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Targeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models / Sandra MARTIN LORENZO in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) Titre : Targeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models Type de document : Texte imprimé et/ou numérique Auteurs : Sandra MARTIN LORENZO, Auteur ; Valérie NALESSO, Auteur ; Claire CHEVALIER, Auteur ; Marie-Christine BIRLING, Auteur ; Yann HERAULT, Auteur Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Copy number variation  Intellectual disability  Kctd13  Mouse model  Neurodevelopment  Preclinical treatment  Recognition memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Gene copy number variants play an important role in the occurrence of neurodevelopmental disorders. Particularly, the deletion of the 16p11.2 locus is associated with autism spectrum disorder, intellectual disability, and several other features. Earlier studies highlighted the implication of Kctd13 genetic imbalance in 16p11.2 deletion through the regulation of the RHOA pathway. METHODS: Here, we generated a new mouse model with a small deletion of two key exons in Kctd13. Then, we targeted the RHOA pathway to rescue the cognitive phenotypes of the Kctd13 and 16p11.2 deletion mouse models in a pure genetic background. We used a chronic administration of fasudil (HA1077), an inhibitor of the Rho-associated protein kinase, for six weeks in mouse models carrying a heterozygous inactivation of Kctd13, or the deletion of the entire 16p11.2 BP4-BP5 homologous region. RESULTS: We found that the small Kctd13 heterozygous deletion induced a cognitive phenotype similar to the whole deletion of the 16p11.2 homologous region, in the Del/+?mice. We then showed that chronic fasudil treatment can restore object recognition memory in adult heterozygous mutant mice for Kctd13 and for 16p11.2 deletion. In addition, learning and memory improvement occurred in parallel to change in the RHOA pathway. LIMITATIONS: The Kcdt13 mutant line does not recapitulate all the phenotypes found in the 16p11.2 Del/+?model. In particular, the locomotor activity was not altered at 12 and 18 weeks of age and the object location memory was not defective in 18-week old mutants. Similarly, the increase in locomotor activity was not modified by the treatment in the 16p11.2 Del/+?mouse model, suggesting that other loci were involved in such defects. Rescue was observed only after four weeks of treatment but no long-term experiment has been carried out so far. Finally, we did not check the social behaviour, which requires working in another hybrid genetic background. CONCLUSION: These findings confirm KCTD13 as one target gene causing cognitive deficits in 16p11.2 deletion patients, and the relevance of the RHOA pathway as a therapeutic path for 16p11.2 deletion. In addition, they reinforce the contribution of other gene(s) involved in cognitive defects found in the 16p11.2 models in older mice. En ligne : http://dx.doi.org/10.1186/s13229-020-00405-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 [article] Targeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models [Texte imprimé et/ou numérique] / Sandra MARTIN LORENZO, Auteur ; Valérie NALESSO, Auteur ; Claire CHEVALIER, Auteur ; Marie-Christine BIRLING, Auteur ; Yann HERAULT, Auteur. Langues : Anglais (eng) in Molecular Autism > 12 (2021) Mots-clés : Autism spectrum disorders  Copy number variation  Intellectual disability  Kctd13  Mouse model  Neurodevelopment  Preclinical treatment  Recognition memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Gene copy number variants play an important role in the occurrence of neurodevelopmental disorders. Particularly, the deletion of the 16p11.2 locus is associated with autism spectrum disorder, intellectual disability, and several other features. Earlier studies highlighted the implication of Kctd13 genetic imbalance in 16p11.2 deletion through the regulation of the RHOA pathway. METHODS: Here, we generated a new mouse model with a small deletion of two key exons in Kctd13. Then, we targeted the RHOA pathway to rescue the cognitive phenotypes of the Kctd13 and 16p11.2 deletion mouse models in a pure genetic background. We used a chronic administration of fasudil (HA1077), an inhibitor of the Rho-associated protein kinase, for six weeks in mouse models carrying a heterozygous inactivation of Kctd13, or the deletion of the entire 16p11.2 BP4-BP5 homologous region. RESULTS: We found that the small Kctd13 heterozygous deletion induced a cognitive phenotype similar to the whole deletion of the 16p11.2 homologous region, in the Del/+?mice. We then showed that chronic fasudil treatment can restore object recognition memory in adult heterozygous mutant mice for Kctd13 and for 16p11.2 deletion. In addition, learning and memory improvement occurred in parallel to change in the RHOA pathway. LIMITATIONS: The Kcdt13 mutant line does not recapitulate all the phenotypes found in the 16p11.2 Del/+?model. In particular, the locomotor activity was not altered at 12 and 18 weeks of age and the object location memory was not defective in 18-week old mutants. Similarly, the increase in locomotor activity was not modified by the treatment in the 16p11.2 Del/+?mouse model, suggesting that other loci were involved in such defects. Rescue was observed only after four weeks of treatment but no long-term experiment has been carried out so far. Finally, we did not check the social behaviour, which requires working in another hybrid genetic background. CONCLUSION: These findings confirm KCTD13 as one target gene causing cognitive deficits in 16p11.2 deletion patients, and the relevance of the RHOA pathway as a therapeutic path for 16p11.2 deletion. In addition, they reinforce the contribution of other gene(s) involved in cognitive defects found in the 16p11.2 models in older mice. En ligne : http://dx.doi.org/10.1186/s13229-020-00405-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438

Major motor and gait deficits with sexual dimorphism in a Shank3 mutant mouse model / Emmanuel MATAS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) Titre : Major motor and gait deficits with sexual dimorphism in a Shank3 mutant mouse model Type de document : Texte imprimé et/ou numérique Auteurs : Emmanuel MATAS, Auteur ; Alexandre MAISTERRENA, Auteur ; Mathieu THABAULT, Auteur ; Eric BALADO, Auteur ; Maureen FRANCHETEAU, Auteur ; Anais BALBOUS, Auteur ; Laurie GALVAN, Auteur ; Mohamed JABER, Auteur Langues : Anglais (eng) Mots-clés : Cerebellum  Crus I  Crus II  Gait  Motor coordination  Purkinje cells  Sociability  mGluR5 Index. décimale : PER Périodiques Résumé : BACKGROUND: Contrasting findings were reported in several animal models with a Shank3 mutation used to induce various autism spectrum disorder (ASD) symptoms. Here, we aimed at investigating behavioral, cellular, and molecular consequences of a C-terminal (frameshift in exon 21) deletion in Shank3 protein in mice, a mutation that is also found in clinical conditions and which results in loss of major isoforms of Shank3. A special focus was made on cerebellar related parameters. METHODS: All three genotypes were analyzed [wild type (WT), heterozygote (Shank3+/?C) and homozygote (Shank3 ?C/?C)] and males and females were separated into two distinct groups. Motor and social behavior, gait, Purkinje cells (PC) and glutamatergic protein levels were determined. Behavioral and cellular procedures used here were previously validated using two environmental animal models of ASD. ANOVA and post-hoc analysis were used for statistical analysis. RESULTS: Shank3 ?C/?C mice showed significant impairments in social novelty preference, stereotyped behavior and gait. These were accompanied by a decreased number of PC in restricted cerebellar sub-regions and decreased cerebellar expression of mGluR5. Females Shank3 ?C/?C were less affected by the mutation than males. Shank3+/?C mice showed impairments only in social novelty preference, grooming, and decreased mGluR5 expression and that were to a much lesser extent than in Shank3 ?C/?C mice. LIMITATIONS: As Shank3 mutation is a haploinsufficiency, it is of interest to emphasize that Shank3+/?C mice showed only mild to no deficiencies compared to Shank3 ?C/?C. CONCLUSIONS: Our findings indicate that several behavioral, cellular, and molecular parameters are affected in this animal model. The reported deficits are more pronounced in males than in females. Additionally, male Shank3 ?C/?C mice show more pronounced alterations than Shank3+/?C. Together with our previous findings in two environmental animal models of ASD, our studies indicate that gait dysfunction constitutes a robust set of motor ASD symptoms that may be considered for implementation in clinical settings as an early and quantitative diagnosis criteria. En ligne : http://dx.doi.org/10.1186/s13229-020-00412-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 [article] Major motor and gait deficits with sexual dimorphism in a Shank3 mutant mouse model [Texte imprimé et/ou numérique] / Emmanuel MATAS, Auteur ; Alexandre MAISTERRENA, Auteur ; Mathieu THABAULT, Auteur ; Eric BALADO, Auteur ; Maureen FRANCHETEAU, Auteur ; Anais BALBOUS, Auteur ; Laurie GALVAN, Auteur ; Mohamed JABER, Auteur. Langues : Anglais (eng) in Molecular Autism > 12 (2021) Mots-clés : Cerebellum  Crus I  Crus II  Gait  Motor coordination  Purkinje cells  Sociability  mGluR5 Index. décimale : PER Périodiques Résumé : BACKGROUND: Contrasting findings were reported in several animal models with a Shank3 mutation used to induce various autism spectrum disorder (ASD) symptoms. Here, we aimed at investigating behavioral, cellular, and molecular consequences of a C-terminal (frameshift in exon 21) deletion in Shank3 protein in mice, a mutation that is also found in clinical conditions and which results in loss of major isoforms of Shank3. A special focus was made on cerebellar related parameters. METHODS: All three genotypes were analyzed [wild type (WT), heterozygote (Shank3+/?C) and homozygote (Shank3 ?C/?C)] and males and females were separated into two distinct groups. Motor and social behavior, gait, Purkinje cells (PC) and glutamatergic protein levels were determined. Behavioral and cellular procedures used here were previously validated using two environmental animal models of ASD. ANOVA and post-hoc analysis were used for statistical analysis. RESULTS: Shank3 ?C/?C mice showed significant impairments in social novelty preference, stereotyped behavior and gait. These were accompanied by a decreased number of PC in restricted cerebellar sub-regions and decreased cerebellar expression of mGluR5. Females Shank3 ?C/?C were less affected by the mutation than males. Shank3+/?C mice showed impairments only in social novelty preference, grooming, and decreased mGluR5 expression and that were to a much lesser extent than in Shank3 ?C/?C mice. LIMITATIONS: As Shank3 mutation is a haploinsufficiency, it is of interest to emphasize that Shank3+/?C mice showed only mild to no deficiencies compared to Shank3 ?C/?C. CONCLUSIONS: Our findings indicate that several behavioral, cellular, and molecular parameters are affected in this animal model. The reported deficits are more pronounced in males than in females. Additionally, male Shank3 ?C/?C mice show more pronounced alterations than Shank3+/?C. Together with our previous findings in two environmental animal models of ASD, our studies indicate that gait dysfunction constitutes a robust set of motor ASD symptoms that may be considered for implementation in clinical settings as an early and quantitative diagnosis criteria. En ligne : http://dx.doi.org/10.1186/s13229-020-00412-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438

Autistic traits and individual brain differences: functional network efficiency reflects attentional and social impairments, structural nodal efficiencies index systemising and theory-of-mind skills / Subhadip PAUL in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 3p. Titre : Autistic traits and individual brain differences: functional network efficiency reflects attentional and social impairments, structural nodal efficiencies index systemising and theory-of-mind skills Type de document : Texte imprimé et/ou numérique Auteurs : Subhadip PAUL, Auteur ; Aditi ARORA, Auteur ; Rashi MIDHA, Auteur ; Dinh VU, Auteur ; Prasun K. ROY, Auteur ; Matthew K. BELMONTE, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Attention  Autism  Dti  Dimensional  Functional connectivity  Graph theory  Social  Theory-of-mind  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism is characterised not only by impaired social cognitive 'empathising' but also by superior rule-based 'systemising'. These cognitive domains intertwine within the categorical diagnosis of autism, yet behavioural genetics suggest largely independent heritability, and separable brain mechanisms. We sought to determine whether quantitative behavioural measures of autistic traits are dimensionally associated with structural and functional brain network integrity, and whether brain bases of autistic traits vary independently across individuals. METHODS: Thirty right-handed neurotypical adults (12 females) were administered psychometric (Social Responsiveness Scale, Autism Spectrum Quotient and Systemising Quotient) and behavioural (Attention Network Test and theory-of-mind reaction time) measures of autistic traits, and structurally (diffusion tensor imaging) and functionally (500 s of 2 Hz eyes-closed resting fMRI) derived graph-theoretic measures of efficiency of information integration were computed throughout the brain and within subregions. RESULTS: Social impairment was positively associated with functional efficiency (r = .47, p = .006), globally and within temporo-parietal and prefrontal cortices. Delayed orienting of attention likewise was associated with greater functional efficiency (r = - .46, p = .0133). Systemising was positively associated with global structural efficiency (r = .38, p = 0.018), driven specifically by temporal pole; theory-of-mind reaction time was related to structural efficiency (r = - .40, p = 0.0153) within right supramarginal gyrus. LIMITATIONS: Interpretation of these relationships is complicated by the many senses of the term 'connectivity', including functional, structural and computational; by the approximation inherent in group functional anatomical parcellations when confronted with individual variation in functional anatomy; and by the validity, sensitivity and specificity of the several survey and experimental behavioural measures applied as correlates of brain structure and function. CONCLUSIONS: Functional connectivities highlight distributed networks associated with domain-general properties such as attentional orienting and social cognition broadly, associating more impaired behaviour with more efficient brain networks that may reflect heightened feedforward information flow subserving autistic strengths and deficits alike. Structural connectivity results highlight specific anatomical nodes of convergence, reflecting cognitive and neuroanatomical independence of systemising and theory-of-mind. In addition, this work shows that individual differences in theory-of-mind related to brain structure can be measured behaviourally, and offers neuroanatomical evidence to pin down the slippery construct of 'systemising' as the capacity to construct invariant contextual associations. En ligne : http://dx.doi.org/10.1186/s13229-020-00377-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Autistic traits and individual brain differences: functional network efficiency reflects attentional and social impairments, structural nodal efficiencies index systemising and theory-of-mind skills [Texte imprimé et/ou numérique] / Subhadip PAUL, Auteur ; Aditi ARORA, Auteur ; Rashi MIDHA, Auteur ; Dinh VU, Auteur ; Prasun K. ROY, Auteur ; Matthew K. BELMONTE, Auteur . - 3p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 3p. Mots-clés : Attention  Autism  Dti  Dimensional  Functional connectivity  Graph theory  Social  Theory-of-mind  fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism is characterised not only by impaired social cognitive 'empathising' but also by superior rule-based 'systemising'. These cognitive domains intertwine within the categorical diagnosis of autism, yet behavioural genetics suggest largely independent heritability, and separable brain mechanisms. We sought to determine whether quantitative behavioural measures of autistic traits are dimensionally associated with structural and functional brain network integrity, and whether brain bases of autistic traits vary independently across individuals. METHODS: Thirty right-handed neurotypical adults (12 females) were administered psychometric (Social Responsiveness Scale, Autism Spectrum Quotient and Systemising Quotient) and behavioural (Attention Network Test and theory-of-mind reaction time) measures of autistic traits, and structurally (diffusion tensor imaging) and functionally (500 s of 2 Hz eyes-closed resting fMRI) derived graph-theoretic measures of efficiency of information integration were computed throughout the brain and within subregions. RESULTS: Social impairment was positively associated with functional efficiency (r = .47, p = .006), globally and within temporo-parietal and prefrontal cortices. Delayed orienting of attention likewise was associated with greater functional efficiency (r = - .46, p = .0133). Systemising was positively associated with global structural efficiency (r = .38, p = 0.018), driven specifically by temporal pole; theory-of-mind reaction time was related to structural efficiency (r = - .40, p = 0.0153) within right supramarginal gyrus. LIMITATIONS: Interpretation of these relationships is complicated by the many senses of the term 'connectivity', including functional, structural and computational; by the approximation inherent in group functional anatomical parcellations when confronted with individual variation in functional anatomy; and by the validity, sensitivity and specificity of the several survey and experimental behavioural measures applied as correlates of brain structure and function. CONCLUSIONS: Functional connectivities highlight distributed networks associated with domain-general properties such as attentional orienting and social cognition broadly, associating more impaired behaviour with more efficient brain networks that may reflect heightened feedforward information flow subserving autistic strengths and deficits alike. Structural connectivity results highlight specific anatomical nodes of convergence, reflecting cognitive and neuroanatomical independence of systemising and theory-of-mind. In addition, this work shows that individual differences in theory-of-mind related to brain structure can be measured behaviourally, and offers neuroanatomical evidence to pin down the slippery construct of 'systemising' as the capacity to construct invariant contextual associations. En ligne : http://dx.doi.org/10.1186/s13229-020-00377-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Application of Airy beam light sheet microscopy to examine early neurodevelopmental structures in 3D hiPSC-derived human cortical spheroids / Dwaipayan ADHYA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 4p. Titre : Application of Airy beam light sheet microscopy to examine early neurodevelopmental structures in 3D hiPSC-derived