding of friendship throughout development. However, as children begin to prioritize dependability and intimacy in friendships, autistic adolescents may have difficulty developing friendships characterized by these constructs. Furthermore, the quantity and/or quality of autistic children's friendships may not be sufficient to alleviate loneliness. En ligne : http://dx.doi.org/10.1186/s13229-023-00542-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Sex differences in social and emotional insight in youth with and without autism / Meredith COLA ; Kimberly G. TENA ; Azia KNOX ; Alison RUSSELL ; Maggie Rose PELELLA ; Aili HAUPTMANN ; Maxine COVELLO ; Julia PARISH-MORRIS ; Joseph P. MCCLEERY in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 10 p. Titre : Sex differences in social and emotional insight in youth with and without autism Type de document : Texte imprimé et/ou numérique Auteurs : Meredith COLA, Auteur ; Kimberly G. TENA, Auteur ; Azia KNOX, Auteur ; Alison RUSSELL, Auteur ; Maggie Rose PELELLA, Auteur ; Aili HAUPTMANN, Auteur ; Maxine COVELLO, Auteur ; Julia PARISH-MORRIS, Auteur ; Joseph P. MCCLEERY, Auteur Article en page(s) : 10 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism was formally recognized by the medical community in the first half of the twentieth century. Almost 100 years later, a small but growing literature has reported sex differences in the behavioral expression of autism. Recent research has also begun to explore the internal experiences of individuals with autism, including social and emotional insight. The current study examines sex differences in language-based markers of social and emotional insight in girls and boys with autism and non-autistic peers during semi-structured clinical interviews. Sixty-four participants aged 5 to 17 years were individually matched on chronological age and full-scale IQ to form four groups: autistic girls, autistic boys, non-autistic girls, and non-autistic boys. Transcribed interviews were scored using four scales that index aspects of social and emotional insight. Results revealed the main effects of diagnosis, such that youth with autism exhibited lower insight than non-autistic youth on scales indexing social cognition and object relations, emotional investment, and social causality. With regards to sex differences, across diagnoses, girls were rated higher than boys on the social cognition and object relations, emotional investment, and social causality scales. Examined within each diagnosis separately, clear sex differences emerged: both autistic and non-autistic girls demonstrated better social cognition and understanding of social causality than boys in their respective diagnostic groups. No within-diagnosis sex differences were found on the emotional insight scales, however. These results suggest that relatively enhanced social cognition and understanding of social causality in girls may be a population-level sex difference that is preserved in autism, despite the core social challenges that characterize this condition. The current findings reveal critical new information about insight into social and emotional thinking and relationships in autistic girls versus boys that have important implications for improving identification and designing effective interventions. En ligne : http://dx.doi.org/10.1186/s13229-023-00541-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Sex differences in social and emotional insight in youth with and without autism [Texte imprimé et/ou numérique] / Meredith COLA, Auteur ; Kimberly G. TENA, Auteur ; Azia KNOX, Auteur ; Alison RUSSELL, Auteur ; Maggie Rose PELELLA, Auteur ; Aili HAUPTMANN, Auteur ; Maxine COVELLO, Auteur ; Julia PARISH-MORRIS, Auteur ; Joseph P. MCCLEERY, Auteur . - 10 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 10 p. Index. décimale : PER Périodiques Résumé : Autism was formally recognized by the medical community in the first half of the twentieth century. Almost 100 years later, a small but growing literature has reported sex differences in the behavioral expression of autism. Recent research has also begun to explore the internal experiences of individuals with autism, including social and emotional insight. The current study examines sex differences in language-based markers of social and emotional insight in girls and boys with autism and non-autistic peers during semi-structured clinical interviews. Sixty-four participants aged 5 to 17 years were individually matched on chronological age and full-scale IQ to form four groups: autistic girls, autistic boys, non-autistic girls, and non-autistic boys. Transcribed interviews were scored using four scales that index aspects of social and emotional insight. Results revealed the main effects of diagnosis, such that youth with autism exhibited lower insight than non-autistic youth on scales indexing social cognition and object relations, emotional investment, and social causality. With regards to sex differences, across diagnoses, girls were rated higher than boys on the social cognition and object relations, emotional investment, and social causality scales. Examined within each diagnosis separately, clear sex differences emerged: both autistic and non-autistic girls demonstrated better social cognition and understanding of social causality than boys in their respective diagnostic groups. No within-diagnosis sex differences were found on the emotional insight scales, however. These results suggest that relatively enhanced social cognition and understanding of social causality in girls may be a population-level sex difference that is preserved in autism, despite the core social challenges that characterize this condition. The current findings reveal critical new information about insight into social and emotional thinking and relationships in autistic girls versus boys that have important implications for improving identification and designing effective interventions. En ligne : http://dx.doi.org/10.1186/s13229-023-00541-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Atypical functional connectivity of temporal cortex with precuneus and visual regions may be an early-age signature of ASD / Teresa H. WEN ; Lauren KUPIS ; Lisa T. EYLER ; Vani TALUJA ; Jaden TROXEL ; Disha GOEL ; Michael V. LOMBARDO ; Karen PIERCE ; Eric COURCHESNE in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 11 p. Titre : Atypical functional connectivity of temporal cortex with precuneus and visual regions may be an early-age signature of ASD Type de document : Texte imprimé et/ou numérique Auteurs : Teresa H. WEN, Auteur ; Lauren KUPIS, Auteur ; Lisa T. EYLER, Auteur ; Vani TALUJA, Auteur ; Jaden TROXEL, Auteur ; Disha GOEL, Auteur ; Michael V. LOMBARDO, Auteur ; Karen PIERCE, Auteur ; Eric COURCHESNE, Auteur Article en page(s) : 11 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Social and language abilities are closely intertwined during early typical development. In autism spectrum disorder (ASD), however, deficits in social and language development are early-age core symptoms. We previously reported that superior temporal cortex, a well-established social and language region, shows reduced activation to social affective speech in ASD toddlers; however, the atypical cortical connectivity that accompanies this deviance remains unknown. METHODS: We collected clinical, eye tracking, and resting-state fMRI data from 86 ASD and non-ASD subjects (mean age 2.3?+?0.7 years). Functional connectivity of left and right superior temporal regions with other cortical regions and correlations between this connectivity and each child's social and language abilities were examined. RESULTS: While there was no group difference in functional connectivity, the connectivity between superior temporal cortex and frontal and parietal regions was significantly correlated with language, communication, and social abilities in non-ASD subjects, but these effects were absent in ASD subjects. Instead, ASD subjects, regardless of different social or nonsocial visual preferences, showed atypical correlations between temporal-visual region connectivity and communication ability (r(49)=0.55, p<0.001) and between temporal-precuneus connectivity and expressive language ability (r(49)=0.58, p<0.001). LIMITATIONS: The distinct connectivity-behavior correlation patterns may be related to different developmental stages in ASD and non-ASD subjects. The use of a prior 2-year-old template for spatial normalization may not be optimal for a few subjects beyond this age range. CONCLUSIONS: Superior temporal cortex is known to have reduced activation to social affective speech in ASD at early ages, and here we find in ASD toddlers that it also has atypical connectivity with visual and precuneus cortices that is correlated with communication and language ability, a pattern not seen in non-ASD toddlers. This atypicality may be an early-age signature of ASD that also explains why the disorder has deviant early language and social development. Given that these atypical connectivity patterns are also present in older individuals with ASD, we conclude these atypical connectivity patterns persist across age and may explain why successful interventions targeting language and social skills at all ages in ASD are so difficult to achieve. En ligne : http://dx.doi.org/10.1186/s13229-023-00543-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Atypical functional connectivity of temporal cortex with precuneus and visual regions may be an early-age signature of ASD [Texte imprimé et/ou numérique] / Teresa H. WEN, Auteur ; Lauren KUPIS, Auteur ; Lisa T. EYLER, Auteur ; Vani TALUJA, Auteur ; Jaden TROXEL, Auteur ; Disha GOEL, Auteur ; Michael V. LOMBARDO, Auteur ; Karen PIERCE, Auteur ; Eric COURCHESNE, Auteur . - 11 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 11 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Social and language abilities are closely intertwined during early typical development. In autism spectrum disorder (ASD), however, deficits in social and language development are early-age core symptoms. We previously reported that superior temporal cortex, a well-established social and language region, shows reduced activation to social affective speech in ASD toddlers; however, the atypical cortical connectivity that accompanies this deviance remains unknown. METHODS: We collected clinical, eye tracking, and resting-state fMRI data from 86 ASD and non-ASD subjects (mean age 2.3?+?0.7 years). Functional connectivity of left and right superior temporal regions with other cortical regions and correlations between this connectivity and each child's social and language abilities were examined. RESULTS: While there was no group difference in functional connectivity, the connectivity between superior temporal cortex and frontal and parietal regions was significantly correlated with language, communication, and social abilities in non-ASD subjects, but these effects were absent in ASD subjects. Instead, ASD subjects, regardless of different social or nonsocial visual preferences, showed atypical correlations between temporal-visual region connectivity and communication ability (r(49)=0.55, p<0.001) and between temporal-precuneus connectivity and expressive language ability (r(49)=0.58, p<0.001). LIMITATIONS: The distinct connectivity-behavior correlation patterns may be related to different developmental stages in ASD and non-ASD subjects. The use of a prior 2-year-old template for spatial normalization may not be optimal for a few subjects beyond this age range. CONCLUSIONS: Superior temporal cortex is known to have reduced activation to social affective speech in ASD at early ages, and here we find in ASD toddlers that it also has atypical connectivity with visual and precuneus cortices that is correlated with communication and language ability, a pattern not seen in non-ASD toddlers. This atypicality may be an early-age signature of ASD that also explains why the disorder has deviant early language and social development. Given that these atypical connectivity patterns are also present in older individuals with ASD, we conclude these atypical connectivity patterns persist across age and may explain why successful interventions targeting language and social skills at all ages in ASD are so difficult to achieve. En ligne : http://dx.doi.org/10.1186/s13229-023-00543-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

A systematic review and meta-analysis of suicidality in autistic and possibly autistic people without co-occurring intellectual disability / Lucy PHILLIPS ; Chris JONES ; Ellen TOWNSEND ; Caroline RICHARDS ; Sarah CASSIDY in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 12 p. Titre : A systematic review and meta-analysis of suicidality in autistic and possibly autistic people without co-occurring intellectual disability Type de document : Texte imprimé et/ou numérique Auteurs : Lucy PHILLIPS, Auteur ; Chris JONES, Auteur ; Ellen TOWNSEND, Auteur ; Caroline RICHARDS, Auteur ; Sarah CASSIDY, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Suicidality is highly prevalent in autistic people without co-occurring intellectual disabilities, and high autistic traits are found in adults who have attempted suicide. However, prevalence rates for both autistic and possibly autistic people have not been synthesised meta-analytically. AIMS: To (1) calculate pooled prevalence estimates of suicidality in autistic people and possibly autistic people without co-occurring intellectual disability; (2) evaluate the influence of participant and study level characteristics on heterogeneity; and (3) determine the quality of evidence. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. PsycINFO, Embase, MEDLINE and Web of Science were systematically searched from 1992 to January 25, 2022. Empirical quantitative studies reporting prevalence of suicidal ideation, suicide plans, or suicide attempts and behaviours were considered for inclusion. Random effects models were used to estimate pooled prevalence of each suicidality outcome with 95% confidence intervals. Heterogeneity was explored using sensitivity and moderator analyses. RESULTS: Data from 48,186 autistic and possibly autistic participants in 36 primary studies were meta-analysed. Pooled prevalence of suicidal ideation was 34.2% (95% CI 27.9-40.5), suicide plans 21.9% (13.4-30.4), and suicidal attempts and behaviours 24.3% (18.9-29.6). High levels of heterogeneity (I(2)>75) were observed in all three analyses. Estimates did not differ between autistic or possibly autistic samples. Geographical location (p=0.005), transgender or gender non-conforming samples (p<0.001) and type of report (p<0.001) significantly moderated suicidal ideation, whereas age group (p=0.001) and measure of suicidality (p=0.001) significantly moderated suicide plans. There was a significant association between the proportion of male participants and prevalence of suicide plans, with a decrease in the proportion of males for every unit change of suicide plan prevalence (p=0.013). No variables were found to moderate estimates of suicide attempts and behaviours. CONCLUSIONS: The results confirm suicidality is highly prevalent in both autistic and possibly autistic people without co-occurring intellectual disability and highlights potential moderators. Possibly autistic individuals require more attention in clinical and research considerations going forward to further understand and prevent suicide in both groups. En ligne : http://dx.doi.org/10.1186/s13229-023-00544-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] A systematic review and meta-analysis of suicidality in autistic and possibly autistic people without co-occurring intellectual disability [Texte imprimé et/ou numérique] / Lucy PHILLIPS, Auteur ; Chris JONES, Auteur ; Ellen TOWNSEND, Auteur ; Caroline RICHARDS, Auteur ; Sarah CASSIDY, Auteur . - 12 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 12 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Suicidality is highly prevalent in autistic people without co-occurring intellectual disabilities, and high autistic traits are found in adults who have attempted suicide. However, prevalence rates for both autistic and possibly autistic people have not been synthesised meta-analytically. AIMS: To (1) calculate pooled prevalence estimates of suicidality in autistic people and possibly autistic people without co-occurring intellectual disability; (2) evaluate the influence of participant and study level characteristics on heterogeneity; and (3) determine the quality of evidence. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. PsycINFO, Embase, MEDLINE and Web of Science were systematically searched from 1992 to January 25, 2022. Empirical quantitative studies reporting prevalence of suicidal ideation, suicide plans, or suicide attempts and behaviours were considered for inclusion. Random effects models were used to estimate pooled prevalence of each suicidality outcome with 95% confidence intervals. Heterogeneity was explored using sensitivity and moderator analyses. RESULTS: Data from 48,186 autistic and possibly autistic participants in 36 primary studies were meta-analysed. Pooled prevalence of suicidal ideation was 34.2% (95% CI 27.9-40.5), suicide plans 21.9% (13.4-30.4), and suicidal attempts and behaviours 24.3% (18.9-29.6). High levels of heterogeneity (I(2)>75) were observed in all three analyses. Estimates did not differ between autistic or possibly autistic samples. Geographical location (p=0.005), transgender or gender non-conforming samples (p<0.001) and type of report (p<0.001) significantly moderated suicidal ideation, whereas age group (p=0.001) and measure of suicidality (p=0.001) significantly moderated suicide plans. There was a significant association between the proportion of male participants and prevalence of suicide plans, with a decrease in the proportion of males for every unit change of suicide plan prevalence (p=0.013). No variables were found to moderate estimates of suicide attempts and behaviours. CONCLUSIONS: The results confirm suicidality is highly prevalent in both autistic and possibly autistic people without co-occurring intellectual disability and highlights potential moderators. Possibly autistic individuals require more attention in clinical and research considerations going forward to further understand and prevent suicide in both groups. En ligne : http://dx.doi.org/10.1186/s13229-023-00544-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Sex differences in the temporal dynamics of autistic children's natural conversations / Meredith COLA ; Azia KNOX ; Maggie Rose PELELLA ; Alison RUSSELL ; Aili HAUPTMANN ; Maxine COVELLO ; Christopher CIERI ; Mark LIBERMAN ; Robert T. SCHULTZ ; Julia PARISH-MORRIS in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 13 p. Titre : Sex differences in the temporal dynamics of autistic children's natural conversations Type de document : Texte imprimé et/ou numérique Auteurs : Meredith COLA, Auteur ; Azia KNOX, Auteur ; Maggie Rose PELELLA, Auteur ; Alison RUSSELL, Auteur ; Aili HAUPTMANN, Auteur ; Maxine COVELLO, Auteur ; Christopher CIERI, Auteur ; Mark LIBERMAN, Auteur ; Robert T. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur Article en page(s) : 13 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic girls are underdiagnosed compared to autistic boys, even when they experience similar clinical impact. Research suggests that girls present with distinct symptom profiles across a variety of domains, such as language, which may contribute to their underdiagnosis. In this study, we examine sex differences in the temporal dynamics of natural conversations between naïve adult confederates and school-aged children with or without autism, with the goal of improving our understanding of conversational behavior in autistic girls and ultimately improving identification. METHODS: Forty-five school-aged children with autism (29 boys and 16 girls) and 47 non-autistic/neurotypical (NT) children (23 boys and 24 girls) engaged in a 5-min "get-to-know-you" conversation with a young adult confederate that was unaware of children's diagnostic status. Groups were matched on IQ estimates. Recordings were time-aligned and orthographically transcribed by trained annotators. Several speech and pause measures were calculated. Groups were compared using analysis of covariance models, controlling for age. RESULTS: Autistic girls used significantly more words than autistic boys, and produced longer speech segments than all other groups. Autistic boys spoke more slowly than NT children, whereas autistic girls did not differ from NT children in total word counts or speaking rate. Autistic boys interrupted confederates' speech less often and produced longer between-turn pauses (i.e., responded more slowly when it was their turn) compared to other children. Within-turn pause duration did not differ by group. LIMITATIONS: Our sample included verbally fluent children and adolescents aged 6-15 years, so our study results may not replicate in samples of younger children, adults, and individuals who are not verbally fluent. The results of this relatively small study, while compelling, should be interpreted with caution and replicated in a larger sample. CONCLUSION: This study investigated the temporal dynamics of everyday conversations and demonstrated that autistic girls and boys have distinct natural language profiles. Specifying differences in verbal communication lays the groundwork for the development of sensitive screening and diagnostic tools to more accurately identify autistic girls, and could inform future personalized interventions that improve short- and long-term social communication outcomes for all autistic children. En ligne : http://dx.doi.org/10.1186/s13229-023-00545-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Sex differences in the temporal dynamics of autistic children's natural conversations [Texte imprimé et/ou numérique] / Meredith COLA, Auteur ; Azia KNOX, Auteur ; Maggie Rose PELELLA, Auteur ; Alison RUSSELL, Auteur ; Aili HAUPTMANN, Auteur ; Maxine COVELLO, Auteur ; Christopher CIERI, Auteur ; Mark LIBERMAN, Auteur ; Robert T. SCHULTZ, Auteur ; Julia PARISH-MORRIS, Auteur . - 13 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 13 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic girls are underdiagnosed compared to autistic boys, even when they experience similar clinical impact. Research suggests that girls present with distinct symptom profiles across a variety of domains, such as language, which may contribute to their underdiagnosis. In this study, we examine sex differences in the temporal dynamics of natural conversations between naïve adult confederates and school-aged children with or without autism, with the goal of improving our understanding of conversational behavior in autistic girls and ultimately improving identification. METHODS: Forty-five school-aged children with autism (29 boys and 16 girls) and 47 non-autistic/neurotypical (NT) children (23 boys and 24 girls) engaged in a 5-min "get-to-know-you" conversation with a young adult confederate that was unaware of children's diagnostic status. Groups were matched on IQ estimates. Recordings were time-aligned and orthographically transcribed by trained annotators. Several speech and pause measures were calculated. Groups were compared using analysis of covariance models, controlling for age. RESULTS: Autistic girls used significantly more words than autistic boys, and produced longer speech segments than all other groups. Autistic boys spoke more slowly than NT children, whereas autistic girls did not differ from NT children in total word counts or speaking rate. Autistic boys interrupted confederates' speech less often and