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The association between social camouflage and mental health among autistic people in Japan and the UK: a cross-cultural study / Fumiyo OSHIMA in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 1p. Titre : The association between social camouflage and mental health among autistic people in Japan and the UK: a cross-cultural study Type de document : Texte imprimé et/ou numérique Auteurs : Fumiyo OSHIMA, Auteur ; Toru TAKAHASHI, Auteur ; Masaki TAMURA, Auteur ; Siqing GUAN, Auteur ; Mikuko SETO, Auteur ; Laura HULL, Auteur ; William MANDY, Auteur ; Kenji TSUCHIYA, Auteur ; Eiji SHIMIZU, Auteur Article en page(s) : 1p. Langues : Anglais (eng) Mots-clés : Male  Adult  Humans  Female  Autistic Disorder/diagnosis  Japan/epidemiology  Mental Health  Cross-Cultural Comparison  Cross-Sectional Studies  United Kingdom/epidemiology  Autistic adults  Cross-cultural study  Japan  Social camouflage  Uk Index. décimale : PER Périodiques Résumé : BACKGROUND: To examine the relationship between social camouflage and mental health in Japanese autistic adults and make an international comparison with a sample from the UK. METHODS: This study analysed secondary data of participants with a self-reported diagnosis of autism from Japan (N = 210; 123 men and 87 women) and the UK (N = 305; 181 women, 104, men, and 18 nonbinary). The relationships between the quadratic term of the Camouflaging Autistic Traits Questionnaire and mental health scales, including depression and anxiety, were assessed. RESULTS: The UK sample showed linear relationships, whereas the Japanese sample showed significant nonlinear relationships. The quadratic terms of the Camouflaging Autistic Traits Questionnaire slightly explained generalised anxiety (? = .168, p = .007), depression (? = .121, p = .045), and well-being (? = -?.127, p = .028). However, they did not explain the association between social anxiety and the Camouflaging Autistic Traits Questionnaire. LIMITATIONS: Participants had self-reported diagnoses, and while the autism-spectrum quotient provides a cut-off value for screening, it does not enable confirming diagnoses. Mean scores of the Japanese version of the Camouflaging Autistic Traits Questionnaire were lower as compared to the original CAT-Q, which implies that the social camouflage strategy types used by autistic people in Japan and the UK could differ. The cross-sectional design limits causal inferences. CONCLUSION: In the UK, more social camouflage was associated with poorer mental health scores, whereas too little or too much social camouflage was associated with a low mental health score in Japan. The Japanese population is seemingly less aware of and educated on autistic characteristics and considers 'average' behaviour a good thing. This could influence Japanese autistic people's social camouflage use, differing from that of autistic people in the UK. The differences in the relationship between social camouflage and mental health between Japan and the UK could be associated with national-level divergence regarding the culture of autism. En ligne : https://dx.doi.org/10.1186/s13229-023-00579-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537 [article] The association between social camouflage and mental health among autistic people in Japan and the UK: a cross-cultural study [Texte imprimé et/ou numérique] / Fumiyo OSHIMA, Auteur ; Toru TAKAHASHI, Auteur ; Masaki TAMURA, Auteur ; Siqing GUAN, Auteur ; Mikuko SETO, Auteur ; Laura HULL, Auteur ; William MANDY, Auteur ; Kenji TSUCHIYA, Auteur ; Eiji SHIMIZU, Auteur . - 1p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 1p. Mots-clés : Male  Adult  Humans  Female  Autistic Disorder/diagnosis  Japan/epidemiology  Mental Health  Cross-Cultural Comparison  Cross-Sectional Studies  United Kingdom/epidemiology  Autistic adults  Cross-cultural study  Japan  Social camouflage  Uk Index. décimale : PER Périodiques Résumé : BACKGROUND: To examine the relationship between social camouflage and mental health in Japanese autistic adults and make an international comparison with a sample from the UK. METHODS: This study analysed secondary data of participants with a self-reported diagnosis of autism from Japan (N = 210; 123 men and 87 women) and the UK (N = 305; 181 women, 104, men, and 18 nonbinary). The relationships between the quadratic term of the Camouflaging Autistic Traits Questionnaire and mental health scales, including depression and anxiety, were assessed. RESULTS: The UK sample showed linear relationships, whereas the Japanese sample showed significant nonlinear relationships. The quadratic terms of the Camouflaging Autistic Traits Questionnaire slightly explained generalised anxiety (? = .168, p = .007), depression (? = .121, p = .045), and well-being (? = -?.127, p = .028). However, they did not explain the association between social anxiety and the Camouflaging Autistic Traits Questionnaire. LIMITATIONS: Participants had self-reported diagnoses, and while the autism-spectrum quotient provides a cut-off value for screening, it does not enable confirming diagnoses. Mean scores of the Japanese version of the Camouflaging Autistic Traits Questionnaire were lower as compared to the original CAT-Q, which implies that the social camouflage strategy types used by autistic people in Japan and the UK could differ. The cross-sectional design limits causal inferences. CONCLUSION: In the UK, more social camouflage was associated with poorer mental health scores, whereas too little or too much social camouflage was associated with a low mental health score in Japan. The Japanese population is seemingly less aware of and educated on autistic characteristics and considers 'average' behaviour a good thing. This could influence Japanese autistic people's social camouflage use, differing from that of autistic people in the UK. The differences in the relationship between social camouflage and mental health between Japan and the UK could be associated with national-level divergence regarding the culture of autism. En ligne : https://dx.doi.org/10.1186/s13229-023-00579-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537

Autistic and non-autistic individuals show the same amygdala activity during emotional face processing / Benedikt P LANGENBACH in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 2p. Titre : Autistic and non-autistic individuals show the same amygdala activity during emotional face processing Type de document : Texte imprimé et/ou numérique Auteurs : Benedikt P LANGENBACH, Auteur ; Dominik GROTEGERD, Auteur ; Peter C R MULDERS, Auteur ; Indira TENDOLKAR, Auteur ; Jasper VAN OORT, Auteur ; Fleur DUYSER, Auteur ; Philip VAN EIJNDHOVEN, Auteur ; Janna N VRIJSEN, Auteur ; Udo DANNLOWSKI, Auteur ; Zarah KAMPMANN, Auteur ; Katja KOELKEBECK, Auteur Article en page(s) : 2p. Langues : Anglais (eng) Mots-clés : Humans  Autistic Disorder  Autism Spectrum Disorder  Facial Recognition  Emotions  Amygdala/diagnostic imaging  Amygdala  Autism  Emotion processing  Face processing  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people's feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples. METHODS: In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns. RESULTS: We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment. LIMITATIONS: Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations. CONCLUSIONS: Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing. En ligne : https://dx.doi.org/10.1186/s13229-024-00582-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537 [article] Autistic and non-autistic individuals show the same amygdala activity during emotional face processing [Texte imprimé et/ou numérique] / Benedikt P LANGENBACH, Auteur ; Dominik GROTEGERD, Auteur ; Peter C R MULDERS, Auteur ; Indira TENDOLKAR, Auteur ; Jasper VAN OORT, Auteur ; Fleur DUYSER, Auteur ; Philip VAN EIJNDHOVEN, Auteur ; Janna N VRIJSEN, Auteur ; Udo DANNLOWSKI, Auteur ; Zarah KAMPMANN, Auteur ; Katja KOELKEBECK, Auteur . - 2p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 2p. Mots-clés : Humans  Autistic Disorder  Autism Spectrum Disorder  Facial Recognition  Emotions  Amygdala/diagnostic imaging  Amygdala  Autism  Emotion processing  Face processing  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic and non-autistic individuals often differ in how they perceive and show emotions, especially in their ability and inclination to infer other people's feelings from subtle cues like facial expressions. Prominent theories of autism have suggested that these differences stem from alterations in amygdala functioning and that amygdala hypoactivation causes problems with emotion recognition. Thus far, however, empirical investigations of this hypothesis have yielded mixed results and largely relied on relatively small samples. METHODS: In a sample of 72 autistic and 79 non-autistic participants, we conducted a study in which we used the Hariri paradigm to test whether amygdala activation during emotional face processing is altered in autism spectrum disorder, and whether common mental disorders like depression, ADHD or anxiety disorders influence any potential alterations in activation patterns. RESULTS: We found no evidence for differences in amygdala activation, neither when comparing autistic and non-autistic participants, nor when taking into account mental disorders or the overall level of functional impairment. LIMITATIONS: Because we used one basic emotion processing task in a Dutch sample, results might not generalise to other tasks and other populations. CONCLUSIONS: Our results challenge the view that autistic and non-autistic processing of emotional faces in the amygdala is vastly different and call for a more nuanced view of differences between non-autistic and autistic emotion processing. En ligne : https://dx.doi.org/10.1186/s13229-024-00582-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537

Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort / Ting MEI in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 3p. Titre : Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort Type de document : Texte imprimé et/ou numérique Auteurs : Ting MEI, Auteur ; Alberto LLERA, Auteur ; Natalie J. FORDE, Auteur ; Daan VAN ROOIJ, Auteur ; Dorothea L. FLORIS, Auteur ; Christian F. BECKMANN, Auteur ; Jan K. BUITELAAR, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Humans  Gray Matter/diagnostic imaging  Autistic Disorder/diagnostic imaging  Autism Spectrum Disorder/diagnostic imaging  Retrospective Studies  Magnetic Resonance Imaging/methods  Brain/diagnostic imaging  Autism  Gray matter volume covariation  Replication  advisory board member of, and a speaker for Janssen Cilag BV, Eli Lilly, Shire,  Lundbeck, Roche, and Servier. He is not an employee of any of these companies,  and not a stock shareholder of any of these companies. He has no other financial  or material support, including expert testimony, patents or royalties. The  present work is unrelated to the above grants and relationships. The other  authors report no biomedical financial interests or potential conflicts of  interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robustness of our previous findings, we aimed to replicate our results using data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) autism working group. METHODS: We studied 781 autistic and 927 non-autistic individuals (6-30 years, IQ???50), across 37 sites. Voxel-based morphometry was used to quantify GM volume as before. Subsequently, we used spatial maps of the two autism-related independent components (ICs) previously identified in the LEAP sample as templates for regression analyses to separately estimate the ENIGMA-participant loadings to each of these two ICs. Between-group differences in participants' loadings on each component were examined, and we additionally investigated the relation between participant loadings and autistic behaviors within the autism group. RESULTS: The two components of interest, previously identified in the LEAP dataset, showed significant between-group differences upon regressions into the ENIGMA cohort. The associated brain patterns were consistent with those found in the initial identification study. The first IC was primarily associated with increased volumes of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and caudate in the autism group relative to the control group (? = 0.129, p = 0.013). The second IC was related to increased volumes of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to non-autistic individuals (? = 0.116, p = 0.024). However, when accounting for the site-by-group interaction effect, no significant main effect of the group can be identified (p > 0.590). We did not find significant univariate association between the brain measures and behavior in autism (p > 0.085). LIMITATIONS: The distributions of age, IQ, and sex between LEAP and ENIGMA are statistically different from each other. Owing to limited access to the behavioral data of the autism group, we were unable to further our understanding of the neural basis of behavioral dimensions of the sample. CONCLUSIONS: The current study is unable to fully replicate the autism-related brain patterns from LEAP in the ENIGMA cohort. The diverse group effects across ENIGMA sites demonstrate the challenges of generalizing the average findings of the GM covariation patterns to a large-scale cohort integrated retrospectively from multiple studies. Further analyses need to be conducted to gain additional insights into the generalizability of these two GM covariation patterns. En ligne : https://dx.doi.org/10.1186/s13229-024-00583-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537 [article] Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort [Texte imprimé et/ou numérique] / Ting MEI, Auteur ; Alberto LLERA, Auteur ; Natalie J. FORDE, Auteur ; Daan VAN ROOIJ, Auteur ; Dorothea L. FLORIS, Auteur ; Christian F. BECKMANN, Auteur ; Jan K. BUITELAAR, Auteur . - 3p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 3p. Mots-clés : Humans  Gray Matter/diagnostic imaging  Autistic Disorder/diagnostic imaging  Autism Spectrum Disorder/diagnostic imaging  Retrospective Studies  Magnetic Resonance Imaging/methods  Brain/diagnostic imaging  Autism  Gray matter volume covariation  Replication  advisory board member of, and a speaker for Janssen Cilag BV, Eli Lilly, Shire,  Lundbeck, Roche, and Servier. He is not an employee of any of these companies,  and not a stock shareholder of any of these companies. He has no other financial  or material support, including expert testimony, patents or royalties. The  present work is unrelated to the above grants and relationships. The other  authors report no biomedical financial interests or potential conflicts of  interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robustness of our previous findings, we aimed to replicate our results using data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) autism working group. METHODS: We studied 781 autistic and 927 non-autistic individuals (6-30 years, IQ???50), across 37 sites. Voxel-based morphometry was used to quantify GM volume as before. Subsequently, we used spatial maps of the two autism-related independent components (ICs) previously identified in the LEAP sample as templates for regression analyses to separately estimate the ENIGMA-participant loadings to each of these two ICs. Between-group differences in participants' loadings on each component were examined, and we additionally investigated the relation between participant loadings and autistic behaviors within the autism group. RESULTS: The two components of interest, previously identified in the LEAP dataset, showed significant between-group differences upon regressions into the ENIGMA cohort. The associated brain patterns were consistent with those found in the initial identification study. The first IC was primarily associated with increased volumes of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and caudate in the autism group relative to the control group (? = 0.129, p = 0.013). The second IC was related to increased volumes of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to non-autistic individuals (? = 0.116, p = 0.024). However, when accounting for the site-by-group interaction effect, no significant main effect of the group can be identified (p > 0.590). We did not find significant univariate association between the brain measures and behavior in autism (p > 0.085). LIMITATIONS: The distributions of age, IQ, and sex between LEAP and ENIGMA are statistically different from each other. Owing to limited access to the behavioral data of the autism group, we were unable to further our understanding of the neural basis of behavioral dimensions of the sample. CONCLUSIONS: The current study is unable to fully replicate the autism-related brain patterns from LEAP in the ENIGMA cohort. The diverse group effects across ENIGMA sites demonstrate the challenges of generalizing the average findings of the GM covariation patterns to a large-scale cohort integrated retrospectively from multiple studies. Further analyses need to be conducted to gain additional insights into the generalizability of these two GM covariation patterns. En ligne : https://dx.doi.org/10.1186/s13229-024-00583-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537

The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers / Nisha E. MATHEW in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 4p. Titre : The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers Type de document : Texte imprimé et/ou numérique Auteurs : Nisha E. MATHEW, Auteur ; Delyse MCCAFFREY, Auteur ; Adam K. WALKER, Auteur ; Kylie-Ann MALLITT, Auteur ; Anne MASI, Auteur ; Margaret J. MORRIS, Auteur ; Chee Y. OOI, Auteur Article en page(s) : 4p. Langues : Anglais (eng) Mots-clés : Adolescent  Child  Humans  Autistic Disorder  Biomarkers/analysis  Gastrointestinal Tract/chemistry/metabolism  Inflammation  Lactoferrin/analysis/metabolism  Leukocyte L1 Antigen Complex/analysis  Autism  Biomarkers  Calprotectin  Gastrointestinal  Lactoferrin Index. décimale : PER Périodiques Résumé : BACKGROUND: Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. METHODS: We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). RESULTS: There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). LIMITATIONS: All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. CONCLUSIONS: There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits. En ligne : https://dx.doi.org/10.1186/s13229-023-00575-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers [Texte imprimé et/ou numérique] / Nisha E. MATHEW, Auteur ; Delyse MCCAFFREY, Auteur ; Adam K. WALKER, Auteur ; Kylie-Ann MALLITT, Auteur ; Anne MASI, Auteur ; Margaret J. MORRIS, Auteur ; Chee Y. OOI, Auteur . - 4p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 4p. Mots-clés : Adolescent  Child  Humans  Autistic Disorder  Biomarkers/analysis  Gastrointestinal Tract/chemistry/metabolism  Inflammation  Lactoferrin/analysis/metabolism  Leukocyte L1 Antigen Complex/analysis  Autism  Biomarkers  Calprotectin  Gastrointestinal  Lactoferrin Index. décimale : PER Périodiques Résumé : BACKGROUND: Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. METHODS: We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). RESULTS: There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). LIMITATIONS: All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. CONCLUSIONS: There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits. En ligne : https://dx.doi.org/10.1186/s13229-023-00575-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Clinical impact and in vitro characterization of ADNP variants in pediatric patients / Chuanhui GE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 5p. Titre : Clinical impact and in vitro characterization of ADNP variants in pediatric patients Type de document : Texte imprimé et/ou numérique Auteurs : Chuanhui GE, Auteur ; Yuxin TIAN, Auteur ; Chunchun HU, Auteur ; Lianni MEI, Auteur ; Dongyun LI, Auteur ; Ping DONG, Auteur ; Ying ZHANG, Auteur ; Huiping LI, Auteur ; Daijing SUN, Auteur ; Wenzhu PENG, Auteur ; Xiu XU, Auteur ; Yan JIANG, Auteur ; Qiong XU, Auteur Article en page(s) : 5p. Langues : Anglais (eng) Mots-clés : Humans  Child  Intellectual Disability/genetics  Autism Spectrum Disorder/genetics  HEK293 Cells  Neuroblastoma  Transcription Factors  Nerve Tissue Proteins  Homeodomain Proteins/genetics  ADNP syndrome  ADNP variants  Autism spectrum disorder  Global developmental delay  Hvdas  Helsmoortel-Van der Aa syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability. METHODS: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells. RESULTS: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells. LIMITATIONS: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants. CONCLUSIONS: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS. En ligne : https://dx.doi.org/10.1186/s13229-024-00584-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Clinical impact and in vitro characterization of ADNP variants in pediatric patients [Texte imprimé et/ou numérique] / Chuanhui GE, Auteur ; Yuxin TIAN, Auteur ; Chunchun HU, Auteur ; Lianni MEI, Auteur ; Dongyun LI, Auteur ; Ping DONG, Auteur ; Ying ZHANG, Auteur ; Huiping LI, Auteur ; Daijing SUN, Auteur ; Wenzhu PENG, Auteur ; Xiu XU, Auteur ; Yan JIANG, Auteur ; Qiong XU, Auteur . - 5p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 5p. Mots-clés : Humans  Child  Intellectual Disability/genetics  Autism Spectrum Disorder/genetics  HEK293 Cells  Neuroblastoma  Transcription Factors  Nerve Tissue Proteins  Homeodomain Proteins/genetics  ADNP syndrome  ADNP variants  Autism spectrum disorder  Global developmental delay  Hvdas  Helsmoortel-Van der Aa syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability. METHODS: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells. RESULTS: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells. LIMITATIONS: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants. CONCLUSIONS: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS. En ligne : https://dx.doi.org/10.1186/s13229-024-00584-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Cortico-basal ganglia white matter microstructure is linked to restricted repetitive behavior in autism spectrum disorder / Bradley J. WILKES in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 6p. Titre : Cortico-basal ganglia white matter microstructure is linked to restricted repetitive behavior in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Bradley J. WILKES, Auteur ; Derek B. ARCHER, Auteur ; Anna L. FARMER, Auteur ; Carly BASS, Auteur ; Hannah KORAH, Auteur ; David E. VAILLANCOURT, Auteur ; Mark H. LEWIS, Auteur Article en page(s) : 6p. Langues : Anglais (eng) Mots-clés : United States  Adolescent  Child  Humans  White Matter/diagnostic imaging  Autism Spectrum Disorder/diagnostic imaging  Basal Ganglia/diagnostic imaging  Brain  Water  Autism spectrum disorder  Basal ganglia  Cerebellum  Cortico-basal ganglia  Diffusion tensor imaging  Free-water  Gray matter  Restricted repetitive behavior  White matter Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted repetitive behavior (RRB) is one of two behavioral domains required for the diagnosis of autism spectrum disorder (ASD). Neuroimaging is widely used to study brain alterations associated with ASD and the domain of social and communication deficits, but there has been less work regarding brain alterations linked to RRB. METHODS: We utilized neuroimaging data from the National Institute of Mental Health Data Archive to assess basal ganglia and cerebellum structure in a cohort of children and adolescents with ASD compared to typically developing (TD) controls. We evaluated regional gray matter volumes from T1-weighted anatomical scans and assessed diffusion-weighted scans to quantify white matter microstructure with free-water imaging. We also investigated the interaction of biological sex and ASD diagnosis on these measures, and their correlation with clinical scales of RRB. RESULTS: Individuals with ASD had significantly lower free-water corrected fractional anisotropy (FA(T)) and higher free-water (FW) in cortico-basal ganglia white matter tracts. These microstructural differences did not interact with biological sex. Moreover, both FA(T) and FW in basal ganglia white matter tracts significantly correlated with measures of RRB. In contrast, we found no significant difference in basal ganglia or cerebellar gray matter volumes. LIMITATIONS: The basal ganglia and cerebellar regions in this study were selected due to their hypothesized relevance to RRB. Differences between ASD and TD individuals that may occur outside the basal ganglia and cerebellum, and their potential relationship to RRB, were not evaluated. CONCLUSIONS: These new findings demonstrate that cortico-basal ganglia white matter microstructure is altered in ASD and linked to RRB. FW in cortico-basal ganglia and intra-basal ganglia white matter was more sensitive to group differences in ASD, whereas cortico-basal ganglia FA(T) was more closely linked to RRB. In contrast, basal ganglia and cerebellar volumes did not differ in ASD. There was no interaction between ASD diagnosis and sex-related differences in brain structure. Future diffusion imaging investigations in ASD may benefit from free-water estimation and correction in order to better understand how white matter is affected in ASD, and how such measures are linked to RRB. En ligne : https://dx.doi.org/10.1186/s13229-023-00581-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Cortico-basal ganglia white matter microstructure is linked to restricted repetitive behavior in autism spectrum disorder [Texte imprimé et/ou numérique] / Bradley J. WILKES, Auteur ; Derek B. ARCHER, Auteur ; Anna L. FARMER, Auteur ; Carly BASS, Auteur ; Hannah KORAH, Auteur ; David E. VAILLANCOURT, Auteur ; Mark H. LEWIS, Auteur . - 6p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 6p. Mots-clés : United States  Adolescent  Child  Humans  White Matter/diagnostic imaging  Autism Spectrum Disorder/diagnostic imaging  Basal Ganglia/diagnostic imaging  Brain  Water  Autism spectrum disorder  Basal ganglia  Cerebellum  Cortico-basal ganglia  Diffusion tensor imaging  Free-water  Gray matter  Restricted repetitive behavior  White matter Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted repetitive behavior (RRB) is one of two behavioral domains required for the diagnosis of autism spectrum disorder (ASD). Neuroimaging is widely used to study brain alterations associated with ASD and the domain of social and communication deficits, but there has been less work regarding brain alterations linked to RRB. METHODS: We utilized neuroimaging data from the National Institute of Mental Health Data Archive to assess basal ganglia and cerebellum structure in a cohort of children and adolescents with ASD compared to typically developing (TD) controls. We evaluated regional gray matter volumes from T1-weighted anatomical scans and assessed diffusion-weighted scans to quantify white matter microstructure with free-water imaging. We also investigated the interaction of biological sex and ASD diagnosis on these measures, and their correlation with clinical scales of RRB. RESULTS: Individuals with ASD had significantly lower free-water corrected fractional anisotropy (FA(T)) and higher free-water (FW) in cortico-basal ganglia white matter tracts. These microstructural differences did not interact with biological sex. Moreover, both FA(T) and FW in basal ganglia white matter tracts significantly correlated with measures of RRB. In contrast, we found no significant difference in basal ganglia or cerebellar gray matter volumes. LIMITATIONS: The basal ganglia and cerebellar regions in this study were selected due to their hypothesized relevance to RRB. Differences between ASD and TD individuals that may occur outside the basal ganglia and cerebellum, and their potential relationship to RRB, were not evaluated. CONCLUSIONS: These new findings demonstrate that cortico-basal ganglia white matter microstructure is altered in ASD and linked to RRB. FW in cortico-basal ganglia and intra-basal ganglia white matter was more sensitive to group differences in ASD, whereas cortico-basal ganglia FA(T) was more closely linked to RRB. In contrast, basal ganglia and cerebellar volumes did not differ in ASD. There was no interaction between ASD diagnosis and sex-related differences in brain structure. Future diffusion imaging investigations in ASD may benefit from free-water estimation and correction in order to better understand how white matter is affected in ASD, and how such measures are linked to RRB. En ligne : https://dx.doi.org/10.1186/s13229-023-00581-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment / Hangnyoung CHOI in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 7p. Titre : Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment Type de document : Texte imprimé et/ou numérique Auteurs : Hangnyoung CHOI, Auteur ; Jae Han KIM, Auteur ; Hee Sang YANG, Auteur ; Jong Yeob KIM, Auteur ; Samuele CORTESE, Auteur ; Lee SMITH, Auteur ; Ai KOYANAGI, Auteur ; Elena DRAGIOTI, Auteur ; Joaquim RADUA, Auteur ; Paolo FUSAR-POLI, Auteur ; Jae Il SHIN, Auteur ; Keun-Ah CHEON, Auteur ; Marco SOLMI, Auteur Article en page(s) : 7p. Langues : Anglais (eng) Mots-clés : Male  Humans  Female  GRADE Approach  Aripiprazole  Risperidone  Autism Spectrum Disorder  Autism spectrum disorder  Irritability  Meta-analysis  Randomized controlled trial  Systematic review  ADHD. PFP received honoraria/has been a consultant for Angelini, Menarini,  Lundbeck, and Sunovion. MS received honoraria/has been a consultant for ABBVie,  Angelini, Lundbeck, and Otsuka. Index. décimale : PER Périodiques Résumé : BACKGROUND: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. RESULTS: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g -?0.857, 95% CI -?1.263 to -?0.451, certainty of evidence: high) and aripiprazole (Hedges' g -?0.559, 95% CI -?0.767 to -?0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g -?0.893, 95% CI -?1.184 to -?0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone?+?adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. LIMITATIONS: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. CONCLUSIONS: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965. En ligne : https://dx.doi.org/10.1186/s13229-024-00585-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment [Texte imprimé et/ou numérique] / Hangnyoung CHOI, Auteur ; Jae Han KIM, Auteur ; Hee Sang YANG, Auteur ; Jong Yeob KIM, Auteur ; Samuele CORTESE, Auteur ; Lee SMITH, Auteur ; Ai KOYANAGI, Auteur ; Elena DRAGIOTI, Auteur ; Joaquim RADUA, Auteur ; Paolo FUSAR-POLI, Auteur ; Jae Il SHIN, Auteur ; Keun-Ah CHEON, Auteur ; Marco SOLMI, Auteur . - 7p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 7p. Mots-clés : Male  Humans  Female  GRADE Approach  Aripiprazole  Risperidone  Autism Spectrum Disorder  Autism spectrum disorder  Irritability  Meta-analysis  Randomized controlled trial  Systematic review  ADHD. PFP received honoraria/has been a consultant for Angelini, Menarini,  Lundbeck, and Sunovion. MS received honoraria/has been a consultant for ABBVie,  Angelini, Lundbeck, and Otsuka. Index. décimale : PER Périodiques Résumé : BACKGROUND: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. RESULTS: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g -?0.857, 95% CI -?1.263 to -?0.451, certainty of evidence: high) and aripiprazole (Hedges' g -?0.559, 95% CI -?0.767 to -?0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g -?0.893, 95% CI -?1.184 to -?0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone?+?adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. LIMITATIONS: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. CONCLUSIONS: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965. En ligne : https://dx.doi.org/10.1186/s13229-024-00585-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not? / Ozge OZTAN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 8p. Titre : Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not? Type de document : Texte imprimé et/ou numérique Auteurs : Ozge OZTAN, Auteur ; Laura A. DEL ROSSO, Auteur ; Sierra M. SIMMONS, Auteur ; Duyen K. K. NGUYEN, Auteur ; Catherine F. TALBOT, Auteur ; John P. CAPITANIO, Auteur ; Joseph P. GARNER, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 8p. Langues : Anglais (eng) Mots-clés : Child  Animals  Humans  Male  Female  Autistic Disorder  Autism Spectrum Disorder  Macaca mulatta  Social Behavior  Arginine Vasopressin/cerebrospinal fluid  Oxytocin  Animal model  Arginine vasopressin  Autism spectrum disorder  Cerebrospinal fluid  Dominance rank  Rhesus macaque  Social functioning  Social responsiveness scale  applications related to data reviewed herein: PCT/US2019/019029 ("Methods for  diagnosing and determining severity of an autism spectrum disorder") and  PCT/US2019/041250 ("Intranasal Vasopressin Treatment for Social Deficits in  Children with Autism"). These patents have not been granted or licensed, and no  study author is receiving any financial compensation at this time. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD. METHODS: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models. RESULTS: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found. LIMITATIONS: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores. CONCLUSIONS: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD. En ligne : https://dx.doi.org/10.1186/s13229-024-00588-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not? [Texte imprimé et/ou numérique] / Ozge OZTAN, Auteur ; Laura A. DEL ROSSO, Auteur ; Sierra M. SIMMONS, Auteur ; Duyen K. K. NGUYEN, Auteur ; Catherine F. TALBOT, Auteur ; John P. CAPITANIO, Auteur ; Joseph P. GARNER, Auteur ; Karen J. PARKER, Auteur . - 8p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 8p. Mots-clés : Child  Animals  Humans  Male  Female  Autistic Disorder  Autism Spectrum Disorder  Macaca mulatta  Social Behavior  Arginine Vasopressin/cerebrospinal fluid  Oxytocin  Animal model  Arginine vasopressin  Autism spectrum disorder  Cerebrospinal fluid  Dominance rank  Rhesus macaque  Social functioning  Social responsiveness scale  applications related to data reviewed herein: PCT/US2019/019029 ("Methods for  diagnosing and determining severity of an autism spectrum disorder") and  PCT/US2019/041250 ("Intranasal Vasopressin Treatment for Social Deficits in  Children with Autism"). These patents have not been granted or licensed, and no  study author is receiving any financial compensation at this time. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD. METHODS: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models. RESULTS: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found. LIMITATIONS: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores. CONCLUSIONS: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD. En ligne : https://dx.doi.org/10.1186/s13229-024-00588-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs / Feipeng ZHU in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 9p. Titre : Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs Type de document : Texte imprimé et/ou numérique Auteurs : Feipeng ZHU, Auteur ; Qi SHI, Auteur ; Yong-hui JIANG, Auteur ; Yong Q. ZHANG, Auteur ; Hui ZHAO, Auteur Article en page(s) : 9p. Langues : Anglais (eng) Mots-clés : Humans  Dogs  Animals  Autistic Disorder/genetics  Autism Spectrum Disorder  Nerve Tissue Proteins/genetics/metabolism  Pyramidal Cells/metabolism  Synaptic Transmission/genetics  Prefrontal Cortex  Anxiety  Disease Models, Animal  Autism spectrum disorder  Dog  Excitability  Shank3  Synaptic transmission Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK3 gene is a highly replicated causative gene for autism spectrum disorder and has been well characterized in multiple Shank3 mutant rodent models. When compared to rodents, domestic dogs are excellent animal models in which to study social cognition as they closely interact with humans and exhibit similar social behaviors. Using CRISPR/Cas9 editing, we recently generated a dog model carrying Shank3 mutations, which displayed a spectrum of autism-like behaviors, such as social impairment and heightened anxiety. However, the neural mechanism underlying these abnormal behaviors remains to be identified. METHODS: We used Shank3 mutant dog models to examine possible relationships between Shank3 mutations and neuronal dysfunction. We studied electrophysiological properties and the synaptic transmission of pyramidal neurons from acute brain slices of the prefrontal cortex (PFC). We also examined dendrite elaboration and dendritic spine morphology in the PFC using biocytin staining and Golgi staining. We analyzed the postsynaptic density using electron microscopy. RESULTS: We established a protocol for the electrophysiological recording of canine brain slices and revealed that excitatory synaptic transmission onto PFC layer 2/3 pyramidal neurons in Shank3 heterozygote dogs was impaired, and this was accompanied by reduced dendrite complexity and spine density when compared to wild-type dogs. Postsynaptic density structures were also impaired in Shank3 mutants; however, pyramidal neurons exhibited hyperexcitability. LIMITATIONS: Causal links between impaired PFC pyramidal neuron function and behavioral alterations remain unclear. Further experiments such as manipulating PFC neuronal activity or restoring synaptic transmission in Shank3 mutant dogs are required to assess PFC roles in altered social behaviors. CONCLUSIONS: Our study demonstrated the feasibility of using canine brain slices as a model system to study neuronal circuitry and disease. Shank3 haploinsufficiency causes morphological and functional abnormalities in PFC pyramidal neurons, supporting the notion that Shank3 mutant dogs are new and valid animal models for autism research. En ligne : https://dx.doi.org/10.1186/s13229-024-00587-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs [Texte imprimé et/ou numérique] / Feipeng ZHU, Auteur ; Qi SHI, Auteur ; Yong-hui JIANG, Auteur ; Yong Q. ZHANG, Auteur ; Hui ZHAO, Auteur . - 9p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 9p. Mots-clés : Humans  Dogs  Animals  Autistic Disorder/genetics  Autism Spectrum Disorder  Nerve Tissue Proteins/genetics/metabolism  Pyramidal Cells/metabolism  Synaptic Transmission/genetics  Prefrontal Cortex  Anxiety  Disease Models, Animal  Autism spectrum disorder  Dog  Excitability  Shank3  Synaptic transmission Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK3 gene is a highly replicated causative gene for autism spectrum disorder and has been well characterized in multiple Shank3 mutant rodent models. When compared to rodents, domestic dogs are excellent animal models in which to study social cognition as they closely interact with humans and exhibit similar social behaviors. Using CRISPR/Cas9 editing, we recently generated a dog model carrying Shank3 mutations, which displayed a spectrum of autism-like behaviors, such as social impairment and heightened anxiety. However, the neural mechanism underlying these abnormal behaviors remains to be identified. METHODS: We used Shank3 mutant dog models to examine possible relationships between Shank3 mutations and neuronal dysfunction. We studied electrophysiological properties and the synaptic transmission of pyramidal neurons from acute brain slices of the prefrontal cortex (PFC). We also examined dendrite elaboration and dendritic spine morphology in the PFC using biocytin staining and Golgi staining. We analyzed the postsynaptic density using electron microscopy. RESULTS: We established a protocol for the electrophysiological recording of canine brain slices and revealed that excitatory synaptic transmission onto PFC layer 2/3 pyramidal neurons in Shank3 heterozygote dogs was impaired, and this was accompanied by reduced dendrite complexity and spine density when compared to wild-type dogs. Postsynaptic density structures were also impaired in Shank3 mutants; however, pyramidal neurons exhibited hyperexcitability. LIMITATIONS: Causal links between impaired PFC pyramidal neuron function and behavioral alterations remain unclear. Further experiments such as manipulating PFC neuronal activity or restoring synaptic transmission in Shank3 mutant dogs are required to assess PFC roles in altered social behaviors. CONCLUSIONS: Our study demonstrated the feasibility of using canine brain slices as a model system to study neuronal circuitry and disease. Shank3 haploinsufficiency causes morphological and functional abnormalities in PFC pyramidal neurons, supporting the notion that Shank3 mutant dogs are new and valid animal models for autism research. En ligne : https://dx.doi.org/10.1186/s13229-024-00587-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines / Ryohei TAKADA in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 10p. Titre : Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines Type de document : Texte imprimé et/ou numérique Auteurs : Ryohei TAKADA, Auteur ; Michihiro TORITSUKA, Auteur ; Takahira YAMAUCHI, Auteur ; Rio ISHIDA, Auteur ; Yoshinori KAYASHIMA, Auteur ; Yuki NISHI, Auteur ; Mitsuru ISHIKAWA, Auteur ; Kazuhiko YAMAMURO, Auteur ; Minobu IKEHARA, Auteur ; Takashi KOMORI, Auteur ; Yuki NORIYAMA, Auteur ; Kohei KAMIKAWA, Auteur ; Yasuhiko SAITO, Auteur ; Hideyuki OKANO, Auteur ; Manabu MAKINODAN, Auteur Article en page(s) : 10p. Langues : Anglais (eng) Mots-clés : Female  Male  Humans  Cytokines  Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/pharmacology  Macrophage Colony-Stimulating Factor/metabolism/pharmacology  Tumor Necrosis Factor-alpha/metabolism/pharmacology  Leukocytes, Mononuclear/metabolism  Interleukin-1alpha/metabolism/pharmacology  Autism Spectrum Disorder/metabolism  Cells, Cultured  Sexism  Macrophages/metabolism  Granulocytes/metabolism  Dendrites/metabolism  Autism spectrum disorder  Dendrite  Human iPS cell  Interleukin-1?  Macrophage  Tumor necrosis factor-? Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-? (TNF-?) expression in granulocyte-macrophage colony-stimulating factor-induced macrophages (GM-CSF M?) and the TNF-? expression ratio in GM-CSF M?/M-CSF M? (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. METHODS: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. RESULTS: Our results of co-culture experiments showed that GM-CSF M? affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1? and TNF-?. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. LIMITATIONS: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. CONCLUSIONS: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF M? in individuals with ASD on neurons, mediated by interleukin-1? and TNF-?. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology. En ligne : https://dx.doi.org/10.1186/s13229-024-00589-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines [Texte imprimé et/ou numérique] / Ryohei TAKADA, Auteur ; Michihiro TORITSUKA, Auteur ; Takahira YAMAUCHI, Auteur ; Rio ISHIDA, Auteur ; Yoshinori KAYASHIMA, Auteur ; Yuki NISHI, Auteur ; Mitsuru ISHIKAWA, Auteur ; Kazuhiko YAMAMURO, Auteur ; Minobu IKEHARA, Auteur ; Takashi KOMORI, Auteur ; Yuki NORIYAMA, Auteur ; Kohei KAMIKAWA, Auteur ; Yasuhiko SAITO, Auteur ; Hideyuki OKANO, Auteur ; Manabu MAKINODAN, Auteur . - 10p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 10p. Mots-clés : Female  Male  Humans  Cytokines  Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/pharmacology  Macrophage Colony-Stimulating Factor/metabolism/pharmacology  Tumor Necrosis Factor-alpha/metabolism/pharmacology  Leukocytes, Mononuclear/metabolism  Interleukin-1alpha/metabolism/pharmacology  Autism Spectrum Disorder/metabolism  Cells, Cultured  Sexism  Macrophages/metabolism  Granulocytes/metabolism  Dendrites/metabolism  Autism spectrum disorder  Dendrite  Human iPS cell  Interleukin-1?  Macrophage  Tumor necrosis factor-? Index. décimale : PER Périodiques Résumé : BACKGROUND: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-? (TNF-?) expression in granulocyte-macrophage colony-stimulating factor-induced macrophages (GM-CSF M?) and the TNF-? expression ratio in GM-CSF M?/M-CSF M? (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. METHODS: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. RESULTS: Our results of co-culture experiments showed that GM-CSF M? affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1? and TNF-?. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. LIMITATIONS: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. CONCLUSIONS: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF M? in individuals with ASD on neurons, mediated by interleukin-1? and TNF-?. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology. En ligne : https://dx.doi.org/10.1186/s13229-024-00589-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Fetal brain growth and infant autistic traits / Ezra AYDIN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 11p. Titre : Fetal brain growth and infant autistic traits Type de document : Texte imprimé et/ou numérique Auteurs : Ezra AYDIN, Auteur ; Alex TSOMPANIDIS, Auteur ; Daren CHAPLIN, Auteur ; Rebecca HAWKES, Auteur ; Carrie ALLISON, Auteur ; Gerald HACKETT, Auteur ; Topun AUSTIN, Auteur ; Egl? PADAIGAIT?, Auteur ; Lidia V. GABIS, Auteur ; John SUCKING, Auteur ; Rosemary HOLT, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 11p. Langues : Anglais (eng) Mots-clés : Male  Infant  Pregnancy  Female  Humans  Autistic Disorder/diagnostic imaging  Brain/diagnostic imaging  Gestational Age  Autistic traits  Early brain development  Q-chat  Transcerebellar diameter  Ultrasound Index. décimale : PER Périodiques Résumé : BACKGROUND: Structural differences exist in the brains of autistic individuals. To date only a few studies have explored the relationship between fetal brain growth and later infant autistic traits, and some have used fetal head circumference (HC) as a proxy for brain development. These findings have been inconsistent. Here we investigate whether fetal subregional brain measurements correlate with autistic traits in toddlers. METHODS: A total of 219 singleton pregnancies (104 males and 115 females) were recruited at the Rosie Hospital, Cambridge, UK. 2D ultrasound was performed at 12-, 20- and between 26 and 30 weeks of pregnancy, measuring head circumference (HC), ventricular atrium (VA) and transcerebellar diameter (TCD). A total of 179 infants were followed up at 18-20 months of age and completed the quantitative checklist for autism in toddlers (Q-CHAT) to measure autistic traits. RESULTS: Q-CHAT scores at 18-20 months of age were positively associated with TCD size at 20 weeks and with HC at 28 weeks, in univariate analyses, and in multiple regression models which controlled for sex, maternal age and birth weight. LIMITATIONS: Due to the nature and location of the study, ascertainment bias could also have contributed to the recruitment of volunteer mothers with a higher than typical range of autistic traits and/or with a significant interest in the neurodevelopment of their children. CONCLUSION: Prenatal brain growth is associated with toddler autistic traits and this can be ascertained via ultrasound starting at 20 weeks gestation. En ligne : https://dx.doi.org/10.1186/s13229-024-00586-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Fetal brain growth and infant autistic traits [Texte imprimé et/ou numérique] / Ezra AYDIN, Auteur ; Alex TSOMPANIDIS, Auteur ; Daren CHAPLIN, Auteur ; Rebecca HAWKES, Auteur ; Carrie ALLISON, Auteur ; Gerald HACKETT, Auteur ; Topun AUSTIN, Auteur ; Egl? PADAIGAIT?, Auteur ; Lidia V. GABIS, Auteur ; John SUCKING, Auteur ; Rosemary HOLT, Auteur ; Simon BARON-COHEN, Auteur . - 11p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 11p. Mots-clés : Male  Infant  Pregnancy  Female  Humans  Autistic Disorder/diagnostic imaging  Brain/diagnostic imaging  Gestational Age  Autistic traits  Early brain development  Q-chat  Transcerebellar diameter  Ultrasound Index. décimale : PER Périodiques Résumé : BACKGROUND: Structural differences exist in the brains of autistic individuals. To date only a few studies have explored the relationship between fetal brain growth and later infant autistic traits, and some have used fetal head circumference (HC) as a proxy for brain development. These findings have been inconsistent. Here we investigate whether fetal subregional brain measurements correlate with autistic traits in toddlers. METHODS: A total of 219 singleton pregnancies (104 males and 115 females) were recruited at the Rosie Hospital, Cambridge, UK. 2D ultrasound was performed at 12-, 20- and between 26 and 30 weeks of pregnancy, measuring head circumference (HC), ventricular atrium (VA) and transcerebellar diameter (TCD). A total of 179 infants were followed up at 18-20 months of age and completed the quantitative checklist for autism in toddlers (Q-CHAT) to measure autistic traits. RESULTS: Q-CHAT scores at 18-20 months of age were positively associated with TCD size at 20 weeks and with HC at 28 weeks, in univariate analyses, and in multiple regression models which controlled for sex, maternal age and birth weight. LIMITATIONS: Due to the nature and location of the study, ascertainment bias could also have contributed to the recruitment of volunteer mothers with a higher than typical range of autistic traits and/or with a significant interest in the neurodevelopment of their children. CONCLUSION: Prenatal brain growth is associated with toddler autistic traits and this can be ascertained via ultrasound starting at 20 weeks gestation. En ligne : https://dx.doi.org/10.1186/s13229-024-00586-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach / Sadhna RAO in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 12p. Titre : Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach Type de document : Texte imprimé et/ou numérique Auteurs : Sadhna RAO, Auteur ; Anastasiia SADYBEKOV, Auteur ; David C. DEWITT, Auteur ; Joanna LIPKA, Auteur ; Vsevolod KATRITCH, Auteur ; Bruce E. HERRING, Auteur Article en page(s) : 12p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics/metabolism  HEK293 Cells  Intellectual Disability/genetics/metabolism  Mutation  Mutation, Missense  Neurons/metabolism  Autism spectrum disorders  Glutamatergic neurotransmission  Missense mutations  Mutation modeling  Synaptic dysfunction  TRIO-related disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Glutamatergic synapse dysfunction is believed to underlie the development of Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) in many individuals. However, identification of genetic markers that contribute to synaptic dysfunction in these individuals is notoriously difficult. Based on genomic analysis, structural modeling, and functional data, we recently established the involvement of the TRIO-RAC1 pathway in ASD and ID. Furthermore, we identified a pathological de novo missense mutation hotspot in TRIO's GEF1 domain. ASD/ID-related missense mutations within this domain compromise glutamatergic synapse function and likely contribute to the development of ASD/ID. The number of ASD/ID cases with mutations identified within TRIO's GEF1 domain is increasing. However, tools for accurately predicting whether such mutations are detrimental to protein function are lacking. METHODS: Here we deployed advanced protein structural modeling techniques to predict potential de novo pathogenic and benign mutations within TRIO's GEF1 domain. Mutant TRIO-9 constructs were generated and expressed in CA1 pyramidal neurons of organotypic cultured hippocampal slices. AMPA receptor-mediated postsynaptic currents were examined in these neurons using dual whole-cell patch clamp electrophysiology. We also validated these findings using orthogonal co-immunoprecipitation and fluorescence lifetime imaging (FLIM-FRET) experiments to assay TRIO mutant overexpression effects on TRIO-RAC1 binding and on RAC1 activity in HEK293/T cells. RESULTS: Missense mutations in TRIO's GEF1 domain that were predicted to disrupt TRIO-RAC1 binding or stability were tested experimentally and found to greatly impair TRIO-9's influence on glutamatergic synapse function. In contrast, missense mutations in TRIO's GEF1 domain that were predicted to have minimal effect on TRIO-RAC1 binding or stability did not impair TRIO-9's influence on glutamatergic synapse function in our experimental assays. In orthogonal assays, we find most of the mutations predicted to disrupt binding display loss of function but mutants predicted to disrupt stability do not reflect our results from neuronal electrophysiological data. LIMITATIONS: We present a method to predict missense mutations in TRIO's GEF1 domain that may compromise TRIO function and test for effects in a limited number of assays. Possible limitations arising from the model systems employed here can be addressed in future studies. Our method does not provide evidence for whether these mutations confer ASD/ID risk or the likelihood that such mutations will result in the development of ASD/ID. CONCLUSIONS: Here we show that a combination of structure-based computational predictions and experimental validation can be employed to reliably predict whether missense mutations in the human TRIO gene impede TRIO protein function and compromise TRIO's role in glutamatergic synapse regulation. With the growing accessibility of genome sequencing, the use of such tools in the accurate identification of pathological mutations will be instrumental in diagnostics of ASD/ID. En ligne : https://dx.doi.org/10.1186/s13229-024-00590-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach [Texte imprimé et/ou numérique] / Sadhna RAO, Auteur ; Anastasiia SADYBEKOV, Auteur ; David C. DEWITT, Auteur ; Joanna LIPKA, Auteur ; Vsevolod KATRITCH, Auteur ; Bruce E. HERRING, Auteur . - 12p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 12p. Mots-clés : Humans  Autism Spectrum Disorder/genetics/metabolism  HEK293 Cells  Intellectual Disability/genetics/metabolism  Mutation  Mutation, Missense  Neurons/metabolism  Autism spectrum disorders  Glutamatergic neurotransmission  Missense mutations  Mutation modeling  Synaptic dysfunction  TRIO-related disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Glutamatergic synapse dysfunction is believed to underlie the development of Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) in many individuals. However, identification of genetic markers that contribute to synaptic dysfunction in these individuals is notoriously difficult. Based on genomic analysis, structural modeling, and functional data, we recently established the involvement of the TRIO-RAC1 pathway in ASD and ID. Furthermore, we identified a pathological de novo missense mutation hotspot in TRIO's GEF1 domain. ASD/ID-related missense mutations within this domain compromise glutamatergic synapse function and likely contribute to the development of ASD/ID. The number of ASD/ID cases with mutations identified within TRIO's GEF1 domain is increasing. However, tools for accurately predicting whether such mutations are detrimental to protein function are lacking. METHODS: Here we deployed advanced protein structural modeling techniques to predict potential de novo pathogenic and benign mutations within TRIO's GEF1 domain. Mutant TRIO-9 constructs were generated and expressed in CA1 pyramidal neurons of organotypic cultured hippocampal slices. AMPA receptor-mediated postsynaptic currents were examined in these neurons using dual whole-cell patch clamp electrophysiology. We also validated these findings using orthogonal co-immunoprecipitation and fluorescence lifetime imaging (FLIM-FRET) experiments to assay TRIO mutant overexpression effects on TRIO-RAC1 binding and on RAC1 activity in HEK293/T cells. RESULTS: Missense mutations in TRIO's GEF1 domain that were predicted to disrupt TRIO-RAC1 binding or stability were tested experimentally and found to greatly impair TRIO-9's influence on glutamatergic synapse function. In contrast, missense mutations in TRIO's GEF1 domain that were predicted to have minimal effect on TRIO-RAC1 binding or stability did not impair TRIO-9's influence on glutamatergic synapse function in our experimental assays. In orthogonal assays, we find most of the mutations predicted to disrupt binding display loss of function but mutants predicted to disrupt stability do not reflect our results from neuronal electrophysiological data. LIMITATIONS: We present a method to predict missense mutations in TRIO's GEF1 domain that may compromise TRIO function and test for effects in a limited number of assays. Possible limitations arising from the model systems employed here can be addressed in future studies. Our method does not provide evidence for whether these mutations confer ASD/ID risk or the likelihood that such mutations will result in the development of ASD/ID. CONCLUSIONS: Here we show that a combination of structure-based computational predictions and experimental validation can be employed to reliably predict whether missense mutations in the human TRIO gene impede TRIO protein function and compromise TRIO's role in glutamatergic synapse regulation. With the growing accessibility of genome sequencing, the use of such tools in the accurate identification of pathological mutations will be instrumental in diagnostics of ASD/ID. En ligne : https://dx.doi.org/10.1186/s13229-024-00590-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice / Tanya LEDUC in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 13p. Titre : Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice Type de document : Texte imprimé et/ou numérique Auteurs : Tanya LEDUC, Auteur ; Hiba EL ALAMI, Auteur ; Khadija BOUGADIR, Auteur ; Erika BÉLANGER-NELSON, Auteur ; Valérie MONGRAIN, Auteur Article en page(s) : 13p. Langues : Anglais (eng) Mots-clés : Animals  Humans  Mice  Electroencephalography  Neuroligins  Quality of Life  Sleep/physiology  Sleep Deprivation/metabolism  Sleep, Slow-Wave  Cerebral cortex  GABAergic neurotransmission  Gene expression  Sleep deprivation  Sleep-wake regulation  Slow waves  Synaptic adhesion molecules Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disturbances are a common comorbidity to most neurodevelopmental disorders and tend to worsen disease symptomatology. It is thus crucial to understand mechanisms underlying sleep disturbances to improve patients' quality of life. Neuroligin-2 (NLGN2) is a synaptic adhesion protein regulating GABAergic transmission. It has been linked to autism spectrum disorders and schizophrenia in humans, and deregulations of its expression were shown to cause epileptic-like hypersynchronized cerebral activity in rodents. Importantly, the absence of Nlgn2 (knockout: KO) was previously shown to alter sleep-wake duration and quality in mice, notably increasing slow-wave sleep (SWS) delta activity (1-4 Hz) and altering its 24-h dynamics. This type of brain oscillation is involved in memory consolidation, and is also a marker of homeostatic sleep pressure. Sleep deprivation (SD) is notably known to impair cognition and the physiological response to sleep loss involves GABAergic transmission. METHODS: Using electrocorticographic (ECoG) recordings, we here first aimed to verify how individual slow wave (SW; 0.5-4 Hz) density and properties (e.g., amplitude, slope, frequency) contribute to the higher SWS delta activity and altered 24-h dynamics observed in Nlgn2 KO mice. We further investigated the response of these animals to SD. Finally, we tested whether sleep loss affects the gene