human cortical spheroids Type de document : Texte imprimé et/ou numérique Auteurs : Dwaipayan ADHYA, Auteur ; George CHENNELL, Auteur ; James A. CROWE, Auteur ; Eva P. VALENCIA-ALARCON, Auteur ; James SEYFORTH, Auteur ; Neveen A. HOSNY, Auteur ; Marina V. YASVOINA, Auteur ; Robert FORSTER, Auteur ; Simon BARON-COHEN, Auteur ; Anthony C. VERNON, Auteur ; Deepak P. SRIVASTAVA, Auteur Article en page(s) : 4p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: The inability to observe relevant biological processes in vivo significantly restricts human neurodevelopmental research. Advances in appropriate in vitro model systems, including patient-specific human brain organoids and human cortical spheroids (hCSs), offer a pragmatic solution to this issue. In particular, hCSs are an accessible method for generating homogenous organoids of dorsal telencephalic fate, which recapitulate key aspects of human corticogenesis, including the formation of neural rosettes-in vitro correlates of the neural tube. These neurogenic niches give rise to neural progenitors that subsequently differentiate into neurons. Studies differentiating induced pluripotent stem cells (hiPSCs) in 2D have linked atypical formation of neural rosettes with neurodevelopmental disorders such as autism spectrum conditions. Thus far, however, conventional methods of tissue preparation in this field limit the ability to image these structures in three-dimensions within intact hCS or other 3D preparations. To overcome this limitation, we have sought to optimise a methodological approach to process hCSs to maximise the utility of a novel Airy-beam light sheet microscope (ALSM) to acquire high resolution volumetric images of internal structures within hCS representative of early developmental time points. RESULTS: Conventional approaches to imaging hCS by confocal microscopy were limited in their ability to image effectively into intact spheroids. Conversely, volumetric acquisition by ALSM offered superior imaging through intact, non-clarified, in vitro tissues, in both speed and resolution when compared to conventional confocal imaging systems. Furthermore, optimised immunohistochemistry and optical clearing of hCSs afforded improved imaging at depth. This permitted visualization of the morphology of the inner lumen of neural rosettes. CONCLUSION: We present an optimized methodology that takes advantage of an ALSM system that can rapidly image intact 3D brain organoids at high resolution while retaining a large field of view. This imaging modality can be applied to both non-cleared and cleared in vitro human brain spheroids derived from hiPSCs for precise examination of their internal 3D structures. This process represents a rapid, highly efficient method to examine and quantify in 3D the formation of key structures required for the coordination of neurodevelopmental processes in both health and disease states. We posit that this approach would facilitate investigation of human neurodevelopmental processes in vitro. En ligne : http://dx.doi.org/10.1186/s13229-021-00413-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Application of Airy beam light sheet microscopy to examine early neurodevelopmental structures in 3D hiPSC-derived human cortical spheroids [Texte imprimé et/ou numérique] / Dwaipayan ADHYA, Auteur ; George CHENNELL, Auteur ; James A. CROWE, Auteur ; Eva P. VALENCIA-ALARCON, Auteur ; James SEYFORTH, Auteur ; Neveen A. HOSNY, Auteur ; Marina V. YASVOINA, Auteur ; Robert FORSTER, Auteur ; Simon BARON-COHEN, Auteur ; Anthony C. VERNON, Auteur ; Deepak P. SRIVASTAVA, Auteur . - 4p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 4p. Index. décimale : PER Périodiques Résumé : BACKGROUND: The inability to observe relevant biological processes in vivo significantly restricts human neurodevelopmental research. Advances in appropriate in vitro model systems, including patient-specific human brain organoids and human cortical spheroids (hCSs), offer a pragmatic solution to this issue. In particular, hCSs are an accessible method for generating homogenous organoids of dorsal telencephalic fate, which recapitulate key aspects of human corticogenesis, including the formation of neural rosettes-in vitro correlates of the neural tube. These neurogenic niches give rise to neural progenitors that subsequently differentiate into neurons. Studies differentiating induced pluripotent stem cells (hiPSCs) in 2D have linked atypical formation of neural rosettes with neurodevelopmental disorders such as autism spectrum conditions. Thus far, however, conventional methods of tissue preparation in this field limit the ability to image these structures in three-dimensions within intact hCS or other 3D preparations. To overcome this limitation, we have sought to optimise a methodological approach to process hCSs to maximise the utility of a novel Airy-beam light sheet microscope (ALSM) to acquire high resolution volumetric images of internal structures within hCS representative of early developmental time points. RESULTS: Conventional approaches to imaging hCS by confocal microscopy were limited in their ability to image effectively into intact spheroids. Conversely, volumetric acquisition by ALSM offered superior imaging through intact, non-clarified, in vitro tissues, in both speed and resolution when compared to conventional confocal imaging systems. Furthermore, optimised immunohistochemistry and optical clearing of hCSs afforded improved imaging at depth. This permitted visualization of the morphology of the inner lumen of neural rosettes. CONCLUSION: We present an optimized methodology that takes advantage of an ALSM system that can rapidly image intact 3D brain organoids at high resolution while retaining a large field of view. This imaging modality can be applied to both non-cleared and cleared in vitro human brain spheroids derived from hiPSCs for precise examination of their internal 3D structures. This process represents a rapid, highly efficient method to examine and quantify in 3D the formation of key structures required for the coordination of neurodevelopmental processes in both health and disease states. We posit that this approach would facilitate investigation of human neurodevelopmental processes in vitro. En ligne : http://dx.doi.org/10.1186/s13229-021-00413-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism / Thomas W FRAZIER in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 5p. Titre : Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism Type de document : Texte imprimé et/ou numérique Auteurs : Thomas W FRAZIER, Auteur ; Ritika JAINI, Auteur ; Robyn M. BUSCH, Auteur ; Matthew WOLF, Auteur ; Tammy SADLER, Auteur ; Patricia KLAAS, Auteur ; Antonio Y. HARDAN, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Mustafa SAHIN, Auteur ; Chari ENG, Auteur Article en page(s) : 5p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Behavior  Cognition  Molecular  Pten  Protein Index. décimale : PER Périodiques Résumé : BACKGROUND: PTEN is a well-established risk gene for autism spectrum disorder (ASD). Yet, little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). The primary aim of the present study was to examine group differences in peripheral blood-derived PTEN pathway protein levels between PTEN-ASD, PTEN no-ASD, and idiopathic macrocephalic ASD patients (macro-ASD). Secondarily, associations between protein levels and neurobehavioral functions were examined in the full cohort. METHODS: Patients were recruited at four tertiary medical centers. Peripheral blood-derived protein levels from canonical PTEN pathways (PI3K/AKT and MAPK/ERK) were analyzed using Western blot analyses blinded to genotype and ASD status. Neurobehavioral measures included standardized assessments of global cognitive ability and multiple neurobehavioral domains. Analysis of variance models examined group differences in demographic, neurobehavioral, and protein measures. Bivariate correlations, structural models, and statistical learning procedures estimated associations between molecular and neurobehavioral variables. To complement patient data, Western blots for downstream proteins were generated to evaluate canonical PTEN pathways in the PTEN-m3m4 mouse model. RESULTS: Participants included 61 patients (25 PTEN-ASD, 16 PTEN no-ASD, and 20 macro-ASD). Decreased PTEN and S6 were observed in both PTEN mutation groups. Reductions in MnSOD and increases in P-S6 were observed in ASD groups. Elevated neural P-AKT/AKT and P-S6/S6 from PTEN murine models parallel our patient observations. Patient PTEN and AKT levels were independently associated with global cognitive ability, and p27 expression was associated with frontal sub-cortical functions. As a group, molecular measures added significant predictive value to several neurobehavioral domains over and above PTEN mutation status. LIMITATIONS: Sample sizes were small, precluding within-group analyses. Protein and neurobehavioral data were limited to a single evaluation. A small number of patients were excluded with invalid protein data, and cognitively impaired patients had missing data on some assessments. CONCLUSIONS: Several canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. Protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. Future longitudinal analyses are needed to replicate these findings and evaluate within-group relationships between protein and neurobehavioral measures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02461446. En ligne : http://dx.doi.org/10.1186/s13229-020-00406-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism [Texte imprimé et/ou numérique] / Thomas W FRAZIER, Auteur ; Ritika JAINI, Auteur ; Robyn M. BUSCH, Auteur ; Matthew WOLF, Auteur ; Tammy SADLER, Auteur ; Patricia KLAAS, Auteur ; Antonio Y. HARDAN, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Mustafa SAHIN, Auteur ; Chari ENG, Auteur . - 5p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 5p. Mots-clés : Autism spectrum disorder  Behavior  Cognition  Molecular  Pten  Protein Index. décimale : PER Périodiques Résumé : BACKGROUND: PTEN is a well-established risk gene for autism spectrum disorder (ASD). Yet, little is known about how PTEN mutations and associated molecular processes influence neurobehavioral function in mutation carriers with (PTEN-ASD) and without ASD (PTEN no-ASD). The primary aim of the present study was to examine group differences in peripheral blood-derived PTEN pathway protein levels between PTEN-ASD, PTEN no-ASD, and idiopathic macrocephalic ASD patients (macro-ASD). Secondarily, associations between protein levels and neurobehavioral functions were examined in the full cohort. METHODS: Patients were recruited at four tertiary medical centers. Peripheral blood-derived protein levels from canonical PTEN pathways (PI3K/AKT and MAPK/ERK) were analyzed using Western blot analyses blinded to genotype and ASD status. Neurobehavioral measures included standardized assessments of global cognitive ability and multiple neurobehavioral domains. Analysis of variance models examined group differences in demographic, neurobehavioral, and protein measures. Bivariate correlations, structural models, and statistical learning procedures estimated associations between molecular and neurobehavioral variables. To complement patient data, Western blots for downstream proteins were generated to evaluate canonical PTEN pathways in the PTEN-m3m4 mouse model. RESULTS: Participants included 61 patients (25 PTEN-ASD, 16 PTEN no-ASD, and 20 macro-ASD). Decreased PTEN and S6 were observed in both PTEN mutation groups. Reductions in MnSOD and increases in P-S6 were observed in ASD groups. Elevated neural P-AKT/AKT and P-S6/S6 from PTEN murine models parallel our patient observations. Patient PTEN and AKT levels were independently associated with global cognitive ability, and p27 expression was associated with frontal sub-cortical functions. As a group, molecular measures added significant predictive value to several neurobehavioral domains over and above PTEN mutation status. LIMITATIONS: Sample sizes were small, precluding within-group analyses. Protein and neurobehavioral data were limited to a single evaluation. A small number of patients were excluded with invalid protein data, and cognitively impaired patients had missing data on some assessments. CONCLUSIONS: Several canonical PTEN pathway molecules appear to influence the presence of ASD and modify neurobehavioral function in PTEN mutation patients. Protein assays of the PTEN pathway may be useful for predicting neurobehavioral outcomes in PTEN patients. Future longitudinal analyses are needed to replicate these findings and evaluate within-group relationships between protein and neurobehavioral measures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02461446. En ligne : http://dx.doi.org/10.1186/s13229-020-00406-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Cannabinoid treatment for autism: a proof-of-concept randomized trial / Adi ARAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 6p. Titre : Cannabinoid treatment for autism: a proof-of-concept randomized trial Type de document : Texte imprimé et/ou numérique Auteurs : Adi ARAN, Auteur ; Moria HAREL, Auteur ; Hanoch CASSUTO, Auteur ; Lola POLYANSKY, Auteur ; Aviad SCHNAPP, Auteur ; Nadia WATTAD, Auteur ; Dorit SHMUELI, Auteur ; Daphna GOLAN, Auteur ; Francisco Xavier CASTELLANOS, Auteur Article en page(s) : 6p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Behavior  Cannabidiol  Cannabinoids  Child psychiatry  Clinical trials randomized controlled  Developmental disorders  Entourage effect  Neuropsychology  Tetrahydrocannabinol Index. décimale : PER Périodiques Résumé : BACKGROUND: Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5-21 years) with ASD. METHODS: We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and ?9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and ?9-tetrahydrocannabinol at the same ratio. Participants (N?=?150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI). RESULTS: Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n?=?45) versus 21% on placebo (n?=?47; p?=?0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n?=?34) versus 3.6 points after placebo (n?=?36); p?=?0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n?=?95); 23% and 21% on pure-cannabinoids (n?=?93), and 8% and 15% on placebo (n?=?94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results. CONCLUSIONS: This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016, https://clinicaltrials.gov/ct2/show/NCT02956226. En ligne : http://dx.doi.org/10.1186/s13229-021-00420-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Cannabinoid treatment for autism: a proof-of-concept randomized trial [Texte imprimé et/ou numérique] / Adi ARAN, Auteur ; Moria HAREL, Auteur ; Hanoch CASSUTO, Auteur ; Lola POLYANSKY, Auteur ; Aviad SCHNAPP, Auteur ; Nadia WATTAD, Auteur ; Dorit SHMUELI, Auteur ; Daphna GOLAN, Auteur ; Francisco Xavier CASTELLANOS, Auteur . - 6p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 6p. Mots-clés : Autism spectrum disorder  Behavior  Cannabidiol  Cannabinoids  Child psychiatry  Clinical trials randomized controlled  Developmental disorders  Entourage effect  Neuropsychology  Tetrahydrocannabinol Index. décimale : PER Périodiques Résumé : BACKGROUND: Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5-21 years) with ASD. METHODS: We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and ?9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and ?9-tetrahydrocannabinol at the same ratio. Participants (N?=?150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI). RESULTS: Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n?=?45) versus 21% on placebo (n?=?47; p?=?0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n?=?34) versus 3.6 points after placebo (n?=?36); p?=?0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n?=?95); 23% and 21% on pure-cannabinoids (n?=?93), and 8% and 15% on placebo (n?=?94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results. CONCLUSIONS: This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016, https://clinicaltrials.gov/ct2/show/NCT02956226. En ligne : http://dx.doi.org/10.1186/s13229-021-00420-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Correction to: Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes / Lucia JANICKOVA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 7p. Titre : Correction to: Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : Lucia JANICKOVA, Auteur ; Karin Farah RECHBERGER, Auteur ; Lucas WEY, Auteur ; Beat SCHWALLER, Auteur Article en page(s) : 7p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-020-00404-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Correction to: Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes [Texte imprimé et/ou numérique] / Lucia JANICKOVA, Auteur ; Karin Farah RECHBERGER, Auteur ; Lucas WEY, Auteur ; Beat SCHWALLER, Auteur . - 7p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 7p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-020-00404-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD / Joana Maria Almeida OSORIO in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 8p. Titre : Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD Type de document : Texte imprimé et/ou numérique Auteurs : Joana Maria Almeida OSORIO, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; David ROMASCANO, Auteur ; Vincent JUNOD, Auteur ; Aline HABEGGER, Auteur ; Aurélie PAIN, Auteur ; Sonia RICHETIN, Auteur ; Paola YU, Auteur ; Bertrand ISIDOR, Auteur ; Lionel VAN MALDERGEM, Auteur ; Linda PONS, Auteur ; Sabine MANIFICAT, Auteur ; Nadia CHABANE, Auteur ; Marine JEQUIER GYGAX, Auteur ; Anne Manuela MAILLARD, Auteur Article en page(s) : 8p. Langues : Anglais (eng) Mots-clés : 16p11.2 deletion  Autism spectrum disorder (ASD)  Children  Copy number variants (CNV)  Olfaction  Sensory processing  Sensory processing measure (SPM)  Touch Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing atypicalities are frequent in Autism Spectrum Disorder (ASD) and neurodevelopmental disorders (NDD). Different domains of sensory processing appear to be differentially altered in these disorders. In this study, we explored the sensory profile of two clinical cohorts, in comparison with a sample of typically developing children. METHODS: Behavioral responses to sensory stimuli were assessed using the Sensory Processing Measure (parent-report questionnaire). We included 121 ASD children, 17 carriers of the 16p11.2 deletion (Del 16p11.2) and 45 typically developing (TD) children. All participants were aged between 2 and 12 years. Additional measures included the Tactile Defensiveness and Discrimination Test-Revised, Wechsler Intelligence Scales and Autism Diagnostic Observation Schedule (ADOS-2). Statistical analyses included MANCOVA and regression analyses. RESULTS: ASD children score significantly higher on all SPM subscales compared to TD. Del16p11.2 also scored higher than TD on all subscales except for tactile and olfactory/taste processing, in which they score similarly to TD. When assessing sensory modulation patterns (hyper-, hypo-responsiveness and seeking), ASD did not significantly differ from del16p11.2. Both groups had significantly higher scores across all patterns than the TD group. There was no significant association between the SPM Touch subscale and the TDDT-R. LIMITATIONS: Sensory processing was assessed using a parent-report