produced longer between-turn pauses (i.e., responded more slowly when it was their turn) compared to other children. Within-turn pause duration did not differ by group. LIMITATIONS: Our sample included verbally fluent children and adolescents aged 6-15 years, so our study results may not replicate in samples of younger children, adults, and individuals who are not verbally fluent. The results of this relatively small study, while compelling, should be interpreted with caution and replicated in a larger sample. CONCLUSION: This study investigated the temporal dynamics of everyday conversations and demonstrated that autistic girls and boys have distinct natural language profiles. Specifying differences in verbal communication lays the groundwork for the development of sensitive screening and diagnostic tools to more accurately identify autistic girls, and could inform future personalized interventions that improve short- and long-term social communication outcomes for all autistic children. En ligne : http://dx.doi.org/10.1186/s13229-023-00545-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome / Alberto Samuel SUÁREZ-PINILLA ; Nuria GARCÍA-FONT ; M. Luisa LAGUNA-LUQUE ; Juan C. LÓPEZ-RAMOS ; María Jesús OSET-GASQUE ; Agnes GRUART ; José M. DELGADO-GARCÍA ; Magdalena TORRES ; José SÁNCHEZ-PRIETO in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 14 p. Titre : The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Alberto Samuel SUÁREZ-PINILLA, Auteur ; Nuria GARCÍA-FONT, Auteur ; M. Luisa LAGUNA-LUQUE, Auteur ; Juan C. LÓPEZ-RAMOS, Auteur ; María Jesús OSET-GASQUE, Auteur ; Agnes GRUART, Auteur ; José M. DELGADO-GARCÍA, Auteur ; Magdalena TORRES, Auteur ; José SÁNCHEZ-PRIETO, Auteur Article en page(s) : 14 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment. METHODS: We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4. RESULTS: We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced asynchronous release, which not only prevents further potentiation, but it also compromises presynaptic parallel fiber long-term potentiation (PF-LTP) mediated by ? adrenergic receptors. A reduction in extracellular Ca(2+) concentration restored the readily releasable pool (RRP) size, basal synaptic transmission, ? adrenergic receptor-mediated potentiation, and PF-LTP. Interestingly, VU 0155041, a selective positive allosteric modulator of mGluR4, also restored both the RRP size and PF-LTP in mice of either sex. Moreover, when injected into Fmr1KO male mice, VU 0155041 improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests, as well as the social behavior alterations of these mice. LIMITATIONS: We cannot rule out that the activation of mGluR4s via systemic administration of VU0155041 can also affect other brain regions. Further studies are needed to stablish the effect of a specific activation of mGluR4 in cerebellar granule cells. CONCLUSIONS: Our study shows that an increase in synaptic vesicles, SV, docking may cause the loss of PF-LTP and motor learning and social deficits of Fmr1KO mice and that the reversal of these changes by pharmacological activation of mGluR4 may offer therapeutic relief for motor learning and social deficits in FXS. En ligne : http://dx.doi.org/10.1186/s13229-023-00547-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] The activation of mGluR4 rescues parallel fiber synaptic transmission and LTP, motor learning and social behavior in a mouse model of Fragile X Syndrome [Texte imprimé et/ou numérique] / Alberto Samuel SUÁREZ-PINILLA, Auteur ; Nuria GARCÍA-FONT, Auteur ; M. Luisa LAGUNA-LUQUE, Auteur ; Juan C. LÓPEZ-RAMOS, Auteur ; María Jesús OSET-GASQUE, Auteur ; Agnes GRUART, Auteur ; José M. DELGADO-GARCÍA, Auteur ; Magdalena TORRES, Auteur ; José SÁNCHEZ-PRIETO, Auteur . - 14 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 14 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), the most common inherited intellectual disability, is caused by the loss of expression of the Fragile X Messenger Ribonucleoprotein (FMRP). FMRP is an RNA-binding protein that negatively regulates the expression of many postsynaptic as well as presynaptic proteins involved in action potential properties, calcium homeostasis and neurotransmitter release. FXS patients and mice lacking FMRP suffer from multiple behavioral alterations, including deficits in motor learning for which there is currently no specific treatment. METHODS: We performed electron microscopy, whole-cell patch-clamp electrophysiology and behavioral experiments to characterise the synaptic mechanisms underlying the motor learning deficits observed in Fmr1KO mice and the therapeutic potential of positive allosteric modulator of mGluR4. RESULTS: We found that enhanced synaptic vesicle docking of cerebellar parallel fiber to Purkinje cell Fmr1KO synapses was associated with enhanced asynchronous release, which not only prevents further potentiation, but it also compromises presynaptic parallel fiber long-term potentiation (PF-LTP) mediated by ? adrenergic receptors. A reduction in extracellular Ca(2+) concentration restored the readily releasable pool (RRP) size, basal synaptic transmission, ? adrenergic receptor-mediated potentiation, and PF-LTP. Interestingly, VU 0155041, a selective positive allosteric modulator of mGluR4, also restored both the RRP size and PF-LTP in mice of either sex. Moreover, when injected into Fmr1KO male mice, VU 0155041 improved motor learning in skilled reaching, classical eyeblink conditioning and vestibuloocular reflex (VOR) tests, as well as the social behavior alterations of these mice. LIMITATIONS: We cannot rule out that the activation of mGluR4s via systemic administration of VU0155041 can also affect other brain regions. Further studies are needed to stablish the effect of a specific activation of mGluR4 in cerebellar granule cells. CONCLUSIONS: Our study shows that an increase in synaptic vesicles, SV, docking may cause the loss of PF-LTP and motor learning and social deficits of Fmr1KO mice and that the reversal of these changes by pharmacological activation of mGluR4 may offer therapeutic relief for motor learning and social deficits in FXS. En ligne : http://dx.doi.org/10.1186/s13229-023-00547-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

A working taxonomy for describing the sensory differences of autism / Zachary J. WILLIAMS ; Ashley HARRIS ; Helen POWELL ; Roseann SCHAAF ; Teresa TAVASSOLI ; Nicolaas A. J. PUTS in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 15 p. Titre : A working taxonomy for describing the sensory differences of autism Type de document : Texte imprimé et/ou numérique Auteurs : Zachary J. WILLIAMS, Auteur ; Ashley HARRIS, Auteur ; Helen POWELL, Auteur ; Roseann SCHAAF, Auteur ; Teresa TAVASSOLI, Auteur ; Nicolaas A. J. PUTS, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals on the autism spectrum have been long described to process sensory information differently than neurotypical individuals. While much effort has been leveraged towards characterizing and investigating the neurobiology underlying the sensory differences of autism, there has been a notable lack of consistency in the terms being used to describe the nature of those differences. MAIN BODY: We argue that inconsistent and interchangeable terminology-use when describing the sensory differences of autism has become problematic beyond mere pedantry and inconvenience. We begin by highlighting popular terms that are currently being used to describe the sensory differences of autism (e.g. "sensitivity", "reactivity" and "responsivity") and discuss why poor nomenclature may hamper efforts towards understanding the aetiology of sensory differences in autism. We then provide a solution to poor terminology-use by proposing a hierarchical taxonomy for describing and referring to various sensory features. CONCLUSION: Inconsistent terminology-use when describing the sensory features of autism has stifled discussion and scientific understanding of the sensory differences of autism. The hierarchical taxonomy proposed was developed to help resolve lack of clarity when discussing the sensory differences of autism and to place future research targets at appropriate levels of analysis. En ligne : http://dx.doi.org/10.1186/s13229-022-00534-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] A working taxonomy for describing the sensory differences of autism [Texte imprimé et/ou numérique] / Zachary J. WILLIAMS, Auteur ; Ashley HARRIS, Auteur ; Helen POWELL, Auteur ; Roseann SCHAAF, Auteur ; Teresa TAVASSOLI, Auteur ; Nicolaas A. J. PUTS, Auteur . - 15 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 15 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals on the autism spectrum have been long described to process sensory information differently than neurotypical individuals. While much effort has been leveraged towards characterizing and investigating the neurobiology underlying the sensory differences of autism, there has been a notable lack of consistency in the terms being used to describe the nature of those differences. MAIN BODY: We argue that inconsistent and interchangeable terminology-use when describing the sensory differences of autism has become problematic beyond mere pedantry and inconvenience. We begin by highlighting popular terms that are currently being used to describe the sensory differences of autism (e.g. "sensitivity", "reactivity" and "responsivity") and discuss why poor nomenclature may hamper efforts towards understanding the aetiology of sensory differences in autism. We then provide a solution to poor terminology-use by proposing a hierarchical taxonomy for describing and referring to various sensory features. CONCLUSION: Inconsistent terminology-use when describing the sensory features of autism has stifled discussion and scientific understanding of the sensory differences of autism. The hierarchical taxonomy proposed was developed to help resolve lack of clarity when discussing the sensory differences of autism and to place future research targets at appropriate levels of analysis. En ligne : http://dx.doi.org/10.1186/s13229-022-00534-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial / Matthijs MOERKERKE ; Jean STEYAERT ; Annelies BAMPS ; Edward DEBBAUT ; Jellina PRINSEN ; Tiffany TANG ; Stephanie VAN DER DONCK ; Bart BOETS ; Kaat ALAERTS in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 16 p. Titre : Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial Type de document : Texte imprimé et/ou numérique Auteurs : Matthijs MOERKERKE, Auteur ; Jean STEYAERT, Auteur ; Annelies BAMPS, Auteur ; Edward DEBBAUT, Auteur ; Jellina PRINSEN, Auteur ; Tiffany TANG, Auteur ; Stephanie VAN DER DONCK, Auteur ; Bart BOETS, Auteur ; Kaat ALAERTS, Auteur Article en page(s) : 16 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Intranasal administration of oxytocin is increasingly explored as a new approach to facilitate social development and reduce disability associated with a diagnosis of autism spectrum disorder (ASD). The efficacy of multiple-dose oxytocin administration in children with ASD is, however, not well established. METHODS: A double-blind, randomized, placebo-controlled trial with parallel design explored the effects of a 4-week intranasal oxytocin administration (12 IU, twice daily) on parent-rated social responsiveness (Social Responsiveness Scale: SRS-2) in pre-pubertal school-aged children (aged 8-12 years, 61 boys, 16 girls). Secondary outcomes included a questionnaire-based assessment of repetitive behaviors, anxiety, and attachment. Effects of oxytocin were assessed immediately after the administration period and at a follow-up, 4 weeks after the last administration. The double-blind phase was followed by a 4-week single-blind phase during which all participants received intranasal oxytocin. RESULTS: In the double-blind phase, both the oxytocin and placebo group displayed significant pre-to-post-improvements in social responsiveness and secondary questionnaires, but improvements were not specific to the intranasal oxytocin. Notably, in the single-blind phase, participants who were first allocated to intranasal placebo and later changed to intranasal oxytocin displayed a significant improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. Participants receiving oxytocin in the first phase also showed a significant further improvement upon receiving a second course of oxytocin, but only at the 4-week follow-up. Further, exploratory moderator analyses indicated that children who received psychosocial trainings (3 or more sessions per month) along with oxytocin administration displayed a more pronounced improvement in social responsiveness. LIMITATIONS: Future studies using larger cohorts and more explicitly controlled concurrent psychosocial trainings are warranted to further explore the preliminary moderator effects, also including understudied populations within the autism spectrum, such as children with co-occurring intellectual disabilities. CONCLUSIONS: Four weeks of oxytocin administration did not induce treatment-specific improvements in social responsiveness in school-aged children with ASD. Future studies are warranted to further explore the clinical efficacy of oxytocin administration paired with targeted psychosocial trainings that stimulate socio-communicative behaviors. Trial registration The trial was registered with the European Clinical Trial Registry (EudraCT 2018-000769-35) on June 7th, 2018 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE ). En ligne : http://dx.doi.org/10.1186/s13229-023-00546-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial [Texte imprimé et/ou numérique] / Matthijs MOERKERKE, Auteur ; Jean STEYAERT, Auteur ; Annelies BAMPS, Auteur ; Edward DEBBAUT, Auteur ; Jellina PRINSEN, Auteur ; Tiffany TANG, Auteur ; Stephanie VAN DER DONCK, Auteur ; Bart BOETS, Auteur ; Kaat ALAERTS, Auteur . - 16 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 16 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intranasal administration of oxytocin is increasingly explored as a new approach to facilitate social development and reduce disability associated with a diagnosis of autism spectrum disorder (ASD). The efficacy of multiple-dose oxytocin administration in children with ASD is, however, not well established. METHODS: A double-blind, randomized, placebo-controlled trial with parallel design explored the effects of a 4-week intranasal oxytocin administration (12 IU, twice daily) on parent-rated social responsiveness (Social Responsiveness Scale: SRS-2) in pre-pubertal school-aged children (aged 8-12 years, 61 boys, 16 girls). Secondary outcomes included a questionnaire-based assessment of repetitive behaviors, anxiety, and attachment. Effects of oxytocin were assessed immediately after the administration period and at a follow-up, 4 weeks after the last administration. The double-blind phase was followed by a 4-week single-blind phase during which all participants received intranasal oxytocin. RESULTS: In the double-blind phase, both the oxytocin and placebo group displayed significant pre-to-post-improvements in social responsiveness and secondary questionnaires, but improvements were not specific to the intranasal oxytocin. Notably, in the single-blind phase, participants who were first allocated to intranasal placebo and later changed to intranasal oxytocin displayed a significant improvement in social responsiveness, over and above the placebo-induced improvements noted in the first phase. Participants receiving oxytocin in the first phase also showed a significant further improvement upon receiving a second course of oxytocin, but only at the 4-week follow-up. Further, exploratory moderator analyses indicated that children who received psychosocial trainings (3 or more sessions per month) along with oxytocin administration displayed a more pronounced improvement in social responsiveness. LIMITATIONS: Future studies using larger cohorts and more explicitly controlled concurrent psychosocial trainings are warranted to further explore the preliminary moderator effects, also including understudied populations within the autism spectrum, such as children with co-occurring intellectual disabilities. CONCLUSIONS: Four weeks of oxytocin administration did not induce treatment-specific improvements in social responsiveness in school-aged children with ASD. Future studies are warranted to further explore the clinical efficacy of oxytocin administration paired with targeted psychosocial trainings that stimulate socio-communicative behaviors. Trial registration The trial was registered with the European Clinical Trial Registry (EudraCT 2018-000769-35) on June 7th, 2018 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-000769-35/BE ). En ligne : http://dx.doi.org/10.1186/s13229-023-00546-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder / Mark J. TAYLOR ; Henrik LARSSON ; Catarina ALMQVIST ; Paul LICHTENSTEIN ; Sebastian LUNDSTROM ; Sven BÖLTE in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 17 p. Titre : Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder Type de document : Texte imprimé et/ou numérique Auteurs : Mark J. TAYLOR, Auteur ; Henrik LARSSON, Auteur ; Catarina ALMQVIST, Auteur ; Paul LICHTENSTEIN, Auteur ; Sebastian LUNDSTROM, Auteur ; Sven BÖLTE, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. METHODS: In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism-Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. RESULTS: Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (r(a)) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (r(a)=0.31), functional diarrhea (r(a)=0.27) as well as mixed gastrointestinal disorders (r(a)=0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (r(a)=0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (r(a)=0.30, 0.17, and 0.17, respectively). LIMITATIONS: Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. CONCLUSIONS: Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity. En ligne : http://dx.doi.org/10.1186/s13229-023-00548-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Genetic and environmental contributions to co-occurring physical health conditions in autism spectrum condition and attention-deficit/hyperactivity disorder [Texte imprimé et/ou numérique] / Mark J. TAYLOR, Auteur ; Henrik LARSSON, Auteur ; Catarina ALMQVIST, Auteur ; Paul LICHTENSTEIN, Auteur ; Sebastian LUNDSTROM, Auteur ; Sven BÖLTE, Auteur . - 17 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 17 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum condition and attention-deficit/hyperactivity disorder (ADHD) are associated with a range of physical health conditions. The aim of this study was to examine the etiological components contributing to co-occurring physical health conditions in autism and ADHD. METHODS: In this nationwide Child and Adolescent Twin Study in Sweden, we analyzed data from 10,347 twin pairs aged 9 and 12. Clinical diagnoses of autism, ADHD, and physical health conditions were identified through the Swedish National Patient Register. Subclinical phenotypes of autism and ADHD were defined by symptom thresholds on a standardized parent-interview, the Autism-Tics, ADHD, and Other Comorbidities inventory. Associations between physical health conditions and autism/ADHD phenotypes were examined using generalized estimating equations. Bivariate twin models were applied to estimate the extent to which genetic and environmental risk factors accounted for physical health comorbidities. RESULTS: Similar patterns of association with physical health conditions were found in clinical and subclinical autism/ADHD, with odds ratios ranging from 1.31 for asthma in subclinical ADHD to 8.03 for epilepsy in clinical autism. The estimated genetic correlation (r(a)) with epilepsy was 0.50 for clinical autism and 0.35 for subclinical autism. In addition, a modest genetic correlation was estimated between clinical autism and constipation (r(a)=0.31), functional diarrhea (r(a)=0.27) as well as mixed gastrointestinal disorders (r(a)=0.30). Genetic effects contributed 0.86 for mixed gastrointestinal disorders in clinical ADHD (r(a)=0.21). Finally, subclinical ADHD shared genetic risk factors with epilepsy, constipation, and mixed gastrointestinal disorders (r(a)=0.30, 0.17, and 0.17, respectively). LIMITATIONS: Importantly, since medical records from primary care were not included in the registry data used, we probably identified only more severe rather than the full range of physical health conditions. Furthermore, it needs to be considered that the higher prevalence of physical health conditions among autistic children and children with ADHD could be associated with the increased number of medical visits. CONCLUSIONS: Shared genetic effects contribute significantly to autism and ADHD phenotypes with the co-occurring physical health conditions across different organ systems, including epilepsy and gastrointestinal disorders. The shared genetic liability with co-occurring physical health conditions was present across different levels of autism and ADHD symptom severity. En ligne : http://dx.doi.org/10.1186/s13229-023-00548-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Understanding the relationship between cerebellar structure and social abilities / Dorothea L. FLORIS ; Pierrick COUPÉ ; Edouard DUCHESNAY ; Angeline MIHAILOV ; Antoine GRIGIS ; Indrit BÈGUE ; Julie VICTOR ; Vincent FROUIN ; Marion LEBOYER ; Josselin HOUENOU ; Charles LAIDI in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 18 p. Titre : Understanding the relationship between cerebellar structure and social abilities Type de document : Texte imprimé et/ou numérique Auteurs : Dorothea L. FLORIS, Auteur ; Pierrick COUPÉ, Auteur ; Edouard DUCHESNAY, Auteur ; Angeline MIHAILOV, Auteur ; Antoine GRIGIS, Auteur ; Indrit BÈGUE, Auteur ; Julie VICTOR, Auteur ; Vincent FROUIN, Auteur ; Marion LEBOYER, Auteur ; Josselin HOUENOU, Auteur ; Charles LAIDI, Auteur Article en page(s) : 18 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: The cerebellum contains more than 50% of all neurons in the brain and is involved in a broad range of cognitive functions, including social communication and social cognition. Inconsistent atypicalities in the cerebellum have been reported in individuals with autism compared to controls suggesting the limits of categorical case control comparisons. Alternatively, investigating how clinical dimensions are related to neuroanatomical features, in line with the Research Domain Criteria approach, might be more relevant. We hypothesized that the volume of the "cognitive" lobules of the cerebellum would be associated with social difficulties. METHODS: We analyzed structural MRI data from a large pediatric and transdiagnostic sample (Healthy Brain Network). We performed cerebellar parcellation with a well-validated automated segmentation pipeline (CERES). We studied how social communication abilities-assessed with the social component of the Social Responsiveness Scale (SRS)-were associated with the cerebellar structure, using linear mixed models and canonical correlation analysis. RESULTS: In 850 children and teenagers (mean age 10.8?