expression of Nlgn2 and related GABAergic transcripts in the cerebral cortex of wild-type mice using RNA sequencing. RESULTS: Our results show that Nlgn2 KO mice have both greater SW amplitude and density, and that SW density is the main property contributing to the altered 24-h dynamics. We also found the absence of Nlgn2 to accelerate paradoxical sleep recovery following SD, together with profound alterations in ECoG activity across vigilance states. Sleep loss, however, did not modify the 24-h distribution of the hypersynchronized ECoG events observed in these mice. Finally, RNA sequencing confirmed an overall decrease in cortical expression of Nlgn2 and related GABAergic transcripts following SD in wild-type mice. CONCLUSIONS: This work brings further insight into potential mechanisms of sleep duration and quality deregulation in neurodevelopmental disorders, notably involving NLGN2 and GABAergic neurotransmission. En ligne : https://dx.doi.org/10.1186/s13229-024-00594-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Neuroligin-2 shapes individual slow waves during slow-wave sleep and the response to sleep deprivation in mice [Texte imprimé et/ou numérique] / Tanya LEDUC, Auteur ; Hiba EL ALAMI, Auteur ; Khadija BOUGADIR, Auteur ; Erika BÉLANGER-NELSON, Auteur ; Valérie MONGRAIN, Auteur . - 13p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 13p. Mots-clés : Animals  Humans  Mice  Electroencephalography  Neuroligins  Quality of Life  Sleep/physiology  Sleep Deprivation/metabolism  Sleep, Slow-Wave  Cerebral cortex  GABAergic neurotransmission  Gene expression  Sleep deprivation  Sleep-wake regulation  Slow waves  Synaptic adhesion molecules Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disturbances are a common comorbidity to most neurodevelopmental disorders and tend to worsen disease symptomatology. It is thus crucial to understand mechanisms underlying sleep disturbances to improve patients' quality of life. Neuroligin-2 (NLGN2) is a synaptic adhesion protein regulating GABAergic transmission. It has been linked to autism spectrum disorders and schizophrenia in humans, and deregulations of its expression were shown to cause epileptic-like hypersynchronized cerebral activity in rodents. Importantly, the absence of Nlgn2 (knockout: KO) was previously shown to alter sleep-wake duration and quality in mice, notably increasing slow-wave sleep (SWS) delta activity (1-4 Hz) and altering its 24-h dynamics. This type of brain oscillation is involved in memory consolidation, and is also a marker of homeostatic sleep pressure. Sleep deprivation (SD) is notably known to impair cognition and the physiological response to sleep loss involves GABAergic transmission. METHODS: Using electrocorticographic (ECoG) recordings, we here first aimed to verify how individual slow wave (SW; 0.5-4 Hz) density and properties (e.g., amplitude, slope, frequency) contribute to the higher SWS delta activity and altered 24-h dynamics observed in Nlgn2 KO mice. We further investigated the response of these animals to SD. Finally, we tested whether sleep loss affects the gene expression of Nlgn2 and related GABAergic transcripts in the cerebral cortex of wild-type mice using RNA sequencing. RESULTS: Our results show that Nlgn2 KO mice have both greater SW amplitude and density, and that SW density is the main property contributing to the altered 24-h dynamics. We also found the absence of Nlgn2 to accelerate paradoxical sleep recovery following SD, together with profound alterations in ECoG activity across vigilance states. Sleep loss, however, did not modify the 24-h distribution of the hypersynchronized ECoG events observed in these mice. Finally, RNA sequencing confirmed an overall decrease in cortical expression of Nlgn2 and related GABAergic transcripts following SD in wild-type mice. CONCLUSIONS: This work brings further insight into potential mechanisms of sleep duration and quality deregulation in neurodevelopmental disorders, notably involving NLGN2 and GABAergic neurotransmission. En ligne : https://dx.doi.org/10.1186/s13229-024-00594-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder / Eya-Mist RØDGAARD in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 15p. Titre : Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Eya-Mist RØDGAARD, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; Abderrahim ZERIBI, Auteur ; Kristian JENSEN, Auteur ; Valérie COURCHESNE, Auteur ; Elise DOUARD, Auteur ; David GAGNON, Auteur ; Guillaume HUGUET, Auteur ; Sebastien JACQUEMONT, Auteur ; Laurent MOTTRON, Auteur Article en page(s) : 15p. Langues : Anglais (eng) Mots-clés : Child  Humans  Adolescent  Child, Preschool  Autistic Disorder/diagnosis  Language  Autism Spectrum Disorder/diagnosis  Ados  Certainty  Diagnosis  Macrocephaly Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinicians diagnosing autism rely on diagnostic criteria and instruments in combination with an implicit knowledge based on clinical expertise of the specific signs and presentations associated with the condition. This implicit knowledge influences how diagnostic criteria are interpreted, but it cannot be directly observed. Instead, insight into clinicians' understanding of autism can be gained by investigating their diagnostic certainty. Modest correlations between the certainty of an autism diagnosis and symptom load have been previously reported. Here, we investigated the associations of diagnostic certainty with specific items of the ADOS as well as other clinical features including head circumference. METHODS: Phenotypic data from the Simons Simplex Collection was used to investigate clinical correlates of diagnostic certainty in individuals diagnosed with Autistic Disorder (n = 1511, age 4 to 18 years). Participants were stratified by the ADOS module used to evaluate them. We investigated how diagnostic certainty was associated with total ADOS scores, age, and ADOS module. We calculated the odds-ratios of being diagnosed with the highest possible certainty given the presence or absence of different signs during the ADOS evaluation. Associations between diagnostic certainty and other cognitive and clinical variables were also assessed. RESULTS: In each ADOS module, some items showed a larger association with diagnostic certainty than others. Head circumference was significantly higher for individuals with the highest certainty rating across all three ADOS modules. In turn, head circumference was positively correlated with some of the ADOS items that were associated with diagnostic certainty, and was negatively correlated with verbal/nonverbal IQ ratio among those assessed with ADOS module 2. LIMITATIONS: The investigated cohort was heterogeneous, e.g. in terms of age, IQ, language level, and total ADOS score, which could impede the identification of associations that only exist in a subgroup of the population. The variability of the certainty ratings in the sample was low, limiting the power to identify potential associations with other variables. Additionally, the scoring of diagnostic certainty may vary between clinicians. CONCLUSION: Some ADOS items may better capture the signs that are most associated with clinicians' implicit knowledge of Autistic Disorder. If replicated in future studies, new diagnostic instruments with differentiated weighting of signs may be needed to better reflect this, possibly resulting in better specificity in standardized assessments. En ligne : https://dx.doi.org/10.1186/s13229-024-00592-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Clinical correlates of diagnostic certainty in children and youths with Autistic Disorder [Texte imprimé et/ou numérique] / Eya-Mist RØDGAARD, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; Abderrahim ZERIBI, Auteur ; Kristian JENSEN, Auteur ; Valérie COURCHESNE, Auteur ; Elise DOUARD, Auteur ; David GAGNON, Auteur ; Guillaume HUGUET, Auteur ; Sebastien JACQUEMONT, Auteur ; Laurent MOTTRON, Auteur . - 15p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 15p. Mots-clés : Child  Humans  Adolescent  Child, Preschool  Autistic Disorder/diagnosis  Language  Autism Spectrum Disorder/diagnosis  Ados  Certainty  Diagnosis  Macrocephaly Index. décimale : PER Périodiques Résumé : BACKGROUND: Clinicians diagnosing autism rely on diagnostic criteria and instruments in combination with an implicit knowledge based on clinical expertise of the specific signs and presentations associated with the condition. This implicit knowledge influences how diagnostic criteria are interpreted, but it cannot be directly observed. Instead, insight into clinicians' understanding of autism can be gained by investigating their diagnostic certainty. Modest correlations between the certainty of an autism diagnosis and symptom load have been previously reported. Here, we investigated the associations of diagnostic certainty with specific items of the ADOS as well as other clinical features including head circumference. METHODS: Phenotypic data from the Simons Simplex Collection was used to investigate clinical correlates of diagnostic certainty in individuals diagnosed with Autistic Disorder (n = 1511, age 4 to 18 years). Participants were stratified by the ADOS module used to evaluate them. We investigated how diagnostic certainty was associated with total ADOS scores, age, and ADOS module. We calculated the odds-ratios of being diagnosed with the highest possible certainty given the presence or absence of different signs during the ADOS evaluation. Associations between diagnostic certainty and other cognitive and clinical variables were also assessed. RESULTS: In each ADOS module, some items showed a larger association with diagnostic certainty than others. Head circumference was significantly higher for individuals with the highest certainty rating across all three ADOS modules. In turn, head circumference was positively correlated with some of the ADOS items that were associated with diagnostic certainty, and was negatively correlated with verbal/nonverbal IQ ratio among those assessed with ADOS module 2. LIMITATIONS: The investigated cohort was heterogeneous, e.g. in terms of age, IQ, language level, and total ADOS score, which could impede the identification of associations that only exist in a subgroup of the population. The variability of the certainty ratings in the sample was low, limiting the power to identify potential associations with other variables. Additionally, the scoring of diagnostic certainty may vary between clinicians. CONCLUSION: Some ADOS items may better capture the signs that are most associated with clinicians' implicit knowledge of Autistic Disorder. If replicated in future studies, new diagnostic instruments with differentiated weighting of signs may be needed to better reflect this, possibly resulting in better specificity in standardized assessments. En ligne : https://dx.doi.org/10.1186/s13229-024-00592-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Shank3 deficiency elicits autistic-like behaviors by activating p38? in hypothalamic AgRP neurons / Shanshan WU in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 14p. Titre : Shank3 deficiency elicits autistic-like behaviors by activating p38? in hypothalamic AgRP neurons Type de document : Texte imprimé et/ou numérique Auteurs : Shanshan WU, Auteur ; Jing WANG, Auteur ; Zicheng ZHANG, Auteur ; Xinchen JIN, Auteur ; Yang XU, Auteur ; Youwen SI, Auteur ; Yixiao LIANG, Auteur ; Yueping GE, Auteur ; Huidong ZHAN, Auteur ; Li PENG, Auteur ; Wenkai BI, Auteur ; Dandan LUO, Auteur ; Mengzhu LI, Auteur ; Bo MENG, Auteur ; Qingbo GUAN, Auteur ; Jiajun ZHAO, Auteur ; Ling GAO, Auteur ; Zhao HE, Auteur Article en page(s) : 14p. Langues : Anglais (eng) Mots-clés : Animals  Mice  Agouti-Related Protein/genetics/metabolism  Arcuate Nucleus of Hypothalamus/metabolism  Autistic Disorder/genetics/metabolism  Hypothalamus/metabolism  Microfilament Proteins/metabolism  Nerve Tissue Proteins/genetics/metabolism  Neurons/metabolism  Mitogen-Activated Protein Kinase 14/metabolism  AgRP  Autism  Shank3  Sociability  Stereotypic behavior  p38? Index. décimale : PER Périodiques Résumé : BACKGROUND: SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) monogenic mutations or deficiency leads to excessive stereotypic behavior and impaired sociability, which frequently occur in autism cases. To date, the underlying mechanisms by which Shank3 mutation or deletion causes autism and the part of the brain in which Shank3 mutation leads to the autistic phenotypes are understudied. The hypothalamus is associated with stereotypic behavior and sociability. p38?, a mediator of inflammatory responses in the brain, has been postulated as a potential gene for certain cases of autism occurrence. However, it is unclear whether hypothalamus and p38? are involved in the development of autism caused by Shank3 mutations or deficiency. METHODS: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and immunoblotting were used to assess alternated signaling pathways in the hypothalamus of Shank3 knockout (Shank3(-/-)) mice. Home-Cage real-time monitoring test was performed to record stereotypic behavior and three-chamber test was used to monitor the sociability of mice. Adeno-associated viruses 9 (AAV9) were used to express p38? in the arcuate nucleus (ARC) or agouti-related peptide (AgRP) neurons. D176A and F327S mutations expressed constitutively active p38?. T180A and Y182F mutations expressed inactive p38?. RESULTS: We found that Shank3 controls stereotypic behavior and sociability by regulating p38? activity in AgRP neurons. Phosphorylated p38 level in hypothalamus is significantly enhanced in Shank3(-/-) mice. Consistently, overexpression of p38? in ARC or AgRP neurons elicits excessive stereotypic behavior and impairs sociability in wild-type (WT) mice. Notably, activated p38? in AgRP neurons increases stereotypic behavior and impairs sociability. Conversely, inactivated p38? in AgRP neurons significantly ameliorates autistic behaviors of Shank3(-/-) mice. In contrast, activated p38? in pro-opiomelanocortin (POMC) neurons does not affect stereotypic behavior and sociability in mice. LIMITATIONS: We demonstrated that SHANK3 regulates the phosphorylated p38 level in the hypothalamus and inactivated p38? in AgRP neurons significantly ameliorates autistic behaviors of Shank3(-/-) mice. However, we did not clarify the biochemical mechanism of SHANK3 inhibiting p38? in AgRP neurons. CONCLUSIONS: These results demonstrate that the Shank3 deficiency caused autistic-like behaviors by activating p38? signaling in AgRP neurons, suggesting that p38? signaling in AgRP neurons is a potential therapeutic target for Shank3 mutant-related autism. En ligne : https://dx.doi.org/10.1186/s13229-024-00595-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Shank3 deficiency elicits autistic-like behaviors by activating p38? in hypothalamic AgRP neurons [Texte imprimé et/ou numérique] / Shanshan WU, Auteur ; Jing WANG, Auteur ; Zicheng ZHANG, Auteur ; Xinchen JIN, Auteur ; Yang XU, Auteur ; Youwen SI, Auteur ; Yixiao LIANG, Auteur ; Yueping GE, Auteur ; Huidong ZHAN, Auteur ; Li PENG, Auteur ; Wenkai BI, Auteur ; Dandan LUO, Auteur ; Mengzhu LI, Auteur ; Bo MENG, Auteur ; Qingbo GUAN, Auteur ; Jiajun ZHAO, Auteur ; Ling GAO, Auteur ; Zhao HE, Auteur . - 14p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 14p. Mots-clés : Animals  Mice  Agouti-Related Protein/genetics/metabolism  Arcuate Nucleus of Hypothalamus/metabolism  Autistic Disorder/genetics/metabolism  Hypothalamus/metabolism  Microfilament Proteins/metabolism  Nerve Tissue Proteins/genetics/metabolism  Neurons/metabolism  Mitogen-Activated Protein Kinase 14/metabolism  AgRP  Autism  Shank3  Sociability  Stereotypic behavior  p38? Index. décimale : PER Périodiques Résumé : BACKGROUND: SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) monogenic mutations or deficiency leads to excessive stereotypic behavior and impaired sociability, which frequently occur in autism cases. To date, the underlying mechanisms by which Shank3 mutation or deletion causes autism and the part of the brain in which Shank3 mutation leads to the autistic phenotypes are understudied. The hypothalamus is associated with stereotypic behavior and sociability. p38?, a mediator of inflammatory responses in the brain, has been postulated as a potential gene for certain cases of autism occurrence. However, it is unclear whether hypothalamus and p38? are involved in the development of autism caused by Shank3 mutations or deficiency. METHODS: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and immunoblotting were used to assess alternated signaling pathways in the hypothalamus of Shank3 knockout (Shank3(-/-)) mice. Home-Cage real-time monitoring test was performed to record stereotypic behavior and three-chamber test was used to monitor the sociability of mice. Adeno-associated viruses 9 (AAV9) were used to express p38? in the arcuate nucleus (ARC) or agouti-related peptide (AgRP) neurons. D176A and F327S mutations expressed constitutively active p38?. T180A and Y182F mutations expressed inactive p38?. RESULTS: We found that Shank3 controls stereotypic behavior and sociability by regulating p38? activity in AgRP neurons. Phosphorylated p38 level in hypothalamus is significantly enhanced in Shank3(-/-) mice. Consistently, overexpression of p38? in ARC or AgRP neurons elicits excessive stereotypic behavior and impairs sociability in wild-type (WT) mice. Notably, activated p38? in AgRP neurons increases stereotypic behavior and impairs sociability. Conversely, inactivated p38? in AgRP neurons significantly ameliorates autistic behaviors of Shank3(-/-) mice. In contrast, activated p38? in pro-opiomelanocortin (POMC) neurons does not affect stereotypic behavior and sociability in mice. LIMITATIONS: We demonstrated that SHANK3 regulates the phosphorylated p38 level in the hypothalamus and inactivated p38? in AgRP neurons significantly ameliorates autistic behaviors of Shank3(-/-) mice. However, we did not clarify the biochemical mechanism of SHANK3 inhibiting p38? in AgRP neurons. CONCLUSIONS: These results demonstrate that the Shank3 deficiency caused autistic-like behaviors by activating p38? signaling in AgRP neurons, suggesting that p38? signaling in AgRP neurons is a potential therapeutic target for Shank3 mutant-related autism. En ligne : https://dx.doi.org/10.1186/s13229-024-00595-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder / Zixuan GUO in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 16p. Titre : Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Zixuan GUO, Auteur ; Xinyue TANG, Auteur ; Shu XIAO, Auteur ; Hong YAN, Auteur ; Shilin SUN, Auteur ; Zibin YANG, Auteur ; Li HUANG, Auteur ; Zhuoming CHEN, Auteur ; Ying WANG, Auteur Article en page(s) : 16p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/diagnostic imaging  Brain/diagnostic imaging  Cerebral Cortex/diagnostic imaging  Gray Matter/diagnostic imaging  Gyrus Cinguli  Magnetic Resonance Imaging/methods  Autism spectrum disorder  Gray matter volume  Meta-analysis  Resting-state functional imaging  Voxel-based morphometry Index. décimale : PER Périodiques Résumé : BACKGROUND: This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). METHODS: A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. RESULTS: A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. CONCLUSIONS: The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD. En ligne : https://dx.doi.org/10.1186/s13229-024-00593-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder [Texte imprimé et/ou numérique] / Zixuan GUO, Auteur ; Xinyue TANG, Auteur ; Shu XIAO, Auteur ; Hong YAN, Auteur ; Shilin SUN, Auteur ; Zibin YANG, Auteur ; Li HUANG, Auteur ; Zhuoming CHEN, Auteur ; Ying WANG, Auteur . - 16p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 16p. Mots-clés : Humans  Autism Spectrum Disorder/diagnostic imaging  Brain/diagnostic imaging  Cerebral Cortex/diagnostic imaging  Gray Matter/diagnostic imaging  Gyrus Cinguli  Magnetic Resonance Imaging/methods  Autism spectrum disorder  Gray matter volume  Meta-analysis  Resting-state functional imaging  Voxel-based morphometry Index. décimale : PER Périodiques Résumé : BACKGROUND: This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). METHODS: A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. RESULTS: A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. CONCLUSIONS: The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD. En ligne : https://dx.doi.org/10.1186/s13229-024-00593-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study / Yi MAO in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 17p. Titre : Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study Type de document : Texte imprimé et/ou numérique Auteurs : Yi MAO, Auteur ; Xindi LIN, Auteur ; Yuhan WU, Auteur ; Jiayi LU, Auteur ; Jiayao SHEN, Auteur ; Shaogen ZHONG, Auteur ; Xingming JIN, Auteur ; Jun MA, Auteur Article en page(s) : 17p. Langues : Anglais (eng) Mots-clés : Child  Humans  Child, Preschool  Autism Spectrum Disorder/epidemiology  Seizures, Febrile/epidemiology  Cross-Sectional Studies  Asphyxia  China/epidemiology  Autism spectrum disorder  Birth asphyxia  Children  Epidemiological study  Febrile seizures  Interaction effect Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual's ability to socially integrate and adapt. It's crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD. METHODS: Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3-12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect. RESULTS: Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42-6.02), for FS alone 3.06 (95%CI 1.48-6.31), and for comorbid BA and FS 21.18 (95%CI 9.10-49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05). LIMITATIONS: This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD. CONCLUSION: In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor. En ligne : https://dx.doi.org/10.1186/s13229-024-00596-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study [Texte imprimé et/ou numérique] / Yi MAO, Auteur ; Xindi LIN, Auteur ; Yuhan WU, Auteur ; Jiayi LU, Auteur ; Jiayao SHEN, Auteur ; Shaogen ZHONG, Auteur ; Xingming JIN, Auteur ; Jun MA, Auteur . - 17p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 17p. Mots-clés : Child  Humans  Child, Preschool  Autism Spectrum Disorder/epidemiology  Seizures, Febrile/epidemiology  Cross-Sectional Studies  Asphyxia  China/epidemiology  Autism spectrum disorder  Birth asphyxia  Children  Epidemiological study  Febrile seizures  Interaction effect Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual's ability to socially integrate and adapt. It's crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD. METHODS: Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3-12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect. RESULTS: Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42-6.02), for FS alone 3.06 (95%CI 1.48-6.31), and for comorbid BA and FS 21.18 (95%CI 9.10-49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05). LIMITATIONS: This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD. CONCLUSION: In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor. En ligne : https://dx.doi.org/10.1186/s13229-024-00596-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Trajectory of depressive symptoms over adolescence in autistic and neurotypical youth / Blythe A. CORBETT in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 18p. Titre : Trajectory of depressive symptoms over adolescence in autistic and neurotypical youth Type de document : Texte imprimé et/ou numérique Auteurs : Blythe A. CORBETT, Auteur ; Rachael A. MUSCATELLO, Auteur ; Trey MCGONIGLE, Auteur ; Simon VANDEKAR, Auteur ; Christina BURROUGHS, Auteur ; Sloane SPARKS, Auteur Article en page(s) : 18p. Langues : Anglais (eng) Mots-clés : Humans  Female  Male  Adolescent  Depression/epidemiology  Child  Longitudinal Studies  Autism Spectrum Disorder/psychology/epidemiology  Autistic Disorder/psychology/epidemiology  Puberty/psychology  Adolescence  Autism  Depression  Development  Puberty Index. décimale : PER Périodiques Résumé : BACKGROUND: Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course. METHOD: The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females). RESULTS: Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development. LIMITATIONS: Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic. CONCLUSIONS: Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles. En ligne : https://dx.doi.org/10.1186/s13229-024-00600-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Trajectory of depressive symptoms over adolescence in autistic and neurotypical youth [Texte imprimé et/ou numérique] / Blythe A. CORBETT, Auteur ; Rachael A. MUSCATELLO, Auteur ; Trey MCGONIGLE, Auteur ; Simon VANDEKAR, Auteur ; Christina BURROUGHS, Auteur ; Sloane SPARKS, Auteur . - 18p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 18p. Mots-clés : Humans  Female  Male  Adolescent  Depression/epidemiology  Child  Longitudinal Studies  Autism Spectrum Disorder/psychology/epidemiology  Autistic Disorder/psychology/epidemiology  Puberty/psychology  Adolescence  Autism  Depression  Development  Puberty Index. décimale : PER Périodiques Résumé : BACKGROUND: Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course. METHOD: The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females). RESULTS: Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development. LIMITATIONS: Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic. CONCLUSIONS: Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles. En ligne : https://dx.doi.org/10.1186/s13229-024-00600-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives / Vardan ARUTIUNIAN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 19p. Titre : The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives Type de document : Texte imprimé et/ou numérique Auteurs : Vardan ARUTIUNIAN, Auteur ; Megha SANTHOSH, Auteur ; Emily NEUHAUS, Auteur ; Heather BORLAND, Auteur ; Chris TOMPKINS, Auteur ; Raphael A. BERNIER, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Mirella DAPRETTO, Auteur ; Abha R. GUPTA, Auteur ; Allison JACK, Auteur ; Shafali JESTE, Auteur ; James C. MCPARTLAND, Auteur ; Adam NAPLES, Auteur ; John D. VAN HORN, Auteur ; Kevin A. PELPHREY, Auteur ; Sara Jane WEBB, Auteur Article en page(s) : 19p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/physiopathology/psychology  Male  Female  Adolescent  Gamma Rhythm  Child  Electroencephalography  Language  Family  Siblings  Autism Spectrum Disorder (ASD)  Excitation/inhibition balance  Gamma power  Language skills  Unaffected siblings  Health, and BlackThorn Therapeutics, has received research funding from Janssen  Research and Development, serves on the Scientific Advisory Boards of Pastorus  and Modern Clinics, and receives royalties from Guilford Press, Lambert, Oxford,  and Springer. The remaining authors have no conflict of interest to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance. METHODS: We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals. RESULTS: First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills. LIMITATIONS: We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis. CONCLUSIONS: Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles. En ligne : https://dx.doi.org/10.1186/s13229-024-00598-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives [Texte imprimé et/ou numérique] / Vardan ARUTIUNIAN, Auteur ; Megha SANTHOSH, Auteur ; Emily NEUHAUS, Auteur ; Heather BORLAND, Auteur ; Chris TOMPKINS, Auteur ; Raphael A. BERNIER, Auteur ; Susan Y. BOOKHEIMER, Auteur ; Mirella DAPRETTO, Auteur ; Abha R. GUPTA, Auteur ; Allison JACK, Auteur ; Shafali JESTE, Auteur ; James C. MCPARTLAND, Auteur ; Adam NAPLES, Auteur ; John D. VAN HORN, Auteur ; Kevin A. PELPHREY, Auteur ; Sara Jane WEBB, Auteur . - 19p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 19p. Mots-clés : Humans  Autism Spectrum Disorder/physiopathology/psychology  Male  Female  Adolescent  Gamma Rhythm  Child  Electroencephalography  Language  Family  Siblings  Autism Spectrum Disorder (ASD)  Excitation/inhibition balance  Gamma power  Language skills  Unaffected siblings  Health, and BlackThorn Therapeutics, has received research funding from Janssen  Research and Development, serves on the Scientific Advisory Boards of Pastorus  and Modern Clinics, and receives royalties from Guilford Press, Lambert, Oxford,  and Springer. The remaining authors have no conflict of interest to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance. METHODS: We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals. RESULTS: First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills. LIMITATIONS: We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis. CONCLUSIONS: Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles. En ligne : https://dx.doi.org/10.1186/s13229-024-00598-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Moral foundations in autistic people and people with systemizing minds / Yeshaya David M. GREENBERG in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 20p. Titre : Moral foundations in autistic people and people with systemizing minds Type de document : Texte imprimé et/ou numérique Auteurs : Yeshaya David M. GREENBERG, Auteur ; Rosemary HOLT, Auteur ; Carrie ALLISON, Auteur ; Paula SMITH, Auteur ; Robbie NEWMAN, Auteur ; Theo BOARDMAN-PRETTY, Auteur ; Jonathan HAIDT, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 20p. Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Autistic Disorder/psychology  Morals  Empathy  Adult  Young Adult  Surveys and Questionnaires  Adolescent  Middle Aged  Autism  Cognitive and affective empathy  Empathizing-systemizing theory  Empathy quotient  Libertarians  Moral foundations theory  Moral judgements  Political identification  Systemizing quotient  authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Do autistic people share the same moral foundations as typical people? Here we built on two prominent theories in psychology, moral foundations theory and the empathizing-systemizing (E-S) theory, to observe the nature of morality in autistic people and systemizers. METHODS: In dataset 1, we measured five foundations of moral judgements (Care, Fairness, Loyalty, Authority, and Sanctity) measured by the Moral Foundations Questionnaire (MFQ) in autistic (n = 307) and typical people (n = 415) along with their scores on the Empathy Quotient (EQ) and Systemizing Quotient (SQ). In dataset 2, we measured these same five foundations along with E-S cognitive types (previously referred to as "brain types") in a large sample of typical people (N = 7595). RESULTS: Autistic people scored the same on Care (i.e., concern for others) as typical people (h1). Their affective empathy (but not their cognitive empathy) scores were positively correlated with Care. Autistic people were more likely to endorse Fairness (i.e., giving people what they are owed, and treating them with justice) over Care (h2). Their systemizing scores were positively correlated with Fairness. Autistic people or those with a systemizing cognitive profile had lower scores on binding foundations: Loyalty, Authority, and Sanctity (h3). Systemizing in typical people was positively correlated with Liberty (i.e., hypervigilance against oppression), which is a sixth moral foundation (h4). Although the majority of people in all five E-S cognitive types self-identified as liberal, with a skew towards empathizing (h5), the percentage of libertarians was highest in systemizing cognitive types (h6). E-S cognitive types accounted for 2 to 3 times more variance for Care than did sex. LIMITATIONS: Our study is limited by its reliance on self-report measures and a focus on moral judgements rather than behavior or decision-making. Further, only dataset 2 measured political identification, therefore we were unable to assess politics in autistic people. CONCLUSIONS: We conclude that some moral foundations in autistic people are similar to those in typical people (despite the difficulties in social interaction that are part of autism), and some are subtly different. These subtle differences vary depending on empathizing and systemizing cognitive types. En ligne : https://dx.doi.org/10.1186/s13229-024-00591-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Moral foundations in autistic people and people with systemizing minds [Texte imprimé et/ou numérique] / Yeshaya David M. GREENBERG, Auteur ; Rosemary HOLT, Auteur ; Carrie ALLISON, Auteur ; Paula SMITH, Auteur ; Robbie NEWMAN, Auteur ; Theo BOARDMAN-PRETTY, Auteur ; Jonathan HAIDT, Auteur ; Simon BARON-COHEN, Auteur . - 20p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 20p. Mots-clés : Humans  Male  Female  Autistic Disorder/psychology  Morals  Empathy  Adult  Young Adult  Surveys and Questionnaires  Adolescent  Middle Aged  Autism  Cognitive and affective empathy  Empathizing-systemizing theory  Empathy quotient  Libertarians  Moral foundations theory  Moral judgements  Political identification  Systemizing quotient  authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Do autistic people share the same moral foundations as typical people? Here we built on two prominent theories in psychology, moral foundations theory and the empathizing-systemizing (E-S) theory, to observe the nature of morality in autistic people and systemizers. METHODS: In dataset 1, we measured five foundations of moral judgements (Care, Fairness, Loyalty, Authority, and Sanctity) measured by the Moral Foundations Questionnaire (MFQ) in autistic (n = 307) and typical people (n = 415) along with their scores on the Empathy Quotient (EQ) and Systemizing Quotient (SQ). In dataset 2, we measured these same five foundations along with E-S cognitive types (previously referred to as "brain types") in a large sample of typical people (N = 7595). RESULTS: Autistic people scored the same on Care (i.e., concern for others) as typical people (h1). Their affective empathy (but not their cognitive empathy) scores were positively correlated with Care. Autistic people were more likely to endorse Fairness (i.e., giving people what they are owed, and treating them with justice) over Care (h2). Their systemizing scores were positively correlated with Fairness. Autistic people or those with a systemizing cognitive profile had lower scores on binding foundations: Loyalty, Authority, and Sanctity (h3). Systemizing in typical people was positively correlated with Liberty (i.e., hypervigilance against oppression), which is a sixth moral foundation (h4). Although the majority of people in all five E-S cognitive types self-identified as liberal, with a skew towards empathizing (h5), the percentage of libertarians was highest in systemizing cognitive types (h6). E-S cognitive types accounted for 2 to 3 times more variance for Care than did sex. LIMITATIONS: Our study is limited by its reliance on self-report measures and a focus on moral judgements rather than behavior or decision-making. Further, only dataset 2 measured political identification, therefore we were unable to assess politics in autistic people. CONCLUSIONS: We conclude that some moral foundations in autistic people are similar to those in typical people (despite the difficulties in social interaction that are part of autism), and some are subtly different. These subtle differences vary depending on empathizing and systemizing cognitive types. En ligne : https://dx.doi.org/10.1186/s13229-024-00591-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Prospective association of the infant gut microbiome with social behaviors in the ECHO consortium / Hannah E. LAUE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 21p. Titre : Prospective association of the infant gut microbiome with social behaviors in the ECHO consortium Type de document : Texte imprimé et/ou numérique Auteurs : Hannah E. LAUE, Auteur ; Kevin S. BONHAM, Auteur ; Modupe O. COKER, Auteur ; Yuka MOROISHI, Auteur ; Wimal PATHMASIRI, Auteur ; Susan MCRITCHIE, Auteur ; Susan SUMNER, Auteur ; Anne G. HOEN, Auteur ; Margaret R. KARAGAS, Auteur ; Vanja KLEPAC-CERAJ, Auteur ; Juliette C. MADAN, Auteur Article en page(s) : 21p. Langues : Anglais (eng) Mots-clés : Humans  Gastrointestinal Microbiome  Female  Male  Infant  Feces/microbiology  Social Behavior  Prospective Studies  Child, Preschool  Autism Spectrum Disorder/microbiology  Autism  Gene set enrichment analysis  Gut metagenome  Microbiome  Social behavior  funder had no role in (1) the study design, (2) data collection, analysis, or  interpretation, 3) writing the report, 4) the decision to submit the manuscript  for publication. The content is solely the responsibility of the authors and does  not necessarily represent the official views of the National Institutes of  Health. HEL, KSB, MOC, YM, MRK, VKC, and JCM wrote the first draft of the  manuscript. No authors received an honorarium, grant, or other form of payment to  produce the manuscript. Index. décimale : PER Périodiques Résumé : BACKGROUND: Identifying modifiable risk factors of autism spectrum disorders (ASDs) may inform interventions to reduce financial burden. The infant/toddler gut microbiome is one such feature that has been associated with social behaviors, but results vary between cohorts. We aimed to identify consistent overall and sex-specific associations between the early-life gut microbiome and autism-related behaviors. METHODS: Utilizing the Environmental influences on Children Health Outcomes (ECHO) consortium of United States (U.S.) pediatric cohorts, we gathered data on 304 participants with fecal metagenomic sequencing between 6-weeks to 2-years postpartum (481 samples). ASD-related social development was assessed with the Social Responsiveness Scale (SRS-2). Linear regression, PERMANOVA, and Microbiome Multivariable Association with Linear Models (MaAsLin2) were adjusted for sociodemographic factors. Stratified models estimated sex-specific effects. RESULTS: Genes encoding pathways for synthesis of short-chain fatty acids were associated with higher SRS-2 scores, indicative of ASDs. Fecal concentrations of butyrate were also positively associated with ASD-related SRS-2 scores, some of which may be explained by formula use. LIMITATIONS: The distribution of age at outcome assessment differed in the cohorts included, potentially limiting comparability between cohorts. Stool sample collection methods also differed between cohorts. Our study population reflects the general U.S. population, and thus includes few participants who met the criteria for being at high risk of developing ASD. CONCLUSIONS: Our study is among the first multicenter studies in the U.S. to describe prospective microbiome development from infancy in relation to neurodevelopment associated with ASDs. Our work contributes to clarifying which microbial features associate with subsequent diagnosis of neuropsychiatric outcomes. This will allow for future interventional research targeting the microbiome to change neurodevelopmental trajectories. En ligne : https://dx.doi.org/10.1186/s13229-024-00597-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Prospective association of the infant gut microbiome with social behaviors in the ECHO consortium [Texte imprimé et/ou numérique] / Hannah E. LAUE, Auteur ; Kevin S. BONHAM, Auteur ; Modupe O. COKER, Auteur ; Yuka MOROISHI, Auteur ; Wimal PATHMASIRI, Auteur ; Susan MCRITCHIE, Auteur ; Susan SUMNER, Auteur ; Anne G. HOEN, Auteur ; Margaret R. KARAGAS, Auteur ; Vanja KLEPAC-CERAJ, Auteur ; Juliette C. MADAN, Auteur . - 21p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 21p. Mots-clés : Humans  Gastrointestinal Microbiome  Female  Male  Infant  Feces/microbiology  Social Behavior  Prospective Studies  Child, Preschool  Autism Spectrum Disorder/microbiology  Autism  Gene set enrichment analysis  Gut metagenome  Microbiome  Social behavior  funder had no role in (1) the study design, (2) data collection, analysis, or  interpretation, 3) writing the report, 4) the decision to submit the manuscript  for publication. The content is solely the responsibility of the authors and does  not necessarily represent the official views of the National Institutes of  Health. HEL, KSB, MOC, YM, MRK, VKC, and JCM wrote the first draft of the  manuscript. No authors received an honorarium, grant, or other form of payment to  produce the manuscript. Index. décimale : PER Périodiques Résumé : BACKGROUND: Identifying modifiable risk factors of autism spectrum disorders (ASDs) may inform interventions to reduce financial burden. The infant/toddler gut microbiome is one such feature that has been associated with social behaviors, but results vary between cohorts. We aimed to identify consistent overall and sex-specific associations between the early-life gut microbiome and autism-related behaviors. METHODS: Utilizing the Environmental influences on Children Health Outcomes (ECHO) consortium of United States (U.S.) pediatric cohorts, we gathered data on 304 participants with fecal metagenomic sequencing between 6-weeks to 2-years postpartum (481 samples). ASD-related social development was assessed with the Social Responsiveness Scale (SRS-2). Linear regression, PERMANOVA, and Microbiome Multivariable Association with Linear Models (MaAsLin2) were adjusted for sociodemographic factors. Stratified models estimated sex-specific effects. RESULTS: Genes encoding pathways for synthesis of short-chain fatty acids were associated with higher SRS-2 scores, indicative of ASDs. Fecal concentrations of butyrate were also positively associated with ASD-related SRS-2 scores, some of which may be explained by formula use. LIMITATIONS: The distribution of age at outcome assessment differed in the cohorts included, potentially limiting comparability between cohorts. Stool sample collection methods also differed between cohorts. Our study population reflects the general U.S. population, and thus includes few participants who met the criteria for being at high risk of developing ASD. CONCLUSIONS: Our study is among the first multicenter studies in the U.S. to describe prospective microbiome development from infancy in relation to neurodevelopment associated with ASDs. Our work contributes to clarifying which microbial features associate with subsequent diagnosis of neuropsychiatric outcomes. This will allow for future interventional research targeting the microbiome to change neurodevelopmental trajectories. En ligne : https://dx.doi.org/10.1186/s13229-024-00597-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms / Eric COURCHESNE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 22p. Titre : Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms Type de document : Texte imprimé et/ou numérique Auteurs : Eric COURCHESNE, Auteur ; Vani TALUJA, Auteur ; Sanaz NAZARI, Auteur ; Caitlin M. AAMODT, Auteur ; Karen PIERCE, Auteur ; Kuaikuai DUAN, Auteur ; Sunny STOPHAEROS, Auteur ; Linda LOPEZ, Auteur ; Cynthia Carter BARNES, Auteur ; Jaden TROXEL, Auteur ; Kathleen CAMPBELL, Auteur ; Tianyun WANG, Auteur ; Kendra HOEKZEMA, Auteur ; Evan E. EICHLER, Auteur ; Joao V. NANI, Auteur ; Wirla PONTES, Auteur ; Sandra SANCHEZ, Auteur ; Michael V. LOMBARDO, Auteur ; Janaina S. DE SOUZA, Auteur ; Mirian A. F. HAYASHI, Auteur ; Alysson R. MUOTRI, Auteur Article en page(s) : 22p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/pathology/physiopathology  Organoids/pathology  Male  Female  Child, Preschool  Cerebral Cortex/pathology  Social Behavior  Organ Size  Infant  Severity of Illness Index  Brain/pathology Index. décimale : PER Périodiques Résumé : BACKGROUND: Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known. METHODS: Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we  tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions. RESULTS: At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences. LIMITATIONS: Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes. CONCLUSIONS: By embryogenesis, the biological bases of two subtypes of ASD social and brain development-profound autism and mild autism-are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler's social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions. En ligne : https://dx.doi.org/10.1186/s13229-024-00602-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms [Texte imprimé et/ou numérique] / Eric COURCHESNE, Auteur ; Vani TALUJA, Auteur ; Sanaz NAZARI, Auteur ; Caitlin M. AAMODT, Auteur ; Karen PIERCE, Auteur ; Kuaikuai DUAN, Auteur ; Sunny STOPHAEROS, Auteur ; Linda LOPEZ, Auteur ; Cynthia Carter BARNES, Auteur ; Jaden TROXEL, Auteur ; Kathleen CAMPBELL, Auteur ; Tianyun WANG, Auteur ; Kendra HOEKZEMA, Auteur ; Evan E. EICHLER, Auteur ; Joao V. NANI, Auteur ; Wirla PONTES, Auteur ; Sandra SANCHEZ, Auteur ; Michael V. LOMBARDO, Auteur ; Janaina S. DE SOUZA, Auteur ; Mirian A. F. HAYASHI, Auteur ; Alysson R. MUOTRI, Auteur . - 22p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 22p. Mots-clés : Humans  Autism Spectrum Disorder/pathology/physiopathology  Organoids/pathology  Male  Female  Child, Preschool  Cerebral Cortex/pathology  Social Behavior  Organ Size  Infant  Severity of Illness Index  Brain/pathology Index. décimale : PER Périodiques Résumé : BACKGROUND: Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known. METHODS: Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we  tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions. RESULTS: At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences. LIMITATIONS: Larger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes. CONCLUSIONS: By embryogenesis, the biological bases of two subtypes of ASD social and brain development-profound autism and mild autism-are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler's social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions. En ligne : https://dx.doi.org/10.1186/s13229-024-00602-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Discrimination sensitivity of visual shapes sharpens in autistic adults but only after explicit category learning / Jaana VAN OVERWALLE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 23p. Titre : Discrimination sensitivity of visual shapes sharpens in autistic adults but only after explicit category learning Type de document : Texte imprimé et/ou numérique Auteurs : Jaana VAN OVERWALLE, Auteur ; Birte GEUSENS, Auteur ; Stephanie VAN DER DONCK, Auteur ; Bart BOETS, Auteur ; Johan WAGEMANS, Auteur Article en page(s) : 23p. Langues : Anglais (eng) Mots-clés : Humans  Male  Adult  Female  Electroencephalography  Young Adult  Autistic Disorder/physiopathology/psychology  Discrimination, Psychological  Learning  Photic Stimulation  Visual Perception  Autism Spectrum Disorder/physiopathology/psychology  Autism  Category learning  Discrimination sensitivity  Frequency-tagging electroencephalography Index. décimale : PER Périodiques Résumé : BACKGROUND: Categorization and its influence on perceptual discrimination are essential processes to organize information efficiently. Individuals with Autism Spectrum Condition (ASC) are suggested to display enhanced discrimination on the one hand, but also to experience difficulties with generalization and ignoring irrelevant differences on the other, which underlie categorization. Studies on categorization and discrimination in ASC have mainly focused on one process at a time, however, and typically only used either behavioral or neural measures in isolation. Here, we aim to investigate the interrelationships between these perceptual processes using novel stimuli sampled from a well-controlled artificial stimulus space. In addition, we complement standard behavioral psychophysical tasks with frequency-tagging EEG (FT-EEG) to obtain a direct, non-task related neural index of discrimination and categorization. METHODS: The study was completed by 38 adults with ASC and 38 matched neurotypical (NT) individuals. First, we assessed baseline discrimination sensitivity by administering FT-EEG measures and a complementary behavioral task. Second, participants were trained to categorize the stimuli into two groups. Finally, participants again completed the neural and behavioral discrimination sensitivity measures. RESULTS: Before training, NT participants immediately revealed a categorical tuning of discrimination, unlike ASC participants who showed largely similar discrimination sensitivity across the stimuli. During training, both autistic and non-autistic participants were able to categorize the stimuli into two groups. However, in the initial training phase, ASC participants were less accurate and showed more variability, as compared to their non-autistic peers. After training, ASC participants showed significantly enhanced neural and behavioral discrimination sensitivity across the category boundary. Behavioral indices of a reduced categorical processing and perception were related to the presence of more severe autistic traits. Bayesian analyses confirmed overall results. LIMITATIONS: Data-collection occurred during the COVID-19 pandemic. CONCLUSIONS: Our behavioral and neural findings indicate that adults with and without ASC are able to categorize highly similar stimuli. However, while categorical tuning of discrimination sensitivity was spontaneously present in the NT group, it only emerged in the autistic group after explicit categorization training. Additionally, during training, adults with autism were slower at category learning. Finally, this multi-level approach sheds light on the mechanisms underlying sensory and information processing issues in ASC. En ligne : https://dx.doi.org/10.1186/s13229-024-00604-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Discrimination sensitivity of visual shapes sharpens in autistic adults but only after explicit category learning [Texte imprimé et/ou numérique] / Jaana VAN OVERWALLE, Auteur ; Birte GEUSENS, Auteur ; Stephanie VAN DER DONCK, Auteur ; Bart BOETS, Auteur ; Johan WAGEMANS, Auteur . - 23p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 23p. Mots-clés : Humans  Male  Adult  Female  Electroencephalography  Young Adult  Autistic Disorder/physiopathology/psychology  Discrimination, Psychological  Learning  Photic Stimulation  Visual Perception  Autism Spectrum Disorder/physiopathology/psychology  Autism  Category learning  Discrimination sensitivity  Frequency-tagging electroencephalography Index. décimale : PER Périodiques Résumé : BACKGROUND: Categorization and its influence on perceptual discrimination are essential processes to organize information efficiently. Individuals with Autism Spectrum Condition (ASC) are suggested to display enhanced discrimination on the one hand, but also to experience difficulties with generalization and ignoring irrelevant differences on the other, which underlie categorization. Studies on categorization and discrimination in ASC have mainly focused on one process at a time, however, and typically only used either behavioral or neural measures in isolation. Here, we aim to investigate the interrelationships between these perceptual processes using novel stimuli sampled from a well-controlled artificial stimulus space. In addition, we complement standard behavioral psychophysical tasks with frequency-tagging EEG (FT-EEG) to obtain a direct, non-task related neural index of discrimination and categorization. METHODS: The study was completed by 38 adults with ASC and 38 matched neurotypical (NT) individuals. First, we assessed baseline discrimination sensitivity by administering FT-EEG measures and a complementary behavioral task. Second, participants were trained to categorize the stimuli into two groups. Finally, participants again completed the neural and behavioral discrimination sensitivity measures. RESULTS: Before training, NT participants immediately revealed a categorical tuning of discrimination, unlike ASC participants who showed largely similar discrimination sensitivity across the stimuli. During training, both autistic and non-autistic participants were able to categorize the stimuli into two groups. However, in the initial training phase, ASC participants were less accurate and showed more variability, as compared to their non-autistic peers. After training, ASC participants showed significantly enhanced neural and behavioral discrimination sensitivity across the category boundary. Behavioral indices of a reduced categorical processing and perception were related to the presence of more severe autistic traits. Bayesian analyses confirmed overall results. LIMITATIONS: Data-collection occurred during the COVID-19 pandemic. CONCLUSIONS: Our behavioral and neural findings indicate that adults with and without ASC are able to categorize highly similar stimuli. However, while categorical tuning of discrimination sensitivity was spontaneously present in the NT group, it only emerged in the autistic group after explicit categorization training. Additionally, during training, adults with autism were slower at category learning. Finally, this multi-level approach sheds light on the mechanisms underlying sensory and information processing issues in ASC. En ligne : https://dx.doi.org/10.1186/s13229-024-00604-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Measuring self and informant perspectives of Restricted and Repetitive Behaviours (RRBs): psychometric evaluation of the Repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settgs / Catherine R. G. JONES in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 24p. Titre : Measuring self and informant perspectives of Restricted and Repetitive Behaviours (RRBs): psychometric evaluation of the Repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settgs Type de document : Texte imprimé et/ou numérique Auteurs : Catherine R. G. JONES, Auteur ; Lucy A. LIVINGSTON, Auteur ; Christine FRETWELL, Auteur ; Mirko ULJAREVI?, Auteur ; Sarah J. CARRINGTON, Auteur ; Punit SHAH, Auteur ; Susan R. LEEKAM, Auteur Article en page(s) : 24p. Langues : Anglais (eng) Mots-clés : Humans  Adult  Male  Psychometrics  Female  Surveys and Questionnaires  Self Report  Middle Aged  Young Adult  Reproducibility of Results  Autistic Disorder/diagnosis/psychology  Adolescent  Autism Spectrum Disorder/diagnosis/psychology  Autism  Clinical service  Disco  Rbq-3  Restricted and repetitive behaviours  Self-report questionnaire  Validity  was conducted in the absence of any commercial or financial relationships that  could be construed as a potential conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Brief questionnaires that comprehensively capture key restricted and repetitive behaviours (RRBs) across different informants have potential to support autism diagnostic services. We tested the psychometric properties of the 20-item Repetitive Behaviours Questionnaire-3 (RBQ-3), a questionnaire that includes self-report and informant-report versions enabling use across the lifespan. METHOD: In Study 1, adults referred to a specialised adult autism diagnostic service (N = 110) completed the RBQ-3 self-report version, and a relative or long-term friend completed the RBQ-3 informant-report version. Clinicians completed the abbreviated version of the Diagnostic Interview for Social and Communication Disorders (DISCO-Abbreviated) with the same adults as part of the diagnostic process. For half of the assessments, clinicians were blind to the RBQ-3 ratings. We tested internal consistency, cross-informant reliability and convergent validity of the RBQ-3. In Study 2, a follow-up online study with autistic (N = 151) and non-autistic (N = 151) adults, we further tested internal consistency of the RBQ-3 self-report version. We also tested group differences and response patterns in this sample. RESULTS: Study 1 showed good to excellent internal consistency for both self- and informant-report versions of the RBQ-3 (total score, ? = 0.90, ? = 0.90, subscales, ? = 0.76-0.89, ? = 0.77-0.88). Study 1 also showed cross-informant reliability as the RBQ-3 self-report scores significantly correlated with RBQ-3 informant-report scores for the total score (r(s) = 0.71) and subscales (r(s)= 0.69-0.72). Convergent validity was found for both self and informant versions of the RBQ-3, which significantly correlated with DISCO-Abbreviated RRB domain scores (r(s) = 0.45-0.54). Moreover, the RBQ-3 scores showed significantly weaker association with DISCO -Abbreviated scores for the Social Communication domain, demonstrating divergent validity. Importantly, these patterns of validity were found even when clinicians were blind to RBQ-3 items. In Study 2, for both autistic and non-autistic groups, internal consistency was found for the total score (? = 0.82-0.89, ? = 0.81-0.81) and for subscales (? = 0.68-0.85, ? = 0.69-0.85). A group difference was found between groups. LIMITATIONS: Due to the characteristics and scope of the specialist autism diagnostic service, further testing is needed to include representative samples of age (including children) and intellectual ability, and those with a non-autistic diagnostic outcome. CONCLUSIONS: The RBQ-3 is a questionnaire of RRBs that can be used across the lifespan. The current study tested its psychometric properties with autistic adults without intellectual disability and supported its utility for both clinical diagnostic and research settings. En ligne : https://dx.doi.org/10.1186/s13229-024-00603-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Measuring self and informant perspectives of Restricted and Repetitive Behaviours (RRBs): psychometric evaluation of the Repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settgs [Texte imprimé et/ou numérique] / Catherine R. G. JONES, Auteur ; Lucy A. LIVINGSTON, Auteur ; Christine FRETWELL, Auteur ; Mirko ULJAREVI?, Auteur ; Sarah J. CARRINGTON, Auteur ; Punit SHAH, Auteur ; Susan R. LEEKAM, Auteur . - 24p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 24p. Mots-clés : Humans  Adult  Male  Psychometrics  Female  Surveys and Questionnaires  Self Report  Middle Aged  Young Adult  Reproducibility of Results  Autistic Disorder/diagnosis/psychology  Adolescent  Autism Spectrum Disorder/diagnosis/psychology  Autism  Clinical service  Disco  Rbq-3  Restricted and repetitive behaviours  Self-report questionnaire  Validity  was conducted in the absence of any commercial or financial relationships that  could be construed as a potential conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Brief questionnaires that comprehensively capture key restricted and repetitive behaviours (RRBs) across different informants have potential to support autism diagnostic services. We tested the psychometric properties of the 20-item Repetitive Behaviours Questionnaire-3 (RBQ-3), a questionnaire that includes self-report and informant-report versions enabling use across the lifespan. METHOD: In Study 1, adults referred to a specialised adult autism diagnostic service (N = 110) completed the RBQ-3 self-report version, and a relative or long-term friend completed the RBQ-3 informant-report version. Clinicians completed the abbreviated version of the Diagnostic Interview for Social and Communication Disorders (DISCO-Abbreviated) with the same adults as part of the diagnostic process. For half of the assessments, clinicians were blind to the RBQ-3 ratings. We tested internal consistency, cross-informant reliability and convergent validity of the RBQ-3. In Study 2, a follow-up online study with autistic (N = 151) and non-autistic (N = 151) adults, we further tested internal consistency of the RBQ-3 self-report version. We also tested group differences and response patterns in this sample. RESULTS: Study 1 showed good to excellent internal consistency for both self- and informant-report versions of the RBQ-3 (total score, ? = 