questionnaire. Even though it captures observable behavior, a questionnaire does not assess sensory processing in all its complexity. The sample size of the genetic cohort and the small subset of ASD children with TDDT-R data render some of our results exploratory. Divergence between SPM Touch and TDDT-R raises important questions about the nature of the process that is assessed. CONCLUSIONS: Touch and olfaction/taste seem to be particularly affected in ASD children compared to del16p11.2. These results indicate that parent report measures can provide a useful perspective on behavioral expression. Sensory phenotyping, when combined with neurobiological and psychophysical methods, might have the potential to provide a better understanding of the sensory processing in ASD and in other NDD. En ligne : http://dx.doi.org/10.1186/s13229-020-00410-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD [Texte imprimé et/ou numérique] / Joana Maria Almeida OSORIO, Auteur ; Borja RODRIGUEZ-HERREROS, Auteur ; David ROMASCANO, Auteur ; Vincent JUNOD, Auteur ; Aline HABEGGER, Auteur ; Aurélie PAIN, Auteur ; Sonia RICHETIN, Auteur ; Paola YU, Auteur ; Bertrand ISIDOR, Auteur ; Lionel VAN MALDERGEM, Auteur ; Linda PONS, Auteur ; Sabine MANIFICAT, Auteur ; Nadia CHABANE, Auteur ; Marine JEQUIER GYGAX, Auteur ; Anne Manuela MAILLARD, Auteur . - 8p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 8p. Mots-clés : 16p11.2 deletion  Autism spectrum disorder (ASD)  Children  Copy number variants (CNV)  Olfaction  Sensory processing  Sensory processing measure (SPM)  Touch Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing atypicalities are frequent in Autism Spectrum Disorder (ASD) and neurodevelopmental disorders (NDD). Different domains of sensory processing appear to be differentially altered in these disorders. In this study, we explored the sensory profile of two clinical cohorts, in comparison with a sample of typically developing children. METHODS: Behavioral responses to sensory stimuli were assessed using the Sensory Processing Measure (parent-report questionnaire). We included 121 ASD children, 17 carriers of the 16p11.2 deletion (Del 16p11.2) and 45 typically developing (TD) children. All participants were aged between 2 and 12 years. Additional measures included the Tactile Defensiveness and Discrimination Test-Revised, Wechsler Intelligence Scales and Autism Diagnostic Observation Schedule (ADOS-2). Statistical analyses included MANCOVA and regression analyses. RESULTS: ASD children score significantly higher on all SPM subscales compared to TD. Del16p11.2 also scored higher than TD on all subscales except for tactile and olfactory/taste processing, in which they score similarly to TD. When assessing sensory modulation patterns (hyper-, hypo-responsiveness and seeking), ASD did not significantly differ from del16p11.2. Both groups had significantly higher scores across all patterns than the TD group. There was no significant association between the SPM Touch subscale and the TDDT-R. LIMITATIONS: Sensory processing was assessed using a parent-report questionnaire. Even though it captures observable behavior, a questionnaire does not assess sensory processing in all its complexity. The sample size of the genetic cohort and the small subset of ASD children with TDDT-R data render some of our results exploratory. Divergence between SPM Touch and TDDT-R raises important questions about the nature of the process that is assessed. CONCLUSIONS: Touch and olfaction/taste seem to be particularly affected in ASD children compared to del16p11.2. These results indicate that parent report measures can provide a useful perspective on behavioral expression. Sensory phenotyping, when combined with neurobiological and psychophysical methods, might have the potential to provide a better understanding of the sensory processing in ASD and in other NDD. En ligne : http://dx.doi.org/10.1186/s13229-020-00410-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome / N. A. COPPING in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 9p. Titre : Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome Type de document : Texte imprimé et/ou numérique Auteurs : N. A. COPPING, Auteur ; J. L. SILVERMAN, Auteur Article en page(s) : 9p. Langues : Anglais (eng) Mots-clés : Angelman Syndrome  Behavior  Genetics  Mouse models  Seizures  Sleep  Spindles  Ube3a Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a rare genetic disorder characterized by impaired communication, motor and balance deficits, intellectual disabilities, recurring seizures and abnormal sleep patterns. The genetic cause of AS is neuronal-specific loss of expression of UBE3A (ubiquitin-protein ligase E6-AP), an imprinted gene. Seizure and sleep disorders are highly prevalent (>?80%) in the AS population. The present experiments were designed to identify translational, neurophysiological outcome measures in a model of AS. METHODS: We used the exon-2 deletion mouse (Ube3a-del) on a C57BL/6J background to assess seizure, sleep and electrophysiological phenotypes. Seizure susceptibility has been reported in Ube3a-del mice with a variety of seizure induction methods. Here, we provoked seizures by a single high-dose injection of 80 mg/kg pentylenetetrazole. Novel experiments included the utilization of wireless telemetry devices to acquire global electroencephalogram (EEG) and neurophysiological data on electrographic seizures, power spectra, light-dark cycles, sleep stages and sleep spindles in Ube3a-del and WT mice. RESULTS: Ube3a-del mice exhibited reduced seizure threshold compared to WT. EEG illustrated that Ube3a-del mice had increased epileptiform spiking activity and delta power, which corroborates findings from other laboratories and recapitulates clinical reports in AS. This is the first report to use a cortical surface-based recording by a wireless telemetry device over tethered/fixed head-mount depth recordings. Less time in both paradoxical and slow-wave sleep, longer latencies to paradoxical sleep stages and total less sleep time in Ube3a-del mice were observed compared to WT. For the first time, we detected fewer sleep spindles in the AS mouse model. LIMITATIONS: This study was limited to the exon 2 deletion mouse model, and future work will investigate the rat model of AS, containing a complete Ube3a deletion and pair EEG with behavior. CONCLUSIONS: Our data enhance rigor and translatability as our study provides important corroboration of previous reports on epileptiform and elevated delta power. For the first time we report neurophysiological phenotypes collected via translational methodology. Furthermore, this is the first report of reduced sleep spindles, a critical marker of memory consolidation during sleep, in an AS model. Our results are useful outcomes for therapeutic testing. En ligne : http://dx.doi.org/10.1186/s13229-021-00416-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome [Texte imprimé et/ou numérique] / N. A. COPPING, Auteur ; J. L. SILVERMAN, Auteur . - 9p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 9p. Mots-clés : Angelman Syndrome  Behavior  Genetics  Mouse models  Seizures  Sleep  Spindles  Ube3a Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a rare genetic disorder characterized by impaired communication, motor and balance deficits, intellectual disabilities, recurring seizures and abnormal sleep patterns. The genetic cause of AS is neuronal-specific loss of expression of UBE3A (ubiquitin-protein ligase E6-AP), an imprinted gene. Seizure and sleep disorders are highly prevalent (>?80%) in the AS population. The present experiments were designed to identify translational, neurophysiological outcome measures in a model of AS. METHODS: We used the exon-2 deletion mouse (Ube3a-del) on a C57BL/6J background to assess seizure, sleep and electrophysiological phenotypes. Seizure susceptibility has been reported in Ube3a-del mice with a variety of seizure induction methods. Here, we provoked seizures by a single high-dose injection of 80 mg/kg pentylenetetrazole. Novel experiments included the utilization of wireless telemetry devices to acquire global electroencephalogram (EEG) and neurophysiological data on electrographic seizures, power spectra, light-dark cycles, sleep stages and sleep spindles in Ube3a-del and WT mice. RESULTS: Ube3a-del mice exhibited reduced seizure threshold compared to WT. EEG illustrated that Ube3a-del mice had increased epileptiform spiking activity and delta power, which corroborates findings from other laboratories and recapitulates clinical reports in AS. This is the first report to use a cortical surface-based recording by a wireless telemetry device over tethered/fixed head-mount depth recordings. Less time in both paradoxical and slow-wave sleep, longer latencies to paradoxical sleep stages and total less sleep time in Ube3a-del mice were observed compared to WT. For the first time, we detected fewer sleep spindles in the AS mouse model. LIMITATIONS: This study was limited to the exon 2 deletion mouse model, and future work will investigate the rat model of AS, containing a complete Ube3a deletion and pair EEG with behavior. CONCLUSIONS: Our data enhance rigor and translatability as our study provides important corroboration of previous reports on epileptiform and elevated delta power. For the first time we report neurophysiological phenotypes collected via translational methodology. Furthermore, this is the first report of reduced sleep spindles, a critical marker of memory consolidation during sleep, in an AS model. Our results are useful outcomes for therapeutic testing. En ligne : http://dx.doi.org/10.1186/s13229-021-00416-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Modified CBT