+?3 years; range 5-18 years), we found a significant association between the cerebellum, IQ and social communication performance in our canonical correlation model. LIMITATIONS: Cerebellar parcellation relies on anatomical boundaries, which does not overlap with functional anatomy. The SRS was originally designed to identify social impairments associated with autism spectrum disorders. CONCLUSION: Our results unravel a complex relationship between cerebellar structure, social performance and IQ and provide support for the involvement of the cerebellum in social and cognitive processes. En ligne : http://dx.doi.org/10.1186/s13229-023-00551-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Understanding the relationship between cerebellar structure and social abilities [Texte imprimé et/ou numérique] / Dorothea L. FLORIS, Auteur ; Pierrick COUPÉ, Auteur ; Edouard DUCHESNAY, Auteur ; Angeline MIHAILOV, Auteur ; Antoine GRIGIS, Auteur ; Indrit BÈGUE, Auteur ; Julie VICTOR, Auteur ; Vincent FROUIN, Auteur ; Marion LEBOYER, Auteur ; Josselin HOUENOU, Auteur ; Charles LAIDI, Auteur . - 18 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 18 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: The cerebellum contains more than 50% of all neurons in the brain and is involved in a broad range of cognitive functions, including social communication and social cognition. Inconsistent atypicalities in the cerebellum have been reported in individuals with autism compared to controls suggesting the limits of categorical case control comparisons. Alternatively, investigating how clinical dimensions are related to neuroanatomical features, in line with the Research Domain Criteria approach, might be more relevant. We hypothesized that the volume of the "cognitive" lobules of the cerebellum would be associated with social difficulties. METHODS: We analyzed structural MRI data from a large pediatric and transdiagnostic sample (Healthy Brain Network). We performed cerebellar parcellation with a well-validated automated segmentation pipeline (CERES). We studied how social communication abilities-assessed with the social component of the Social Responsiveness Scale (SRS)-were associated with the cerebellar structure, using linear mixed models and canonical correlation analysis. RESULTS: In 850 children and teenagers (mean age 10.8?+?3 years; range 5-18 years), we found a significant association between the cerebellum, IQ and social communication performance in our canonical correlation model. LIMITATIONS: Cerebellar parcellation relies on anatomical boundaries, which does not overlap with functional anatomy. The SRS was originally designed to identify social impairments associated with autism spectrum disorders. CONCLUSION: Our results unravel a complex relationship between cerebellar structure, social performance and IQ and provide support for the involvement of the cerebellum in social and cognitive processes. En ligne : http://dx.doi.org/10.1186/s13229-023-00551-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Identifying the neurodevelopmental and psychiatric signatures of genomic disorders associated with intellectual disability: a machine learning approach / Adam CUNNINGHAM ; Sergio Marco SALAS ; Matthew BRACHER-SMITH ; Samuel CHAWNER ; Jan STOCHL ; Tamsin FORD ; F. Lucy RAYMOND ; Valentina ESCOTT-PRICE ; Marianne B. M. VAN DEN BREE in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 19 p. Titre : Identifying the neurodevelopmental and psychiatric signatures of genomic disorders associated with intellectual disability: a machine learning approach Type de document : Texte imprimé et/ou numérique Auteurs : Adam CUNNINGHAM, Auteur ; Sergio Marco SALAS, Auteur ; Matthew BRACHER-SMITH, Auteur ; Samuel CHAWNER, Auteur ; Jan STOCHL, Auteur ; Tamsin FORD, Auteur ; F. Lucy RAYMOND, Auteur ; Valentina ESCOTT-PRICE, Auteur ; Marianne B. M. VAN DEN BREE, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Genomic conditions can be associated with developmental delay, intellectual disability, autism spectrum disorder, and physical and mental health symptoms. They are individually rare and highly variable in presentation, which limits the use of standard clinical guidelines for diagnosis and treatment. A simple screening tool to identify young people with genomic conditions associated with neurodevelopmental disorders (ND-GCs) who could benefit from further support would be of considerable value. We used machine learning approaches to address this question. METHOD: A total of 493 individuals were included: 389 with a ND-GC, mean age=9.01, 66% male) and 104 siblings without known genomic conditions (controls, mean age=10.23, 53% male). Primary carers completed assessments of behavioural, neurodevelopmental and psychiatric symptoms and physical health and development. Machine learning techniques (penalised logistic regression, random forests, support vector machines and artificial neural networks) were used to develop classifiers of ND-GC status and identified limited sets of variables that gave the best classification performance. Exploratory graph analysis was used to understand associations within the final variable set. RESULTS: All machine learning methods identified variable sets giving high classification accuracy (AUROC between 0.883 and 0.915). We identified a subset of 30 variables best discriminating between individuals with ND-GCs and controls which formed 5 dimensions: conduct, separation anxiety, situational anxiety, communication and motor development. LIMITATIONS: This study used cross-sectional data from a cohort study which was imbalanced with respect to ND-GC status. Our model requires validation in independent datasets and with longitudinal follow-up data for validation before clinical application. CONCLUSIONS: In this study, we developed models that identified a compact set of psychiatric and physical health measures that differentiate individuals with a ND-GC from controls and highlight higher-order structure within these measures. This work is a step towards developing a screening instrument to identify young people with ND-GCs who might benefit from further specialist assessment. En ligne : http://dx.doi.org/10.1186/s13229-023-00549-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Identifying the neurodevelopmental and psychiatric signatures of genomic disorders associated with intellectual disability: a machine learning approach [Texte imprimé et/ou numérique] / Adam CUNNINGHAM, Auteur ; Sergio Marco SALAS, Auteur ; Matthew BRACHER-SMITH, Auteur ; Samuel CHAWNER, Auteur ; Jan STOCHL, Auteur ; Tamsin FORD, Auteur ; F. Lucy RAYMOND, Auteur ; Valentina ESCOTT-PRICE, Auteur ; Marianne B. M. VAN DEN BREE, Auteur . - 19 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 19 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Genomic conditions can be associated with developmental delay, intellectual disability, autism spectrum disorder, and physical and mental health symptoms. They are individually rare and highly variable in presentation, which limits the use of standard clinical guidelines for diagnosis and treatment. A simple screening tool to identify young people with genomic conditions associated with neurodevelopmental disorders (ND-GCs) who could benefit from further support would be of considerable value. We used machine learning approaches to address this question. METHOD: A total of 493 individuals were included: 389 with a ND-GC, mean age=9.01, 66% male) and 104 siblings without known genomic conditions (controls, mean age=10.23, 53% male). Primary carers completed assessments of behavioural, neurodevelopmental and psychiatric symptoms and physical health and development. Machine learning techniques (penalised logistic regression, random forests, support vector machines and artificial neural networks) were used to develop classifiers of ND-GC status and identified limited sets of variables that gave the best classification performance. Exploratory graph analysis was used to understand associations within the final variable set. RESULTS: All machine learning methods identified variable sets giving high classification accuracy (AUROC between 0.883 and 0.915). We identified a subset of 30 variables best discriminating between individuals with ND-GCs and controls which formed 5 dimensions: conduct, separation anxiety, situational anxiety, communication and motor development. LIMITATIONS: This study used cross-sectional data from a cohort study which was imbalanced with respect to ND-GC status. Our model requires validation in independent datasets and with longitudinal follow-up data for validation before clinical application. CONCLUSIONS: In this study, we developed models that identified a compact set of psychiatric and physical health measures that differentiate individuals with a ND-GC from controls and highlight higher-order structure within these measures. This work is a step towards developing a screening instrument to identify young people with ND-GCs who might benefit from further specialist assessment. En ligne : http://dx.doi.org/10.1186/s13229-023-00549-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

SETD5 haploinsufficiency affects mitochondrial compartment in neural cells / Fabiana LONGO ; Luca MASSIMINO ; Alicia RUBIO ; Simone BIDO ; Pietro Giuseppe MAZZARA ; Edoardo BELLINI ; Federica BANFI ; Paola PODINI ; Francesca MALTECCA ; Alessio ZIPPO ; Vania BROCCOLI ; Alessandro SESSA in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 20 p. Titre : SETD5 haploinsufficiency affects mitochondrial compartment in neural cells Type de document : Texte imprimé et/ou numérique Auteurs : Fabiana LONGO, Auteur ; Luca MASSIMINO, Auteur ; Alicia RUBIO, Auteur ; Simone BIDO, Auteur ; Pietro Giuseppe MAZZARA, Auteur ; Edoardo BELLINI, Auteur ; Federica BANFI, Auteur ; Paola PODINI, Auteur ; Francesca MALTECCA, Auteur ; Alessio ZIPPO, Auteur ; Vania BROCCOLI, Auteur ; Alessandro SESSA, Auteur Article en page(s) : 20 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs) are heterogeneous conditions due to alterations of a variety of molecular mechanisms and cell dysfunctions. SETD5 haploinsufficiency leads to NDDs due to chromatin defects. Epigenetic basis of NDDs has been reported in an increasing number of cases while mitochondrial dysfunctions are more common within NDD patients than in the general population. METHODS: We investigated in vitro neural stem cells as well as the brain of the Setd5 haploinsufficiency mouse model interrogating its transcriptome, analyzing mitochondrial structure, biochemical composition, and dynamics, as well as mitochondrial functionality. RESULTS: Mitochondrial impairment is facilitated by transcriptional aberrations originated by the decrease of the SETD5 enzyme. Low levels of SETD5 resulted in fragmented mitochondria, reduced mitochondrial membrane potential, and ATP production both in neural precursors and neurons. Mitochondria were also mislocalized in mutant neurons, with reduced organelles within neurites and synapses. LIMITATIONS: We found several defects in the mitochondrial compartment; however, we can only speculate about their position in the hierarchy of the pathological mechanisms at the basis of the disease. CONCLUSIONS: Our study explores the interplay between chromatin regulation and mitochondria functions as a possible important aspect of SETD5-associated NDD pathophysiology. Our data, if confirmed in patient context, suggest that the mitochondrial activity and dynamics may represent new therapeutic targets for disorders associated with the loss of SETD5. En ligne : http://dx.doi.org/10.1186/s13229-023-00550-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] SETD5 haploinsufficiency affects mitochondrial compartment in neural cells [Texte imprimé et/ou numérique] / Fabiana LONGO, Auteur ; Luca MASSIMINO, Auteur ; Alicia RUBIO, Auteur ; Simone BIDO, Auteur ; Pietro Giuseppe MAZZARA, Auteur ; Edoardo BELLINI, Auteur ; Federica BANFI, Auteur ; Paola PODINI, Auteur ; Francesca MALTECCA, Auteur ; Alessio ZIPPO, Auteur ; Vania BROCCOLI, Auteur ; Alessandro SESSA, Auteur . - 20 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 20 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs) are heterogeneous conditions due to alterations of a variety of molecular mechanisms and cell dysfunctions. SETD5 haploinsufficiency leads to NDDs due to chromatin defects. Epigenetic basis of NDDs has been reported in an increasing number of cases while mitochondrial dysfunctions are more common within NDD patients than in the general population. METHODS: We investigated in vitro neural stem cells as well as the brain of the Setd5 haploinsufficiency mouse model interrogating its transcriptome, analyzing mitochondrial structure, biochemical composition, and dynamics, as well as mitochondrial functionality. RESULTS: Mitochondrial impairment is facilitated by transcriptional aberrations originated by the decrease of the SETD5 enzyme. Low levels of SETD5 resulted in fragmented mitochondria, reduced mitochondrial membrane potential, and ATP production both in neural precursors and neurons. Mitochondria were also mislocalized in mutant neurons, with reduced organelles within neurites and synapses. LIMITATIONS: We found several defects in the mitochondrial compartment; however, we can only speculate about their position in the hierarchy of the pathological mechanisms at the basis of the disease. CONCLUSIONS: Our study explores the interplay between chromatin regulation and mitochondria functions as a possible important aspect of SETD5-associated NDD pathophysiology. Our data, if confirmed in patient context, suggest that the mitochondrial activity and dynamics may represent new therapeutic targets for disorders associated with the loss of SETD5. En ligne : http://dx.doi.org/10.1186/s13229-023-00550-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model / Najwa OUALI ALAMI ; Oumayma AOUSJI ; Esther POGATZKI-ZAHN ; Peter K. ZAHN ; Hanna WILHELM ; Dhruva DESHPANDE ; Elmira KHATAMSAZ ; Alberto CATANESE ; Sarah WOELFLE ; Michael SCHÖN ; Sanjay JAIN ; Stefanie GRABRUCKER ; Albert C. LUDOLPH ; Chiara VERPELLI ; Jens MICHAELIS ; Tobias M. BOECKERS ; Francesco ROSELLI in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 21 p. Titre : Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model Type de document : Texte imprimé et/ou numérique Auteurs : Najwa OUALI ALAMI, Auteur ; Oumayma AOUSJI, Auteur ; Esther POGATZKI-ZAHN, Auteur ; Peter K. ZAHN, Auteur ; Hanna WILHELM, Auteur ; Dhruva DESHPANDE, Auteur ; Elmira KHATAMSAZ, Auteur ; Alberto CATANESE, Auteur ; Sarah WOELFLE, Auteur ; Michael SCHÖN, Auteur ; Sanjay JAIN, Auteur ; Stefanie GRABRUCKER, Auteur ; Albert C. LUDOLPH, Auteur ; Chiara VERPELLI, Auteur ; Jens MICHAELIS, Auteur ; Tobias M. BOECKERS, Auteur ; Francesco ROSELLI, Auteur Article en page(s) : 21 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism Spectrum Disorders (ASD) patients experience disturbed nociception in the form of either hyposensitivity to pain or allodynia. A substantial amount of processing of somatosensory and nociceptive stimulus takes place in the dorsal spinal cord. However, many of these circuits are not very well understood in the context of nociceptive processing in ASD. METHODS: We have used a Shank2(-/-) mouse model, which displays a set of phenotypes reminiscent of ASD, and performed behavioural and microscopic analysis to investigate the role of dorsal horn circuitry in nociceptive processing of ASD. RESULTS: We determined that Shank2(-/-) mice display increased sensitivity to formalin pain and thermal preference, but a sensory specific mechanical allodynia. We demonstrate that high levels of Shank2 expression identifies a subpopulation of neurons in murine and human dorsal spinal cord, composed mainly by glycinergic interneurons and that loss of Shank2 causes the decrease in NMDAR in excitatory synapses on these inhibitory interneurons. In fact, in the subacute phase of the formalin test, glycinergic interneurons are strongly activated in wild type (WT) mice but not in Shank2(-/-) mice. Consequently, nociception projection neurons in laminae I are activated in larger numbers in Shank2(-/-) mice. LIMITATIONS: Our investigation is limited to male mice, in agreement with the higher representation of ASD in males; therefore, caution should be applied to extrapolate the findings to females. Furthermore, ASD is characterized by extensive genetic diversity and therefore the findings related to Shank2 mutant mice may not necessarily apply to patients with different gene mutations. Since nociceptive phenotypes in ASD range between hyper- and hypo-sensitivity, diverse mutations may affect the circuit in opposite ways. CONCLUSION: Our findings prove that Shank2 expression identifies a new subset of inhibitory interneurons involved in reducing the transmission of nociceptive stimuli and whose unchecked activation is associated with pain hypersensitivity. We provide evidence that dysfunction in spinal cord pain processing may contribute to the nociceptive phenotypes in ASD. En ligne : http://dx.doi.org/10.1186/s13229-023-00552-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model [Texte imprimé et/ou numérique] / Najwa OUALI ALAMI, Auteur ; Oumayma AOUSJI, Auteur ; Esther POGATZKI-ZAHN, Auteur ; Peter K. ZAHN, Auteur ; Hanna WILHELM, Auteur ; Dhruva DESHPANDE, Auteur ; Elmira KHATAMSAZ, Auteur ; Alberto CATANESE, Auteur ; Sarah WOELFLE, Auteur ; Michael SCHÖN, Auteur ; Sanjay JAIN, Auteur ; Stefanie GRABRUCKER, Auteur ; Albert C. LUDOLPH, Auteur ; Chiara VERPELLI, Auteur ; Jens MICHAELIS, Auteur ; Tobias M. BOECKERS, Auteur ; Francesco ROSELLI, Auteur . - 21 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 21 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism Spectrum Disorders (ASD) patients experience disturbed nociception in the form of either hyposensitivity to pain or allodynia. A substantial amount of processing of somatosensory and nociceptive stimulus takes place in the dorsal spinal cord. However, many of these circuits are not very well understood in the context of nociceptive processing in ASD. METHODS: We have used a Shank2(-/-) mouse model, which displays a set of phenotypes reminiscent of ASD, and performed behavioural and microscopic analysis to investigate the role of dorsal horn circuitry in nociceptive processing of ASD. RESULTS: We determined that Shank2(-/-) mice display increased sensitivity to formalin pain and thermal preference, but a sensory specific mechanical allodynia. We demonstrate that high levels of Shank2 expression identifies a subpopulation of neurons in murine and human dorsal spinal cord, composed mainly by glycinergic interneurons and that loss of Shank2 causes the decrease in NMDAR in excitatory synapses on these inhibitory interneurons. In fact, in the subacute phase of the formalin test, glycinergic interneurons are strongly activated in wild type (WT) mice but not in Shank2(-/-) mice. Consequently, nociception projection neurons in laminae I are activated in larger numbers in Shank2(-/-) mice. LIMITATIONS: Our investigation is limited to male mice, in agreement with the higher representation of ASD in males; therefore, caution should be applied to extrapolate the findings to females. Furthermore, ASD is characterized by extensive genetic diversity and therefore the findings related to Shank2 mutant mice may not necessarily apply to patients with different gene mutations. Since nociceptive phenotypes in ASD range between hyper- and hypo-sensitivity, diverse mutations may affect the circuit in opposite ways. CONCLUSION: Our findings prove that Shank2 expression identifies a new subset of inhibitory interneurons involved in reducing the transmission of nociceptive stimuli and whose unchecked activation is associated with pain hypersensitivity. We provide evidence that dysfunction in spinal cord pain processing may contribute to the nociceptive phenotypes in ASD. En ligne : http://dx.doi.org/10.1186/s13229-023-00552-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Exploratory analysis of L1 retrotransposons expression in autism? / Michele FILOSI ; Enrico DOMENICI ; Damiano MANGONI ; Stefano GUSTINCICH ; Remo SANGES in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 22 p. Titre : Exploratory analysis of L1 retrotransposons expression in autism? Type de document : Texte imprimé et/ou numérique Auteurs : Michele FILOSI, Auteur ; Enrico DOMENICI, Auteur ; Damiano MANGONI, Auteur ; Stefano GUSTINCICH, Auteur ; Remo SANGES, Auteur Article en page(s) : 22 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a set of highly heterogeneous neurodevelopmental diseases whose genetic etiology is not completely understood. Several investigations have relied on transcriptome analysis from peripheral tissues to dissect ASD into homogenous molecular phenotypes. Recently, analysis of changes in gene expression from postmortem brain tissues has identified sets of genes that are involved in pathways previously associated with ASD etiology. In addition to protein-coding transcripts, the human transcriptome is composed by a large set of non-coding RNAs and transposable elements (TEs). Advancements in sequencing technologies have proven that TEs can be transcribed in a regulated fashion, and their dysregulation might have a role in brain diseases. METHODS: We exploited published datasets comprising RNA-seq data from (1) postmortem brain of ASD subjects, (2) in vitro cell cultures where ten different ASD-relevant genes were knocked out and (3) blood of discordant siblings. We measured the expression levels of evolutionarily young full-length transposable L1 elements and characterized the genomic location of deregulated L1s assessing their potential impact on the transcription of ASD-relevant genes. We analyzed every sample independently, avoiding to pool together the disease subjects to unmask the heterogeneity of the molecular phenotypes. RESULTS: We detected a strong upregulation of intronic full-length L1s in a subset of postmortem brain samples and in in vitro differentiated neurons from iPSC knocked out for ATRX. L1 upregulation correlated with an high number of deregulated genes and retained introns. In the anterior cingulate cortex of one subject, a small number of significantly upregulated L1s overlapped with ASD-relevant genes that were significantly downregulated, suggesting the possible existence of a negative effect of L1 transcription on host transcripts. LIMITATIONS: Our analyses must be considered exploratory and will need to be validated in bigger cohorts. The main limitation is given by the small sample size and by the lack of replicates for postmortem brain samples. Measuring the transcription of locus-specific TEs is complicated by the repetitive nature of their sequence, which reduces the accuracy in mapping sequencing reads to the correct genomic locus. CONCLUSIONS: L1 upregulation in ASD appears to be limited to a subset of subjects that are also characterized by a general deregulation of the expression of canonical genes and an increase in intron retention. In some samples from the anterior cingulate cortex, L1s upregulation seems to directly impair the expression of some ASD-relevant genes by a still unknown mechanism. L1s upregulation may therefore identify a group of ASD subjects with common molecular features and helps stratifying individuals for novel strategies of therapeutic intervention. En ligne : http://dx.doi.org/10.1186/s13229-023-00554-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Exploratory analysis of L1 retrotransposons expression in autism? [Texte imprimé et/ou numérique] / Michele FILOSI, Auteur ; Enrico DOMENICI, Auteur ; Damiano MANGONI, Auteur ; Stefano GUSTINCICH, Auteur ; Remo SANGES, Auteur . - 22 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 22 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a set of highly heterogeneous neurodevelopmental diseases whose genetic etiology is not completely understood. Several investigations have relied on transcriptome analysis from peripheral tissues to dissect ASD into homogenous molecular phenotypes. Recently, analysis of changes in gene expression from postmortem brain tissues has identified sets of genes that are involved in pathways previously associated with ASD etiology. In addition to protein-coding transcripts, the human transcriptome is composed by a large