0.90, ? = 0.90, subscales, ? = 0.76-0.89, ? = 0.77-0.88). Study 1 also showed cross-informant reliability as the RBQ-3 self-report scores significantly correlated with RBQ-3 informant-report scores for the total score (r(s) = 0.71) and subscales (r(s)= 0.69-0.72). Convergent validity was found for both self and informant versions of the RBQ-3, which significantly correlated with DISCO-Abbreviated RRB domain scores (r(s) = 0.45-0.54). Moreover, the RBQ-3 scores showed significantly weaker association with DISCO -Abbreviated scores for the Social Communication domain, demonstrating divergent validity. Importantly, these patterns of validity were found even when clinicians were blind to RBQ-3 items. In Study 2, for both autistic and non-autistic groups, internal consistency was found for the total score (? = 0.82-0.89, ? = 0.81-0.81) and for subscales (? = 0.68-0.85, ? = 0.69-0.85). A group difference was found between groups. LIMITATIONS: Due to the characteristics and scope of the specialist autism diagnostic service, further testing is needed to include representative samples of age (including children) and intellectual ability, and those with a non-autistic diagnostic outcome. CONCLUSIONS: The RBQ-3 is a questionnaire of RRBs that can be used across the lifespan. The current study tested its psychometric properties with autistic adults without intellectual disability and supported its utility for both clinical diagnostic and research settings. En ligne : https://dx.doi.org/10.1186/s13229-024-00603-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study / Laura HEGEMANN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 25p. Titre : Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study Type de document : Texte imprimé et/ou numérique Auteurs : Laura HEGEMANN, Auteur ; Elizabeth C. CORFIELD, Auteur ; Adrian Dahl ASKELUND, Auteur ; Andrea G. ALLEGRINI, Auteur ; Ragna Bugge ASKELAND, Auteur ; Angelica RONALD, Auteur ; Helga ASK, Auteur ; Beate ST POURCAIN, Auteur ; Ole A. ANDREASSEN, Auteur ; Laurie J. HANNIGAN, Auteur ; Alexandra. HAVDAHL, Auteur Article en page(s) : 25p. Langues : Anglais (eng) Mots-clés : Humans  Norway  Female  Male  Phenotype  Child, Preschool  Cohort Studies  Neurodevelopmental Disorders/genetics/diagnosis  Mothers  Autistic Disorder/genetics  Genetic Predisposition to Disease  Adult  Fathers  Genome-Wide Association Study  Attention Deficit Disorder with Hyperactivity/genetics/diagnosis  Schizophrenia/genetics  Genetic Heterogeneity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations. METHODS: In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. RESULTS: We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items r(g) range = -?0.27-0.78), ADHD (items r(g) range = -?0.40-1), and schizophrenia (items r(g) range = -?0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other. CONCLUSIONS: These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs. En ligne : https://dx.doi.org/10.1186/s13229-024-00599-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study [Texte imprimé et/ou numérique] / Laura HEGEMANN, Auteur ; Elizabeth C. CORFIELD, Auteur ; Adrian Dahl ASKELUND, Auteur ; Andrea G. ALLEGRINI, Auteur ; Ragna Bugge ASKELAND, Auteur ; Angelica RONALD, Auteur ; Helga ASK, Auteur ; Beate ST POURCAIN, Auteur ; Ole A. ANDREASSEN, Auteur ; Laurie J. HANNIGAN, Auteur ; Alexandra. HAVDAHL, Auteur . - 25p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 25p. Mots-clés : Humans  Norway  Female  Male  Phenotype  Child, Preschool  Cohort Studies  Neurodevelopmental Disorders/genetics/diagnosis  Mothers  Autistic Disorder/genetics  Genetic Predisposition to Disease  Adult  Fathers  Genome-Wide Association Study  Attention Deficit Disorder with Hyperactivity/genetics/diagnosis  Schizophrenia/genetics  Genetic Heterogeneity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations. METHODS: In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. RESULTS: We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items r(g) range = -?0.27-0.78), ADHD (items r(g) range = -?0.40-1), and schizophrenia (items r(g) range = -?0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other. CONCLUSIONS: These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs. En ligne : https://dx.doi.org/10.1186/s13229-024-00599-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Enhanced interest in letters and numbers in autistic children / Alexia OSTROLENK in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 26p. Titre : Enhanced interest in letters and numbers in autistic children Type de document : Texte imprimé et/ou numérique Auteurs : Alexia OSTROLENK, Auteur ; David GAGNON, Auteur ; Mélanie BOISVERT, Auteur ; Océane LEMIRE, Auteur ; Sophie-Catherine DICK, Auteur ; Marie-Pier CÔTÉ, Auteur ; Laurent MOTTRON, Auteur Article en page(s) : 26p. Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Autistic Disorder/diagnosis/psychology  Child, Preschool  Child  Reading  Surveys and Questionnaires  Autism  Hyperlexia  Interests  Language development  Reading Index. décimale : PER Périodiques Résumé : BACKGROUND: An intense and precocious interest in written material, together with a discrepancy between decoding and reading comprehension skills are defining criteria for hyperlexia, which is found in up to 20% of autistic individuals. It may represent the extreme end of a broader interest in written material in autism. This study examines the magnitude and nature of the interest in written material in a large population of autistic and non-autistic children. METHODS: All 701 children (391 autistic, 310 non-autistic) under the age of 7 referred to an autism assessment clinic over a span of 4 years were included. Ordinal logistic regressions assessed the association between diagnosis and the level of interest in letters and numbers. A nested sample of parents of 138 autistic, 99 non-autistic clinical, and 76 typically developing (TD) children completed a detailed questionnaire. Cox proportional hazards models analyzed the age of emergence of these interests. Linear regressions evaluated the association between diagnosis and interest level. The frequency of each behaviour showing interest and competence with letters and numbers were compared. RESULTS: In the two studies, 22 to 37% of autistic children had an intense or exclusive interest in letters. The odds of having a greater interest in letters was 2.78 times higher for autistic children than for non-autistic clinical children of the same age, and 3.49 times higher for the interest in numbers, even if 76% of autistic children were minimally or non-verbal. The age of emergence of these interests did not differ between autistic and TD children and did not depend on their level of oral language. Non-autistic children showed more interest in letters within a social context. LIMITATIONS: The study holds limitations inherent to the use of a phone questionnaire with caregivers and missing sociodemographic information. CONCLUSIONS: The emergence of the interest of autistic children toward written language is contemporaneous to the moment in their development where they display a strong deficit in oral language. Together with recent demonstrations of non-social development of oral language in some autistic children, precocious and intense interest in written material suggests that language acquisition in autism may follow an alternative developmental pathway. En ligne : https://dx.doi.org/10.1186/s13229-024-00606-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Enhanced interest in letters and numbers in autistic children [Texte imprimé et/ou numérique] / Alexia OSTROLENK, Auteur ; David GAGNON, Auteur ; Mélanie BOISVERT, Auteur ; Océane LEMIRE, Auteur ; Sophie-Catherine DICK, Auteur ; Marie-Pier CÔTÉ, Auteur ; Laurent MOTTRON, Auteur . - 26p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 26p. Mots-clés : Humans  Male  Female  Autistic Disorder/diagnosis/psychology  Child, Preschool  Child  Reading  Surveys and Questionnaires  Autism  Hyperlexia  Interests  Language development  Reading Index. décimale : PER Périodiques Résumé : BACKGROUND: An intense and precocious interest in written material, together with a discrepancy between decoding and reading comprehension skills are defining criteria for hyperlexia, which is found in up to 20% of autistic individuals. It may represent the extreme end of a broader interest in written material in autism. This study examines the magnitude and nature of the interest in written material in a large population of autistic and non-autistic children. METHODS: All 701 children (391 autistic, 310 non-autistic) under the age of 7 referred to an autism assessment clinic over a span of 4 years were included. Ordinal logistic regressions assessed the association between diagnosis and the level of interest in letters and numbers. A nested sample of parents of 138 autistic, 99 non-autistic clinical, and 76 typically developing (TD) children completed a detailed questionnaire. Cox proportional hazards models analyzed the age of emergence of these interests. Linear regressions evaluated the association between diagnosis and interest level. The frequency of each behaviour showing interest and competence with letters and numbers were compared. RESULTS: In the two studies, 22 to 37% of autistic children had an intense or exclusive interest in letters. The odds of having a greater interest in letters was 2.78 times higher for autistic children than for non-autistic clinical children of the same age, and 3.49 times higher for the interest in numbers, even if 76% of autistic children were minimally or non-verbal. The age of emergence of these interests did not differ between autistic and TD children and did not depend on their level of oral language. Non-autistic children showed more interest in letters within a social context. LIMITATIONS: The study holds limitations inherent to the use of a phone questionnaire with caregivers and missing sociodemographic information. CONCLUSIONS: The emergence of the interest of autistic children toward written language is contemporaneous to the moment in their development where they display a strong deficit in oral language. Together with recent demonstrations of non-social development of oral language in some autistic children, precocious and intense interest in written material suggests that language acquisition in autism may follow an alternative developmental pathway. En ligne : https://dx.doi.org/10.1186/s13229-024-00606-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder / Laura SIMÕES DE OLIVEIRA in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 28p. Titre : Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder Type de document : Texte imprimé et/ou numérique Auteurs : Laura SIMÕES DE OLIVEIRA, Auteur ; Heather E. O'LEARY, Auteur ; Sarfaraz NAWAZ, Auteur ; Rita LOUREIRO, Auteur ; Elizabeth C. DAVENPORT, Auteur ; Paul BAXTER, Auteur ; Susana R LOUROS, Auteur ; Owen DANDO, Auteur ; Emma PERKINS, Auteur ; Julien PELTIER, Auteur ; Matthias TROST, Auteur ; Emily K. OSTERWEIL, Auteur ; Giles E. HARDINGHAM, Auteur ; Michael A. COUSIN, Auteur ; Sumantra CHATTARJI, Auteur ; Sam A. BOOKER, Auteur ; Tim A. BENKE, Auteur ; David J. A. WYLLIE, Auteur ; Peter C. KIND, Auteur Article en page(s) : 28p. Langues : Anglais (eng) Mots-clés : Animals  Male  Rats  CA1 Region, Hippocampal/metabolism/pathology/physiopathology  Disease Models, Animal  Epileptic Syndromes/genetics/metabolism  Excitatory Postsynaptic Potentials  Genetic Diseases, X-Linked/genetics/metabolism/physiopathology  Hippocampus/metabolism  Long-Term Potentiation  Protein Serine-Threonine Kinases/metabolism/genetics  Pyramidal Cells/metabolism/pathology  Receptors, AMPA/metabolism/genetics  Receptors, N-Methyl-D-Aspartate/metabolism/genetics  Spasms, Infantile/genetics/metabolism  Synapses/metabolism  AMPA receptor  Cdkl5  NMDA receptor  hippocampus  intrinsic properties  rat  synaptic plasticity Index. décimale : PER Périodiques Résumé : BACKGROUND: Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5(-/y) rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5(-/y) rats. METHODS: To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology. RESULTS: Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5(-/y) rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca(2+) permeable AMPA receptor mediated currents are unchanged in Cdkl5(-/y) rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses. CONCLUSIONS: Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity. LIMITATIONS: This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD. En ligne : https://dx.doi.org/10.1186/s13229-024-00601-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder [Texte imprimé et/ou numérique] / Laura SIMÕES DE OLIVEIRA, Auteur ; Heather E. O'LEARY, Auteur ; Sarfaraz NAWAZ, Auteur ; Rita LOUREIRO, Auteur ; Elizabeth C. DAVENPORT, Auteur ; Paul BAXTER, Auteur ; Susana R LOUROS, Auteur ; Owen DANDO, Auteur ; Emma PERKINS, Auteur ; Julien PELTIER, Auteur ; Matthias TROST, Auteur ; Emily K. OSTERWEIL, Auteur ; Giles E. HARDINGHAM, Auteur ; Michael A. COUSIN, Auteur ; Sumantra CHATTARJI, Auteur ; Sam A. BOOKER, Auteur ; Tim A. BENKE, Auteur ; David J. A. WYLLIE, Auteur ; Peter C. KIND, Auteur . - 28p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 28p. Mots-clés : Animals  Male  Rats  CA1 Region, Hippocampal/metabolism/pathology/physiopathology  Disease Models, Animal  Epileptic Syndromes/genetics/metabolism  Excitatory Postsynaptic Potentials  Genetic Diseases, X-Linked/genetics/metabolism/physiopathology  Hippocampus/metabolism  Long-Term Potentiation  Protein Serine-Threonine Kinases/metabolism/genetics  Pyramidal Cells/metabolism/pathology  Receptors, AMPA/metabolism/genetics  Receptors, N-Methyl-D-Aspartate/metabolism/genetics  Spasms, Infantile/genetics/metabolism  Synapses/metabolism  AMPA receptor  Cdkl5  NMDA receptor  hippocampus  intrinsic properties  rat  synaptic plasticity Index. décimale : PER Périodiques Résumé : BACKGROUND: Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5(-/y) rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5(-/y) rats. METHODS: To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology. RESULTS: Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5(-/y) rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca(2+) permeable AMPA receptor mediated currents are unchanged in Cdkl5(-/y) rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses. CONCLUSIONS: Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity. LIMITATIONS: This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD. En ligne : https://dx.doi.org/10.1186/s13229-024-00601-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Phenotypic and ancestry-related assortative mating in autism / Jing ZHANG in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 27p. Titre : Phenotypic and ancestry-related assortative mating in autism Type de document : Texte imprimé et/ou numérique Auteurs : Jing ZHANG, Auteur ; J. Dylan WEISSENKAMPEN, Auteur ; Rachel L. KEMBER, Auteur ; iPSYCH CONSORTIUM, Auteur ; Jakob GROVE, Auteur ; Anders D. BØRGLUM, Auteur ; Elise B. ROBINSON, Auteur ; Edward S. BRODKIN, Auteur ; Laura ALMASY, Auteur ; Maja BUCAN, Auteur ; Ronnie SEBRO, Auteur Article en page(s) : 27p. Langues : Anglais (eng) Mots-clés : Humans  Autistic Disorder/genetics  Phenotype  Male  Female  Linkage Disequilibrium  Multifactorial Inheritance  Child  Genetic Predisposition to Disease  Polymorphism, Single Nucleotide  Adult  Intellectual Disability/genetics  Assortative mating  Autism  Genetic ancestry  Intellectual disability  Linkage disequilibrium  Polygenic scores Index. décimale : PER Périodiques Résumé : BACKGROUND: Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population. METHODS: To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families). RESULTS: We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|>?0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D(2) on the order of 1?*?10(-5)). LIMITATIONS: We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification. CONCLUSIONS: This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for En ligne : https://dx.doi.org/10.1186/s13229-024-00605-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Phenotypic and ancestry-related assortative mating in autism [Texte imprimé et/ou numérique] / Jing ZHANG, Auteur ; J. Dylan WEISSENKAMPEN, Auteur ; Rachel L. KEMBER, Auteur ; iPSYCH CONSORTIUM, Auteur ; Jakob GROVE, Auteur ; Anders D. BØRGLUM, Auteur ; Elise B. ROBINSON, Auteur ; Edward S. BRODKIN, Auteur ; Laura ALMASY, Auteur ; Maja BUCAN, Auteur ; Ronnie SEBRO, Auteur . - 27p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 27p. Mots-clés : Humans  Autistic Disorder/genetics  Phenotype  Male  Female  Linkage Disequilibrium  Multifactorial Inheritance  Child  Genetic Predisposition to Disease  Polymorphism, Single Nucleotide  Adult  Intellectual Disability/genetics  Assortative mating  Autism  Genetic ancestry  Intellectual disability  Linkage disequilibrium  Polygenic scores Index. décimale : PER Périodiques Résumé : BACKGROUND: Positive assortative mating (AM) in several neuropsychiatric traits, including autism, has been noted. However, it is unknown whether the pattern of AM is different in phenotypically defined autism subgroups [e.g., autism with and without intellectually disability (ID)]. It is also unclear what proportion of the phenotypic AM can be explained by the genetic similarity between parents of children with an autism diagnosis, and the consequences of AM on the genetic structure of the population. METHODS: To address these questions, we analyzed two family-based autism collections: the Simons Foundation Powering Autism Research for Knowledge (SPARK) (1575 families) and the Simons Simplex Collection (SSC) (2283 families). RESULTS: We found a similar degree of phenotypic and ancestry-related AM in parents of children with an autism diagnosis regardless of the presence of ID. We did not find evidence of AM for autism based on autism polygenic scores (PGS) (at a threshold of |r|>?0.1). The adjustment of ancestry-related AM or autism PGS accounted for only 0.3-4% of the fractional change in the estimate of the phenotypic AM. The ancestry-related AM introduced higher long-range linkage disequilibrium (LD) between single nucleotide polymorphisms (SNPs) on different chromosomes that are highly ancestry-informative compared to SNPs that are less ancestry-informative (D(2) on the order of 1?*?10(-5)). LIMITATIONS: We only analyzed participants of European ancestry, limiting the generalizability of our results to individuals of non-European ancestry. SPARK and SSC were both multicenter studies. Therefore, there could be ancestry-related AM in SPARK and SSC due to geographic stratification. The study participants from each site were unknown, so we were unable to evaluate for geographic stratification. CONCLUSIONS: This study showed similar patterns of AM in autism with and without ID, and demonstrated that the common genetic influences of autism are likely relevant to both autism groups. The adjustment of ancestry-related AM and autism PGS accounted for En ligne : https://dx.doi.org/10.1186/s13229-024-00605-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Mate selection and current trends in the prevalence of autism / Elizabeth FORSEN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 29p. Titre : Mate selection and current trends in the prevalence of autism Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth FORSEN, Auteur ; Natasha MARRUS, Auteur ; Jacqueline JOYCE, Auteur ; Yi ZHANG, Auteur ; John N. CONSTANTINO, Auteur Article en page(s) : 29p. Langues : Anglais (eng) Mots-clés : Adult  Child  Female  Humans  Male  Autistic Disorder/epidemiology/genetics  California/epidemiology  Hispanic or Latino  Missouri/epidemiology  Prevalence  White  Assortative mating  Autism  Autism prevalence  Mate selection  Racial and ethnic minorities  Responsiveness Scale-2, a quantitative measure of autistic traits. The remaining  authors declare that they have no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children. METHODS: Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2). RESULTS: We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30). LIMITATIONS: The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report. CONCLUSION: Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations. En ligne : https://dx.doi.org/10.1186/s13229-024-00607-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Mate selection and current trends in the prevalence of autism [Texte imprimé et/ou numérique] / Elizabeth FORSEN, Auteur ; Natasha MARRUS, Auteur ; Jacqueline JOYCE, Auteur ; Yi ZHANG, Auteur ; John N. CONSTANTINO, Auteur . - 29p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 29p. Mots-clés : Adult  Child  Female  Humans  Male  Autistic Disorder/epidemiology/genetics  California/epidemiology  Hispanic or Latino  Missouri/epidemiology  Prevalence  White  Assortative mating  Autism  Autism prevalence  Mate selection  Racial and ethnic minorities  Responsiveness Scale-2, a quantitative measure of autistic traits. The remaining  authors declare that they have no conflict of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: According to the most recent U.S. CDC surveillance data, the rise in prevalence of childhood autism spectrum disorder among minority children has begun to outpace that of non-Hispanic white children. Since prior research has identified possible differences in the extent of mate selection for autistic traits across families of different ethnicity, this study examined variation in autism related traits in contemporaneous, epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white populations. The purpose was to determine whether discrepancies by ethnicity could contribute to differential increases in prevalence in the current generation of young children. METHODS: Birth records were used to identify all twin pairs born between 2011 and 2013 in California and Missouri. Families were selected at random from pools of English-speaking Hispanic families in California and Non-Hispanic White families in Missouri. Autistic trait data of parents was obtained using the Adult Report Form of the Social Responsiveness Scale (SRS-2). RESULTS: We did not identify a statistically significant difference in the degree of mate selection for autism related traits between Hispanic and non-Hispanic white spousal pairs. However, the degree of spousal correlation observed in this recent cohort was pronounced (on the order of ICC 0.45) and exceeded that typically reported in prior research (on the order of 0.30), surpassing also widely reported estimates for sibling correlation (also on the order of 0.30). LIMITATIONS: The sample did not allow for a direct appraisal of change in the magnitude of spousal correlation over time and the ascertainments of trait burden were derived from spouse report. CONCLUSION: Across two epidemiologically ascertained samples of spousal pairs representing Hispanic and non-Hispanic white families across two U.S. states (respectively, California and Missouri), the extent of autism-related trait co-variation for parents of the current generation of young children is substantial and exceeds correlations typically observed for siblings. Given the heritability of these traits and their relation to autism risk, societal trends in the degree of mate selection for these traits should be considered as possible contributors to subtle increases in the incidence of autism over time and across generations. En ligne : https://dx.doi.org/10.1186/s13229-024-00607-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Publisher Correction: Measuring self and informant perspectives of restricted and repetitive behaviours (RRBs): psychometric evaluation of the repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settings / Catherine R. G. JONES in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 30p. Titre : Publisher Correction: Measuring self and informant perspectives of restricted and repetitive behaviours (RRBs): psychometric evaluation of the repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settings Type de document : Texte imprimé et/ou numérique Auteurs : Catherine R. G. JONES, Auteur ; Lucy A. LIVINGSTON, Auteur ; Christine FRETWELL, Auteur ; Mirko ULJAREVI?, Auteur ; Sarah J. CARRINGTON, Auteur ; Punit SHAH, Auteur ; Susan R. LEEKAM, Auteur Article en page(s) : 30p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s13229-024-00609-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Publisher Correction: Measuring self and informant perspectives of restricted and repetitive behaviours (RRBs): psychometric evaluation of the repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settings [Texte imprimé et/ou numérique] / Catherine R. G. JONES, Auteur ; Lucy A. LIVINGSTON, Auteur ; Christine FRETWELL, Auteur ; Mirko ULJAREVI?, Auteur ; Sarah J. CARRINGTON, Auteur ; Punit SHAH, Auteur ; Susan R. LEEKAM, Auteur . - 30p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 30p. Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s13229-024-00609-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

(1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome / Pooja Kri GUPTA in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 31p. Titre : (1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Pooja Kri GUPTA, Auteur ; Sharon BARAK, Auteur ; Yonatan FEUERMANN, Auteur ; Gil GOOBES, Auteur ; Hanoch KAPHZAN, Auteur Article en page(s) : 31p. Langues : Anglais (eng) Mots-clés : Animals  Angelman Syndrome/metabolism/genetics  Metabolomics  Disease Models, Animal  Brain/metabolism/diagnostic imaging  Mice  Proton Magnetic Resonance Spectroscopy  Metabolome  Ubiquitin-Protein Ligases/metabolism/genetics  Female  Acetate  Angelman syndrome  Developmental disorders  Glycolysis  Lactate  Metabolite  Mitochondria  Pyruvate metabolism  Reactive oxygen species  Succinate Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. METHODS: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. RESULTS: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. LIMITATIONS: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. CONCLUSIONS: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development. En ligne : https://dx.doi.org/10.1186/s13229-024-00608-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] (1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome [Texte imprimé et/ou numérique] / Pooja Kri GUPTA, Auteur ; Sharon BARAK, Auteur ; Yonatan FEUERMANN, Auteur ; Gil GOOBES, Auteur ; Hanoch KAPHZAN, Auteur . - 31p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 31p. Mots-clés : Animals  Angelman Syndrome/metabolism/genetics  Metabolomics  Disease Models, Animal  Brain/metabolism/diagnostic imaging  Mice  Proton Magnetic Resonance Spectroscopy  Metabolome  Ubiquitin-Protein Ligases/metabolism/genetics  Female  Acetate  Angelman syndrome  Developmental disorders  Glycolysis  Lactate  Metabolite  Mitochondria  Pyruvate metabolism  Reactive oxygen species  Succinate Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. METHODS: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. RESULTS: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. LIMITATIONS: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. CONCLUSIONS: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development. En ligne : https://dx.doi.org/10.1186/s13229-024-00608-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Correction: Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice / Kyung Ah HAN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 32p. Titre : Correction: Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice Type de document : Texte imprimé et/ou numérique Auteurs : Kyung Ah HAN, Auteur ; Taek Han YOON, Auteur ; Jungsu SHIN, Auteur ; Ji Won UM, Auteur ; Jaewon KO, Auteur Article en page(s) : 32p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s13229-024-00612-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Correction: Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice [Texte imprimé et/ou numérique] / Kyung Ah HAN, Auteur ; Taek Han YOON, Auteur ; Jungsu SHIN, Auteur ; Ji Won UM, Auteur ; Jaewon KO, Auteur . - 32p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 32p. Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s13229-024-00612-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Spontaneous instrumental approach-avoidance learning in social contexts in autism / Morgan BEAURENAUT in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 33p. Titre : Spontaneous instrumental approach-avoidance learning in social contexts in autism Type de document : Texte imprimé et/ou numérique Auteurs : Morgan BEAURENAUT, Auteur ; Klara KOVARSKI, Auteur ; Constance DESTAIS, Auteur ; Rocco MENNELLA, Auteur ; Julie GREZES, Auteur Article en page(s) : 33p. Langues : Anglais (eng) Mots-clés : Humans  Female  Male  Adult  Autistic Disorder/psychology  Young Adult  Avoidance Learning  Adolescent  Autism Spectrum Disorder/psychology  Social Behavior  Emotions  Social Interaction  Approach/avoidance  Autism  Emotional expressions  Gender bias  Social reinforcement learning Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with Autism Spectrum Condition (ASC) are characterized by atypicalities in social interactions, compared to Typically Developing individuals (TD). The social motivation theory posits that these difficulties stem from diminished anticipation, reception, and/or learning from social rewards. Although learning from socioemotional outcomes is core to the theory, studies to date have been sparse and inconsistent. This possibly arises from a combination of theoretical, methodological and sample-related issues. Here, we assessed participants' ability to develop a spontaneous preference for actions that lead to desirable socioemotional outcomes (approaching/avoiding of happy/angry individuals, respectively), in an ecologically valid social scenario. We expected that learning abilities would be impaired in ASC individuals, particularly in response to affiliative social feedback. METHOD: We ran an online social reinforcement learning task, on two large online cohorts with (n = 274) and without (n = 290) ASC, matched for gender, age and education. Participants had to indicate where they would sit in a waiting room. Each seat was associated with different probabilities of approaching/avoiding emotional individuals. Importantly, the task was implicit, as participants were not instructed to learn, and emotional expressions were never mentioned. We applied both categorical analyses contrasting the ASC and TD groups and dimensional factor analysis on affective questionnaires. RESULTS: Contrary to our hypothesis, participants showed spontaneous learning from socioemotional outcomes, regardless of their diagnostic group. Yet, when accounting for dimensional variations in autistic traits, as well as depression and anxiety, two main findings emerged among females who failed to develop explicit learning strategies: (1) autism severity in ASC correlated with reduced learning to approach happy individuals; (2) anxiety-depression severity across both ASC and TD participants correlated with reduced learning to approach/avoid happy/angry individuals, respectively. CONCLUSIONS: Implicit spontaneous learning from socioemotional outcomes is not generally impaired in autism but may be specifically associated with autism severity in females with ASC, when they do not have an explicit strategy for adapting to their social environment. Clinical diagnosis and intervention ought to take into account individual differences in their full complexity, including the presence of co-morbid anxiety and depression, when dealing with social atypicalities in autism. En ligne : https://dx.doi.org/10.1186/s13229-024-00610-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Spontaneous instrumental approach-avoidance learning in social contexts in autism [Texte imprimé et/ou numérique] / Morgan BEAURENAUT, Auteur ; Klara KOVARSKI, Auteur ; Constance DESTAIS, Auteur ; Rocco MENNELLA, Auteur ; Julie GREZES, Auteur . - 33p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 33p. Mots-clés : Humans  Female  Male  Adult  Autistic Disorder/psychology  Young Adult  Avoidance Learning  Adolescent  Autism Spectrum Disorder/psychology  Social Behavior  Emotions  Social Interaction  Approach/avoidance  Autism  Emotional expressions  Gender bias  Social reinforcement learning Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with Autism Spectrum Condition (ASC) are characterized by atypicalities in social interactions, compared to Typically Developing individuals (TD). The social motivation theory posits that these difficulties stem from diminished anticipation, reception, and/or learning from social rewards. Although learning from socioemotional outcomes is core to the theory, studies to date have been sparse and inconsistent. This possibly arises from a combination of theoretical, methodological and sample-related issues. Here, we assessed participants' ability to develop a spontaneous preference for actions that lead to desirable socioemotional outcomes (approaching/avoiding of happy/angry individuals, respectively), in an ecologically valid social scenario. We expected that learning abilities would be impaired in ASC individuals, particularly in response to affiliative social feedback. METHOD: We ran an online social reinforcement learning task, on two large online cohorts with (n = 274) and without (n = 290) ASC, matched for gender, age and education. Participants had to indicate where they would sit in a waiting room. Each seat was associated with different probabilities of approaching/avoiding emotional individuals. Importantly, the task was implicit, as participants were not instructed to learn, and emotional expressions were never mentioned. We applied both categorical analyses contrasting the ASC and TD groups and dimensional factor analysis on affective questionnaires. RESULTS: Contrary to our hypothesis, participants showed spontaneous learning from socioemotional outcomes, regardless of their diagnostic group. Yet, when accounting for dimensional variations in autistic traits, as well as depression and anxiety, two main findings emerged among females who failed to develop explicit learning strategies: (1) autism severity in ASC correlated with reduced learning to approach happy individuals; (2) anxiety-depression severity across both ASC and TD participants correlated with reduced learning to approach/avoid happy/angry individuals, respectively. CONCLUSIONS: Implicit spontaneous learning from socioemotional outcomes is not generally impaired in autism but may be specifically associated with autism severity in females with ASC, when they do not have an explicit strategy for adapting to their social environment. Clinical diagnosis and intervention ought to take into account individual differences in their full complexity, including the presence of co-morbid anxiety and depression, when dealing with social atypicalities in autism. En ligne : https://dx.doi.org/10.1186/s13229-024-00610-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults / Salahuddin MOHAMMAD in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 34p. Titre : Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults Type de document : Texte imprimé et/ou numérique Auteurs : Salahuddin MOHAMMAD, Auteur ; Mélissa GENTREAU, Auteur ; Manon DUBOL, Auteur ; Gull RUKH, Auteur ; Jessica MWINYI, Auteur ; Helgi B. SCHIÖTH, Auteur Article en page(s) : 34p. Langues : Anglais (eng) Mots-clés : Humans  Cerebellum/diagnostic imaging/pathology  Brain Stem/diagnostic imaging/pathology  Magnetic Resonance Imaging  Male  Female  Phenotype  Adult  Multifactorial Inheritance  Genetic Predisposition to Disease  Organ Size  Middle Aged  Autistic Disorder/genetics/diagnostic imaging  Genome-Wide Association Study  Autism Spectrum Disorder/genetics/diagnostic imaging  Gray Matter/diagnostic imaging/pathology  Case-Control Studies  Autism  Brain MRI  Brainstem  Cerebellum  Polygenic risk score Index. décimale : PER Périodiques Résumé : Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~?31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain. En ligne : https://dx.doi.org/10.1186/s13229-024-00611-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Association of polygenic scores for autism with volumetric MRI phenotypes in cerebellum and brainstem in adults [Texte imprimé et/ou numérique] / Salahuddin MOHAMMAD, Auteur ; Mélissa GENTREAU, Auteur ; Manon DUBOL, Auteur ; Gull RUKH, Auteur ; Jessica MWINYI, Auteur ; Helgi B. SCHIÖTH, Auteur . - 34p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 34p. Mots-clés : Humans  Cerebellum/diagnostic imaging/pathology  Brain Stem/diagnostic imaging/pathology  Magnetic Resonance Imaging  Male  Female  Phenotype  Adult  Multifactorial Inheritance  Genetic Predisposition to Disease  Organ Size  Middle Aged  Autistic Disorder/genetics/diagnostic imaging  Genome-Wide Association Study  Autism Spectrum Disorder/genetics/diagnostic imaging  Gray Matter/diagnostic imaging/pathology  Case-Control Studies  Autism  Brain MRI  Brainstem  Cerebellum  Polygenic risk score Index. décimale : PER Périodiques Résumé : Previous research on autism spectrum disorders (ASD) have showed important volumetric alterations in the cerebellum and brainstem. Most of these studies are however limited to case-control studies with small clinical samples and including mainly children or adolescents. Herein, we aimed to explore the association between the cumulative genetic load (polygenic risk score, PRS) for ASD and volumetric alterations in the cerebellum and brainstem, as well as global brain tissue volumes of the brain among adults at the population level. We utilized the latest genome-wide association study of ASD by the Psychiatric Genetics Consortium (18,381 cases, 27,969 controls) and constructed the ASD PRS in an independent cohort, the UK Biobank. Regression analyses controlled for multiple comparisons with the false-discovery rate (FDR) at 5% were performed to investigate the association between ASD PRS and forty-four brain magnetic resonance imaging (MRI) phenotypes among ~?31,000 participants. Primary analyses included sixteen MRI phenotypes: total volumes of the brain, cerebrospinal fluid (CSF), grey matter (GM), white matter (WM), GM of whole cerebellum, brainstem, and ten regions of the cerebellum (I_IV, V, VI, VIIb, VIIIa, VIIIb, IX, X, CrusI and CrusII). Secondary analyses included twenty-eight MRI phenotypes: the sub-regional volumes of cerebellum including the GM of the vermis and both left and right lobules of each cerebellar region. ASD PRS were significantly associated with the volumes of seven brain areas, whereby higher PRS were associated to reduced volumes of the whole brain, WM, brainstem, and cerebellar regions I-IV, IX, and X, and an increased volume of the CSF. Three sub-regional volumes including the left cerebellar lobule I-IV, cerebellar vermes VIIIb, and X were significantly and negatively associated with ASD PRS. The study highlights a substantial connection between susceptibility to ASD, its underlying genetic etiology, and neuroanatomical alterations of the adult brain. En ligne : https://dx.doi.org/10.1186/s13229-024-00611-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography / Dalin YANG in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 35p. Titre : Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography Type de document : Texte imprimé et/ou numérique Auteurs : Dalin YANG, Auteur ; Alexandra M. SVOBODA, Auteur ; Tessa G. GEORGE, Auteur ; Patricia K. MANSFIELD, Auteur ; Muriah D. WHEELOCK, Auteur ; Mariel L. SCHROEDER, Auteur ; Sean M. RAFFERTY, Auteur ; Arefeh SHERAFATI, Auteur ; Kalyan TRIPATHY, Auteur ; Tracy BURNS-YOCUM, Auteur ; Elizabeth FORSEN, Auteur ; John R. PRUETT, Auteur ; Natasha M. MARRUS, Auteur ; Joseph P CULVER, Auteur ; John N. CONSTANTINO, Auteur ; Adam T. EGGEBRECHT, Auteur Article en page(s) : 35p. Langues : Anglais (eng) Mots-clés : Humans  Tomography, Optical/methods  Male  Child  Female  Motion Perception/physiology  Brain Mapping/methods  Autism Spectrum Disorder/diagnostic imaging/physiopathology  Brain/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology/diagnostic imaging  Magnetic Resonance Imaging/methods  Adolescent  Autism spectrum disorder  Biological motion  High-density diffuse optical tomography  Neuroimaging  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits. METHODS: We used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models. RESULTS: We found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits. LIMITATIONS: Optical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism. CONCLUSIONS: This study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits. En ligne : https://dx.doi.org/10.1186/s13229-024-00614-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Mapping neural correlates of biological motion perception in autistic children using high-density diffuse optical tomography [Texte imprimé et/ou numérique] / Dalin YANG, Auteur ; Alexandra M. SVOBODA, Auteur ; Tessa G. GEORGE, Auteur ; Patricia K. MANSFIELD, Auteur ; Muriah D. WHEELOCK, Auteur ; Mariel L. SCHROEDER, Auteur ; Sean M. RAFFERTY, Auteur ; Arefeh SHERAFATI, Auteur ; Kalyan TRIPATHY, Auteur ; Tracy BURNS-YOCUM, Auteur ; Elizabeth FORSEN, Auteur ; John R. PRUETT, Auteur ; Natasha M. MARRUS, Auteur ; Joseph P CULVER, Auteur ; John N. CONSTANTINO, Auteur ; Adam T. EGGEBRECHT, Auteur . - 35p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 35p. Mots-clés : Humans  Tomography, Optical/methods  Male  Child  Female  Motion Perception/physiology  Brain Mapping/methods  Autism Spectrum Disorder/diagnostic imaging/physiopathology  Brain/diagnostic imaging/physiopathology  Autistic Disorder/physiopathology/diagnostic imaging  Magnetic Resonance Imaging/methods  Adolescent  Autism spectrum disorder  Biological motion  High-density diffuse optical tomography  Neuroimaging  Social perception Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD), a neurodevelopmental disorder defined by social communication deficits plus repetitive behaviors and restricted interests, currently affects 1/36 children in the general population. Recent advances in functional brain imaging show promise to provide useful biomarkers of ASD diagnostic likelihood, behavioral trait severity, and even response to therapeutic intervention. However, current gold-standard neuroimaging methods (e.g., functional magnetic resonance imaging, fMRI) are limited in naturalistic studies of brain function underlying ASD-associated behaviors due to the constrained imaging environment. Compared to fMRI, high-density diffuse optical tomography (HD-DOT), a non-invasive and minimally constraining optical neuroimaging modality, can overcome these limitations. Herein, we aimed to establish HD-DOT to evaluate brain function in autistic and non-autistic school-age children as they performed a biological motion perception task previously shown to yield results related to both ASD diagnosis and behavioral traits. METHODS: We used HD-DOT to image brain function in 46 ASD school-age participants and 49 non-autistic individuals (NAI) as they viewed dynamic point-light displays of coherent biological and scrambled motion. We assessed group-level cortical brain function with statistical parametric mapping. Additionally, we tested for brain-behavior associations with dimensional metrics of autism traits, as measured with the Social Responsiveness Scale-2, with hierarchical regression models. RESULTS: We found that NAI participants presented stronger brain activity contrast (coherent > scrambled) than ASD children in cortical regions related to visual, motor, and social processing. Additionally, regression models revealed multiple cortical regions in autistic participants where brain function is significantly associated with dimensional measures of ASD traits. LIMITATIONS: Optical imaging methods are limited in depth sensitivity and so cannot measure brain activity within deep subcortical regions. However, the field of view of this HD-DOT system includes multiple brain regions previously implicated in both task-based and task-free studies on autism. CONCLUSIONS: This study demonstrates that HD-DOT is sensitive to brain function that both differentiates between NAI and ASD groups and correlates with dimensional measures of ASD traits. These findings establish HD-DOT as an effective tool for investigating brain function in autistic and non-autistic children. Moreover, this study established neural correlates related to biological motion perception and its association with dimensional measures of ASD traits. En ligne : https://dx.doi.org/10.1186/s13229-024-00614-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Enhanced motor noise in an autism subtype with poor motor skills / Veronica MANDELLI in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 36p. Titre : Enhanced motor noise in an autism subtype with poor motor skills Type de document : Texte imprimé et/ou numérique Auteurs : Veronica MANDELLI, Auteur ; Isotta LANDI, Auteur ; Silvia Busti CECCARELLI, Auteur ; Massimo MOLTENI, Auteur ; Maria NOBILE, Auteur ; Alessandro D'AUSILIO, Auteur ; Luciano FADIGA, Auteur ; Alessandro CRIPPA, Auteur ; Michael V. LOMBARDO, Auteur Article en page(s) : 36p. Langues : Anglais (eng) Mots-clés : Humans  Child  Male  Female  Adolescent  Motor Skills  Autistic Disorder/physiopathology  Child, Preschool  Biomechanical Phenomena  Clustering  Kinematics  Motor  Stratification  Subtypes  competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Motor difficulties are common in many, but not all, autistic individuals. These difficulties can co-occur with other problems, such as delays in language, intellectual, and adaptive functioning. Biological mechanisms underpinning such difficulties are less well understood. Poor motor skills tend to be more common in individuals carrying highly penetrant rare genetic mutations. Such mechanisms may have downstream consequences of altering neurophysiological excitation-inhibition balance and lead to enhanced behavioral motor noise. METHODS: This study combined publicly available and in-house datasets of autistic (n = 156), typically-developing (TD, n = 149), and developmental coordination disorder (DCD, n = 23) children (age 3-16 years). Autism motor subtypes were identified based on patterns of motor abilities measured from the Movement Assessment Battery for Children 2nd edition. Stability-based relative clustering validation was used to identify autism motor subtypes and evaluate generalization accuracy in held-out data. Autism motor subtypes were tested for differences in motor noise, operationalized as the degree of dissimilarity between repeated motor kinematic trajectories recorded during a simple reach-to-drop task. RESULTS: Relatively 'high' (n = 87) versus 'low' (n = 69) autism motor subtypes could be detected and which generalize with 89% accuracy in held-out data. The relatively 'low' subtype was lower in general intellectual ability and older at age of independent walking, but did not differ in age at first words or autistic traits or symptomatology. Motor noise was considerably higher in the 'low' subtype compared to 'high' (Cohen's d = 0.77) or TD children (Cohen's d = 0.85), but similar between autism 'high' and TD children (Cohen's d = 0.08). Enhanced motor noise in the 'low' subtype was also most pronounced during the feedforward phase of reaching actions. LIMITATIONS: The sample size of this work is limited. Future work in larger samples along with independent replication is important. Motor noise was measured only on one specific motor task. Thus, a more comprehensive assessment of motor noise on many other motor tasks is needed. CONCLUSIONS: Autism can be split into at least two discrete motor subtypes that are characterized by differing levels of motor noise. This suggests that autism motor subtypes may be underpinned by different biological mechanisms. En ligne : https://dx.doi.org/10.1186/s13229-024-00618-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Enhanced motor noise in an autism subtype with poor motor skills [Texte imprimé et/ou numérique] / Veronica MANDELLI, Auteur ; Isotta LANDI, Auteur ; Silvia Busti CECCARELLI, Auteur ; Massimo MOLTENI, Auteur ; Maria NOBILE, Auteur ; Alessandro D'AUSILIO, Auteur ; Luciano FADIGA, Auteur ; Alessandro CRIPPA, Auteur ; Michael V. LOMBARDO, Auteur . - 36p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 36p. Mots-clés : Humans  Child  Male  Female  Adolescent  Motor Skills  Autistic Disorder/physiopathology  Child, Preschool  Biomechanical Phenomena  Clustering  Kinematics  Motor  Stratification  Subtypes  competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Motor difficulties are common in many, but not all, autistic individuals. These difficulties can co-occur with other problems, such as delays in language, intellectual, and adaptive functioning. Biological mechanisms underpinning such difficulties are less well understood. Poor motor skills tend to be more common in individuals carrying highly penetrant rare genetic mutations. Such mechanisms may have downstream consequences of altering neurophysiological excitation-inhibition balance and lead to enhanced behavioral motor noise. METHODS: This study combined publicly available and in-house datasets of autistic (n = 156), typically-developing (TD, n = 149), and developmental coordination disorder (DCD, n = 23) children (age 3-16 years). Autism motor subtypes were identified based on patterns of motor abilities measured from the Movement Assessment Battery for Children 2nd edition. Stability-based relative clustering validation was used to identify autism motor subtypes and evaluate generalization accuracy in held-out data. Autism motor subtypes were tested for differences in motor noise, operationalized as the degree of dissimilarity between repeated motor kinematic trajectories recorded during a simple reach-to-drop task. RESULTS: Relatively 'high' (n = 87) versus 'low' (n = 69) autism motor subtypes could be detected and which generalize with 89% accuracy in held-out data. The relatively 'low' subtype was lower in general intellectual ability and older at age of independent walking, but did not differ in age at first words or autistic traits or symptomatology. Motor noise was considerably higher in the 'low' subtype compared to 'high' (Cohen's d = 0.77) or TD children (Cohen's d = 0.85), but similar between autism 'high' and TD children (Cohen's d = 0.08). Enhanced motor noise in the 'low' subtype was also most pronounced during the feedforward phase of reaching actions. LIMITATIONS: The sample size of this work is limited. Future work in larger samples along with independent replication is important. Motor noise was measured only on one specific motor task. Thus, a more comprehensive assessment of motor noise on many other motor tasks is needed. CONCLUSIONS: Autism can be split into at least two discrete motor subtypes that are characterized by differing levels of motor noise. This suggests that autism motor subtypes may be underpinned by different biological mechanisms. En ligne : https://dx.doi.org/10.1186/s13229-024-00618-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Task-based functional neural correlates of social cognition across autism and schizophrenia spectrum disorders / Lindsay D. OLIVER in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 37p. Titre : Task-based functional neural correlates of social cognition across autism and schizophrenia spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Lindsay D. OLIVER, Auteur ; Iska MOXON-EMRE, Auteur ; Colin HAWCO, Auteur ; Erin W. DICKIE, Auteur ; Arla DAKLI, Auteur ; Rachael E. LYON, Auteur ; Peter SZATMARI, Auteur ; John D. HALTIGAN, Auteur ; Anna GOLDENBERG, Auteur ; Ayesha G. RASHIDI, Auteur ; Vinh TAN, Auteur ; Maria T. SECARA, Auteur ; Pushpal DESARKAR, Auteur ; George FOUSSIAS, Auteur ; Robert W. BUCHANAN, Auteur ; Anil K. MALHOTRA, Auteur ; Meng-Chuan LAI, Auteur ; Aristotle N VOINESKOS, Auteur ; Stephanie H. AMEIS, Auteur Article en page(s) : 37p. Langues : Anglais (eng) Mots-clés : Humans  Social Cognition  Male  Female  Adult  Magnetic Resonance Imaging  Adolescent  Young Adult  Brain/diagnostic imaging/physiopathology  Schizophrenia/physiopathology/diagnostic imaging  Autism Spectrum Disorder/physiopathology/diagnostic imaging/psychology  Autistic Disorder/physiopathology/psychology  Brain Mapping  Case-Control Studies  Autism  Schizophrenia spectrum disorders  Social cognition  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism and schizophrenia spectrum disorders (SSDs) both feature atypical social cognition. Despite evidence for comparable group-level performance in lower-level emotion processing and higher-level mentalizing, limited research has examined the neural basis of social cognition across these conditions. Our goal was to compare the neural correlates of social cognition in autism, SSDs, and typically developing controls (TDCs). METHODS: Data came from two harmonized studies in individuals diagnosed with autism or SSDs and TDCs (aged 16-35 years), including behavioral social cognitive metrics and two functional magnetic resonance imaging (fMRI) tasks: a social mirroring Imitate/Observe (ImObs) task and the Empathic Accuracy (EA) task. Group-level comparisons, and transdiagnostic analyses incorporating social cognitive performance, were run using FSL's PALM for each task, covarying for age and sex (1000 permutations, thresholded at p < 0.05 FWE-corrected). Exploratory region of interest (ROI)-based analyses were also conducted. RESULTS: ImObs and EA analyses included 164 and 174 participants, respectively (autism N = 56/59, SSD N = 50/56, TDC N = 58/59). EA and both lower- and higher-level social cognition scores differed across groups. While canonical social cognitive networks were activated, no significant whole-brain or ROI-based group-level differences in neural correlates for either task were detected. Transdiagnostically, neural activity during the EA task, but not the ImObs task, was associated with lower- and higher-level social cognitive performance. LIMITATIONS: Despite attempting to match our groups on age, sex, and race, significant group differences remained. Power to detect regional brain differences is also influenced by sample size and multiple comparisons in whole-brain analyses. Our findings may not generalize to autism and SSD individuals with co-occurring intellectual disabilities. CONCLUSIONS: The lack of whole-brain and ROI-based group-level differences identified and the dimensional EA brain-behavior relationship observed across our sample suggest that the EA task may be well-suited to target engagement in novel intervention testing. Our results also emphasize the potential utility of cross-condition approaches to better understand social cognition across autism and SSDs. En ligne : https://dx.doi.org/10.1186/s13229-024-00615-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Task-based functional neural correlates of social cognition across autism and schizophrenia spectrum disorders [Texte imprimé et/ou numérique] / Lindsay D. OLIVER, Auteur ; Iska MOXON-EMRE, Auteur ; Colin HAWCO, Auteur ; Erin W. DICKIE, Auteur ; Arla DAKLI, Auteur ; Rachael E. LYON, Auteur ; Peter SZATMARI, Auteur ; John D. HALTIGAN, Auteur ; Anna GOLDENBERG, Auteur ; Ayesha G. RASHIDI, Auteur ; Vinh TAN, Auteur ; Maria T. SECARA, Auteur ; Pushpal DESARKAR, Auteur ; George FOUSSIAS, Auteur ; Robert W. BUCHANAN, Auteur ; Anil K. MALHOTRA, Auteur ; Meng-Chuan LAI, Auteur ; Aristotle N VOINESKOS, Auteur ; Stephanie H. AMEIS, Auteur . - 37p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 37p. Mots-clés : Humans  Social Cognition  Male  Female  Adult  Magnetic Resonance Imaging  Adolescent  Young Adult  Brain/diagnostic imaging/physiopathology  Schizophrenia/physiopathology/diagnostic imaging  Autism Spectrum Disorder/physiopathology/diagnostic imaging/psychology  Autistic Disorder/physiopathology/psychology  Brain Mapping  Case-Control Studies  Autism  Schizophrenia spectrum disorders  Social cognition  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism and schizophrenia spectrum disorders (SSDs) both feature atypical social cognition. Despite evidence for comparable group-level performance in lower-level emotion processing and higher-level mentalizing, limited research has examined the neural basis of social cognition across these conditions. Our goal was to compare the neural correlates of social cognition in autism, SSDs, and typically developing controls (TDCs). METHODS: Data came from two harmonized studies in individuals diagnosed with autism or SSDs and TDCs (aged 16-35 years), including behavioral social cognitive metrics and two functional magnetic resonance imaging (fMRI) tasks: a social mirroring Imitate/Observe (ImObs) task and the Empathic Accuracy (EA) task. Group-level comparisons, and transdiagnostic analyses incorporating social cognitive performance, were run using FSL's PALM for each task, covarying for age and sex (1000 permutations, thresholded at p < 0.05 FWE-corrected). Exploratory region of interest (ROI)-based analyses were also conducted. RESULTS: ImObs and EA analyses included 164 and 174 participants, respectively (autism N = 56/59, SSD N = 50/56, TDC N = 58/59). EA and both lower- and higher-level social cognition scores differed across groups. While canonical social cognitive networks were activated, no significant whole-brain or ROI-based group-level differences in neural correlates for either task were detected. Transdiagnostically, neural activity during the EA task, but not the ImObs task, was associated with lower- and higher-level social cognitive performance. LIMITATIONS: Despite attempting to match our groups on age, sex, and race, significant group differences remained. Power to detect regional brain differences is also influenced by sample size and multiple comparisons in whole-brain analyses. Our findings may not generalize to autism and SSD individuals with co-occurring intellectual disabilities. CONCLUSIONS: The lack of whole-brain and ROI-based group-level differences identified and the dimensional EA brain-behavior relationship observed across our sample suggest that the EA task may be well-suited to target engagement in novel intervention testing. Our results also emphasize the potential utility of cross-condition approaches to better understand social cognition across autism and SSDs. En ligne : https://dx.doi.org/10.1186/s13229-024-00615-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Contracted functional connectivity profiles in autism / Clara F. WEBER in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 38p. Titre : Contracted functional connectivity profiles in autism Type de document : Texte imprimé et/ou numérique Auteurs : Clara F. WEBER, Auteur ; Valeria KEBETS, Auteur ; Oualid BENKARIM, Auteur ; Sara LARIVIERE, Auteur ; Yezhou WANG, Auteur ; Alexander NGO, Auteur ; Hongxiu JIANG, Auteur ; Xiaoqian CHAI, Auteur ; Bo-Yong PARK, Auteur ; Michael P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur ; Sofie VALK, Auteur ; Seok-Jun HONG, Auteur ; Boris C. BERNHARDT, Auteur Article en page(s) : 38p. Langues : Anglais (eng) Mots-clés : Humans  Male  Connectome  Young Adult  Adult  Magnetic Resonance Imaging  Adolescent  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Autistic Disorder/physiopathology/diagnostic imaging  Brain/diagnostic imaging/physiopathology  Case-Control Studies  Child  Nerve Net/diagnostic imaging/physiopathology  Neural Pathways/physiopathology/diagnostic imaging  Autism spectrum disorder  Connectivity disruptions  Distance profiling  Functional connectivity  Magnetic resonance imaging  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition that is associated with atypical brain network organization, with prior work suggesting differential connectivity alterations with respect to functional connection length. Here, we tested whether functional connectopathy in ASD specifically relates to disruptions in long- relative to short-range functional connections. Our approach combined functional connectomics with geodesic distance mapping, and we studied associations to macroscale networks, microarchitectural patterns, as well as socio-demographic and clinical phenotypes. METHODS: We studied 211 males from three sites of the ABIDE-I dataset comprising 103 participants with an ASD diagnosis (mean?