for social anxiety and social functioning in young adults with autism spectrum disorder / Emily R. BEMMER in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 11p. Titre : Modified CBT for social anxiety and social functioning in young adults with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Emily R. BEMMER, Auteur ; Kelsie A. BOULTON, Auteur ; Emma E. THOMAS, Auteur ; Ben LARKE, Auteur ; Suncica LAH, Auteur ; Ian B. HICKIE, Auteur ; Adam J. GUASTELLA, Auteur Article en page(s) : 11p. Langues : Anglais (eng) Mots-clés : Autism  Cognitive–behavioural therapy  Group  Intervention  Mental health  Social anxiety  Social skills Index. décimale : PER Périodiques Résumé : BACKGROUND: There is a strong research imperative to investigate effective treatment options for adolescents and adults with autism spectrum disorder (ASD). Elevated social anxiety, difficulties with social functioning and poor mental health have all been identified as core treatment targets for this group. While theoretical models posit a strong bidirectionality between social anxiety and ASD social functioning deficits, few interventions have targeted both domains concurrently. Of the two group interventions previously conducted with adolescents and adults with ASD, significant results have only been observed in either social anxiety or social functioning, and have not generalised to changes in overall mood. The aim of this study was to evaluate the potential benefit, tolerability and acceptability of a group cognitive-behaviour therapy (CBT) intervention in young adults with ASD. Primary treatment outcomes were social anxiety symptoms and social functioning difficulties; secondary outcomes were self-reported mood and overall distress. METHOD: Ten groups of participants completed an eight-week, modified group CBT intervention targeting both social anxiety and social functioning, that included social skills training, exposure tasks and behavioural experiment components. Seventy-eight adolescents and young adults with ASD, without intellectual impairment, aged between 16 and 38 (M?=?22.77; SD?=?5.31), were recruited from the community, Headspace centres and the Autism Clinic for Translational Research at the Brain and Mind Centre, University of Sydney. Outcomes (social anxiety, social functioning and mood) were measured pre- and post-intervention via self-report questionnaires (administered either online or through the return of hard-copy booklets), and participants were invited to provide anonymous feedback on the intervention (at the mid-point and end of the intervention). RESULTS: Participants demonstrated statistically significant improvements on all outcome measures in response to the intervention. Specifically, social anxiety symptoms decreased (p? En ligne : http://dx.doi.org/10.1186/s13229-021-00418-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Modified CBT for social anxiety and social functioning in young adults with autism spectrum disorder [Texte imprimé et/ou numérique] / Emily R. BEMMER, Auteur ; Kelsie A. BOULTON, Auteur ; Emma E. THOMAS, Auteur ; Ben LARKE, Auteur ; Suncica LAH, Auteur ; Ian B. HICKIE, Auteur ; Adam J. GUASTELLA, Auteur . - 11p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 11p. Mots-clés : Autism  Cognitive–behavioural therapy  Group  Intervention  Mental health  Social anxiety  Social skills Index. décimale : PER Périodiques Résumé : BACKGROUND: There is a strong research imperative to investigate effective treatment options for adolescents and adults with autism spectrum disorder (ASD). Elevated social anxiety, difficulties with social functioning and poor mental health have all been identified as core treatment targets for this group. While theoretical models posit a strong bidirectionality between social anxiety and ASD social functioning deficits, few interventions have targeted both domains concurrently. Of the two group interventions previously conducted with adolescents and adults with ASD, significant results have only been observed in either social anxiety or social functioning, and have not generalised to changes in overall mood. The aim of this study was to evaluate the potential benefit, tolerability and acceptability of a group cognitive-behaviour therapy (CBT) intervention in young adults with ASD. Primary treatment outcomes were social anxiety symptoms and social functioning difficulties; secondary outcomes were self-reported mood and overall distress. METHOD: Ten groups of participants completed an eight-week, modified group CBT intervention targeting both social anxiety and social functioning, that included social skills training, exposure tasks and behavioural experiment components. Seventy-eight adolescents and young adults with ASD, without intellectual impairment, aged between 16 and 38 (M?=?22.77; SD?=?5.31), were recruited from the community, Headspace centres and the Autism Clinic for Translational Research at the Brain and Mind Centre, University of Sydney. Outcomes (social anxiety, social functioning and mood) were measured pre- and post-intervention via self-report questionnaires (administered either online or through the return of hard-copy booklets), and participants were invited to provide anonymous feedback on the intervention (at the mid-point and end of the intervention). RESULTS: Participants demonstrated statistically significant improvements on all outcome measures in response to the intervention. Specifically, social anxiety symptoms decreased (p? En ligne : http://dx.doi.org/10.1186/s13229-021-00418-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Mind the translational gap: using iPS cell models to bridge from genetic discoveries to perturbed pathways and therapeutic targets / Greta PINTACUDA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 10p. Titre : Mind the translational gap: using iPS cell models to bridge from genetic discoveries to perturbed pathways and therapeutic targets Type de document : Texte imprimé et/ou numérique Auteurs : Greta PINTACUDA, Auteur ; Jacqueline M. MARTIN, Auteur ; Kevin C. EGGAN, Auteur Article en page(s) : 10p. Langues : Anglais (eng) Mots-clés : Differentiation  Npc  Neurodevelopment  Neurons  iPSC (induced-pluripotent stem cells)  currently employed at BioMarin Pharmaceutical. Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by impaired social interactions as well as the presentation of restrictive and repetitive behaviors. ASD is highly heritable but genetically heterogenous with both common and rare genetic variants collaborating to predispose individuals to the disorder. In this review, we synthesize recent efforts to develop human induced pluripotent stem cell (iPSC)-derived models of ASD-related phenotypes. We firstly address concerns regarding the relevance and validity of available neuronal iPSC-derived models. We then critically evaluate the robustness of various differentiation and cell culture protocols used for producing cell types of relevance to ASD. By exploring iPSC models of ASD reported thus far, we examine to what extent cellular and neuronal phenotypes with potential relevance to ASD can be linked to genetic variants found to underlie it. Lastly, we outline promising strategies by which iPSC technology can both enhance the power of genetic studies to identify ASD risk factors and nominate pathways that are disrupted across groups of ASD patients that might serve as common points for therapeutic intervention. En ligne : http://dx.doi.org/10.1186/s13229-021-00417-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Mind the translational gap: using iPS cell models to bridge from genetic discoveries to perturbed pathways and therapeutic targets [Texte imprimé et/ou numérique] / Greta PINTACUDA, Auteur ; Jacqueline M. MARTIN, Auteur ; Kevin C. EGGAN, Auteur . - 10p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 10p. Mots-clés : Differentiation  Npc  Neurodevelopment  Neurons  iPSC (induced-pluripotent stem cells)  currently employed at BioMarin Pharmaceutical. Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by impaired social interactions as well as the presentation of restrictive and repetitive behaviors. ASD is highly heritable but genetically heterogenous with both common and rare genetic variants collaborating to predispose individuals to the disorder. In this review, we synthesize recent efforts to develop human induced pluripotent stem cell (iPSC)-derived models of ASD-related phenotypes. We firstly address concerns regarding the relevance and validity of available neuronal iPSC-derived models. We then critically evaluate the robustness of various differentiation and cell culture protocols used for producing cell types of relevance to ASD. By exploring iPSC models of ASD reported thus far, we examine to what extent cellular and neuronal phenotypes with potential relevance to ASD can be linked to genetic variants found to underlie it. Lastly, we outline promising strategies by which iPSC technology can both enhance the power of genetic studies to identify ASD risk factors and nominate pathways that are disrupted across groups of ASD patients that might serve as common points for therapeutic intervention. En ligne : http://dx.doi.org/10.1186/s13229-021-00417-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank / Chloe X. YAP in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 12p. Titre : Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank Type de document : Texte imprimé et/ou numérique Auteurs : Chloe X. YAP, Auteur ; Gail A. ALVARES, Auteur ; Anjali K. HENDERS, Auteur ; Tian LIN, Auteur ; Leanne WALLACE, Auteur ; Alaina FARRELLY, Auteur ; Tiana MCLAREN, Auteur ; Jolene BERRY, Auteur ; Anna A. E. VINKHUYZEN, Auteur ; Maciej TRZASKOWSKI, Auteur ; Jian ZENG, Auteur ; Yuanhao YANG, Auteur ; Dominique CLEARY, Auteur ; Rachel GROVE, Auteur ; Claire HAFEKOST, Auteur ; Alexis HARUN, Auteur ; Helen HOLDSWORTH, Auteur ; Rachel JELLETT, Auteur ; Feroza KHAN, Auteur ; Lauren LAWSON, Auteur ; Jodie LESLIE, Auteur ; Mira LEVIS FRENK, Auteur ; Anne MASI, Auteur ; Nisha E. MATHEW, Auteur ; Melanie MUNIANDY, Auteur ; Michaela NOTHARD, Auteur ; Peter M. VISSCHER, Auteur ; Paul A. DAWSON, Auteur ; Cheryl DISSANAYAKE, Auteur ; Valsamma EAPEN, Auteur ; Helen S. HEUSSLER, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Naomi R. WRAY, Auteur ; Jacob GRATTEN, Auteur Article en page(s) : 12p. Langues : Anglais (eng) Mots-clés : Australian autism biobank  Autism spectrum disorder  Copy number variation  Genetics  Polygenic score Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism. METHODS: Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n?