set of non-coding RNAs and transposable elements (TEs). Advancements in sequencing technologies have proven that TEs can be transcribed in a regulated fashion, and their dysregulation might have a role in brain diseases. METHODS: We exploited published datasets comprising RNA-seq data from (1) postmortem brain of ASD subjects, (2) in vitro cell cultures where ten different ASD-relevant genes were knocked out and (3) blood of discordant siblings. We measured the expression levels of evolutionarily young full-length transposable L1 elements and characterized the genomic location of deregulated L1s assessing their potential impact on the transcription of ASD-relevant genes. We analyzed every sample independently, avoiding to pool together the disease subjects to unmask the heterogeneity of the molecular phenotypes. RESULTS: We detected a strong upregulation of intronic full-length L1s in a subset of postmortem brain samples and in in vitro differentiated neurons from iPSC knocked out for ATRX. L1 upregulation correlated with an high number of deregulated genes and retained introns. In the anterior cingulate cortex of one subject, a small number of significantly upregulated L1s overlapped with ASD-relevant genes that were significantly downregulated, suggesting the possible existence of a negative effect of L1 transcription on host transcripts. LIMITATIONS: Our analyses must be considered exploratory and will need to be validated in bigger cohorts. The main limitation is given by the small sample size and by the lack of replicates for postmortem brain samples. Measuring the transcription of locus-specific TEs is complicated by the repetitive nature of their sequence, which reduces the accuracy in mapping sequencing reads to the correct genomic locus. CONCLUSIONS: L1 upregulation in ASD appears to be limited to a subset of subjects that are also characterized by a general deregulation of the expression of canonical genes and an increase in intron retention. In some samples from the anterior cingulate cortex, L1s upregulation seems to directly impair the expression of some ASD-relevant genes by a still unknown mechanism. L1s upregulation may therefore identify a group of ASD subjects with common molecular features and helps stratifying individuals for novel strategies of therapeutic intervention. En ligne : http://dx.doi.org/10.1186/s13229-023-00554-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Autism-associated gene shank3 is necessary for social contagion in zebrafish / Magda C. TELES ; Elena DREOSTI ; Rui F. OLIVEIRA in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 23 p. Titre : Autism-associated gene shank3 is necessary for social contagion in zebrafish Type de document : Texte imprimé et/ou numérique Auteurs : Magda C. TELES, Auteur ; Elena DREOSTI, Auteur ; Rui F. OLIVEIRA, Auteur Article en page(s) : 23 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Animal models enable targeting autism-associated genes, such as the shank3 gene, to assess their impact on behavioural phenotypes. However, this is often limited to simple behaviours relevant for social interaction. Social contagion is a complex phenotype forming the basis of human empathic behaviour and involves attention to the behaviour of others for recognizing and sharing their emotional or affective state. Thus, it is a form of social communication, which constitutes the most common developmental impairment across autism spectrum disorders (ASD). METHODS: Here we describe the development of a zebrafish model that identifies the neurocognitive mechanisms by which shank3 mutation drives deficits in social contagion. We used a CRISPR-Cas9 technique to generate mutations to the shank3a gene, a zebrafish paralogue found to present greater orthology and functional conservation relative to the human gene. Mutants were first compared to wild types during a two-phase protocol that involves the observation of two conflicting states, distress and neutral, and the later recall and discrimination of others when no longer presenting such differences. Then, the whole-brain expression of different neuroplasticity markers was compared between genotypes and their contribution to cluster-specific phenotypic variation was assessed. RESULTS: The shank3 mutation markedly reduced social contagion via deficits in attention contributing to difficulties in recognising affective states. Also, the mutation changed the expression of neuronal plasticity genes. However, only downregulated neuroligins clustered with shank3a expression under a combined synaptogenesis component that contributed specifically to variation in attention. LIMITATIONS: While zebrafish are extremely useful in identifying the role of shank3 mutations to composite social behaviour, they are unlikely to represent the full complexity of socio-cognitive and communication deficits presented by human ASD pathology. Moreover, zebrafish cannot represent the scaling up of these deficits to higher-order empathic and prosocial phenotypes seen in humans. CONCLUSIONS: We demonstrate a causal link between the zebrafish orthologue of an ASD-associated gene and the attentional control of affect recognition and consequent social contagion. This models autistic affect-communication pathology in zebrafish and reveals a genetic attention-deficit mechanism, addressing the ongoing debate for such mechanisms accounting for emotion recognition difficulties in autistic individuals. En ligne : http://dx.doi.org/10.1186/s13229-023-00555-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Autism-associated gene shank3 is necessary for social contagion in zebrafish [Texte imprimé et/ou numérique] / Magda C. TELES, Auteur ; Elena DREOSTI, Auteur ; Rui F. OLIVEIRA, Auteur . - 23 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 23 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Animal models enable targeting autism-associated genes, such as the shank3 gene, to assess their impact on behavioural phenotypes. However, this is often limited to simple behaviours relevant for social interaction. Social contagion is a complex phenotype forming the basis of human empathic behaviour and involves attention to the behaviour of others for recognizing and sharing their emotional or affective state. Thus, it is a form of social communication, which constitutes the most common developmental impairment across autism spectrum disorders (ASD). METHODS: Here we describe the development of a zebrafish model that identifies the neurocognitive mechanisms by which shank3 mutation drives deficits in social contagion. We used a CRISPR-Cas9 technique to generate mutations to the shank3a gene, a zebrafish paralogue found to present greater orthology and functional conservation relative to the human gene. Mutants were first compared to wild types during a two-phase protocol that involves the observation of two conflicting states, distress and neutral, and the later recall and discrimination of others when no longer presenting such differences. Then, the whole-brain expression of different neuroplasticity markers was compared between genotypes and their contribution to cluster-specific phenotypic variation was assessed. RESULTS: The shank3 mutation markedly reduced social contagion via deficits in attention contributing to difficulties in recognising affective states. Also, the mutation changed the expression of neuronal plasticity genes. However, only downregulated neuroligins clustered with shank3a expression under a combined synaptogenesis component that contributed specifically to variation in attention. LIMITATIONS: While zebrafish are extremely useful in identifying the role of shank3 mutations to composite social behaviour, they are unlikely to represent the full complexity of socio-cognitive and communication deficits presented by human ASD pathology. Moreover, zebrafish cannot represent the scaling up of these deficits to higher-order empathic and prosocial phenotypes seen in humans. CONCLUSIONS: We demonstrate a causal link between the zebrafish orthologue of an ASD-associated gene and the attentional control of affect recognition and consequent social contagion. This models autistic affect-communication pathology in zebrafish and reveals a genetic attention-deficit mechanism, addressing the ongoing debate for such mechanisms accounting for emotion recognition difficulties in autistic individuals. En ligne : http://dx.doi.org/10.1186/s13229-023-00555-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Correction: Understanding the relationship between cerebellar structure and social abilities / Dorothea L. FLORIS ; Pierrick COUPÉ ; Edouard DUCHESNAY ; Angeline MIHAILOV ; Antoine GRIGIS ; Indrit BÈGUE ; Julie VICTOR ; Vincent FROUIN ; Marion LEBOYER ; Josselin HOUENOU ; Charles LAIDI in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 24 p. Titre : Correction: Understanding the relationship between cerebellar structure and social abilities Type de document : Texte imprimé et/ou numérique Auteurs : Dorothea L. FLORIS, Auteur ; Pierrick COUPÉ, Auteur ; Edouard DUCHESNAY, Auteur ; Angeline MIHAILOV, Auteur ; Antoine GRIGIS, Auteur ; Indrit BÈGUE, Auteur ; Julie VICTOR, Auteur ; Vincent FROUIN, Auteur ; Marion LEBOYER, Auteur ; Josselin HOUENOU, Auteur ; Charles LAIDI, Auteur Article en page(s) : 24 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-023-00553-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Correction: Understanding the relationship between cerebellar structure and social abilities [Texte imprimé et/ou numérique] / Dorothea L. FLORIS, Auteur ; Pierrick COUPÉ, Auteur ; Edouard DUCHESNAY, Auteur ; Angeline MIHAILOV, Auteur ; Antoine GRIGIS, Auteur ; Indrit BÈGUE, Auteur ; Julie VICTOR, Auteur ; Vincent FROUIN, Auteur ; Marion LEBOYER, Auteur ; Josselin HOUENOU, Auteur ; Charles LAIDI, Auteur . - 24 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 24 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-023-00553-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism / Catherine F. TALBOT ; Laura A. DEL ROSSO ; Brenda MCCOWAN ; Sreetharan KANTHASWAMY ; David HAIG ; John P. CAPITANIO ; Karen J. PARKER in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 25 p. Titre : Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism Type de document : Texte imprimé et/ou numérique Auteurs : Catherine F. TALBOT, Auteur ; Laura A. DEL ROSSO, Auteur ; Brenda MCCOWAN, Auteur ; Sreetharan KANTHASWAMY, Auteur ; David HAIG, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 25 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N=407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (?(2)(P)) between sons that could uniquely be attributed to their shared genetics (?(2)(g)), expressed as ?(2)(g)/?(2)(P) (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h(2)). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability. En ligne : http://dx.doi.org/10.1186/s13229-023-00556-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism [Texte imprimé et/ou numérique] / Catherine F. TALBOT, Auteur ; Laura A. DEL ROSSO, Auteur ; Brenda MCCOWAN, Auteur ; Sreetharan KANTHASWAMY, Auteur ; David HAIG, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - 25 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 25 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N=407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (?(2)(P)) between sons that could uniquely be attributed to their shared genetics (?(2)(g)), expressed as ?(2)(g)/?(2)(P) (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h(2)). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability. En ligne : http://dx.doi.org/10.1186/s13229-023-00556-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Neurodevelopmental impairments in children with septo-optic dysplasia spectrum conditions: a systematic review / Arameh AGHABABAIE ; Jennifer KALITSI ; Daniel MARTINS ; Yannis PALOYELIS ; Ritika R. KAPOOR in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 26 p. Titre : Neurodevelopmental impairments in children with septo-optic dysplasia spectrum conditions: a systematic review Type de document : Texte imprimé et/ou numérique Auteurs : Arameh AGHABABAIE, Auteur ; Jennifer KALITSI, Auteur ; Daniel MARTINS, Auteur ; Yannis PALOYELIS, Auteur ; Ritika R. KAPOOR, Auteur Article en page(s) : 26 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions. METHODS: The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children ( En ligne : http://dx.doi.org/10.1186/s13229-023-00559-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Neurodevelopmental impairments in children with septo-optic dysplasia spectrum conditions: a systematic review [Texte imprimé et/ou numérique] / Arameh AGHABABAIE, Auteur ; Jennifer KALITSI, Auteur ; Daniel MARTINS, Auteur ; Yannis PALOYELIS, Auteur ; Ritika R. KAPOOR, Auteur . - 26 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 26 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions. METHODS: The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children ( En ligne : http://dx.doi.org/10.1186/s13229-023-00559-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Personalized estimates of brain cortical structural variability in individuals with Autism spectrum disorder: the predictor of brain age and neurobiology relevance / Jie SUN ; Weiqi MAN ; Zhang ZHANG ; Ningnannan ZHANG in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 27 p. Titre : Personalized estimates of brain cortical structural variability in individuals with Autism spectrum disorder: the predictor of brain age and neurobiology relevance Type de document : Texte imprimé et/ou numérique Auteurs : Jie SUN, Auteur ; Weiqi MAN, Auteur ; Zhang ZHANG, Auteur ; Ningnannan ZHANG, Auteur Article en page(s) : 27 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a heritable condition related to brain development that affects a person's perception and socialization with others. Here, we examined variability in the brain morphology in ASD children and adolescent individuals at the level of brain cortical structural profiles and the level of each brain regional measure. METHODS: We selected brain structural MRI data in 600 ASDs and 729 normal controls (NCs) from Autism Brain Imaging Data Exchange (ABIDE). The personalized estimate of similarity between gray matter volume (GMV) profiles of an individual to that of others in the same group was assessed by using the person-based similarity index (PBSI). Regional contributions to PBSI score were utilized for brain age gap estimation (BrainAGE) prediction model establishment, including support vector regression (SVR), relevance vector regression (RVR), and Gaussian process regression (GPR). The association between BrainAGE prediction in ASD and clinical performance was investigated. We further explored the related inter-regional profiles of gene expression from the Allen Human Brain Atlas with variability differences in the brain morphology between groups. RESULTS: The PBSI score of GMV was negatively related to age regardless of the sample group, and the PBSI score was significantly lower in ASDs than in NCs. The regional contributions to the PBSI score of 126 brain regions in ASDs showed significant differences compared to NCs. RVR model achieved the best performance for predicting brain age. Higher inter-individual brain morphology variability was related to increased brain age, specific to communication symptoms. A total of 430 genes belonging to various pathways were identified as associated with brain cortical morphometric variation. The pathways, including short-term memory, regulation of system process, and regulation of nervous system process, were dominated mainly by gene sets for manno midbrain neurotypes. LIMITATIONS: There is a sample mismatch between the gene expression data and brain imaging data from ABIDE. A larger sample size can contribute to the model training of BrainAGE and the validation of the results. CONCLUSIONS: ASD has personalized heterogeneity brain morphology. The brain age gap estimation and transcription-neuroimaging associations derived from this trait are replenished in an additional direction to boost the understanding of the ASD brain. En ligne : http://dx.doi.org/10.1186/s13229-023-00558-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Personalized estimates of brain cortical structural variability in individuals with Autism spectrum disorder: the predictor of brain age and neurobiology relevance [Texte imprimé et/ou numérique] / Jie SUN, Auteur ; Weiqi MAN, Auteur ; Zhang ZHANG, Auteur ; Ningnannan ZHANG, Auteur . - 27 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 27 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a heritable condition related to brain development that affects a person's perception and socialization with others. Here, we examined variability in the brain morphology in ASD children and adolescent individuals at the level of brain cortical structural profiles and the level of each brain regional measure. METHODS: We selected brain structural MRI data in 600 ASDs and 729 normal controls (NCs) from Autism Brain Imaging Data Exchange (ABIDE). The personalized estimate of similarity between gray matter volume (GMV) profiles of an individual to that of others in the same group was assessed by using the person-based similarity index (PBSI). Regional contributions to PBSI score were utilized for brain age gap estimation (BrainAGE) prediction model establishment, including support vector regression (SVR), relevance vector regression (RVR), and Gaussian process regression (GPR). The association between BrainAGE prediction in ASD and clinical performance was investigated. We further explored the related inter-regional profiles of gene expression from the Allen Human Brain Atlas with variability differences in the brain morphology between groups. RESULTS: The PBSI score of GMV was negatively related to age regardless of the sample group, and the PBSI score was significantly lower in ASDs than in NCs. The regional contributions to the PBSI score of 126 brain regions in ASDs showed significant differences compared to NCs. RVR model achieved the best performance for predicting brain age. Higher inter-individual brain morphology variability was related to increased brain age, specific to communication symptoms. A total of 430 genes belonging to various pathways were identified as associated with brain cortical morphometric variation. The pathways, including short-term memory, regulation of system process, and regulation of nervous system process, were dominated mainly by gene sets for manno midbrain neurotypes. LIMITATIONS: There is a sample mismatch between the gene expression data and brain imaging data from ABIDE. A larger sample size can contribute to the model training of BrainAGE and the validation of the results. CONCLUSIONS: ASD has personalized heterogeneity brain morphology. The brain age gap estimation and transcription-neuroimaging associations derived from this trait are replenished in an additional direction to boost the understanding of the ASD brain. En ligne : http://dx.doi.org/10.1186/s13229-023-00558-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling / Silvia LANDI ; Alessia STEFANONI ; Gabriele NARDI ; Marica ALBANESI ; Helen F. BAUER ; Enrico PRACUCCI ; Michael SCHÖN ; Gian Michele RATTO ; Tobias M. BOECKERS ; Carlo SALA ; Chiara VERPELLI in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 28 p. Titre : Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling Type de document : Texte imprimé et/ou numérique Auteurs : Silvia LANDI, Auteur ; Alessia STEFANONI, Auteur ; Gabriele NARDI, Auteur ; Marica ALBANESI, Auteur ; Helen F. BAUER, Auteur ; Enrico PRACUCCI, Auteur ; Michael SCHÖN, Auteur ; Gian Michele RATTO, Auteur ; Tobias M. BOECKERS, Auteur ; Carlo SALA, Auteur ; Chiara VERPELLI, Auteur Article en page(s) : 28 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and autistic-like behaviors and is primarily caused by haploinsufficiency of SHANK3 gene. Currently, there is no specific treatment for PMS, highlighting the need for a better understanding of SHANK3 functions and the underlying pathophysiological mechanisms in the brain. We hypothesize that SHANK3 haploinsufficiency may lead to alterations in the inhibitory system, which could be linked to the excitatory/inhibitory imbalance observed in models of autism spectrum disorder (ASD). Investigation of these neuropathological features may shed light on the pathogenesis of PMS and potential therapeutic interventions. METHODS: We recorded local field potentials and visual evoked responses in the visual cortex of Shank3?11(-/-) mice. Then, to understand the impact of Shank3 in inhibitory neurons, we generated Pv-cre(+/-) Shank3(Fl/Wt) conditional mice, in which Shank3 was deleted in parvalbumin-positive neurons. We characterized the phenotype of this murine model and we compared this phenotype before and after ganaxolone administration. RESULTS: We found, in the primary visual cortex, an alteration of the gain control of Shank3 KO compared with Wt mice, indicating a deficit of inhibition on pyramidal neurons. This alteration was rescued after the potentiation of GABA(A) receptor activity by Midazolam. Behavioral analysis showed an impairment in grooming, memory, and motor coordination of Pv-cre(+/-) Shank3(Fl/Wt) compared with Pv-cre(+/-) Shank3(Wt/Wt) mice. These deficits were rescued with ganaxolone, a positive modulator of GABA(A) receptors. Furthermore, we demonstrated that treatment with ganaxolone also ameliorated evocative memory deficits and repetitive behavior of Shank3 KO mice. LIMITATIONS: Despite the significant findings of our study, some limitations remain. Firstly, the neurobiological mechanisms underlying the link between Shank3 deletion in PV neurons and behavioral alterations need further investigation. Additionally, the impact of Shank3 on other classes of inhibitory neurons requires further exploration. Finally, the pharmacological activity of ganaxolone needs further characterization to improve our understanding of its potential therapeutic effects. CONCLUSIONS: Our study provides evidence that Shank3 deletion leads to an alteration in inhibitory feedback on cortical pyramidal neurons, resulting in cortical hyperexcitability and ASD-like behavioral problems. Specifically, cell type-specific deletion of Shank3 in PV neurons was associated with these behavioral deficits. Our findings suggest that ganaxolone may be a potential pharmacological approach for treating PMS, as it was able to rescue the behavioral deficits in Shank3 KO mice. Overall, our study highlights the importance of investigating the role of inhibitory neurons and potential therapeutic interventions in neurodevelopmental disorders such as PMS. En ligne : http://dx.doi.org/10.1186/s13229-023-00557-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling [Texte imprimé et/ou numérique] / Silvia LANDI, Auteur ; Alessia STEFANONI, Auteur ; Gabriele NARDI, Auteur ; Marica ALBANESI, Auteur ; Helen F. BAUER, Auteur ; Enrico PRACUCCI, Auteur ; Michael SCHÖN, Auteur ; Gian Michele RATTO, Auteur ; Tobias M. BOECKERS, Auteur ; Carlo SALA, Auteur ; Chiara VERPELLI, Auteur . - 28 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 28 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and autistic-like behaviors and is primarily caused by haploinsufficiency of SHANK3 gene. Currently, there is no specific treatment for PMS, highlighting the need for a better understanding of SHANK3 functions and the underlying pathophysiological mechanisms in the brain. We hypothesize that SHANK3 haploinsufficiency may lead to alterations in the inhibitory system, which could be linked to the excitatory/inhibitory imbalance observed in models of autism spectrum disorder (ASD). Investigation of these