+?SD age = 20.8?+?8.1 years) and 108 neurotypical controls (NT, 19.2?+?7.2 years). For each participant, we computed cortex-wide connectivity distance (CD) measures by combining geodesic distance mapping with resting-state functional connectivity profiling. We compared CD between ASD and NT participants using surface-based linear models, and studied associations with age, symptom severity, and intelligence scores. We contextualized CD alterations relative to canonical networks and explored spatial associations with functional and microstructural cortical gradients as well as cytoarchitectonic cortical types. RESULTS: Compared to NT, ASD participants presented with widespread reductions in CD, generally indicating shorter average connection length and thus suggesting reduced long-range connectivity but increased short-range connections. Peak reductions were localized in transmodal systems (i.e., heteromodal and paralimbic regions in the prefrontal, temporal, and parietal and temporo-parieto-occipital cortex), and effect sizes correlated with the sensory-transmodal gradient of brain function. ASD-related CD reductions appeared consistent across inter-individual differences in age and symptom severity, and we observed a positive correlation of CD to IQ scores. LIMITATIONS: Despite rigorous harmonization across the three different acquisition sites, heterogeneity in autism poses a potential limitation to the generalizability of our results. Additionally, we focussed male participants, warranting future studies in more balanced cohorts. CONCLUSIONS: Our study showed reductions in CD as a relatively stable imaging phenotype of ASD that preferentially impacted paralimbic and heteromodal association systems. CD reductions in ASD corroborate previous reports of ASD-related imbalance between short-range overconnectivity and long-range underconnectivity. En ligne : https://dx.doi.org/10.1186/s13229-024-00616-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Contracted functional connectivity profiles in autism [Texte imprimé et/ou numérique] / Clara F. WEBER, Auteur ; Valeria KEBETS, Auteur ; Oualid BENKARIM, Auteur ; Sara LARIVIERE, Auteur ; Yezhou WANG, Auteur ; Alexander NGO, Auteur ; Hongxiu JIANG, Auteur ; Xiaoqian CHAI, Auteur ; Bo-Yong PARK, Auteur ; Michael P. MILHAM, Auteur ; Adriana DI MARTINO, Auteur ; Sofie VALK, Auteur ; Seok-Jun HONG, Auteur ; Boris C. BERNHARDT, Auteur . - 38p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 38p. Mots-clés : Humans  Male  Connectome  Young Adult  Adult  Magnetic Resonance Imaging  Adolescent  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Autistic Disorder/physiopathology/diagnostic imaging  Brain/diagnostic imaging/physiopathology  Case-Control Studies  Child  Nerve Net/diagnostic imaging/physiopathology  Neural Pathways/physiopathology/diagnostic imaging  Autism spectrum disorder  Connectivity disruptions  Distance profiling  Functional connectivity  Magnetic resonance imaging  Neurodevelopmental disorders Index. décimale : PER Périodiques Résumé : OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition that is associated with atypical brain network organization, with prior work suggesting differential connectivity alterations with respect to functional connection length. Here, we tested whether functional connectopathy in ASD specifically relates to disruptions in long- relative to short-range functional connections. Our approach combined functional connectomics with geodesic distance mapping, and we studied associations to macroscale networks, microarchitectural patterns, as well as socio-demographic and clinical phenotypes. METHODS: We studied 211 males from three sites of the ABIDE-I dataset comprising 103 participants with an ASD diagnosis (mean?+?SD age = 20.8?+?8.1 years) and 108 neurotypical controls (NT, 19.2?+?7.2 years). For each participant, we computed cortex-wide connectivity distance (CD) measures by combining geodesic distance mapping with resting-state functional connectivity profiling. We compared CD between ASD and NT participants using surface-based linear models, and studied associations with age, symptom severity, and intelligence scores. We contextualized CD alterations relative to canonical networks and explored spatial associations with functional and microstructural cortical gradients as well as cytoarchitectonic cortical types. RESULTS: Compared to NT, ASD participants presented with widespread reductions in CD, generally indicating shorter average connection length and thus suggesting reduced long-range connectivity but increased short-range connections. Peak reductions were localized in transmodal systems (i.e., heteromodal and paralimbic regions in the prefrontal, temporal, and parietal and temporo-parieto-occipital cortex), and effect sizes correlated with the sensory-transmodal gradient of brain function. ASD-related CD reductions appeared consistent across inter-individual differences in age and symptom severity, and we observed a positive correlation of CD to IQ scores. LIMITATIONS: Despite rigorous harmonization across the three different acquisition sites, heterogeneity in autism poses a potential limitation to the generalizability of our results. Additionally, we focussed male participants, warranting future studies in more balanced cohorts. CONCLUSIONS: Our study showed reductions in CD as a relatively stable imaging phenotype of ASD that preferentially impacted paralimbic and heteromodal association systems. CD reductions in ASD corroborate previous reports of ASD-related imbalance between short-range overconnectivity and long-range underconnectivity. En ligne : https://dx.doi.org/10.1186/s13229-024-00616-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Pharmacological inhibition of the CB1 cannabinoid receptor restores abnormal brain mitochondrial CB1 receptor expression and rescues bioenergetic and cognitive defects in a female mouse model of Rett syndrome / Livia COSENTINO in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 39p. Titre : Pharmacological inhibition of the CB1 cannabinoid receptor restores abnormal brain mitochondrial CB1 receptor expression and rescues bioenergetic and cognitive defects in a female mouse model of Rett syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Livia COSENTINO, Auteur ; Chiara URBINATI, Auteur ; Chiara LANZILLOTTA, Auteur ; Domenico DE RASMO, Auteur ; Daniela VALENTI, Auteur ; Mattia PELLAS, Auteur ; Maria Cristina QUATTRINI, Auteur ; Fabiana PISCITELLI, Auteur ; Magdalena KOSTRZEWA, Auteur ; Fabio DI DOMENICO, Auteur ; Donatella PIETRAFORTE, Auteur ; Tiziana BISOGNO, Auteur ; Anna SIGNORILE, Auteur ; Rosa Anna VACCA, Auteur ; Bianca DE FILIPPIS, Auteur Article en page(s) : 39p. Langues : Anglais (eng) Mots-clés : Animals  Female  Mice  Brain/metabolism/drug effects  Disease Models, Animal  Energy Metabolism/drug effects  Methyl-CpG-Binding Protein 2/metabolism/genetics  Mitochondria/metabolism/drug effects  Receptor, Cannabinoid, CB1/metabolism/genetics/antagonists & inhibitors  Rett Syndrome/metabolism/drug therapy/genetics  Rimonabant/pharmacology  Brain mitochondria  CB1 cannabinoid receptor  Energy metabolism  Intellectual disability  Mouse model  Pka  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Defective mitochondria and aberrant brain mitochondrial bioenergetics are consistent features in syndromic intellectual disability disorders, such as Rett syndrome (RTT), a rare neurologic disorder that severely affects mainly females carrying mutations in the X-linked MECP2 gene. A pool of CB1 cannabinoid receptors (CB1R), the primary receptor subtype of the endocannabinoid system in the brain, is located on brain mitochondrial membranes (mtCB1R), where it can locally regulate energy production, synaptic transmission and memory abilities through the inhibition of the intra-mitochondrial protein kinase A (mtPKA). In the present study, we asked whether an overactive mtCB1R-mtPKA signaling might underlie the brain mitochondrial alterations in RTT and whether its modulation by systemic administration of the CB1R inverse agonist rimonabant might improve bioenergetics and cognitive defects in mice modeling RTT. METHODS: Rimonabant (0.3 mg/kg/day, intraperitoneal injections) was administered daily to symptomatic female mice carrying a truncating mutation of the Mecp2 gene and its effects on brain mitochondria functionality, systemic oxidative status, and memory function were assessed. RESULTS: mtCB1R is overexpressed in the RTT mouse brain. Subchronic treatment with rimonabant normalizes mtCB1R expression in RTT mouse brains, boosts mtPKA signaling, and restores the defective brain mitochondrial bioenergetics, abnormal peripheral redox homeostasis, and impaired cognitive abilities in RTT mice. LIMITATIONS: The lack of selectivity of the rimonabant treatment towards mtCB1R does not allow us to exclude that the beneficial effects exerted by the treatment in the RTT mouse model may be ascribed more broadly to the modulation of CB1R activity and distribution among intracellular compartments, rather than to a selective effect on mtCB1R-mediated signaling. The low sample size of few experiments is a further limitation that has been addressed replicating the main findings under different experimental conditions. CONCLUSIONS: The present data identify mtCB1R overexpression as a novel molecular alteration in the RTT mouse brain that may underlie defective brain mitochondrial bioenergetics and cognitive dysfunction. En ligne : https://dx.doi.org/10.1186/s13229-024-00617-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Pharmacological inhibition of the CB1 cannabinoid receptor restores abnormal brain mitochondrial CB1 receptor expression and rescues bioenergetic and cognitive defects in a female mouse model of Rett syndrome [Texte imprimé et/ou numérique] / Livia COSENTINO, Auteur ; Chiara URBINATI, Auteur ; Chiara LANZILLOTTA, Auteur ; Domenico DE RASMO, Auteur ; Daniela VALENTI, Auteur ; Mattia PELLAS, Auteur ; Maria Cristina QUATTRINI, Auteur ; Fabiana PISCITELLI, Auteur ; Magdalena KOSTRZEWA, Auteur ; Fabio DI DOMENICO, Auteur ; Donatella PIETRAFORTE, Auteur ; Tiziana BISOGNO, Auteur ; Anna SIGNORILE, Auteur ; Rosa Anna VACCA, Auteur ; Bianca DE FILIPPIS, Auteur . - 39p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 39p. Mots-clés : Animals  Female  Mice  Brain/metabolism/drug effects  Disease Models, Animal  Energy Metabolism/drug effects  Methyl-CpG-Binding Protein 2/metabolism/genetics  Mitochondria/metabolism/drug effects  Receptor, Cannabinoid, CB1/metabolism/genetics/antagonists & inhibitors  Rett Syndrome/metabolism/drug therapy/genetics  Rimonabant/pharmacology  Brain mitochondria  CB1 cannabinoid receptor  Energy metabolism  Intellectual disability  Mouse model  Pka  Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Defective mitochondria and aberrant brain mitochondrial bioenergetics are consistent features in syndromic intellectual disability disorders, such as Rett syndrome (RTT), a rare neurologic disorder that severely affects mainly females carrying mutations in the X-linked MECP2 gene. A pool of CB1 cannabinoid receptors (CB1R), the primary receptor subtype of the endocannabinoid system in the brain, is located on brain mitochondrial membranes (mtCB1R), where it can locally regulate energy production, synaptic transmission and memory abilities through the inhibition of the intra-mitochondrial protein kinase A (mtPKA). In the present study, we asked whether an overactive mtCB1R-mtPKA signaling might underlie the brain mitochondrial alterations in RTT and whether its modulation by systemic administration of the CB1R inverse agonist rimonabant might improve bioenergetics and cognitive defects in mice modeling RTT. METHODS: Rimonabant (0.3 mg/kg/day, intraperitoneal injections) was administered daily to symptomatic female mice carrying a truncating mutation of the Mecp2 gene and its effects on brain mitochondria functionality, systemic oxidative status, and memory function were assessed. RESULTS: mtCB1R is overexpressed in the RTT mouse brain. Subchronic treatment with rimonabant normalizes mtCB1R expression in RTT mouse brains, boosts mtPKA signaling, and restores the defective brain mitochondrial bioenergetics, abnormal peripheral redox homeostasis, and impaired cognitive abilities in RTT mice. LIMITATIONS: The lack of selectivity of the rimonabant treatment towards mtCB1R does not allow us to exclude that the beneficial effects exerted by the treatment in the RTT mouse model may be ascribed more broadly to the modulation of CB1R activity and distribution among intracellular compartments, rather than to a selective effect on mtCB1R-mediated signaling. The low sample size of few experiments is a further limitation that has been addressed replicating the main findings under different experimental conditions. CONCLUSIONS: The present data identify mtCB1R overexpression as a novel molecular alteration in the RTT mouse brain that may underlie defective brain mitochondrial bioenergetics and cognitive dysfunction. En ligne : https://dx.doi.org/10.1186/s13229-024-00617-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

A 3D approach to understanding heterogeneity in early developing autisms / Veronica MANDELLI in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 41p. Titre : A 3D approach to understanding heterogeneity in early developing autisms Type de document : Texte imprimé et/ou numérique Auteurs : Veronica MANDELLI, Auteur ; Ines SEVERINO, Auteur ; Lisa EYLER, Auteur ; Karen PIERCE, Auteur ; Eric COURCHESNE, Auteur ; Michael V. LOMBARDO, Auteur Article en page(s) : 41p. Langues : Anglais (eng) Mots-clés : Humans  Child, Preschool  Autistic Disorder/diagnostic imaging/diagnosis  Female  Male  Child  Phenotype  Imaging, Three-Dimensional  Clustering  Gene expression  Stratification  Subtypes  fMRI  for the Collection in this journal entitled 'Neuroimaging in Autism Spectrum  Disorders'. All other authors have no competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phenotypic heterogeneity in early language, intellectual, motor, and adaptive functioning (LIMA) features are amongst the most striking features that distinguish different types of autistic individuals. Yet the current diagnostic criteria uses a single label of autism and implicitly emphasizes what individuals have in common as core social-communicative and restricted repetitive behavior difficulties. Subtype labels based on the non-core LIMA features may help to more meaningfully distinguish types of autisms with differing developmental paths and differential underlying biology. METHODS: Unsupervised data-driven subtypes were identified using stability-based relative clustering validation on publicly available Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS) data (n = 615; age = 24-68 months) from the National Institute of Mental Health Data Archive (NDA). Differential developmental trajectories between subtypes were tested on longitudinal data from NDA and from an independent in-house dataset from UCSD. A subset of the UCSD dataset was also tested for subtype differences in functional and structural neuroimaging phenotypes and relationships with blood gene expression. The current subtyping model was also compared to early language outcome subtypes derived from past work. RESULTS: Two autism subtypes can be identified based on early phenotypic LIMA features. These data-driven subtypes are robust in the population and can be identified in independent data with 98% accuracy. The subtypes can be described as Type I versus Type II autisms differentiated by relatively high versus low scores on LIMA features. These two types of autisms are also distinguished by different developmental trajectories over the first decade of life. Finally, these two types of autisms reveal striking differences in functional and structural neuroimaging phenotypes and their relationships with gene expression and may highlight unique biological mechanisms. LIMITATIONS: Sample sizes for the neuroimaging and gene expression dataset are relatively small and require further independent replication. The current work is also limited to subtyping based on MSEL and VABS phenotypic measures. CONCLUSIONS: This work emphasizes the potential importance of stratifying autism by a Type I versus Type II distinction focused on LIMA features and which may be of high prognostic and biological significance. En ligne : https://dx.doi.org/10.1186/s13229-024-00613-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] A 3D approach to understanding heterogeneity in early developing autisms [Texte imprimé et/ou numérique] / Veronica MANDELLI, Auteur ; Ines SEVERINO, Auteur ; Lisa EYLER, Auteur ; Karen PIERCE, Auteur ; Eric COURCHESNE, Auteur ; Michael V. LOMBARDO, Auteur . - 41p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 41p. Mots-clés : Humans  Child, Preschool  Autistic Disorder/diagnostic imaging/diagnosis  Female  Male  Child  Phenotype  Imaging, Three-Dimensional  Clustering  Gene expression  Stratification  Subtypes  fMRI  for the Collection in this journal entitled 'Neuroimaging in Autism Spectrum  Disorders'. All other authors have no competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phenotypic heterogeneity in early language, intellectual, motor, and adaptive functioning (LIMA) features are amongst the most striking features that distinguish different types of autistic individuals. Yet the current diagnostic criteria uses a single label of autism and implicitly emphasizes what individuals have in common as core social-communicative and restricted repetitive behavior difficulties. Subtype labels based on the non-core LIMA features may help to more meaningfully distinguish types of autisms with differing developmental paths and differential underlying biology. METHODS: Unsupervised data-driven subtypes were identified using stability-based relative clustering validation on publicly available Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS) data (n = 615; age = 24-68 months) from the National Institute of Mental Health Data Archive (NDA). Differential developmental trajectories between subtypes were tested on longitudinal data from NDA and from an independent in-house dataset from UCSD. A subset of the UCSD dataset was also tested for subtype differences in functional and structural neuroimaging phenotypes and relationships with blood gene expression. The current subtyping model was also compared to early language outcome subtypes derived from past work. RESULTS: Two autism subtypes can be identified based on early phenotypic LIMA features. These data-driven subtypes are robust in the population and can be identified in independent data with 98% accuracy. The subtypes can be described as Type I versus Type II autisms differentiated by relatively high versus low scores on LIMA features. These two types of autisms are also distinguished by different developmental trajectories over the first decade of life. Finally, these two types of autisms reveal striking differences in functional and structural neuroimaging phenotypes and their relationships with gene expression and may highlight unique biological mechanisms. LIMITATIONS: Sample sizes for the neuroimaging and gene expression dataset are relatively small and require further independent replication. The current work is also limited to subtyping based on MSEL and VABS phenotypic measures. CONCLUSIONS: This work emphasizes the potential importance of stratifying autism by a Type I versus Type II distinction focused on LIMA features and which may be of high prognostic and biological significance. En ligne : https://dx.doi.org/10.1186/s13229-024-00613-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling / Nicole C. SHAW in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 42p. Titre : Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling Type de document : Texte imprimé et/ou numérique Auteurs : Nicole C. SHAW, Auteur ; Kevin CHEN, Auteur ; Kathryn O. FARLEY, Auteur ; Mitchell HEDGES, Auteur ; Catherine FORBES, Auteur ; Gareth BAYNAM, Auteur ; Timo LASSMANN, Auteur ; Vanessa S. FEAR, Auteur Article en page(s) : 42p. Langues : Anglais (eng) Mots-clés : Induced Pluripotent Stem Cells/metabolism/cytology  Humans  Haploinsufficiency  Cell Differentiation  Carrier Proteins/genetics  Nuclear Proteins/genetics/metabolism  Mutation  GATA2 Transcription Factor/genetics/metabolism  Neurons/metabolism  Neural Stem Cells/metabolism  Wnt Signaling Pathway/genetics  Intellectual Disability/genetics  Phenotype  Crispr  Neural cell modelling  Neurodevelopmental disorders  SETBP1 haploinsufficiency disorder  Variants of unknown significance  iPSC Index. décimale : PER Périodiques Résumé : BACKGROUND: SETBP1 Haploinsufficiency Disorder (SETBP1-HD) is characterised by mild to moderate intellectual disability, speech and language impairment, mild motor developmental delay, behavioural issues, hypotonia, mild facial dysmorphisms, and vision impairment. Despite a clear link between SETBP1 mutations and neurodevelopmental disorders the precise role of SETBP1 in neural development remains elusive. We investigate the functional effects of three SETBP1 genetic variants including two pathogenic mutations p.Glu545Ter and SETBP1 p.Tyr1066Ter, resulting in removal of SKI and/or SET domains, and a point mutation p.Thr1387Met in the SET domain. METHODS: Genetic variants were introduced into induced pluripotent stem cells (iPSCs) and subsequently differentiated into neurons to model the disease. We measured changes in cellular differentiation, SETBP1 protein localisation, and gene expression changes. RESULTS: The data indicated a change in the WNT pathway, RNA polymerase II pathway and identified GATA2 as a central transcription factor in disease perturbation. In addition, the genetic variants altered the expression of gene sets related to neural forebrain development matching characteristics typical of the SETBP1-HD phenotype. LIMITATIONS: The study investigates changes in cellular function in differentiation of iPSC to neural progenitor cells as a human model of SETBP1 HD disorder. Future studies may provide additional information relevant to disease on further neural cell specification, to derive mature neurons, neural forebrain cells, or brain organoids. CONCLUSIONS: We developed a human SETBP1-HD model and identified perturbations to the WNT and POL2RA pathway, genes regulated by GATA2. Strikingly neural cells for both the SETBP1 truncation mutations and the single nucleotide variant displayed a SETBP1-HD-like phenotype. En ligne : https://dx.doi.org/10.1186/s13229-024-00625-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling [Texte imprimé et/ou numérique] / Nicole C. SHAW, Auteur ; Kevin CHEN, Auteur ; Kathryn O. FARLEY, Auteur ; Mitchell HEDGES, Auteur ; Catherine FORBES, Auteur ; Gareth BAYNAM, Auteur ; Timo LASSMANN, Auteur ; Vanessa S. FEAR, Auteur . - 42p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 42p. Mots-clés : Induced Pluripotent Stem Cells/metabolism/cytology  Humans  Haploinsufficiency  Cell Differentiation  Carrier Proteins/genetics  Nuclear Proteins/genetics/metabolism  Mutation  GATA2 Transcription Factor/genetics/metabolism  Neurons/metabolism  Neural Stem Cells/metabolism  Wnt Signaling Pathway/genetics  Intellectual Disability/genetics  Phenotype  Crispr  Neural cell modelling  Neurodevelopmental disorders  SETBP1 haploinsufficiency disorder  Variants of unknown significance  iPSC Index. décimale : PER Périodiques Résumé : BACKGROUND: SETBP1 Haploinsufficiency Disorder (SETBP1-HD) is characterised by mild to moderate intellectual disability, speech and language impairment, mild motor developmental delay, behavioural issues, hypotonia, mild facial dysmorphisms, and vision impairment. Despite a clear link between SETBP1 mutations and neurodevelopmental disorders the precise role of SETBP1 in neural development remains elusive. We investigate the functional effects of three SETBP1 genetic variants including two pathogenic mutations p.Glu545Ter and SETBP1 p.Tyr1066Ter, resulting in removal of SKI and/or SET domains, and a point mutation p.Thr1387Met in the SET domain. METHODS: Genetic variants were introduced into induced pluripotent stem cells (iPSCs) and subsequently differentiated into neurons to model the disease. We measured changes in cellular differentiation, SETBP1 protein localisation, and gene expression changes. RESULTS: The data indicated a change in the WNT pathway, RNA polymerase II pathway and identified GATA2 as a central transcription factor in disease perturbation. In addition, the genetic variants altered the expression of gene sets related to neural forebrain development matching characteristics typical of the SETBP1-HD phenotype. LIMITATIONS: The study investigates changes in cellular function in differentiation of iPSC to neural progenitor cells as a human model of SETBP1 HD disorder. Future studies may provide additional information relevant to disease on further neural cell specification, to derive mature neurons, neural forebrain cells, or brain organoids. CONCLUSIONS: We developed a human SETBP1-HD model and identified perturbations to the WNT and POL2RA pathway, genes regulated by GATA2. Strikingly neural cells for both the SETBP1 truncation mutations and the single nucleotide variant displayed a SETBP1-HD-like phenotype. En ligne : https://dx.doi.org/10.1186/s13229-024-00625-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Phenome-wide profiling identifies genotype-phenotype associations in Phelan-McDermid syndrome using family-sourced data from an international registry / Rui YIN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 40p. Titre : Phenome-wide profiling identifies genotype-phenotype associations in Phelan-McDermid syndrome using family-sourced data from an international registry Type de document : Texte imprimé et/ou numérique Auteurs : Rui YIN, Auteur ; Maxime WACK, Auteur ; Claire HASSEN-KHODJA, Auteur ; Michael T. MCDUFFIE, Auteur ; Geraldine BLISS, Auteur ; Elizabeth J. HORN, Auteur ; Cartik KOTHARI, Auteur ; Brittany MCLARNEY, Auteur ; Rebecca DAVIS, Auteur ; Kristen HANSON, Auteur ; Megan O'BOYLE, Auteur ; Catalina BETANCUR, Auteur ; Paul AVILLACH, Auteur Article en page(s) : 40p. Langues : Anglais (eng) Mots-clés : Humans  Registries  Chromosome Deletion  Chromosomes, Human, Pair 22/genetics  Male  Chromosome Disorders/genetics  Female  Phenotype  Genetic Association Studies  Child  Child, Preschool  Nerve Tissue Proteins/genetics  Adolescent  Adult  Young Adult  Family  Infant  Shank3  22q13.3 deletion  Phelan-McDermid syndrome  Phenome-wide association study  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by 22q13 deletions that include the SHANK3 gene or pathogenic sequence variants in SHANK3. It is characterized by global developmental delay, intellectual disability, speech impairment, autism spectrum disorder, and hypotonia; other variable features include epilepsy, brain and renal malformations, and mild dysmorphic features. Here, we conducted genotype-phenotype correlation analyses using the PMS International Registry, a family-driven registry that compiles clinical data in the form of family-reported outcomes and family-sourced genetic test results. METHODS: Data from the registry were harmonized and integrated into the i2b2/tranSMART clinical and genomics data warehouse. We gathered information from 401 individuals with 22q13 deletions including SHANK3 (n = 350, ranging in size from 10 kb to 9.1 Mb) or pathogenic or likely pathogenic SHANK3 sequence variants (n = 51), and used regression models with deletion size as a potential predictor of clinical outcomes for 328 phenotypes. RESULTS: Our results showed that increased deletion size was significantly associated with delay in gross and fine motor acquisitions, a spectrum of conditions related to poor muscle tone, renal malformations, mild dysmorphic features (e.g., large fleshy hands, sacral dimple, dysplastic toenails, supernumerary teeth), lymphedema, congenital heart defects, and more frequent neuroimaging abnormalities and infections. These findings indicate that genes upstream of SHANK3 also contribute to some of the manifestations of PMS in individuals with larger deletions. We also showed that self-help skills, verbal ability and a range of psychiatric diagnoses (e.g., autism, ADHD, anxiety disorder) were more common among individuals with smaller deletions and SHANK3 variants. LIMITATIONS: Some participants were tested with targeted 22q microarrays rather than genome-wide arrays, and karyotypes were unavailable in many cases, thus precluding the analysis of the effect of other copy number variants or chromosomal rearrangements on the phenotype. CONCLUSIONS: This is the largest reported case series of individuals with PMS. Overall, we demonstrate the feasibility of using data from a family-sourced registry to conduct genotype-phenotype analyses in rare genetic disorders. We replicate and strengthen previous findings, and reveal novel