neuropathological features may shed light on the pathogenesis of PMS and potential therapeutic interventions. METHODS: We recorded local field potentials and visual evoked responses in the visual cortex of Shank3?11(-/-) mice. Then, to understand the impact of Shank3 in inhibitory neurons, we generated Pv-cre(+/-) Shank3(Fl/Wt) conditional mice, in which Shank3 was deleted in parvalbumin-positive neurons. We characterized the phenotype of this murine model and we compared this phenotype before and after ganaxolone administration. RESULTS: We found, in the primary visual cortex, an alteration of the gain control of Shank3 KO compared with Wt mice, indicating a deficit of inhibition on pyramidal neurons. This alteration was rescued after the potentiation of GABA(A) receptor activity by Midazolam. Behavioral analysis showed an impairment in grooming, memory, and motor coordination of Pv-cre(+/-) Shank3(Fl/Wt) compared with Pv-cre(+/-) Shank3(Wt/Wt) mice. These deficits were rescued with ganaxolone, a positive modulator of GABA(A) receptors. Furthermore, we demonstrated that treatment with ganaxolone also ameliorated evocative memory deficits and repetitive behavior of Shank3 KO mice. LIMITATIONS: Despite the significant findings of our study, some limitations remain. Firstly, the neurobiological mechanisms underlying the link between Shank3 deletion in PV neurons and behavioral alterations need further investigation. Additionally, the impact of Shank3 on other classes of inhibitory neurons requires further exploration. Finally, the pharmacological activity of ganaxolone needs further characterization to improve our understanding of its potential therapeutic effects. CONCLUSIONS: Our study provides evidence that Shank3 deletion leads to an alteration in inhibitory feedback on cortical pyramidal neurons, resulting in cortical hyperexcitability and ASD-like behavioral problems. Specifically, cell type-specific deletion of Shank3 in PV neurons was associated with these behavioral deficits. Our findings suggest that ganaxolone may be a potential pharmacological approach for treating PMS, as it was able to rescue the behavioral deficits in Shank3 KO mice. Overall, our study highlights the importance of investigating the role of inhibitory neurons and potential therapeutic interventions in neurodevelopmental disorders such as PMS. En ligne : http://dx.doi.org/10.1186/s13229-023-00557-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels / Baiba SVALBE ; Gundega STELFA ; Solveiga GRINBERGA ; Liga ZVEJNIECE ; Helgi B. SCHIÖTH ; Maija DAMBROVA in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 29 p. Titre : Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels Type de document : Texte imprimé et/ou numérique Auteurs : Baiba SVALBE, Auteur ; Gundega STELFA, Auteur ; Solveiga GRINBERGA, Auteur ; Liga ZVEJNIECE, Auteur ; Helgi B. SCHIÖTH, Auteur ; Maija DAMBROVA, Auteur Article en page(s) : 29 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice. En ligne : http://dx.doi.org/10.1186/s13229-023-00560-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels [Texte imprimé et/ou numérique] / Baiba SVALBE, Auteur ; Gundega STELFA, Auteur ; Solveiga GRINBERGA, Auteur ; Liga ZVEJNIECE, Auteur ; Helgi B. SCHIÖTH, Auteur ; Maija DAMBROVA, Auteur . - 29 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 29 p. Index. décimale : PER Périodiques Résumé : Deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice. En ligne : http://dx.doi.org/10.1186/s13229-023-00560-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism / Whitney WORSHAM ; Scott SULLIVAN ; M. Sean ESPLIN ; Paul BURGHARDT ; Alison FRASER ; Amanda V. BAKIAN in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 30 p. Titre : Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism Type de document : Texte imprimé et/ou numérique Auteurs : Whitney WORSHAM, Auteur ; Scott SULLIVAN, Auteur ; M. Sean ESPLIN, Auteur ; Paul BURGHARDT, Auteur ; Alison FRASER, Auteur ; Amanda V. BAKIAN, Auteur Article en page(s) : 30 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism. OBJECTIVE: This study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure. STUDY DESIGN: Early second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N=68) and without (N=68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure. RESULTS: Increased estradiol was significantly associated with autism only in males (AOR=1.13 per 100 pg/ml, 95% CI 1.01-1.27, p=0.036) and only term pregnancies (AOR=1.17 per 100 pg/ml, 95% CI 1.04-1.32, p=0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR=0.65 per 50 nmol/L, 95% CI 0.55-0.78, p<0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure. LIMITATIONS: The relative racial and ethnic homogeneity of Utah's population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power. CONCLUSION: Both elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester. En ligne : http://dx.doi.org/10.1186/s13229-023-00562-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism [Texte imprimé et/ou numérique] / Whitney WORSHAM, Auteur ; Scott SULLIVAN, Auteur ; M. Sean ESPLIN, Auteur ; Paul BURGHARDT, Auteur ; Alison FRASER, Auteur ; Amanda V. BAKIAN, Auteur . - 30 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 30 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism. OBJECTIVE: This study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure. STUDY DESIGN: Early second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N=68) and without (N=68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure. RESULTS: Increased estradiol was significantly associated with autism only in males (AOR=1.13 per 100 pg/ml, 95% CI 1.01-1.27, p=0.036) and only term pregnancies (AOR=1.17 per 100 pg/ml, 95% CI 1.04-1.32, p=0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR=0.65 per 50 nmol/L, 95% CI 0.55-0.78, p<0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure. LIMITATIONS: The relative racial and ethnic homogeneity of Utah's population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power. CONCLUSION: Both elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester. En ligne : http://dx.doi.org/10.1186/s13229-023-00562-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Examining the latent structure and correlates of sensory reactivity in autism: a multi-site integrative data analysis by the autism sensory research consortium / Roseann SCHAAF ; Karla K. AUSDERAU ; Grace T. BARANEK ; D Jonah BARRETT ; Carissa J. CASCIO ; Rachel L. DUMONT ; Ekomobong E. Eyoh ; Michelle D. FAILLA ; Jacob I. FELDMAN ; Jennifer H. FOSS-FEIG ; Heather L. GREEN ; Shulamite A. GREEN ; Jason L. HE ; Elizabeth A. KAPLAN-KAHN ; Bahar KEÇELI-KAYS?L? ; Keren MACLENNAN ; Zoe MAILLOUX ; Elysa J. MARCO ; Lisa E. MASH ; Elizabeth P. MCKERNAN ; Sophie MOLHOLM ; Stewart H. MOSTOFSKY ; Nicolaas A. J. PUTS ; Caroline E. ROBERTSON ; Natalie RUSSO ; Nicole SHEA ; John SIDERIS ; James S. SUTCLIFFE ; Teresa TAVASSOLI ; Mark T. WALLACE ; Ericka L. WODKA ; Tiffany G. WOYNAROSKI in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 31 p. Titre : Examining the latent structure and correlates of sensory reactivity in autism: a multi-site integrative data analysis by the autism sensory research consortium Type de document : Texte imprimé et/ou numérique Auteurs : Roseann SCHAAF, Auteur ; Karla K. AUSDERAU, Auteur ; Grace T. BARANEK, Auteur ; D Jonah BARRETT, Auteur ; Carissa J. CASCIO, Auteur ; Rachel L. DUMONT, Auteur ; Ekomobong E. Eyoh, Auteur ; Michelle D. FAILLA, Auteur ; Jacob I. FELDMAN, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Heather L. GREEN, Auteur ; Shulamite A. GREEN, Auteur ; Jason L. HE, Auteur ; Elizabeth A. KAPLAN-KAHN, Auteur ; Bahar KEÇELI-KAYS?L?, Auteur ; Keren MACLENNAN, Auteur ; Zoe MAILLOUX, Auteur ; Elysa J. MARCO, Auteur ; Lisa E. MASH, Auteur ; Elizabeth P. MCKERNAN, Auteur ; Sophie MOLHOLM, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Nicolaas A. J. PUTS, Auteur ; Caroline E. ROBERTSON, Auteur ; Natalie RUSSO, Auteur ; Nicole SHEA, Auteur ; John SIDERIS, Auteur ; James S. SUTCLIFFE, Auteur ; Teresa TAVASSOLI, Auteur ; Mark T. WALLACE, Auteur ; Ericka L. WODKA, Auteur ; Tiffany G. WOYNAROSKI, Auteur Article en page(s) : 31 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (?(H)=.800) but not a supra-modal HYPO construct (?(H)=.653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (?(H)=.800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations. En ligne : http://dx.doi.org/10.1186/s13229-023-00563-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Examining the latent structure and correlates of sensory reactivity in autism: a multi-site integrative data analysis by the autism sensory research consortium [Texte imprimé et/ou numérique] / Roseann SCHAAF, Auteur ; Karla K. AUSDERAU, Auteur ; Grace T. BARANEK, Auteur ; D Jonah BARRETT, Auteur ; Carissa J. CASCIO, Auteur ; Rachel L. DUMONT, Auteur ; Ekomobong E. Eyoh, Auteur ; Michelle D. FAILLA, Auteur ; Jacob I. FELDMAN, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Heather L. GREEN, Auteur ; Shulamite A. GREEN, Auteur ; Jason L. HE, Auteur ; Elizabeth A. KAPLAN-KAHN, Auteur ; Bahar KEÇELI-KAYS?L?, Auteur ; Keren MACLENNAN, Auteur ; Zoe MAILLOUX, Auteur ; Elysa J. MARCO, Auteur ; Lisa E. MASH, Auteur ; Elizabeth P. MCKERNAN, Auteur ; Sophie MOLHOLM, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Nicolaas A. J. PUTS, Auteur ; Caroline E. ROBERTSON, Auteur ; Natalie RUSSO, Auteur ; Nicole SHEA, Auteur ; John SIDERIS, Auteur ; James S. SUTCLIFFE, Auteur ; Teresa TAVASSOLI, Auteur ; Mark T. WALLACE, Auteur ; Ericka L. WODKA, Auteur ; Tiffany G. WOYNAROSKI, Auteur . - 31 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 31 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population. METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to both evaluate the strength of a "general response pattern" factor for each supra-modal construct and determine the added value of "modality-specific response pattern" scores (e.g., Visual HYPER). Bayesian random-effects integrative data analysis models were used to examine the clinical and demographic correlates of all interpretable HYPER, HYPO, and SEEK (sub)constructs. RESULTS: All modality-specific HYPER subconstructs could be reliably and validly measured, whereas certain modality-specific HYPO and SEEK subconstructs were psychometrically inadequate when measured using existing items. Bifactor analyses supported the validity of a supra-modal HYPER construct (?(H)=.800) but not a supra-modal HYPO construct (?(H)=.653), and supra-modal SEEK models suggested a more limited version of the construct that excluded some sensory modalities (?(H)=.800; 4/7 modalities). Modality-specific subscales demonstrated significant added value for all response patterns. Meta-analytic correlations varied by construct, although sensory features tended to correlate most with other domains of core autism features and co-occurring psychiatric symptoms (with general HYPER and speech HYPO demonstrating the largest numbers of practically significant correlations). LIMITATIONS: Conclusions may not be generalizable beyond the specific pool of items used in the current study, which was limited to caregiver report of observable behaviors and excluded multisensory items that reflect many "real-world" sensory experiences. CONCLUSION: Of the three sensory response patterns, only HYPER demonstrated sufficient evidence for valid interpretation at the supra-modal level, whereas supra-modal HYPO/SEEK constructs demonstrated substantial psychometric limitations. For clinicians and researchers seeking to characterize sensory reactivity in autism, modality-specific response pattern scores may represent viable alternatives that overcome many of these limitations. En ligne : http://dx.doi.org/10.1186/s13229-023-00563-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Linking functional and structural brain organisation with behaviour in autism: a multimodal EU-AIMS Longitudinal European Autism Project (LEAP) study / Alberto LLERA ; Ting MEI ; Koen HAAK ; Christina ISAKOGLOU ; Dorothea L. FLORIS ; Sarah DURSTON ; Carolin MOESSNANG ; Tobias BANASCHEWSKI ; Simon BARON-COHEN ; Eva LOTH ; Flavio DELL'ACQUA ; Tony CHARMAN ; Declan G. M. MURPHY ; Christine ECKER ; Jan K. BUITELAAR ; Christian F. BECKMANN in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 32 p. Titre : Linking functional and structural brain organisation with behaviour in autism: a multimodal EU-AIMS Longitudinal European Autism Project (LEAP) study Type de document : Texte imprimé et/ou numérique Auteurs : Alberto LLERA, Auteur ; Ting MEI, Auteur ; Koen HAAK, Auteur ; Christina ISAKOGLOU, Auteur ; Dorothea L. FLORIS, Auteur ; Sarah DURSTON, Auteur ; Carolin MOESSNANG, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Eva LOTH, Auteur ; Flavio DELL'ACQUA, Auteur ; Tony CHARMAN, Auteur ; Declan G. M. MURPHY, Auteur ; Christine ECKER, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur Article en page(s) : 32 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We utilised multimodal MRI (T1-, diffusion-weighted and resting state functional), behavioural and clinical data from the EU AIMS Longitudinal European Autism Project (LEAP) from autistic (n=206) and non-autistic (n=196) participants. Of these, 97 had data from 2 timepoints resulting in a total scan number of 466. Grey matter density maps, probabilistic tractography connectivity matrices and connectopic maps were extracted from respective MRI modalities and were then integrated with Linked Independent Component Analysis. Linear mixed-effects models were used to evaluate the relationship between components and group while accounting for covariates and non-independence of participants with longitudinal data. Additional models were run to investigate associations with dimensional measures of behaviour. We identified one component that differed significantly between groups (coefficient=0.33, p(adj)=0.02). This was driven (99%) by variance of the right fusiform gyrus connectopic map 2. While there were multiple nominal (uncorrected p<0.05) associations with behavioural measures, none were significant following multiple comparison correction. Our analysis considered the relative contributions of both structural and functional brain phenotypes simultaneously, finding that functional phenotypes drive associations with autism. These findings expanded on previous unimodal studies by revealing the topographic organisation of functional connectivity patterns specific to autism and warrant further investigation. En ligne : http://dx.doi.org/10.1186/s13229-023-00564-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Linking functional and structural brain organisation with behaviour in autism: a multimodal EU-AIMS Longitudinal European Autism Project (LEAP) study [Texte imprimé et/ou numérique] / Alberto LLERA, Auteur ; Ting MEI, Auteur ; Koen HAAK, Auteur ; Christina ISAKOGLOU, Auteur ; Dorothea L. FLORIS, Auteur ; Sarah DURSTON, Auteur ; Carolin MOESSNANG, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Eva LOTH, Auteur ; Flavio DELL'ACQUA, Auteur ; Tony CHARMAN, Auteur ; Declan G. M. MURPHY, Auteur ; Christine ECKER, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur . - 32 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 32 p. Index. décimale : PER Périodiques Résumé : Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We utilised multimodal MRI (T1-, diffusion-weighted and resting state functional), behavioural and clinical data from the EU AIMS Longitudinal European Autism Project (LEAP) from autistic (n=206) and non-autistic (n=196) participants. Of these, 97 had data from 2 timepoints resulting in a total scan number of 466. Grey matter density maps, probabilistic tractography connectivity matrices and connectopic maps were extracted from respective MRI modalities and were then integrated with Linked Independent Component Analysis. Linear mixed-effects models were used to evaluate the relationship between components and group while accounting for covariates and non-independence of participants with longitudinal data. Additional models were run to investigate associations with dimensional measures of behaviour. We identified one component that differed significantly between groups (coefficient=0.33, p(adj)=0.02). This was driven (99%) by variance of the right fusiform gyrus connectopic map 2. While there were multiple nominal (uncorrected p<0.05) associations with behavioural measures, none were significant following multiple comparison correction. Our analysis considered the relative contributions of both structural and functional brain phenotypes simultaneously, finding that functional phenotypes drive associations with autism. These findings expanded on previous unimodal studies by revealing the topographic organisation of functional connectivity patterns specific to autism and warrant further investigation. En ligne : http://dx.doi.org/10.1186/s13229-023-00564-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Autistic adults benefit from and enjoy learning via social interaction as much as neurotypical adults do / A. HATILOVA ; F. TROJAN ; I. TSUI ; Antonia F. de C. HAMILTON in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 33 p. Titre : Autistic adults benefit from and enjoy learning via social interaction as much as neurotypical adults do Type de document : Texte imprimé et/ou numérique Auteurs : A. HATILOVA, Auteur ; F. TROJAN, Auteur ; I. TSUI, Auteur ; Antonia F. de C. HAMILTON, Auteur Article en page(s) : 33 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic people show poor processing of social signals (i.e. about the social world). But how do they learn via social interaction? METHODS: 68 neurotypical adults and 60 autistic adults learned about obscure items (e.g. exotic animals) over Zoom (i) in a live video-call with the teacher, (ii) from a recorded learner-teacher interaction video and (iii) from a recorded teacher-alone video. Data were analysed via analysis of variance and multi-level regression models. RESULTS: Live teaching provided the most optimal learning condition, with no difference between groups. Enjoyment was the strongest predictor of learning: both groups enjoyed the live interaction significantly more than other condition and reported similar anxiety levels across conditions. LIMITATIONS: Some of the autistic participants were self-diagnosed-however, further analysis where these participants were excluded showed the same results. Recruiting participants over online platforms may have introduced bias in our sample. Future work should investigate learning in social contexts via diverse sources (e.g. schools). CONCLUSIONS: These findings advocate for a distinction between learning about the social versus learning via the social: cognitive models of autism should be revisited to consider social interaction not just as a puzzle to decode but rather a medium through which people, including neuro-diverse groups, learn about the world around them. Trial registration Part of this work has been pre-registered before data collection https://doi.org/10.17605/OSF.IO/5PGA3. En ligne : http://dx.doi.org/10.1186/s13229-023-00561-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Autistic adults benefit from and enjoy learning via social interaction as much as neurotypical adults do [Texte imprimé et/ou numérique] / A. HATILOVA, Auteur ; F. TROJAN, Auteur ; I. TSUI, Auteur ; Antonia F. de C. HAMILTON, Auteur . - 33 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 33 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic people show poor processing of social signals (i.e. about the social world). But how do they learn via social interaction? METHODS: 68 neurotypical adults and 60 autistic adults learned about obscure items (e.g. exotic animals) over Zoom (i) in a live video-call with the teacher, (ii) from a recorded learner-teacher interaction video and (iii) from a recorded teacher-alone video. Data were analysed via analysis of variance and multi-level regression models. RESULTS: Live teaching provided the most optimal learning condition, with no difference between groups. Enjoyment was the strongest predictor of learning: both groups enjoyed the live interaction significantly more than other condition and reported similar anxiety levels across conditions. LIMITATIONS: Some of the autistic participants were self-diagnosed-however, further analysis where these participants were excluded showed the same results. Recruiting participants over online platforms may have introduced bias in our sample. Future work should investigate learning in social contexts via diverse sources (e.g. schools). CONCLUSIONS: These findings advocate for a distinction between learning about the social versus learning via the social: cognitive models of autism should be revisited to consider social interaction not just as a puzzle to decode but rather a medium through which people, including neuro-diverse groups, learn about the world around them. Trial registration Part of this work has been pre-registered before data collection https://doi.org/10.17605/OSF.IO/5PGA3. En ligne : http://dx.doi.org/10.1186/s13229-023-00561-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism / Shishuai HAO ; Shimin ZOU ; Xiaomeng TU ; Weixi KONG ; Tian JIANG ; Jie-Guang CHEN in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 34 p. Titre : Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism Type de document : Texte imprimé et/ou numérique Auteurs : Shishuai HAO, Auteur ; Shimin ZOU, Auteur ; Xiaomeng TU, Auteur ; Weixi KONG, Auteur ; Tian JIANG, Auteur ; Jie-Guang CHEN, Auteur Article en page(s) : 34 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood. METHODS: We employed cortex-specific Foxp1 knockout (Foxp1-cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice's behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence. RESULTS: Foxp1-cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses. LIMITATIONS: It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism. CONCLUSIONS: Foxp1-cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors. En ligne : http://dx.doi.org/10.1186/s13229-023-00567-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism [Texte imprimé et/ou numérique] / Shishuai HAO, Auteur ; Shimin ZOU, Auteur ; Xiaomeng TU, Auteur ; Weixi KONG, Auteur ; Tian JIANG, Auteur ; Jie-Guang CHEN, Auteur . - 34 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 34 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood. METHODS: We employed cortex-specific Foxp1 knockout (Foxp1-cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice's behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence. RESULTS: Foxp1-cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses. LIMITATIONS: It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism. CONCLUSIONS: Foxp1-cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors. En ligne : http://dx.doi.org/10.1186/s13229-023-00567-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Increased rates of chronic physical health conditions across all organ systems in autistic adolescents and adults / Elizabeth WEIR ; Carrie ALLISON ; Simon BARON-COHEN in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 35 p. Titre : Increased rates of chronic physical health conditions across all organ systems in autistic adolescents and adults Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth WEIR, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 35 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: The poorer physical health of autistic adults compared to non-autistic adults has been highlighted by several epidemiological studies. However, research has so far been limited to specific geographical areas and has primarily focused on young autistic individuals (aged 35 years and younger). Recent studies indicate a higher rate of mortality in autistic people, as well as poorer quality of self-reported healthcare interactions. This study aims to determine, first, whether autistic people experience greater levels of non-communicable health conditions and second, whether these are explained by differences in demographics (i.e. sex, country of residence, ethnicity, education level), alcohol use, smoking, body mass index (BMI), or family history of medical conditions. METHOD: We employed a cross-sectional, convenience-sampling study via an anonymous, online survey of autistic and non-autistic adults (n=2305, mean age=41.6, 65.9% female, 49% autistic). The survey asked participants to self-report information about their demographics, autism diagnosis, diet, exercise, sleep, sexual health, substance use, personal medical history, and family medical history (for all first-degree, biological relatives). Binomial logistic regression across four iterative models of increasing complexity was applied to assess rates of physical health conditions. The Benjamini-Hochberg correction was used to account for multiple testing, and only physical health conditions that achieved at least 1% endorsement within the overall sample (n>22) were included in the analysis to reduce risk of Type I errors. We also used novel network analysis methods to test whether there are increased levels of multimorbidity between autistic and non-autistic people. RESULTS: There were significantly elevated rates of non-communicable conditions across all organ systems in autistic people, including gastrointestinal, neurological, endocrine, visual, ear/nose/throat, skin, liver and kidney, and haematological conditions. We confirmed previous findings by showing highly significant differences in rates of neurological and gastrointestinal symptoms (p<0.0001). In addition, we established in the largest sample to date that Ehler-Danlos Syndrome (EDS) was more likely to occur among autistic females compared to non-autistic females. Finally, we found a higher prevalence of Coeliac's disease among autistic individuals compared to non-autistic individuals after controlling for sex, ethnicity, country of residence, alcohol use, smoking, and BMI, but these results became non-significant after accounting for family history. LIMITATIONS: Our study is biased towards females, white individuals, highly educated people, and UK residents, likely due to sampling biases. Our self-report study design may also exclude those who lack access to computers, or those with intellectual disability. Our network analysis is also limited in size. CONCLUSIONS: This study provides evidence of widespread, physical health comorbidity that spans nearly all major organ systems in autistic adults compared to non-autistic adults, using both binary logistic regression and network models. Healthcare professionals must be made aware of the range of co-occurring physical health conditions that may be more common among autistic people. However, our findings also point towards potential avenues requiring further exploration, such as the association of autism with both Coeliac's disease and EDS. En ligne : http://dx.doi.org/10.1186/s13229-023-00565-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Increased rates of chronic physical health conditions across all organ systems in autistic adolescents and adults [Texte imprimé et/ou numérique] / Elizabeth WEIR, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur . - 35 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 35 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: The poorer physical health of autistic adults compared to non-autistic adults has been highlighted by several epidemiological studies. However, research has so far been limited to specific geographical areas and has primarily focused on young autistic individuals (aged 35 years and younger). Recent studies indicate a higher rate of mortality in autistic people, as well as poorer quality of self-reported healthcare interactions. This study aims to determine, first, whether autistic people experience greater levels of non-communicable health conditions and second, whether these are explained by differences in demographics (i.e. sex, country of residence, ethnicity, education level), alcohol use, smoking, body mass index (BMI), or family history of medical conditions. METHOD: We employed a cross-sectional, convenience-sampling study via an anonymous, online survey of autistic and non-autistic adults (n=2305, mean age=41.6, 65.9% female, 49% autistic). The survey asked participants to self-report information about their demographics, autism diagnosis, diet, exercise, sleep, sexual health, substance use, personal medical history, and family medical history (for all first-degree, biological relatives). Binomial logistic regression across four iterative models of increasing complexity was applied to assess rates of physical health conditions. The Benjamini-Hochberg correction was used to account for multiple testing, and only physical health conditions that achieved at least 1% endorsement within the overall sample (n>22) were included in the analysis to reduce risk of Type I errors. We also used novel network analysis methods to test whether there are increased levels of multimorbidity between autistic and non-autistic people. RESULTS: There were significantly elevated rates of non-communicable conditions across all organ systems in autistic people, including gastrointestinal, neurological, endocrine, visual, ear/nose/throat, skin, liver and kidney, and haematological conditions. We confirmed previous findings by showing highly significant differences in rates of neurological and gastrointestinal symptoms (p<0.0001). In addition, we established in the largest sample to date that Ehler-Danlos Syndrome (EDS) was more likely to occur among autistic females compared to non-autistic females. Finally, we found a higher prevalence of Coeliac's disease among autistic individuals compared to non-autistic individuals after controlling for sex, ethnicity, country of residence, alcohol use, smoking, and BMI, but these results became non-significant after accounting for family history. LIMITATIONS: Our study is biased towards females, white individuals, highly educated people, and UK residents, likely due to sampling biases. Our self-report study design may also exclude those who lack access to computers, or those with intellectual disability. Our network analysis is also limited in size. CONCLUSIONS: This study provides evidence of widespread, physical health comorbidity that spans nearly all major organ systems in autistic adults compared to non-autistic adults, using both binary logistic regression and network models. Healthcare professionals must be made aware of the range of co-occurring physical health conditions that may be more common among autistic people. However, our findings also point towards potential avenues requiring further exploration, such as the association of autism with both Coeliac's disease and EDS. En ligne : http://dx.doi.org/10.1186/s13229-023-00565-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings / Caroline GURR ; Johanna LEYHAUSEN ; Hanna SEELEMEYER ; Anke BLETSCH ; Tim SCHAEFER ; Charlotte M. PRETZSCH ; Bethany OAKLEY ; Eva LOTH ; Dorothea L. FLORIS ; Jan K. BUITELAAR ; Christian F. BECKMANN ; Tobias BANASCHEWSKI ; Tony CHARMAN ; Emily J. H. JONES ; Julian TILLMANN ; Chris H CHATHAM ; Thomas BOURGERON ; EU-AIMS LEAP Group ; Declan G. M. MURPHY ; Christine ECKER in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 36 p. Titre : The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings Type de document : Texte imprimé et/ou numérique Auteurs : Caroline GURR, Auteur ; Johanna LEYHAUSEN, Auteur ; Hanna SEELEMEYER, Auteur ; Anke BLETSCH, Auteur ; Tim SCHAEFER, Auteur ; Charlotte M. PRETZSCH, Auteur ; Bethany OAKLEY, Auteur ; Eva LOTH, Auteur ; Dorothea L. FLORIS, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Tony CHARMAN, Auteur ; Emily J. H. JONES, Auteur ; Julian TILLMANN, Auteur ; Chris H CHATHAM, Auteur ; Thomas BOURGERON, Auteur ; EU-AIMS LEAP Group, Auteur ; Declan G. M. MURPHY, Auteur ; Christine ECKER, Auteur Article en page(s) : 36 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to (1) investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to (2) link these variances to putative genomic underpinnings. METHODS: We examined differences in cortical thickness (CT) and surface area (SA) and their genomic associations in a sample of 533 individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an ASD-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings. RESULTS: In addition to significant main effects for ASD and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant ASD-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of CT and SA, respectively. Moreover, individuals with ASD?+?ADHD differed in CT to those without. Both main effects and the interaction were enriched for ASD-but not for ADHD-related genes. LIMITATIONS: Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N=25 individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-5 rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting. CONCLUSION: Thus, our findings suggest that the neuroanatomy of ASD is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression. En ligne : http://dx.doi.org/10.1186/s13229-023-00568-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] The neuroanatomical substrates of autism and ADHD and their link to putative genomic underpinnings [Texte imprimé et/ou numérique] / Caroline GURR, Auteur ; Johanna LEYHAUSEN, Auteur ; Hanna SEELEMEYER, Auteur ; Anke BLETSCH, Auteur ; Tim SCHAEFER, Auteur ; Charlotte M. PRETZSCH, Auteur ; Bethany OAKLEY, Auteur ; Eva LOTH, Auteur ; Dorothea L. FLORIS, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Tony CHARMAN, Auteur ; Emily J. H. JONES, Auteur ; Julian TILLMANN, Auteur ; Chris H CHATHAM, Auteur ; Thomas BOURGERON, Auteur ; EU-AIMS LEAP Group, Auteur ; Declan G. M. MURPHY, Auteur ; Christine ECKER, Auteur . - 36 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 36 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental conditions accompanied by differences in brain development. Neuroanatomical differences in autism are variable across individuals and likely underpin distinct clinical phenotypes. To parse heterogeneity, it is essential to establish how the neurobiology of ASD is modulated by differences associated with co-occurring conditions, such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to (1) investigate between-group differences in autistic individuals with and without co-occurring ADHD, and to (2) link these variances to putative genomic underpinnings. METHODS: We examined differences in cortical thickness (CT) and surface area (SA) and their genomic associations in a sample of 533 individuals from the Longitudinal European Autism Project. Using a general linear model including main effects of autism and ADHD, and an ASD-by-ADHD interaction, we examined to which degree ADHD modulates the autism-related neuroanatomy. Further, leveraging the spatial gene expression data of the Allen Human Brain Atlas, we identified genes whose spatial expression patterns resemble our neuroimaging findings. RESULTS: In addition to significant main effects for ASD and ADHD in fronto-temporal, limbic, and occipital regions, we observed a significant ASD-by-ADHD interaction in the left precentral gyrus and the right frontal gyrus for measures of CT and SA, respectively. Moreover, individuals with ASD?+?ADHD differed in CT to those without. Both main effects and the interaction were enriched for ASD-but not for ADHD-related genes. LIMITATIONS: Although we employed a multicenter design to overcome single-site recruitment limitations, our sample size of N=25 individuals in the ADHD only group is relatively small compared to the other subgroups, which limits the generalizability of the results. Also, we assigned subjects into ADHD positive groupings according to the DSM-5 rating scale. While this is sufficient for obtaining a research diagnosis of ADHD, our approach did not take into account for how long the symptoms have been present, which is typically considered when assessing ADHD in the clinical setting. CONCLUSION: Thus, our findings suggest that the neuroanatomy of ASD is significantly modulated by ADHD, and that autistic individuals with co-occurring ADHD may have specific neuroanatomical underpinnings potentially mediated by atypical gene expression. En ligne : http://dx.doi.org/10.1186/s13229-023-00568-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

EEG functional connectivity in infants at elevated familial likelihood for autism spectrum disorder / Scott HUBERTY ; Stefon VAN NOORDT ; James DESJARDINS ; Nicky WRIGHT ; Julie SCORAH ; Sara Jane WEBB ; Mayada ELSABBAGH in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 37 p. Titre : EEG functional connectivity in infants at elevated familial likelihood for autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Scott HUBERTY, Auteur ; Stefon VAN NOORDT, Auteur ; James DESJARDINS, Auteur ; Nicky WRIGHT, Auteur ; Julie SCORAH, Auteur ; Sara Jane WEBB, Auteur ; Mayada ELSABBAGH, Auteur Article en page(s) : 37 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, we know relatively little about the development of these differences in infancy. METHODS: We used a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life. EEG was recorded at 6 and 12 months of age in infants at typical (N=92) or elevated likelihood for ASD (N=90), determined by the presence of an older sibling with ASD. We computed the functional connectivity between cortical sources of EEG during video watching using the corrected imaginary part of phase-locking values. RESULTS: Our main analysis found no significant association between functional connectivity and ASD, showing only significant effects for age, sex, age-sex interaction, and site. Given these null results, we performed an exploratory analysis and observed, at 12 months, a negative correlation between functional connectivity and ADOS calibrated severity scores for restrictive and repetitive behaviors (RRB). LIMITATIONS: The small sample of ASD participants inherent to sibling studies limits diagnostic group comparisons. Also, results from our secondary exploratory analysis should be considered only as potential relationships to further explore, given their increased vulnerability to false positives. CONCLUSIONS: These results are inconclusive concerning an association between EEG functional connectivity and ASD in infancy. Exploratory analyses provided preliminary support for a relationship between RRB and functional connectivity specifically, but these preliminary observations need corroboration on larger samples. En ligne : http://dx.doi.org/10.1186/s13229-023-00570-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] EEG functional connectivity in infants at elevated familial likelihood for autism spectrum disorder [Texte imprimé et/ou numérique] / Scott HUBERTY, Auteur ; Stefon VAN NOORDT, Auteur ; James DESJARDINS, Auteur ; Nicky WRIGHT, Auteur ; Julie SCORAH, Auteur ; Sara Jane WEBB, Auteur ; Mayada ELSABBAGH, Auteur . - 37 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 37 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, we know relatively little about the development of these differences in infancy. METHODS: We used a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life. EEG was recorded at 6 and 12 months of age in infants at typical (N=92) or elevated likelihood for ASD (N=90), determined by the presence of an older sibling with ASD. We computed the functional connectivity between cortical sources of EEG during video watching using the corrected imaginary part of phase-locking values. RESULTS: Our main analysis found no significant association between functional connectivity and ASD, showing only significant effects for age, sex, age-sex interaction, and site. Given these null results, we performed an exploratory analysis and observed, at 12 months, a negative correlation between functional connectivity and ADOS calibrated severity scores for restrictive and repetitive behaviors (RRB). LIMITATIONS: The small sample of ASD participants inherent to sibling studies limits diagnostic group comparisons. Also, results from our secondary exploratory analysis should be considered only as potential relationships to further explore, given their increased vulnerability to false positives. CONCLUSIONS: These results are inconclusive concerning an association between EEG functional connectivity and ASD in infancy. Exploratory analyses provided preliminary support for a relationship between RRB and functional connectivity specifically, but these preliminary observations need corroboration on larger samples. En ligne : http://dx.doi.org/10.1186/s13229-023-00570-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

Age-related changes in neural responses to sensory stimulation in autism: a cross-sectional study / Kaitlin K. CUMMINGS ; Susan Y. BOOKHEIMER ; Mirella DAPRETTO ; Shulamite A. GREEN in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 38 p. Titre : Age-related changes in neural responses to sensory stimulation in autism: a cross-sectional study Type de document : Texte imprimé et/ou numérique Auteurs : Kaitlin K. CUMMINGS, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Mirella DAPRETTO, Auteur ; Shulamite A. GREEN, Auteur Article en page(s) : 38 p. Langues : Anglais (eng) Mots-clés : Adolescent  Child  Humans  *Autistic Disorder/diagnostic imaging  *Autism Spectrum Disorder  Cross-Sectional Studies  Prefrontal Cortex/diagnostic imaging  Cerebellum  Magnetic Resonance Imaging/methods  Autism spectrum disorder  Development  Neural activity  Sensory over-responsivity  Sensory processing  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory over-responsivity (SOR) is an impairing sensory processing challenge in autism spectrum disorder (ASD) which shows heterogenous developmental trajectories and appears to improve into adulthood in some but not all autistic individuals. However, the neural mechanisms underlying interindividual differences in these trajectories are currently unknown. METHODS: Here, we used functional magnetic resonance imaging (fMRI) to investigate the association between age and neural activity linearly and nonlinearly in response to mildly aversive sensory stimulation as well as how SOR severity moderates this association. Participants included 52 ASD (14F) and 41 (13F) typically developing (TD) youth, aged 8.6-18.0 years. RESULTS: We found that in pre-teens, ASD children showed widespread activation differences in sensorimotor, frontal and cerebellar regions compared to TD children, while there were fewer differences between ASD and TD teens. In TD youth, older age was associated with less activation in the prefrontal cortex. In contrast, in ASD youth, older age was associated with more engagement of sensory integration and emotion regulation regions. In particular, orbitofrontal and medial prefrontal cortices showed a nonlinear relationship with age in ASD, with an especially steep increase in sensory-evoked neural activity during the mid-to-late teen years. There was also an interaction between age and SOR severity in ASD youth such that these age-related trends were more apparent in youth with higher SOR. LIMITATIONS: The cross-sectional design limits causal interpretations of the data. Future longitudinal studies will be instrumental in determining how prefrontal engagement and SOR co-develop across adolescence. CONCLUSIONS: Our results suggest that enhanced recruitment of prefrontal regions may underlie age-related decreases in SOR for a subgroup of ASD youth. En ligne : https://dx.doi.org/10.1186/s13229-023-00571-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Age-related changes in neural responses to sensory stimulation in autism: a cross-sectional study [Texte imprimé et/ou numérique] / Kaitlin K. CUMMINGS, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Mirella DAPRETTO, Auteur ; Shulamite A. GREEN, Auteur . - 38 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 38 p. Mots-clés : Adolescent  Child  Humans  *Autistic Disorder/diagnostic imaging  *Autism Spectrum Disorder  Cross-Sectional Studies  Prefrontal Cortex/diagnostic imaging  Cerebellum  Magnetic Resonance Imaging/methods  Autism spectrum disorder  Development  Neural activity  Sensory over-responsivity  Sensory processing  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory over-responsivity (SOR) is an impairing sensory processing challenge in autism spectrum disorder (ASD) which shows heterogenous developmental trajectories and appears to improve into adulthood in some but not all autistic individuals. However, the neural mechanisms underlying interindividual differences in these trajectories are currently unknown. METHODS: Here, we used functional magnetic resonance imaging (fMRI) to investigate the association between age and neural activity linearly and nonlinearly in response to mildly aversive sensory stimulation as well as how SOR severity moderates this association. Participants included 52 ASD (14F) and 41 (13F) typically developing (TD) youth, aged 8.6-18.0 years. RESULTS: We found that in pre-teens, ASD children showed widespread activation differences in sensorimotor, frontal and cerebellar regions compared to TD children, while there were fewer differences between ASD and TD teens. In TD youth, older age was associated with less activation in the prefrontal cortex. In contrast, in ASD youth, older age was associated with more engagement of sensory integration and emotion regulation regions. In particular, orbitofrontal and medial prefrontal cortices showed a nonlinear relationship with age in ASD, with an especially steep increase in sensory-evoked neural activity during the mid-to-late teen years. There was also an interaction between age and SOR severity in ASD youth such that these age-related trends were more apparent in youth with higher SOR. LIMITATIONS: The cross-sectional design limits causal interpretations of the data. Future longitudinal studies will be instrumental in determining how prefrontal engagement and SOR co-develop across adolescence. CONCLUSIONS: Our results suggest that enhanced recruitment of prefrontal regions may underlie age-related decreases in SOR for a subgroup of ASD youth. En ligne : https://dx.doi.org/10.1186/s13229-023-00571-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations / Pauline MARTIN ; Francis ROBERT ; Krzysztof J. SZKOP ; Nicholas E. REDMOND ; Srirupa BHATTACHARYYA ; Jennifer WANG ; Shan CHEN ; Roberta L. BEAUCHAMP ; Irene NOBELI ; Jerry PELLETIER ; Ola LARSSON ; Vijaya RAMESH in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 39 p. Titre : Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations Type de document : Texte imprimé et/ou numérique Auteurs : Pauline MARTIN, Auteur ; Francis ROBERT, Auteur ; Krzysztof J. SZKOP, Auteur ; Nicholas E. REDMOND, Auteur ; Srirupa BHATTACHARYYA, Auteur ; Jennifer WANG, Auteur ; Shan CHEN, Auteur ; Roberta L. BEAUCHAMP, Auteur ; Irene NOBELI, Auteur ; Jerry PELLETIER, Auteur ; Ola LARSSON, Auteur ; Vijaya RAMESH, Auteur Article en page(s) : 39 p. Langues : Anglais (eng) Mots-clés : Humans  *Tuberous Sclerosis/genetics/metabolism  Tumor Suppressor Proteins/genetics  Sirolimus/pharmacology  *Autism Spectrum Disorder  Mechanistic Target of Rapamycin Complex 1  Stem Cells/metabolism  Autism spectrum disorder  Early neurodevelopment  Neural progenitor cells  Polysome profiling  Rmc-6272  Tsc1  Translatome  Tuberous sclerosis complex  mTORC1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder caused by mutations in the TSC1 or TSC2 genes, with patients often exhibiting neurodevelopmental (ND) manifestations termed TSC-associated neuropsychiatric disorders (TAND) including autism spectrum disorder (ASD) and intellectual disability. Hamartin (TSC1) and tuberin (TSC2) proteins form a complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. Loss of TSC1 or TSC2 activates mTORC1 that, among several targets, controls protein synthesis by inhibiting translational repressor eIF4E-binding proteins. Using TSC1 patient-derived neural progenitor cells (NPCs), we recently reported early ND phenotypic changes, including increased cell proliferation and altered neurite outgrowth in TSC1-null NPCs, which were unaffected by the mTORC1 inhibitor rapamycin. METHODS: Here, we used polysome profiling, which quantifies changes in mRNA abundance and translational efficiencies at a transcriptome-wide level, to compare CRISPR-edited TSC1-null with CRISPR-corrected TSC1-WT NPCs generated from one TSC donor (one clone/genotype). To assess the relevance of identified gene expression alterations, we performed polysome profiling in postmortem brains from ASD donors and age-matched controls. We further compared effects on translation of a subset of transcripts and rescue of early ND phenotypes in NPCs following inhibition of mTORC1 using the allosteric inhibitor rapamycin versus a third-generation bi-steric, mTORC1-selective inhibitor RMC-6272. RESULTS: Polysome profiling of NPCs revealed numerous TSC1-associated alterations in mRNA translation that were largely recapitulated in human ASD brains. Moreover, although rapamycin treatment partially reversed the TSC1-associated alterations in mRNA translation, most genes related to neural activity/synaptic regulation or ASD were rapamycin-insensitive. In contrast, treatment with RMC-6272 inhibited rapamycin-insensitive translation and reversed TSC1-associated early ND phenotypes including proliferation and neurite outgrowth that were unaffected by rapamycin. CONCLUSIONS: Our work reveals ample mRNA translation alterations in TSC1 patient-derived NPCs that recapitulate mRNA translation in ASD brain samples. Further, suppression of TSC1-associated but rapamycin-insensitive translation and ND phenotypes by RMC-6272 unveils potential implications for more efficient targeting of mTORC1 as a superior treatment strategy for TAND. En ligne : https://dx.doi.org/10.1186/s13229-023-00572-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations [Texte imprimé et/ou numérique] / Pauline MARTIN, Auteur ; Francis ROBERT, Auteur ; Krzysztof J. SZKOP, Auteur ; Nicholas E. REDMOND, Auteur ; Srirupa BHATTACHARYYA, Auteur ; Jennifer WANG, Auteur ; Shan CHEN, Auteur ; Roberta L. BEAUCHAMP, Auteur ; Irene NOBELI, Auteur ; Jerry PELLETIER, Auteur ; Ola LARSSON, Auteur ; Vijaya RAMESH, Auteur . - 39 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 39 p. Mots-clés : Humans  *Tuberous Sclerosis/genetics/metabolism  Tumor Suppressor Proteins/genetics  Sirolimus/pharmacology  *Autism Spectrum Disorder  Mechanistic Target of Rapamycin Complex 1  Stem Cells/metabolism  Autism spectrum disorder  Early neurodevelopment  Neural progenitor cells  Polysome profiling  Rmc-6272  Tsc1  Translatome  Tuberous sclerosis complex  mTORC1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder caused by mutations in the TSC1 or TSC2 genes, with patients often exhibiting neurodevelopmental (ND) manifestations termed TSC-associated neuropsychiatric disorders (TAND) including autism spectrum disorder (ASD) and intellectual disability. Hamartin (TSC1) and tuberin (TSC2) proteins form a complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. Loss of TSC1 or TSC2 activates mTORC1 that, among several targets, controls protein synthesis by inhibiting translational repressor eIF4E-binding proteins. Using TSC1 patient-derived neural progenitor cells (NPCs), we recently reported early ND phenotypic changes, including increased cell proliferation and altered neurite outgrowth in TSC1-null NPCs, which were unaffected by the mTORC1 inhibitor rapamycin. METHODS: Here, we used polysome profiling, which quantifies changes in mRNA abundance and translational efficiencies at a transcriptome-wide level, to compare CRISPR-edited TSC1-null with CRISPR-corrected TSC1-WT NPCs generated from one TSC donor (one clone/genotype). To assess the relevance of identified gene expression alterations, we performed polysome profiling in postmortem brains from ASD donors and age-matched controls. We further compared effects on translation of a subset of transcripts and rescue of early ND phenotypes in NPCs following inhibition of mTORC1 using the allosteric inhibitor rapamycin versus a third-generation bi-steric, mTORC1-selective inhibitor RMC-6272. RESULTS: Polysome profiling of NPCs revealed numerous TSC1-associated alterations in mRNA translation that were largely recapitulated in human ASD brains. Moreover, although rapamycin treatment partially reversed the TSC1-associated alterations in mRNA translation, most genes related to neural activity/synaptic regulation or ASD were rapamycin-insensitive. In contrast, treatment with RMC-6272 inhibited rapamycin-insensitive translation and reversed TSC1-associated early ND phenotypes including proliferation and neurite outgrowth that were unaffected by rapamycin. CONCLUSIONS: Our work reveals ample mRNA translation alterations in TSC1 patient-derived NPCs that recapitulate mRNA translation in ASD brain samples. Further, suppression of TSC1-associated but rapamycin-insensitive translation and ND phenotypes by RMC-6272 unveils potential implications for more efficient targeting of mTORC1 as a superior treatment strategy for TAND. En ligne : https://dx.doi.org/10.1186/s13229-023-00572-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Effect of presentation rate on auditory processing in Rett syndrome: event-related potential study / Anna REBREIKINA ; Victoria VOINOVA ; Olga SYSOEVA in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 40 p. Titre : Effect of presentation rate on auditory processing in Rett syndrome: event-related potential study Type de document : Texte imprimé et/ou numérique Auteurs : Anna REBREIKINA, Auteur ; Victoria VOINOVA, Auteur ; Olga SYSOEVA, Auteur Article en page(s) : 40 p. Langues : Anglais (eng) Mots-clés : Child  Humans  Child, Preschool  Adolescent  *Rett Syndrome/diagnosis/genetics  Evoked Potentials, Auditory/physiology  Acoustic Stimulation  Evoked Potentials  Electroencephalography  Auditory Perception/physiology  Auditory event-related potential (ERP)  Presentation rate  Rett syndrome  Stimulus-specific adaptation Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RS) is a rare neurodevelopmental disorder characterized by mutations in the MECP2 gene. Patients with RS have severe motor abnormalities and are often unable to walk, use hands and speak. The preservation of perceptual and cognitive functions is hard to assess, while clinicians and care-givers point out that these patients need more time to process information than typically developing peers. Neurophysiological correlates of auditory processing have been also found to be distorted in RS, but sound presentation rates were relatively quick in these studies (stimulus onset asynchrony, SOA<1000 ms). As auditory event-related potential (ERP) is typically increased with prolongation of SOA we aim to study if SOA prolongation might compensate for observed abnormalities. METHODS: We presented a repetitive stimulus (1000 Hz) at three different SOAs of 900 ms, 1800 ms, and 3600 ms in children with RS (N=24, Mean age=9.0?+?3.1) and their typical development (TD) peers (N=27, Mean age=9.7?+?3.4) while recording 28-channels electroencephalogram, EEG. Some RS participants (n=10) did not show clear ERP and were excluded from the analysis. RESULTS: Major ERP components (here assessed as N1P1 and P2N1 peak-to-peak values) were smaller at SOA 900 than at longer SOAs in both groups, pointing out that the basic mechanism of adaptation in the auditory system is preserved in at least in RS patients with evident ERPs. At the same time the latencies of these components were significantly delayed in the RS than in TD. Moreover, late components (P2N1 and N2P2) were drastically reduced in Rett syndrome irrespective of the SOA, suggesting a largely affected mechanism of integration of upcoming sensory input with memory. Moreover, developmental stagnation of auditory ERP characterized patients with RS: absence of typical P2N1 enlargement and P1 and N1 shortening with age at least for shortest SOA. LIMITATIONS: We could not figure out the cause for the high percentage of no-evident ERP RS participants and our final sample of the RS group was rather small. Also, our study did not include a control clinical group. CONCLUSIONS: Thus, auditory ERPs inform us about abnormalities within auditory processing that cannot be fully overcomed by slowing presentation rate. En ligne : https://dx.doi.org/10.1186/s13229-023-00566-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Effect of presentation rate on auditory processing in Rett syndrome: event-related potential study [Texte imprimé et/ou numérique] / Anna REBREIKINA, Auteur ; Victoria VOINOVA, Auteur ; Olga SYSOEVA, Auteur . - 40 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 40 p. Mots-clés : Child  Humans  Child, Preschool  Adolescent  *Rett Syndrome/diagnosis/genetics  Evoked Potentials, Auditory/physiology  Acoustic Stimulation  Evoked Potentials  Electroencephalography  Auditory Perception/physiology  Auditory event-related potential (ERP)  Presentation rate  Rett syndrome  Stimulus-specific adaptation Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RS) is a rare neurodevelopmental disorder characterized by mutations in the MECP2 gene. Patients with RS have severe motor abnormalities and are often unable to walk, use hands and speak. The preservation of perceptual and cognitive functions is hard to assess, while clinicians and care-givers point out that these patients need more time to process information than typically developing peers. Neurophysiological correlates of auditory processing have been also found to be distorted in RS, but sound presentation rates were relatively quick in these studies (stimulus onset asynchrony, SOA<1000 ms). As auditory event-related potential (ERP) is typically increased with prolongation of SOA we aim to study if SOA prolongation might compensate for observed abnormalities. METHODS: We presented a repetitive stimulus (1000 Hz) at three different SOAs of 900 ms, 1800 ms, and 3600 ms in children with RS (N=24, Mean age=9.0?+?3.1) and their typical development (TD) peers (N=27, Mean age=9.7?+?3.4) while recording 28-channels electroencephalogram, EEG. Some RS participants (n=10) did not show clear ERP and were excluded from the analysis. RESULTS: Major ERP components (here assessed as N1P1 and P2N1 peak-to-peak values) were smaller at SOA 900 than at longer SOAs in both groups, pointing out that the basic mechanism of adaptation in the auditory system is preserved in at least in RS patients with evident ERPs. At the same time the latencies of these components were significantly delayed in the RS than in TD. Moreover, late components (P2N1 and N2P2) were drastically reduced in Rett syndrome irrespective of the SOA, suggesting a largely affected mechanism of integration of upcoming sensory input with memory. Moreover, developmental stagnation of auditory ERP characterized patients with RS: absence of typical P2N1 enlargement and P1 and N1 shortening with age at least for shortest SOA. LIMITATIONS: We could not figure out the cause for the high percentage of no-evident ERP RS participants and our final sample of the RS group was rather small. Also, our study did not include a control clinical group. CONCLUSIONS: Thus, auditory ERPs inform us about abnormalities within auditory processing that cannot be fully overcomed by slowing presentation rate. En ligne : https://dx.doi.org/10.1186/s13229-023-00566-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Developmental prediction modeling based on diffusion tensor imaging uncovering age-dependent heterogeneity in early childhood autistic brain / Yating MING ; Weixing ZHAO ; Rui FENG ; Yuanyue ZHOU ; Lijie WU ; Jia WANG ; Jinming XIAO ; Lei LI ; Xiaolong SHAN ; Jing CAO ; Xiaodong KANG ; Huafu CHEN ; Xujun DUAN in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 41 p. Titre : Developmental prediction modeling based on diffusion tensor imaging uncovering age-dependent heterogeneity in early childhood autistic brain Type de document : Texte imprimé et/ou numérique Auteurs : Yating MING, Auteur ; Weixing ZHAO, Auteur ; Rui FENG, Auteur ; Yuanyue ZHOU, Auteur ; Lijie WU, Auteur ; Jia WANG, Auteur ; Jinming XIAO, Auteur ; Lei LI, Auteur ; Xiaolong SHAN, Auteur ; Jing CAO, Auteur ; Xiaodong KANG, Auteur ; Huafu CHEN, Auteur ; Xujun DUAN, Auteur Article en page(s) : 41 p. Langues : Anglais (eng) Mots-clés : Child  Humans  Child, Preschool  Diffusion Tensor Imaging/methods  *Autistic Disorder/diagnostic imaging  Brain/diagnostic imaging  *White Matter/diagnostic imaging  Cluster Analysis Index. décimale : PER Périodiques Résumé : OBJECTIVE: There has been increasing evidence for atypical white matter (WM) microstructure in autistic people, but findings have been divergent. The development of autistic people in early childhood is clouded by the concurrently rapid brain growth, which might lead to the inconsistent findings of atypical WM microstructure in autism. Here, we aimed to reveal the developmental nature of autistic children and delineate atypical WM microstructure throughout early childhood while taking developmental considerations into account. METHOD: In this study, diffusion tensor imaging was acquired from two independent cohorts, containing 91 autistic children and 100 typically developing children (TDC), aged 4-7 years. Developmental prediction modeling using support vector regression based on TDC participants was conducted to estimate the WM atypical development index of autistic children. Then, subgroups of autistic children were identified by using the k-means clustering method and were compared to each other on the basis of demographic information, WM atypical development index, and autistic trait by using two-sample t-test. Relationship of the WM atypical development index with age was estimated by using partial correlation. Furthermore, we performed threshold-free cluster enhancement-based two-sample t-test for the group comparison in WM microstructures of each subgroup of autistic children with the rematched subsets of TDC. RESULTS: We clustered autistic children into two subgroups according to WM atypical development index. The two subgroups exhibited distinct developmental stages and age-dependent diversity. WM atypical development index was found negatively associated with age. Moreover, an inverse pattern of atypical WM microstructures and different clinical manifestations in the two stages, with subgroup 1 showing overgrowth with low level of autistic traits and subgroup 2 exhibiting delayed maturation with high level of autistic traits, were revealed. CONCLUSION: This study illustrated age-dependent heterogeneity in early childhood autistic children and delineated developmental stage-specific difference that ranged from an overgrowth pattern to a delayed pattern. Trial registration This study has been registered at ClinicalTrials.gov (Identifier: NCT02807766) on June 21, 2016 ( https://clinicaltrials.gov/ct2/show/NCT02807766 ). En ligne : https://dx.doi.org/10.1186/s13229-023-00573-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Developmental prediction modeling based on diffusion tensor imaging uncovering age-dependent heterogeneity in early childhood autistic brain [Texte imprimé et/ou numérique] / Yating MING, Auteur ; Weixing ZHAO, Auteur ; Rui FENG, Auteur ; Yuanyue ZHOU, Auteur ; Lijie WU, Auteur ; Jia WANG, Auteur ; Jinming XIAO, Auteur ; Lei LI, Auteur ; Xiaolong SHAN, Auteur ; Jing CAO, Auteur ; Xiaodong KANG, Auteur ; Huafu CHEN, Auteur ; Xujun DUAN, Auteur . - 41 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 41 p. Mots-clés : Child  Humans  Child, Preschool  Diffusion Tensor Imaging/methods  *Autistic Disorder/diagnostic imaging  Brain/diagnostic imaging  *White Matter/diagnostic imaging  Cluster Analysis Index. décimale : PER Périodiques Résumé : OBJECTIVE: There has been increasing evidence for atypical white matter (WM) microstructure in autistic people, but findings have been divergent. The development of autistic people in early childhood is clouded by the concurrently rapid brain growth, which might lead to the inconsistent findings of atypical WM microstructure in autism. Here, we aimed to reveal the developmental nature of autistic children and delineate atypical WM microstructure throughout early childhood while taking developmental considerations into account. METHOD: In this study, diffusion tensor imaging was acquired from two independent cohorts, containing 91 autistic children and 100 typically developing children (TDC), aged 4-7 years. Developmental prediction modeling using support vector regression based on TDC participants was conducted to estimate the WM atypical development index of autistic children. Then, subgroups of autistic children were identified by using the k-means clustering method and were compared to each other on the basis of demographic information, WM atypical development index, and autistic trait by using two-sample t-test. Relationship of the WM atypical development index with age was estimated by using partial correlation. Furthermore, we performed threshold-free cluster enhancement-based two-sample t-test for the group comparison in WM microstructures of each subgroup of autistic children with the rematched subsets of TDC. RESULTS: We clustered autistic children into two subgroups according to WM atypical development index. The two subgroups exhibited distinct developmental stages and age-dependent diversity. WM atypical development index was found negatively associated with age. Moreover, an inverse pattern of atypical WM microstructures and different clinical manifestations in the two stages, with subgroup 1 showing overgrowth with low level of autistic traits and subgroup 2 exhibiting delayed maturation with high level of autistic traits, were revealed. CONCLUSION: This study illustrated age-dependent heterogeneity in early childhood autistic children and delineated developmental stage-specific difference that ranged from an overgrowth pattern to a delayed pattern. Trial registration This study has been registered at ClinicalTrials.gov (Identifier: NCT02807766) on June 21, 2016 ( https://clinicaltrials.gov/ct2/show/NCT02807766 ). En ligne : https://dx.doi.org/10.1186/s13229-023-00573-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Tau reduction attenuates autism-like features in Fmr1 knockout mice / Xiangyu JIANG ; Linkun HAN ; Yiru JIANG ; Yong WANG ; Jian MENG ; Xiang ZHU ; Xian ZHANG ; Hong LUO ; Yun-Wu ZHANG in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 42 p. Titre : Tau reduction attenuates autism-like features in Fmr1 knockout mice Type de document : Texte imprimé et/ou numérique Auteurs : Xiangyu JIANG, Auteur ; Linkun HAN, Auteur ; Yiru JIANG, Auteur ; Yong WANG, Auteur ; Jian MENG, Auteur ; Xiang ZHU, Auteur ; Xian ZHANG, Auteur ; Hong LUO, Auteur ; Yun-Wu ZHANG, Auteur Article en page(s) : 42 p. Langues : Anglais (eng) Mots-clés : Animals  Mice  Male  Female  Mice, Knockout  *Autism Spectrum Disorder  *Autistic Disorder/genetics  tau Proteins/genetics/metabolism  Fragile X Mental Retardation Protein/genetics/metabolism  *Fragile X Syndrome/genetics/metabolism  Disease Models, Animal  Antisense oligonucleotide  Autism spectrum disorder  Fmr1  Fragile X syndrome  P38/MAPK signaling  Tau Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. METHODS: Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1(+) female mice with Mapt(+) male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. RESULTS: Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. LIMITATIONS: Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. CONCLUSION: Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment. En ligne : https://dx.doi.org/10.1186/s13229-023-00574-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Tau reduction attenuates autism-like features in Fmr1 knockout mice [Texte imprimé et/ou numérique] / Xiangyu JIANG, Auteur ; Linkun HAN, Auteur ; Yiru JIANG, Auteur ; Yong WANG, Auteur ; Jian MENG, Auteur ; Xiang ZHU, Auteur ; Xian ZHANG, Auteur ; Hong LUO, Auteur ; Yun-Wu ZHANG, Auteur . - 42 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 42 p. Mots-clés : Animals  Mice  Male  Female  Mice, Knockout  *Autism Spectrum Disorder  *Autistic Disorder/genetics  tau Proteins/genetics/metabolism  Fragile X Mental Retardation Protein/genetics/metabolism  *Fragile X Syndrome/genetics/metabolism  Disease Models, Animal  Antisense oligonucleotide  Autism spectrum disorder  Fmr1  Fragile X syndrome  P38/MAPK signaling  Tau Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. METHODS: Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1(+) female mice with Mapt(+) male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. RESULTS: Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. LIMITATIONS: Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. CONCLUSION: Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment. En ligne : https://dx.doi.org/10.1186/s13229-023-00574-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder / Carol L. MURRAY ; John KEALY ; Clodagh TOWNS ; Andrew ROCHE ; Arshed NAZMI ; Michelle DORAN ; John P. LOWRY ; Colm CUNNINGHAM in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 43 p. Titre : Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Carol L. MURRAY, Auteur ; John KEALY, Auteur ; Clodagh TOWNS, Auteur ; Andrew ROCHE, Auteur ; Arshed NAZMI, Auteur ; Michelle DORAN, Auteur ; John P. LOWRY, Auteur ; Colm CUNNINGHAM, Auteur Article en page(s) : 43 p. Langues : Anglais (eng) Mots-clés : Humans  Mice  Animals  *Autism Spectrum Disorder/therapy  Lipopolysaccharides/toxicity  Temperature  Disease Models, Animal  Mice, Inbred Strains  Brain  *Hyperthermia, Induced/methods Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are predominantly neurodevelopmental and largely genetically determined. However, there are human data supporting the idea that fever can improve symptoms in some individuals, but those data are limited and there are almost no data to support this from animal models. We aimed to test the hypothesis that elevated body temperature would improve function in two animal models of ASD. METHODS: We used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 ug/kg, to dissociate temperature and inflammatory elements of fever in two ASD animal models: C58/J and Shank3B- mice. We used one- or two-way ANOVA and t-tests with normally distributed data and Kruskal-Wallis or Mann-Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p<0.05. For correlation analyses, data were adjusted by a linear regression model. RESULTS: Only LPS induced inflammatory signatures in the brain while only WBH produced fever-range hyperthermia. WBH reduced repetitive behaviours and improved social interaction in C58/J mice and significantly reduced compulsive grooming in Shank3B- mice. LPS significantly suppressed most activities over 5-48 h. LIMITATIONS: We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements. CONCLUSIONS: The data are the first, to our knowledge, to demonstrate that elevated body temperature can improve behavioural signs in 2 distinct ASD models. Given the developmental nature of ASD, evidence that symptoms may be improved by environmental