associations between larger 22q13 deletions and congenital heart defects, neuroimaging abnormalities and recurrent infections. En ligne : https://dx.doi.org/10.1186/s13229-024-00619-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Phenome-wide profiling identifies genotype-phenotype associations in Phelan-McDermid syndrome using family-sourced data from an international registry [Texte imprimé et/ou numérique] / Rui YIN, Auteur ; Maxime WACK, Auteur ; Claire HASSEN-KHODJA, Auteur ; Michael T. MCDUFFIE, Auteur ; Geraldine BLISS, Auteur ; Elizabeth J. HORN, Auteur ; Cartik KOTHARI, Auteur ; Brittany MCLARNEY, Auteur ; Rebecca DAVIS, Auteur ; Kristen HANSON, Auteur ; Megan O'BOYLE, Auteur ; Catalina BETANCUR, Auteur ; Paul AVILLACH, Auteur . - 40p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 40p. Mots-clés : Humans  Registries  Chromosome Deletion  Chromosomes, Human, Pair 22/genetics  Male  Chromosome Disorders/genetics  Female  Phenotype  Genetic Association Studies  Child  Child, Preschool  Nerve Tissue Proteins/genetics  Adolescent  Adult  Young Adult  Family  Infant  Shank3  22q13.3 deletion  Phelan-McDermid syndrome  Phenome-wide association study  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by 22q13 deletions that include the SHANK3 gene or pathogenic sequence variants in SHANK3. It is characterized by global developmental delay, intellectual disability, speech impairment, autism spectrum disorder, and hypotonia; other variable features include epilepsy, brain and renal malformations, and mild dysmorphic features. Here, we conducted genotype-phenotype correlation analyses using the PMS International Registry, a family-driven registry that compiles clinical data in the form of family-reported outcomes and family-sourced genetic test results. METHODS: Data from the registry were harmonized and integrated into the i2b2/tranSMART clinical and genomics data warehouse. We gathered information from 401 individuals with 22q13 deletions including SHANK3 (n = 350, ranging in size from 10 kb to 9.1 Mb) or pathogenic or likely pathogenic SHANK3 sequence variants (n = 51), and used regression models with deletion size as a potential predictor of clinical outcomes for 328 phenotypes. RESULTS: Our results showed that increased deletion size was significantly associated with delay in gross and fine motor acquisitions, a spectrum of conditions related to poor muscle tone, renal malformations, mild dysmorphic features (e.g., large fleshy hands, sacral dimple, dysplastic toenails, supernumerary teeth), lymphedema, congenital heart defects, and more frequent neuroimaging abnormalities and infections. These findings indicate that genes upstream of SHANK3 also contribute to some of the manifestations of PMS in individuals with larger deletions. We also showed that self-help skills, verbal ability and a range of psychiatric diagnoses (e.g., autism, ADHD, anxiety disorder) were more common among individuals with smaller deletions and SHANK3 variants. LIMITATIONS: Some participants were tested with targeted 22q microarrays rather than genome-wide arrays, and karyotypes were unavailable in many cases, thus precluding the analysis of the effect of other copy number variants or chromosomal rearrangements on the phenotype. CONCLUSIONS: This is the largest reported case series of individuals with PMS. Overall, we demonstrate the feasibility of using data from a family-sourced registry to conduct genotype-phenotype analyses in rare genetic disorders. We replicate and strengthen previous findings, and reveal novel associations between larger 22q13 deletions and congenital heart defects, neuroimaging abnormalities and recurrent infections. En ligne : https://dx.doi.org/10.1186/s13229-024-00619-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Structure-function coupling in white matter uncovers the hypoconnectivity in autism spectrum disorder / Peng QING in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 43p. Titre : Structure-function coupling in white matter uncovers the hypoconnectivity in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Peng QING, Auteur ; Xiaodong ZHANG, Auteur ; Qi LIU, Auteur ; Linghong HUANG, Auteur ; Dan XU, Auteur ; Jiao LE, Auteur ; Keith M. KENDRICK, Auteur ; Hua LAI, Auteur ; Weihua ZHAO, Auteur Article en page(s) : 43p. Langues : Anglais (eng) Mots-clés : Humans  White Matter/diagnostic imaging/pathology/physiopathology  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Male  Female  Diffusion Tensor Imaging  Adolescent  Child  Adult  Young Adult  Structure-Activity Relationship  Magnetic Resonance Imaging  Autism spectrum disorder  Diffusion tensor  Functional connectivity tensor  Structure-function coupling  White matter tracts Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder associated with alterations in structural and functional coupling in gray matter. However, despite the detectability and modulation of brain signals in white matter, the structure-function coupling in white matter in autism remains less explored. METHODS: In this study, we investigated structural-functional coupling in white matter (WM) regions, by integrating diffusion tensor data that contain fiber orientation information from WM tracts, with functional connectivity tensor data that reflect local functional anisotropy information. Using functional and diffusion magnetic resonance images, we analyzed a cohort of 89 ASD and 63 typically developing (TD) individuals from the Autism Brain Imaging Data Exchange II (ABIDE-II). Subsequently, the associations between structural-functional coupling in WM regions and ASD severity symptoms assessed by Autism Diagnostic Observation Schedule-2 were examined via supervised machine learning in an independent test cohort of 29 ASD individuals. Furthermore, we also compared the performance of multi-model features (i.e. structural-functional coupling) with single-model features (i.e. functional or structural models alone). RESULTS: In the discovery cohort (ABIDE-II), individuals with ASD exhibited widespread reductions in structural-functional coupling in WM regions compared to TD individuals, particularly in commissural tracts (e.g. corpus callosum), association tracts (sagittal stratum), and projection tracts (e.g. internal capsule). Notably, supervised machine learning analysis in the independent test cohort revealed a significant correlation between these alterations in structural-functional coupling and ASD severity scores. Furthermore, compared to single-model features, the integration of multi-model features (i.e., structural-functional coupling) performed best in predicting ASD severity scores. CONCLUSION: This work provides novel evidence for atypical structural-functional coupling in ASD in white matter regions, further refining our understanding of the critical role of WM networks in the pathophysiology of ASD. En ligne : https://dx.doi.org/10.1186/s13229-024-00620-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Structure-function coupling in white matter uncovers the hypoconnectivity in autism spectrum disorder [Texte imprimé et/ou numérique] / Peng QING, Auteur ; Xiaodong ZHANG, Auteur ; Qi LIU, Auteur ; Linghong HUANG, Auteur ; Dan XU, Auteur ; Jiao LE, Auteur ; Keith M. KENDRICK, Auteur ; Hua LAI, Auteur ; Weihua ZHAO, Auteur . - 43p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 43p. Mots-clés : Humans  White Matter/diagnostic imaging/pathology/physiopathology  Autism Spectrum Disorder/physiopathology/diagnostic imaging  Male  Female  Diffusion Tensor Imaging  Adolescent  Child  Adult  Young Adult  Structure-Activity Relationship  Magnetic Resonance Imaging  Autism spectrum disorder  Diffusion tensor  Functional connectivity tensor  Structure-function coupling  White matter tracts Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder associated with alterations in structural and functional coupling in gray matter. However, despite the detectability and modulation of brain signals in white matter, the structure-function coupling in white matter in autism remains less explored. METHODS: In this study, we investigated structural-functional coupling in white matter (WM) regions, by integrating diffusion tensor data that contain fiber orientation information from WM tracts, with functional connectivity tensor data that reflect local functional anisotropy information. Using functional and diffusion magnetic resonance images, we analyzed a cohort of 89 ASD and 63 typically developing (TD) individuals from the Autism Brain Imaging Data Exchange II (ABIDE-II). Subsequently, the associations between structural-functional coupling in WM regions and ASD severity symptoms assessed by Autism Diagnostic Observation Schedule-2 were examined via supervised machine learning in an independent test cohort of 29 ASD individuals. Furthermore, we also compared the performance of multi-model features (i.e. structural-functional coupling) with single-model features (i.e. functional or structural models alone). RESULTS: In the discovery cohort (ABIDE-II), individuals with ASD exhibited widespread reductions in structural-functional coupling in WM regions compared to TD individuals, particularly in commissural tracts (e.g. corpus callosum), association tracts (sagittal stratum), and projection tracts (e.g. internal capsule). Notably, supervised machine learning analysis in the independent test cohort revealed a significant correlation between these alterations in structural-functional coupling and ASD severity scores. Furthermore, compared to single-model features, the integration of multi-model features (i.e., structural-functional coupling) performed best in predicting ASD severity scores. CONCLUSION: This work provides novel evidence for atypical structural-functional coupling in ASD in white matter regions, further refining our understanding of the critical role of WM networks in the pathophysiology of ASD. En ligne : https://dx.doi.org/10.1186/s13229-024-00620-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Superior temporal sulcus folding, functional network connectivity, and autistic-like traits in a non-clinical population / Igor NENADI? in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 44p. Titre : Superior temporal sulcus folding, functional network connectivity, and autistic-like traits in a non-clinical population Type de document : Texte imprimé et/ou numérique Auteurs : Igor NENADI?, Auteur ; Yvonne SCHRÖDER, Auteur ; Jonas HOFFMANN, Auteur ; Ulrika EVERMANN, Auteur ; Julia-Katharina PFARR, Auteur ; Aliénor BERGMANN, Auteur ; Daniela Michelle HOHMANN, Auteur ; Boris KEIL, Auteur ; Ahmad ABU-AKEL, Auteur ; Sanna STROTH, Auteur ; Inge KAMP-BECKER, Auteur ; Andreas JANSEN, Auteur ; Sarah GREZELLSCHAK, Auteur ; Tina MELLER, Auteur Article en page(s) : 44p. Langues : Anglais (eng) Mots-clés : Humans  Male  Female  Adult  Temporal Lobe/diagnostic imaging  Magnetic Resonance Imaging  Young Adult  Autistic Disorder/diagnostic imaging/physiopathology  Adolescent  Middle Aged  Nerve Net/diagnostic imaging  Autism Spectrum Disorder/diagnostic imaging/physiopathology  Brain Mapping/methods  Phenotype  Autism quotient (AQ)  Autism spectrum disorder (ASD)  Cortical surface complexity  Interpersonal  Subclinical Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic-like traits (ALT) are prevalent across the general population and might be linked to some facets of a broader autism spectrum disorder (ASD) phenotype. Recent studies suggest an association of these traits with both genetic and brain structural markers in non-autistic individuals, showing similar spatial location of findings observed in ASD and thus suggesting a potential neurobiological continuum. METHODS: In this study, we first tested an association of ALTs (assessed with the AQ questionnaire) with cortical complexity, a cortical surface marker of early neurodevelopment, and then the association with disrupted functional connectivity. We analysed structural T1-weighted and resting-state functional MRI scans in 250 psychiatrically healthy individuals without a history of early developmental disorders, in a first step using the CAT12 toolbox for cortical complexity analysis and in a second step we used regional cortical complexity findings to apply the CONN toolbox for seed-based functional connectivity analysis. RESULTS: Our findings show a significant negative correlation of both AQ total and AQ attention switching subscores with left superior temporal sulcus (STS) cortical folding complexity, with the former being significantly correlated with STS to left lateral occipital cortex connectivity, while the latter showed significant positive correlation of STS to left inferior/middle frontal gyrus connectivity (n = 233; all p < 0.05, FWE cluster-level corrected). Additional analyses also revealed a significant correlation of AQ attention to detail subscores with STS to left lateral occipital cortex connectivity. LIMITATIONS: Phenotyping might affect association results (e.g. choice of inventories); in addition, our study was limited to subclinical expressions of autistic-like traits. CONCLUSIONS: Our findings provide further evidence for biological correlates of ALT even in the absence of clinical ASD, while establishing a link between structural variation of early developmental origin and functional connectivity. En ligne : https://dx.doi.org/10.1186/s13229-024-00623-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Superior temporal sulcus folding, functional network connectivity, and autistic-like traits in a non-clinical population [Texte imprimé et/ou numérique] / Igor NENADI?, Auteur ; Yvonne SCHRÖDER, Auteur ; Jonas HOFFMANN, Auteur ; Ulrika EVERMANN, Auteur ; Julia-Katharina PFARR, Auteur ; Aliénor BERGMANN, Auteur ; Daniela Michelle HOHMANN, Auteur ; Boris KEIL, Auteur ; Ahmad ABU-AKEL, Auteur ; Sanna STROTH, Auteur ; Inge KAMP-BECKER, Auteur ; Andreas JANSEN, Auteur ; Sarah GREZELLSCHAK, Auteur ; Tina MELLER, Auteur . - 44p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 44p. Mots-clés : Humans  Male  Female  Adult  Temporal Lobe/diagnostic imaging  Magnetic Resonance Imaging  Young Adult  Autistic Disorder/diagnostic imaging/physiopathology  Adolescent  Middle Aged  Nerve Net/diagnostic imaging  Autism Spectrum Disorder/diagnostic imaging/physiopathology  Brain Mapping/methods  Phenotype  Autism quotient (AQ)  Autism spectrum disorder (ASD)  Cortical surface complexity  Interpersonal  Subclinical Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic-like traits (ALT) are prevalent across the general population and might be linked to some facets of a broader autism spectrum disorder (ASD) phenotype. Recent studies suggest an association of these traits with both genetic and brain structural markers in non-autistic individuals, showing similar spatial location of findings observed in ASD and thus suggesting a potential neurobiological continuum. METHODS: In this study, we first tested an association of ALTs (assessed with the AQ questionnaire) with cortical complexity, a cortical surface marker of early neurodevelopment, and then the association with disrupted functional connectivity. We analysed structural T1-weighted and resting-state functional MRI scans in 250 psychiatrically healthy individuals without a history of early developmental disorders, in a first step using the CAT12 toolbox for cortical complexity analysis and in a second step we used regional cortical complexity findings to apply the CONN toolbox for seed-based functional connectivity analysis. RESULTS: Our findings show a significant negative correlation of both AQ total and AQ attention switching subscores with left superior temporal sulcus (STS) cortical folding complexity, with the former being significantly correlated with STS to left lateral occipital cortex connectivity, while the latter showed significant positive correlation of STS to left inferior/middle frontal gyrus connectivity (n = 233; all p < 0.05, FWE cluster-level corrected). Additional analyses also revealed a significant correlation of AQ attention to detail subscores with STS to left lateral occipital cortex connectivity. LIMITATIONS: Phenotyping might affect association results (e.g. choice of inventories); in addition, our study was limited to subclinical expressions of autistic-like traits. CONCLUSIONS: Our findings provide further evidence for biological correlates of ALT even in the absence of clinical ASD, while establishing a link between structural variation of early developmental origin and functional connectivity. En ligne : https://dx.doi.org/10.1186/s13229-024-00623-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Characterizing genetic pathways unique to autism spectrum disorder at multiple levels of biological analysis / Lukas S. SCHAFFER in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 46p. Titre : Characterizing genetic pathways unique to autism spectrum disorder at multiple levels of biological analysis Type de document : Texte imprimé et/ou numérique Auteurs : Lukas S. SCHAFFER, Auteur ; Sophie BREUNIG, Auteur ; Jeremy M. LAWRENCE, Auteur ; Isabelle F FOOTE, Auteur ; Andrew D. GROTZINGER, Auteur Article en page(s) : 46p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics  Genome-Wide Association Study  Genetic Predisposition to Disease  Attention Deficit Disorder with Hyperactivity/genetics  Phenotype  Transcriptome  Male  Female  Child  Polymorphism, Single Nucleotide  Latent Class Analysis  Attention-deficit/hyperactivity disorder  Autism spectrum disorder  Comorbidity  Genomic SEM  Multivariate genomics  Neurodevelopmental disorders  Psychiatric genetics Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by atypical patterns of social functioning and repetitive/restricted behaviors. ASD commonly co-occurs with ADHD and, despite their clinical distinctiveness, the two share considerable genetic overlap. Given their shared genetic liability, it is unclear which genetic pathways increase the likelihood of ASD independently of ADHD. METHODS: We applied Genomic Structural Equation Modeling (SEM) to GWAS summary statistics for ASD and childhood-diagnosed ADHD, decomposing the genetic variance for ASD into that which is unique to ASD (uASD) and that which is shared with ADHD. We computed genetic correlations between uASD and 83 external traits to estimate genetic overlap between uASD and other clinically relevant phenotypes. We went on to apply Stratified Genomic SEM to identify classes of genes enriched for uASD. Finally, we implemented Transcriptome-Wide SEM (T-SEM) to explore patterns of gene-expression associated with uASD. RESULTS: We observed positive genetic correlations between uASD and several external traits, most notably those relating to cognitive/educational outcomes and internalizing psychiatric traits. Stratified Genomic SEM showed that heritability for uASD was significantly enriched in genes involved in evolutionarily conserved processes, as well as for a histone mark in the germinal matrix. T-SEM revealed 83 unique genes with expression associated with uASD, 34 of which were novel with respect to univariate analyses. These genes were overrepresented in skin-related pathologies. LIMITATIONS: Our study was limited by summary statistics derived exclusively from individuals of European ancestry. Additionally, using data based on a general ASD diagnosis limits our ability to understand genetic factors contributing to the pronounced clinical heterogeneity in ASD. CONCLUSIONS: Our findings delineate the unique genetic underpinnings of ASD that are independent of ADHD at the genome-wide, functional, and gene expression level of analysis. In addition, we identify novel associations previously masked by their diametric effects on ADHD. Collectively, these results provide insight into the processes that make ASD biologically unique. En ligne : https://dx.doi.org/10.1186/s13229-024-00624-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Characterizing genetic pathways unique to autism spectrum disorder at multiple levels of biological analysis [Texte imprimé et/ou numérique] / Lukas S. SCHAFFER, Auteur ; Sophie BREUNIG, Auteur ; Jeremy M. LAWRENCE, Auteur ; Isabelle F FOOTE, Auteur ; Andrew D. GROTZINGER, Auteur . - 46p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 46p. Mots-clés : Humans  Autism Spectrum Disorder/genetics  Genome-Wide Association Study  Genetic Predisposition to Disease  Attention Deficit Disorder with Hyperactivity/genetics  Phenotype  Transcriptome  Male  Female  Child  Polymorphism, Single Nucleotide  Latent Class Analysis  Attention-deficit/hyperactivity disorder  Autism spectrum disorder  Comorbidity  Genomic SEM  Multivariate genomics  Neurodevelopmental disorders  Psychiatric genetics Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by atypical patterns of social functioning and repetitive/restricted behaviors. ASD commonly co-occurs with ADHD and, despite their clinical distinctiveness, the two share considerable genetic overlap. Given their shared genetic liability, it is unclear which genetic pathways increase the likelihood of ASD independently of ADHD. METHODS: We applied Genomic Structural Equation Modeling (SEM) to GWAS summary statistics for ASD and childhood-diagnosed ADHD, decomposing the genetic variance for ASD into that which is unique to ASD (uASD) and that which is shared with ADHD. We computed genetic correlations between uASD and 83 external traits to estimate genetic overlap between uASD and other clinically relevant phenotypes. We went on to apply Stratified Genomic SEM to identify classes of genes enriched for uASD. Finally, we implemented Transcriptome-Wide SEM (T-SEM) to explore patterns of gene-expression associated with uASD. RESULTS: We observed positive genetic correlations between uASD and several external traits, most notably those relating to cognitive/educational outcomes and internalizing psychiatric traits. Stratified Genomic SEM showed that heritability for uASD was significantly enriched in genes involved in evolutionarily conserved processes, as well as for a histone mark in the germinal matrix. T-SEM revealed 83 unique genes with expression associated with uASD, 34 of which were novel with respect to univariate analyses. These genes were overrepresented in skin-related pathologies. LIMITATIONS: Our study was limited by summary statistics derived exclusively from individuals of European ancestry. Additionally, using data based on a general ASD diagnosis limits our ability to understand genetic factors contributing to the pronounced clinical heterogeneity in ASD. CONCLUSIONS: Our findings delineate the unique genetic underpinnings of ASD that are independent of ADHD at the genome-wide, functional, and gene expression level of analysis. In addition, we identify novel associations previously masked by their diametric effects on ADHD. Collectively, these results provide insight into the processes that make ASD biologically unique. En ligne : https://dx.doi.org/10.1186/s13229-024-00624-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Developmental trajectories in infants and pre-school children with Neurofibromatosis 1 / Hannah SLEVIN in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 45p. Titre : Developmental trajectories in infants and pre-school children with Neurofibromatosis 1 Type de document : Texte imprimé et/ou numérique Auteurs : Hannah SLEVIN, Auteur ; Fiona KEHINDE, Auteur ; Jannath BEGUM-ALI, Auteur ; Ceri ELLIS, Auteur ; Emma BURKITT-WRIGHT, Auteur ; Jonathan GREEN, Auteur ; Mark H. JOHNSON, Auteur ; Greg PASCO, Auteur ; Tony CHARMAN, Auteur ; Emily J. H. JONES, Auteur ; Shruti GARG, Auteur ; EDEN-STAARS TEAM, Auteur Article en page(s) : 45p. Langues : Anglais (eng) Mots-clés : Humans  Neurofibromatosis 1  Infant  Female  Male  Child, Preschool  Cognition  Child Development  Attention Deficit Disorder with Hyperactivity/diagnosis  Prospective Studies  Autistic Disorder/diagnosis  Adhd  Autism  Children  Cohort  Nf1  Neurofibromatosis  Trajectories  has received royalties from Sage Publications and Guilford Publications. The  other authors have no conflicts of interest to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with Neurofibromatosis 1 (NF1) show cognitive, behavioural and social differences compared to their peers. However, the age and sequence at which these differences begin to emerge is not fully understood. This prospective cohort study examines the cognitive, behavioural, ADHD trait and autism symptom development in infant and pre-school children with NF1 compared with typically developing (TD) children without a family history of neurodevelopmental conditions. METHODS: Data from standardised tests was gathered at 5, 10, 14, 24 and 36 months of age (NF1 n = 35, TD n = 29). Developmental trajectories of cognitive (Mullen Scales of Early Learning, MSEL) and adaptive behavioural (Vineland Adaptive Behavior Scales, VABS) development from 5 to 36 months were analysed using linear mixed modelling. Measures of ADHD (Child Behavior Checklist) and autism traits (ADOS-2, BOSA-MV and ADI-R) were assessed at 24 and 36 months. RESULTS: The developmental trajectory of cognitive skills (all domains of the MSEL) and behavioural skills (four domains of the VABS) differed significantly between NF1 and TD groups. Post-hoc tests demonstrated that the NF1 participants scored significantly lower than TD participants at 24 months on all MSEL and VABS domains. The NF1 cohort demonstrated higher mean autism and ADHD traits at 24 months and 14% of the NF1 cohort met a research diagnostic classification for autism at 36 months. LIMITATIONS: The study has a relatively small sample size due to variable retention and rolling recruitment. Due to limitations imposed by the COVID-19 pandemic, we utilised the Brief Observation of Symptoms of Autism for Minimally Verbal children (BOSA-MV) for some participants, which was administered online and may not gather as accurate a picture of traits as ADOS-2. The BOSA-MV was utilised for 41% of participants with NF1 at 36 months compared to 11% at 24 months. This may explain the reduction in the percentage of children with NF1 that met autism criteria at 36 months. CONCLUSIONS: By 24 months of age, the NF1 cohort show lower cognitive skills and adaptive behaviour and higher levels of autism and ADHD traits as compared to TD children. This has implications for developmental monitoring and referral for early interventions. TRIAL REGISTRATION: Not applicable. En ligne : https://dx.doi.org/10.1186/s13229-024-00621-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Developmental trajectories in infants and pre-school children with Neurofibromatosis 1 [Texte imprimé et/ou numérique] / Hannah SLEVIN, Auteur ; Fiona KEHINDE, Auteur ; Jannath BEGUM-ALI, Auteur ; Ceri ELLIS, Auteur ; Emma BURKITT-WRIGHT, Auteur ; Jonathan GREEN, Auteur ; Mark H. JOHNSON, Auteur ; Greg PASCO, Auteur ; Tony CHARMAN, Auteur ; Emily J. H. JONES, Auteur ; Shruti GARG, Auteur ; EDEN-STAARS TEAM, Auteur . - 45p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 45p. Mots-clés : Humans  Neurofibromatosis 1  Infant  Female  Male  Child, Preschool  Cognition  Child Development  Attention Deficit Disorder with Hyperactivity/diagnosis  Prospective Studies  Autistic Disorder/diagnosis  Adhd  Autism  Children  Cohort  Nf1  Neurofibromatosis  Trajectories  has received royalties from Sage Publications and Guilford Publications. The  other authors have no conflicts of interest to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Children with Neurofibromatosis 1 (NF1) show cognitive, behavioural and social differences compared to their peers. However, the age and sequence at which these differences begin to emerge is not fully understood. This prospective cohort study examines the cognitive, behavioural, ADHD trait and autism symptom development in infant and pre-school children with NF1 compared with typically developing (TD) children without a family history of neurodevelopmental conditions. METHODS: Data from standardised tests was gathered at 5, 10, 14, 24 and 36 months of age (NF1 n = 35, TD n = 29). Developmental trajectories of cognitive (Mullen Scales of Early Learning, MSEL) and adaptive behavioural (Vineland Adaptive Behavior Scales, VABS) development from 5 to 36 months were analysed using linear mixed modelling. Measures of ADHD (Child Behavior Checklist) and autism traits (ADOS-2, BOSA-MV and ADI-R) were assessed at 24 and 36 months. RESULTS: The developmental trajectory of cognitive skills (all domains of the MSEL) and behavioural skills (four domains of the VABS) differed significantly between NF1 and TD groups. Post-hoc tests demonstrated that the NF1 participants scored significantly lower than TD participants at 24 months on all MSEL and VABS domains. The NF1 cohort demonstrated higher mean autism and ADHD traits at 24 months and 14% of the NF1 cohort met a research diagnostic classification for autism at 36 months. LIMITATIONS: The study has a relatively small sample size due to variable retention and rolling recruitment. Due to limitations imposed by the COVID-19 pandemic, we utilised the Brief Observation of Symptoms of Autism for Minimally Verbal children (BOSA-MV) for some participants, which was administered online and may not gather as accurate a picture of traits as ADOS-2. The BOSA-MV was utilised for 41% of participants with NF1 at 36 months compared to 11% at 24 months. This may explain the reduction in the percentage of children with NF1 that met autism criteria at 36 months. CONCLUSIONS: By 24 months of age, the NF1 cohort show lower cognitive skills and adaptive behaviour and higher levels of autism and ADHD traits as compared to TD children. This has implications for developmental monitoring and referral for early interventions. TRIAL REGISTRATION: Not applicable. En ligne : https://dx.doi.org/10.1186/s13229-024-00621-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538