perturbations indicates possibilities for improving function in these individuals. Since experimental hyperthermia in patients would carry significant risks, it is now essential to pursue molecular mechanisms through which hyperthermia might bring about the observed benefits. En ligne : https://dx.doi.org/10.1186/s13229-023-00569-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder [Texte imprimé et/ou numérique] / Carol L. MURRAY, Auteur ; John KEALY, Auteur ; Clodagh TOWNS, Auteur ; Andrew ROCHE, Auteur ; Arshed NAZMI, Auteur ; Michelle DORAN, Auteur ; John P. LOWRY, Auteur ; Colm CUNNINGHAM, Auteur . - 43 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 43 p. Mots-clés : Humans  Mice  Animals  *Autism Spectrum Disorder/therapy  Lipopolysaccharides/toxicity  Temperature  Disease Models, Animal  Mice, Inbred Strains  Brain  *Hyperthermia, Induced/methods Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are predominantly neurodevelopmental and largely genetically determined. However, there are human data supporting the idea that fever can improve symptoms in some individuals, but those data are limited and there are almost no data to support this from animal models. We aimed to test the hypothesis that elevated body temperature would improve function in two animal models of ASD. METHODS: We used a 4 h whole-body hyperthermia (WBH) protocol and, separately, systemic inflammation induced by bacterial endotoxin (LPS) at 250 ug/kg, to dissociate temperature and inflammatory elements of fever in two ASD animal models: C58/J and Shank3B- mice. We used one- or two-way ANOVA and t-tests with normally distributed data and Kruskal-Wallis or Mann-Whitney with nonparametric data. Post hoc comparisons were made with a level of significance set at p<0.05. For correlation analyses, data were adjusted by a linear regression model. RESULTS: Only LPS induced inflammatory signatures in the brain while only WBH produced fever-range hyperthermia. WBH reduced repetitive behaviours and improved social interaction in C58/J mice and significantly reduced compulsive grooming in Shank3B- mice. LPS significantly suppressed most activities over 5-48 h. LIMITATIONS: We show behavioural, cellular and molecular changes, but provide no specific mechanistic explanation for the observed behavioural improvements. CONCLUSIONS: The data are the first, to our knowledge, to demonstrate that elevated body temperature can improve behavioural signs in 2 distinct ASD models. Given the developmental nature of ASD, evidence that symptoms may be improved by environmental perturbations indicates possibilities for improving function in these individuals. Since experimental hyperthermia in patients would carry significant risks, it is now essential to pursue molecular mechanisms through which hyperthermia might bring about the observed benefits. En ligne : https://dx.doi.org/10.1186/s13229-023-00569-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study / Kathrin NICKEL ; Thomas LANGE ; Georg OELTZSCHNER ; Michael DACKO ; Dominique ENDRES ; Kimon RUNGE ; Anke SCHUMANN ; Katharina DOMSCHKE ; Michalis ROUSOS ; Ludger TEBARTZ VAN ELST in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 44 p. Titre : Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study Type de document : Texte imprimé et/ou numérique Auteurs : Kathrin NICKEL, Auteur ; Thomas LANGE, Auteur ; Georg OELTZSCHNER, Auteur ; Michael DACKO, Auteur ; Dominique ENDRES, Auteur ; Kimon RUNGE, Auteur ; Anke SCHUMANN, Auteur ; Katharina DOMSCHKE, Auteur ; Michalis ROUSOS, Auteur ; Ludger TEBARTZ VAN ELST, Auteur Article en page(s) : 44 p. Langues : Anglais (eng) Mots-clés : Humans  Adult  *Autism Spectrum Disorder/diagnostic imaging/metabolism  Magnetic Resonance Spectroscopy/methods  Magnetic Resonance Imaging  Lactic Acid/metabolism  Biomarkers  Autism spectrum disorder  Lactate  Magnetic resonance spectroscopy  Mitochondria  Mitochondrial dysfunction  Posterior cingulate cortex  or travel grants within the last 3 years: Roche, Eli Lilly, Janssen-Cilag,  Novartis, Shire, UCB, GSK, Servier, Janssen, and Cyberonics. All other authors  declare that they do not have any conflicts of interest. Index. décimale : PER Périodiques Résumé : INTRODUCTION: Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs). MATERIALS AND METHODS: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated. RESULTS: Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p=0.028; Cohen's d=0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p=0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels. LIMITATIONS: A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality. CONCLUSION: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function. En ligne : https://dx.doi.org/10.1186/s13229-023-00577-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study [Texte imprimé et/ou numérique] / Kathrin NICKEL, Auteur ; Thomas LANGE, Auteur ; Georg OELTZSCHNER, Auteur ; Michael DACKO, Auteur ; Dominique ENDRES, Auteur ; Kimon RUNGE, Auteur ; Anke SCHUMANN, Auteur ; Katharina DOMSCHKE, Auteur ; Michalis ROUSOS, Auteur ; Ludger TEBARTZ VAN ELST, Auteur . - 44 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 44 p. Mots-clés : Humans  Adult  *Autism Spectrum Disorder/diagnostic imaging/metabolism  Magnetic Resonance Spectroscopy/methods  Magnetic Resonance Imaging  Lactic Acid/metabolism  Biomarkers  Autism spectrum disorder  Lactate  Magnetic resonance spectroscopy  Mitochondria  Mitochondrial dysfunction  Posterior cingulate cortex  or travel grants within the last 3 years: Roche, Eli Lilly, Janssen-Cilag,  Novartis, Shire, UCB, GSK, Servier, Janssen, and Cyberonics. All other authors  declare that they do not have any conflicts of interest. Index. décimale : PER Périodiques Résumé : INTRODUCTION: Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs). MATERIALS AND METHODS: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated. RESULTS: Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p=0.028; Cohen's d=0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p=0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels. LIMITATIONS: A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality. CONCLUSION: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function. En ligne : https://dx.doi.org/10.1186/s13229-023-00577-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications / Nicolas TRAUT ; Amandine PEDOUX ; Anna MARUANI ; Anita BEGGIATO ; Monique ELMALEH ; David GERMANAUD ; Anouck AMESTOY ; Myriam LY-LE MOAL ; Christopher CHATHAM ; Lorraine MURTAGH ; Manuel BOUVARD ; Marianne ALISSON ; Marion LEBOYER ; Thomas BOURGERON ; Roberto TORO ; Guillaume DUMAS ; Clara MOREAU ; Richard DELORME in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 45 p. Titre : Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications Type de document : Texte imprimé et/ou numérique Auteurs : Nicolas TRAUT, Auteur ; Amandine PEDOUX, Auteur ; Anna MARUANI, Auteur ; Anita BEGGIATO, Auteur ; Monique ELMALEH, Auteur ; David GERMANAUD, Auteur ; Anouck AMESTOY, Auteur ; Myriam LY-LE MOAL, Auteur ; Christopher CHATHAM, Auteur ; Lorraine MURTAGH, Auteur ; Manuel BOUVARD, Auteur ; Marianne ALISSON, Auteur ; Marion LEBOYER, Auteur ; Thomas BOURGERON, Auteur ; Roberto TORO, Auteur ; Guillaume DUMAS, Auteur ; Clara MOREAU, Auteur ; Richard DELORME, Auteur Article en page(s) : 45 p. Langues : Anglais (eng) Mots-clés : Humans  *Autistic Disorder/diagnostic imaging  *Autism Spectrum Disorder/diagnosis  Neuroanatomy  Magnetic Resonance Imaging  Principal Component Analysis  Cortico-striatal-thalamo-cortical loop  Phenotype  Rrb Index. décimale : PER Périodiques Résumé : BACKGROUND: Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into 'motor-driven' and 'cognitively driven'. RRBI symptomatology depends on the individual's clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context [autistic individuals, their relatives and typical developing (TD) individuals]. We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI and that these dimensions are associated with neuroanatomical signatures-involving cortical and subcortical areas. METHOD: A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n=152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models. RESULTS: We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the 'motor-driven' RRBI symptoms; Factor 2 and 3 (respectively, 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the 'cognitively driven' RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 and FA3 (all uncorrected p<0.05). FA1 was negatively associated with the left amygdala (uncorrected p<0.05), and FA2 was positively associated with the left parietal structure (uncorrected p=0.001). CONCLUSION: Our results suggested 3 coherent RRBI dimensions involving the putamen commonly and other structures according to the RRBI dimension. The exploration of the putamen's integrative role in RSBI needs to be strengthened in further studies. En ligne : https://dx.doi.org/10.1186/s13229-023-00576-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications [Texte imprimé et/ou numérique] / Nicolas TRAUT, Auteur ; Amandine PEDOUX, Auteur ; Anna MARUANI, Auteur ; Anita BEGGIATO, Auteur ; Monique ELMALEH, Auteur ; David GERMANAUD, Auteur ; Anouck AMESTOY, Auteur ; Myriam LY-LE MOAL, Auteur ; Christopher CHATHAM, Auteur ; Lorraine MURTAGH, Auteur ; Manuel BOUVARD, Auteur ; Marianne ALISSON, Auteur ; Marion LEBOYER, Auteur ; Thomas BOURGERON, Auteur ; Roberto TORO, Auteur ; Guillaume DUMAS, Auteur ; Clara MOREAU, Auteur ; Richard DELORME, Auteur . - 45 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 45 p. Mots-clés : Humans  *Autistic Disorder/diagnostic imaging  *Autism Spectrum Disorder/diagnosis  Neuroanatomy  Magnetic Resonance Imaging  Principal Component Analysis  Cortico-striatal-thalamo-cortical loop  Phenotype  Rrb Index. décimale : PER Périodiques Résumé : BACKGROUND: Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into 'motor-driven' and 'cognitively driven'. RRBI symptomatology depends on the individual's clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context [autistic individuals, their relatives and typical developing (TD) individuals]. We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI and that these dimensions are associated with neuroanatomical signatures-involving cortical and subcortical areas. METHOD: A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n=152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models. RESULTS: We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the 'motor-driven' RRBI symptoms; Factor 2 and 3 (respectively, 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the 'cognitively driven' RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 and FA3 (all uncorrected p<0.05). FA1 was negatively associated with the left amygdala (uncorrected p<0.05), and FA2 was positively associated with the left parietal structure (uncorrected p=0.001). CONCLUSION: Our results suggested 3 coherent RRBI dimensions involving the putamen commonly and other structures according to the RRBI dimension. The exploration of the putamen's integrative role in RSBI needs to be strengthened in further studies. En ligne : https://dx.doi.org/10.1186/s13229-023-00576-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Is the association between mothers' autistic traits and childhood autistic traits moderated by maternal pre-pregnancy body mass index? / Alexandros TSOMPANIDIS ; Rama J. WAHAB ; Romy GAILLARD ; Ezra AYDIN ; Rosemary HOLT ; Carrie ALLISON ; Simon BARON-COHEN ; Marinus H. VAN IJZENDOORN ; Pauline W. JANSEN in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 46 p. Titre : Is the association between mothers' autistic traits and childhood autistic traits moderated by maternal pre-pregnancy body mass index? Type de document : Texte imprimé et/ou numérique Auteurs : Alexandros TSOMPANIDIS, Auteur ; Rama J. WAHAB, Auteur ; Romy GAILLARD, Auteur ; Ezra AYDIN, Auteur ; Rosemary HOLT, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur ; Marinus H. VAN IJZENDOORN, Auteur ; Pauline W. JANSEN, Auteur Article en page(s) : 46 p. Langues : Anglais (eng) Mots-clés : Pregnancy  Female  Adolescent  Humans  Child, Preschool  Body Mass Index  *Autistic Disorder  Mothers  Parents  Autistic traits  Children  Pre-pregnancy body mass index Index. décimale : PER Périodiques Résumé : BACKGROUND: Previous studies showed that there is a positive association between mothers' and children's autistic traits. We also tested if this association is more pronounced in mothers with a higher pre-pregnancy body mass index (BMI). METHOD: The study was embedded in two cohorts with information available for 4,659 participants from the Generation R and for 179 participants from the Cambridge Ultrasound Siblings and Parents Project (CUSP) cohort. In both cohorts, maternal autistic traits were assessed using the short form of the Autism Spectrum Quotient, and information about maternal height and weight before pregnancy was obtained by questionnaire. Child autistic traits were assessed with the short form of Social Responsiveness Scale in Generation R (M=13.5 years) and with the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in the CUSP cohort (M=1.6 years). RESULT: Higher maternal autistic traits were associated with higher autistic traits in toddlerhood (CUSP cohort; ?(adjusted)=0.20, p<0.01), in early childhood (Generation R; ?(adjusted)=0.19, p<0.01), and in early adolescence (Generation R; ?(adjusted)=0.16, p<0.01). Furthermore, a higher maternal pre-pregnancy BMI was associated with higher child autistic traits, but only in Generation R (?(adjusted)=0.03, p<0.01). There was no significant moderating effect of maternal pre-pregnancy BMI on the association between autistic traits of mothers and children, neither in Generation R nor in CUSP. In addition, child autistic traits scores were significantly higher in mothers who were underweight and in mothers who were overweight compared to mothers with a healthy weight. CONCLUSION: We confirm the association between maternal and child autistic traits in toddlerhood, early childhood, and early adolescence. Potential interacting neurobiological processes remain to be confirmed. En ligne : https://dx.doi.org/10.1186/s13229-023-00578-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Is the association between mothers' autistic traits and childhood autistic traits moderated by maternal pre-pregnancy body mass index? [Texte imprimé et/ou numérique] / Alexandros TSOMPANIDIS, Auteur ; Rama J. WAHAB, Auteur ; Romy GAILLARD, Auteur ; Ezra AYDIN, Auteur ; Rosemary HOLT, Auteur ; Carrie ALLISON, Auteur ; Simon BARON-COHEN, Auteur ; Marinus H. VAN IJZENDOORN, Auteur ; Pauline W. JANSEN, Auteur . - 46 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 46 p. Mots-clés : Pregnancy  Female  Adolescent  Humans  Child, Preschool  Body Mass Index  *Autistic Disorder  Mothers  Parents  Autistic traits  Children  Pre-pregnancy body mass index Index. décimale : PER Périodiques Résumé : BACKGROUND: Previous studies showed that there is a positive association between mothers' and children's autistic traits. We also tested if this association is more pronounced in mothers with a higher pre-pregnancy body mass index (BMI). METHOD: The study was embedded in two cohorts with information available for 4,659 participants from the Generation R and for 179 participants from the Cambridge Ultrasound Siblings and Parents Project (CUSP) cohort. In both cohorts, maternal autistic traits were assessed using the short form of the Autism Spectrum Quotient, and information about maternal height and weight before pregnancy was obtained by questionnaire. Child autistic traits were assessed with the short form of Social Responsiveness Scale in Generation R (M=13.5 years) and with the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in the CUSP cohort (M=1.6 years). RESULT: Higher maternal autistic traits were associated with higher autistic traits in toddlerhood (CUSP cohort; ?(adjusted)=0.20, p<0.01), in early childhood (Generation R; ?(adjusted)=0.19, p<0.01), and in early adolescence (Generation R; ?(adjusted)=0.16, p<0.01). Furthermore, a higher maternal pre-pregnancy BMI was associated with higher child autistic traits, but only in Generation R (?(adjusted)=0.03, p<0.01). There was no significant moderating effect of maternal pre-pregnancy BMI on the association between autistic traits of mothers and children, neither in Generation R nor in CUSP. In addition, child autistic traits scores were significantly higher in mothers who were underweight and in mothers who were overweight compared to mothers with a healthy weight. CONCLUSION: We confirm the association between maternal and child autistic traits in toddlerhood, early childhood, and early adolescence. Potential interacting neurobiological processes remain to be confirmed. En ligne : https://dx.doi.org/10.1186/s13229-023-00578-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

The biosocial correlates and predictors of emotion dysregulation in autistic adults compared to borderline personality disorder and nonclinical controls / Doha BEMMOUNA in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 47 p. Titre : The biosocial correlates and predictors of emotion dysregulation in autistic adults compared to borderline personality disorder and nonclinical controls Type de document : Texte imprimé et/ou numérique Auteurs : Doha BEMMOUNA, Auteur ; Amine LAGZOULI, Auteur ; Luisa WEINER, Auteur Article en page(s) : 47 p. Langues : Anglais (eng) Mots-clés : Adult  Humans  Female  Autistic Disorder  Borderline Personality Disorder/complications/diagnosis/psychology  Cross-Sectional Studies  Surveys and Questionnaires  Emotions  Aetiology  Autism spectrum condition  Biosocial  Borderline personality disorder  Emotion dysregulation  Non-suicidal self-injury  Suicidality Index. décimale : PER Périodiques Résumé : BACKGROUND: Emotion dysregulation (ED) is a core symptom of borderline personality disorder (BPD), whose aetiology has been attributed to biosocial factors. In autism spectrum condition (ASC), although ED is prevalent and is associated with decreased well-being (e.g. self-harm, suicidality), it has been understudied, especially in adults. It is therefore crucial to further understand ED in autistic adults to improve its treatment. Our study investigates ED, its behavioural correlates (e.g. self-harm, suicidality) and biosocial predictors in autistic adults relative to BPD and nonclinical controls (NC). METHODS: A total of 724 participants (ASC?=?154; BPD?=?111; NC?=?459) completed 11 self-reported questionnaires assessing ED, ASC and BPD traits, co-occurring disorders, alexithymia, emotional vulnerability and invalidating experiences (e.g. bullying, autistic camouflaging). The occurrence of ED behavioural correlates (i.e. self-harm, history of suicide attempts, and psychiatric hospitalizations) was collected. In addition, between-groups analyses, linear regressions and machine learning (ML) models were used to identify ED predictors in each group. RESULTS: ED and its behavioural correlates were higher in ASC compared to NC, but milder than in BPD. While gender did not predict ED scores, autistic women had increased risk factors to ED, including sexual abuse and camouflaging. Interestingly, BPD traits, emotional vulnerability and alexithymia strongly predicted ED scores across the groups. Using ML models, sensory sensitivity and autistic camouflaging were associated with ED in ASC, and ADHD symptoms with ED in BPD. LIMITATIONS: ASC and BPD diagnoses were self-reported, which did not allow us to check their accuracy. Additionally, we did not explore the transactional and the moderating/mediating relationships between the different variables. Moreover, our research is cross-sectional and cannot draw conclusions regarding the direction and causality of relationships between ED and other clinical dimensions. CONCLUSIONS: ED and its behavioural correlates are heightened in BPD compared to ASC and nonclinical controls. In the ASC group, there were no gender differences in ED, despite the heightened exposure of autistic women to ED risk factors. BPD traits, emotional vulnerability, and alexithymia are core to ED regardless of diagnosis. Although less central, sensory sensitivity and autistic camouflaging seem to be specific predictors of ED in autistic adults. En ligne : https://dx.doi.org/10.1186/s13229-023-00580-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537 [article] The biosocial correlates and predictors of emotion dysregulation in autistic adults compared to borderline personality disorder and nonclinical controls [Texte imprimé et/ou numérique] / Doha BEMMOUNA, Auteur ; Amine LAGZOULI, Auteur ; Luisa WEINER, Auteur . - 47 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 47 p. Mots-clés : Adult  Humans  Female  Autistic Disorder  Borderline Personality Disorder/complications/diagnosis/psychology  Cross-Sectional Studies  Surveys and Questionnaires  Emotions  Aetiology  Autism spectrum condition  Biosocial  Borderline personality disorder  Emotion dysregulation  Non-suicidal self-injury  Suicidality Index. décimale : PER Périodiques Résumé : BACKGROUND: Emotion dysregulation (ED) is a core symptom of borderline personality disorder (BPD), whose aetiology has been attributed to biosocial factors. In autism spectrum condition (ASC), although ED is prevalent and is associated with decreased well-being (e.g. self-harm, suicidality), it has been understudied, especially in adults. It is therefore crucial to further understand ED in autistic adults to improve its treatment. Our study investigates ED, its behavioural correlates (e.g. self-harm, suicidality) and biosocial predictors in autistic adults relative to BPD and nonclinical controls (NC). METHODS: A total of 724 participants (ASC?=?154; BPD?=?111; NC?=?459) completed 11 self-reported questionnaires assessing ED, ASC and BPD traits, co-occurring disorders, alexithymia, emotional vulnerability and invalidating experiences (e.g. bullying, autistic camouflaging). The occurrence of ED behavioural correlates (i.e. self-harm, history of suicide attempts, and psychiatric hospitalizations) was collected. In addition, between-groups analyses, linear regressions and machine learning (ML) models were used to identify ED predictors in each group. RESULTS: ED and its behavioural correlates were higher in ASC compared to NC, but milder than in BPD. While gender did not predict ED scores, autistic women had increased risk factors to ED, including sexual abuse and camouflaging. Interestingly, BPD traits, emotional vulnerability and alexithymia strongly predicted ED scores across the groups. Using ML models, sensory sensitivity and autistic camouflaging were associated with ED in ASC, and ADHD symptoms with ED in BPD. LIMITATIONS: ASC and BPD diagnoses were self-reported, which did not allow us to check their accuracy. Additionally, we did not explore the transactional and the moderating/mediating relationships between the different variables. Moreover, our research is cross-sectional and cannot draw conclusions regarding the direction and causality of relationships between ED and other clinical dimensions. CONCLUSIONS: ED and its behavioural correlates are heightened in BPD compared to ASC and nonclinical controls. In the ASC group, there were no gender differences in ED, despite the heightened exposure of autistic women to ED risk factors. BPD traits, emotional vulnerability, and alexithymia are core to ED regardless of diagnosis. Although less central, sensory sensitivity and autistic camouflaging seem to be specific predictors of ED in autistic adults. En ligne : https://dx.doi.org/10.1186/s13229-023-00580-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537