=?871) or suspected (n?=?15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n?=?1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain. RESULTS: The ASD (p?=?6.1e-13), sibling (p?=?4.9e-3) and unrelated (p?=?3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r?=?0.24, p?=?2.1e-3) and parents (r?=?0.17, p?=?8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r?=?0.13, p?=?1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants. LIMITATIONS: This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered. CONCLUSIONS: We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair). En ligne : http://dx.doi.org/10.1186/s13229-020-00407-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank [Texte imprimé et/ou numérique] / Chloe X. YAP, Auteur ; Gail A. ALVARES, Auteur ; Anjali K. HENDERS, Auteur ; Tian LIN, Auteur ; Leanne WALLACE, Auteur ; Alaina FARRELLY, Auteur ; Tiana MCLAREN, Auteur ; Jolene BERRY, Auteur ; Anna A. E. VINKHUYZEN, Auteur ; Maciej TRZASKOWSKI, Auteur ; Jian ZENG, Auteur ; Yuanhao YANG, Auteur ; Dominique CLEARY, Auteur ; Rachel GROVE, Auteur ; Claire HAFEKOST, Auteur ; Alexis HARUN, Auteur ; Helen HOLDSWORTH, Auteur ; Rachel JELLETT, Auteur ; Feroza KHAN, Auteur ; Lauren LAWSON, Auteur ; Jodie LESLIE, Auteur ; Mira LEVIS FRENK, Auteur ; Anne MASI, Auteur ; Nisha E. MATHEW, Auteur ; Melanie MUNIANDY, Auteur ; Michaela NOTHARD, Auteur ; Peter M. VISSCHER, Auteur ; Paul A. DAWSON, Auteur ; Cheryl DISSANAYAKE, Auteur ; Valsamma EAPEN, Auteur ; Helen S. HEUSSLER, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Naomi R. WRAY, Auteur ; Jacob GRATTEN, Auteur . - 12p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 12p. Mots-clés : Australian autism biobank  Autism spectrum disorder  Copy number variation  Genetics  Polygenic score Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism. METHODS: Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n?=?871) or suspected (n?=?15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n?=?1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain. RESULTS: The ASD (p?=?6.1e-13), sibling (p?=?4.9e-3) and unrelated (p?=?3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r?=?0.24, p?=?2.1e-3) and parents (r?=?0.17, p?=?8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r?=?0.13, p?=?1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants. LIMITATIONS: This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered. CONCLUSIONS: We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair). En ligne : http://dx.doi.org/10.1186/s13229-020-00407-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Is social camouflaging associated with anxiety and depression in autistic adults? / L. HULL in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 13 p. Titre : Is social camouflaging associated with anxiety and depression in autistic adults? Type de document : Texte imprimé et/ou numérique Auteurs : L. HULL, Auteur ; L. LEVY, Auteur ; Meng-Chuan LAI, Auteur ; K. V. PETRIDES, Auteur ; Simon BARON-COHEN, Auteur ; Carrie ALLISON, Auteur ; P. SMITH, Auteur ; W. MANDY, Auteur Article en page(s) : 13 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Aged  Anxiety/diagnosis/psychology  Autistic Disorder/diagnosis/etiology/psychology  Depression/diagnosis/etiology/psychology  Disease Susceptibility  Female  Humans  Male  Mental Health  Middle Aged  Public Health Surveillance  Self Report  Social Behavior  Surveys and Questionnaires  Young Adult  Adults  Camouflaging  Gender  Mental health Index. décimale : PER Périodiques Résumé : BACKGROUND: There is inconsistent evidence for a clear pattern of association between 'camouflaging' (strategies used to mask and/or compensate for autism characteristics during social interactions) and mental health. METHODS: This study explored the relationship between self-reported camouflaging and generalised anxiety, depression, and social anxiety in a large sample of autistic adults and, for the first time, explored the moderating effect of gender, in an online survey. RESULTS: Overall, camouflaging was associated with greater symptoms of generalised anxiety, depression, and social anxiety, although only to a small extent beyond the contribution of autistic traits and age. Camouflaging more strongly predicted generalised and social anxiety than depression. No interaction between camouflaging and gender was found. LIMITATIONS: These results cannot be generalised to autistic people with intellectual disability, or autistic children and young people. The sample did not include sufficient numbers of non-binary people to run separate analyses; therefore, it is possible that camouflaging impacts mental health differently in this population. CONCLUSIONS: The findings suggest that camouflaging is a risk factor for mental health problems in autistic adults without intellectual disability, regardless of gender. We also identified levels of camouflaging at which risk of mental health problems is highest, suggesting clinicians should be particularly aware of mental health problems in those who score at or above these levels. En ligne : http://dx.doi.org/10.1186/s13229-021-00421-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Is social camouflaging associated with anxiety and depression in autistic adults? [Texte imprimé et/ou numérique] / L. HULL, Auteur ; L. LEVY, Auteur ; Meng-Chuan LAI, Auteur ; K. V. PETRIDES, Auteur ; Simon BARON-COHEN, Auteur ; Carrie ALLISON, Auteur ; P. SMITH, Auteur ; W. MANDY, Auteur . - 13 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 13 p. Mots-clés : Adolescent  Adult  Aged  Anxiety/diagnosis/psychology  Autistic Disorder/diagnosis/etiology/psychology  Depression/diagnosis/etiology/psychology  Disease Susceptibility  Female  Humans  Male  Mental Health  Middle Aged  Public Health Surveillance  Self Report  Social Behavior  Surveys and Questionnaires  Young Adult  Adults  Camouflaging  Gender  Mental health Index. décimale : PER Périodiques Résumé : BACKGROUND: There is inconsistent evidence for a clear pattern of association between 'camouflaging' (strategies used to mask and/or compensate for autism characteristics during social interactions) and mental health. METHODS: This study explored the relationship between self-reported camouflaging and generalised anxiety, depression, and social anxiety in a large sample of autistic adults and, for the first time, explored the moderating effect of gender, in an online survey. RESULTS: Overall, camouflaging was associated with greater symptoms of generalised anxiety, depression, and social anxiety, although only to a small extent beyond the contribution of autistic traits and age. Camouflaging more strongly predicted generalised and social anxiety than depression. No interaction between camouflaging and gender was found. LIMITATIONS: These results cannot be generalised to autistic people with intellectual disability, or autistic children and young people. The sample did not include sufficient numbers of non-binary people to run separate analyses; therefore, it is possible that camouflaging impacts mental health differently in this population. CONCLUSIONS: The findings suggest that camouflaging is a risk factor for mental health problems in autistic adults without intellectual disability, regardless of gender. We also identified levels of camouflaging at which risk of mental health problems is highest, suggesting clinicians should be particularly aware of mental health problems in those who score at or above these levels. En ligne : http://dx.doi.org/10.1186/s13229-021-00421-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine / R. H. WICHERS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 14 p. Titre : Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine Type de document : Texte imprimé et/ou numérique Auteurs : R. H. WICHERS, Auteur ; J. L. FINDON, Auteur ; A. JELSMA, Auteur ; V. GIAMPIETRO, Auteur ; V. STOENCHEVA, Auteur ; D. M. ROBERTSON, Auteur ; C. M. MURPHY, Auteur ; S. BLAINEY, Auteur ; G. MCALONAN, Auteur ; C. ECKER, Auteur ; K. RUBIA, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Adult  Antidepressive Agents, Tricyclic/therapeutic use  Attention/drug effects  Autistic Disorder/diagnostic imaging/drug therapy/physiopathology/psychology  Brain/diagnostic imaging/physiopathology  Cross-Over Studies  Double-Blind Method  Executive Function/drug effects  Humans  Magnetic Resonance Imaging  Male  Middle Aged  Pilot Projects  Thiazepines/therapeutic use  Young Adult  Autism spectrum disorder  Executive functioning  Serotonin  Tianeptine  fMRI  grants from Lilly and Shire. The other authors declare that they have no competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD: We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. RESULTS: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS: We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms. En ligne : http://dx.doi.org/10.1186/s13229-021-00422-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine [Texte imprimé et/ou numérique] / R. H. WICHERS, Auteur ; J. L. FINDON, Auteur ; A. JELSMA, Auteur ; V. GIAMPIETRO, Auteur ; V. STOENCHEVA, Auteur ; D. M. ROBERTSON, Auteur ; C. M. MURPHY, Auteur ; S. BLAINEY, Auteur ; G. MCALONAN, Auteur ; C. ECKER, Auteur ; K. RUBIA, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur . - 14 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 14 p. Mots-clés : Adult  Antidepressive Agents, Tricyclic/therapeutic use  Attention/drug effects  Autistic Disorder/diagnostic imaging/drug therapy/physiopathology/psychology  Brain/diagnostic imaging/physiopathology  Cross-Over Studies  Double-Blind Method  Executive Function/drug effects  Humans  Magnetic Resonance Imaging  Male  Middle Aged  Pilot Projects  Thiazepines/therapeutic use  Young Adult  Autism spectrum disorder  Executive functioning  Serotonin  Tianeptine  fMRI  grants from Lilly and Shire. The other authors declare that they have no competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD: We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. RESULTS: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS: We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms. En ligne : http://dx.doi.org/10.1186/s13229-021-00422-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms / Y. KATO in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 15 p. Titre : Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms Type de document : Texte imprimé et/ou numérique Auteurs : Y. KATO, Auteur ; H. KUWABARA, Auteur ; T. OKADA, Auteur ; T. MUNESUE, Auteur ; S. BENNER, Auteur ; M. KURODA, Auteur ; M. KOJIMA, Auteur ; W. YASSIN, Auteur ; Y. ERIGUCHI, Auteur ; Y. KAMENO, Auteur ; C. MURAYAMA, Auteur ; T. NISHIMURA, Auteur ; K. TSUCHIYA, Auteur ; Kiyoto KASAI, Auteur ; N. OZAKI, Auteur ; H. KOSAKA, Auteur ; H. YAMASUE, Auteur Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : Administration, Intranasal  Adolescent  Adult  Autistic Disorder/blood/drug therapy/metabolism/psychology  Double-Blind Method  Facial Expression  Humans  Male  Metabolomics  Middle Aged  Oxytocin/administration & dosage/blood/pharmacokinetics  Sarcosine/analogs & derivatives/blood  Social Behavior  Treatment Outcome  Young Adult  Asperger  Autism  Clinical trial  Developmental disorders  Facial expression  N,N-Dimethylglycine  Neuropeptide  Oxytocin  Plasticity  collection, management, analysis, and interpretation of the data  preparation,  review, or approval of the manuscript  or decision to submit the manuscript for  publication. There are no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N?=?106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P?=?0.043, d?=?0.74, N?=?83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P(FDR)?=?0.004, d?=?1.13, N?=?60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (P(FDR)?=?0.006, r?=?-?0.485, N?=?43) and deteriorations between 2 and 4 weeks (P(FDR)?=?0.032, r?=?0.415, N?=?37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264). En ligne : http://dx.doi.org/10.1186/s13229-021-00423-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms [Texte imprimé et/ou numérique] / Y. KATO, Auteur ; H. KUWABARA, Auteur ; T. OKADA, Auteur ; T. MUNESUE, Auteur ; S. BENNER, Auteur ; M. KURODA, Auteur ; M. KOJIMA, Auteur ; W. YASSIN, Auteur ; Y. ERIGUCHI, Auteur ; Y. KAMENO, Auteur ; C. MURAYAMA, Auteur ; T. NISHIMURA, Auteur ; K. TSUCHIYA, Auteur ; Kiyoto KASAI, Auteur ; N. OZAKI, Auteur ; H. KOSAKA, Auteur ; H. YAMASUE, Auteur . - 15 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 15 p. Mots-clés : Administration, Intranasal  Adolescent  Adult  Autistic Disorder/blood/drug therapy/metabolism/psychology  Double-Blind Method  Facial Expression  Humans  Male  Metabolomics  Middle Aged  Oxytocin/administration & dosage/blood/pharmacokinetics  Sarcosine/analogs & derivatives/blood  Social Behavior  Treatment Outcome  Young Adult  Asperger  Autism  Clinical trial  Developmental disorders  Facial expression  N,N-Dimethylglycine  Neuropeptide  Oxytocin  Plasticity  collection, management, analysis, and interpretation of the data  preparation,  review, or approval of the manuscript  or decision to submit the manuscript for  publication. There are no conflicts of interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. METHODS: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N?=?106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. RESULTS: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P?=?0.043, d?=?0.74, N?=?83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P(FDR)?=?0.004, d?=?1.13, N?=?60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (P(FDR)?=?0.006, r?=?-?0.485, N?=?43) and deteriorations between 2 and 4 weeks (P(FDR)?=?0.032, r?=?0.415, N?=?37). LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. CONCLUSION: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy. TRIAL REGISTRATION: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264). En ligne : http://dx.doi.org/10.1186/s13229-021-00423-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development / S. HURLEY in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 16 p. Titre : Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development Type de document : Texte imprimé et/ou numérique Auteurs : S. HURLEY, Auteur ; C. MOHAN, Auteur ; P. SUETTERLIN, Auteur ; R. ELLINGFORD, Auteur ; K. L. H. RIEGMAN, Auteur ; J. ELLEGOOD, Auteur ; A. CARUSO, Auteur ; C. MICHETTI, Auteur ; O. BROCK, Auteur ; R. EVANS, Auteur ; F. RUDARI, Auteur ; A. DELOGU, Auteur ; M. L. SCATTONI, Auteur ; J. P. LERCH, Auteur ; C. FERNANDES, Auteur ; M. A. BASSON, Auteur Article en page(s) : 16 p. Langues : Anglais (eng) Mots-clés : Animals  Animals, Newborn  Autistic Disorder/genetics  Behavior, Animal  Brain/diagnostic imaging/embryology/growth & development  Cell Proliferation  DNA-Binding Proteins/deficiency/genetics  Disease Models, Animal  Female  Gene Expression Regulation, Developmental  Mice, Transgenic  Phenotype  Pregnancy  Stem Cells  Tumor Suppressor Protein p53/genetics  Apoptosis  Autism  Chd8  Chromatin  Conditional knockout  Cortex  Gene expression  Hypomorph  Intermediate progenitor  Mouse  Neural progenitor  Proliferation  Tbr2  p53  Pathways plc. This work is unrelated to COMPASS Pathways plc. No other competing  interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: CHD8 haploinsufficiency causes autism and macrocephaly with high penetrance in the human population. Chd8 heterozygous mice exhibit relatively subtle brain overgrowth and little gene expression changes in the embryonic neocortex. The purpose of this study was to generate new, sub-haploinsufficient Chd8 mouse models to allow us to identify and study the functions of CHD8 during embryonic cortical development. METHODS: To examine the possibility that certain phenotypes may only appear at sub-heterozygous Chd8 levels in the mouse, we created an allelic series of Chd8-deficient mice to reduce CHD8 protein levels to approximately 35% (mild hypomorph), 10% (severe hypomorph) and 0% (neural-specific conditional knockout) of wildtype levels. We used RNA sequencing to compare transcriptional dysregulation, structural MRI and brain weight to investigate effects on brain size, and cell proliferation, differentiation and apoptosis markers in immunostaining assays to quantify changes in neural progenitor fate. RESULTS: Mild Chd8 hypomorphs displayed significant postnatal lethality, with surviving animals exhibiting more pronounced brain hyperplasia than heterozygotes. Over 2000 genes were dysregulated in mild hypomorphs, including autism-associated neurodevelopmental and cell cycle genes. We identify increased proliferation of non-ventricular zone TBR2+ intermediate progenitors as one potential cause of brain hyperplasia in these mutants. Severe Chd8 hypomorphs displayed even greater transcriptional dysregulation, including evidence for p53 pathway upregulation. In contrast to mild hypomorphs, these mice displayed reduced brain size and increased apoptosis in the embryonic neocortex. Homozygous, conditional deletion of Chd8 in early neuronal progenitors resulted in pronounced brain hypoplasia, partly caused by p53 target gene derepression and apoptosis in the embryonic neocortex. Limitations Our findings identify an important role for the autism-associated factor CHD8 in controlling the proliferation of intermediate progenitors in the mouse neocortex. We propose that CHD8 has a similar function in human brain development, but studies on human cells are required to confirm this. Because many of our mouse mutants with reduced CHD8 function die shortly after birth, it is not possible to fully determine to what extent reduced CHD8 function results in autism-associated behaviours in mice. CONCLUSIONS: Together, these findings identify important, dosage-sensitive functions for CHD8 in p53 pathway repression, neurodevelopmental gene expression and neural progenitor fate in the embryonic neocortex. We conclude that brain development is acutely sensitive to reduced CHD8 expression and that the varying sensitivities of different progenitor populations and cellular processes to CHD8 dosage result in non-linear effects on gene transcription and brain growth. Shaun Hurley, Conor Mohan and Philipp Suetterlin have contributed equally to this work. En ligne : http://dx.doi.org/10.1186/s13229-020-00409-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Distinct, dosage-sensitive requirements for the autism-associated factor CHD8 during cortical development [Texte imprimé et/ou numérique] / S. HURLEY, Auteur ; C. MOHAN, Auteur ; P. SUETTERLIN, Auteur ; R. ELLINGFORD, Auteur ; K. L. H. RIEGMAN, Auteur ; J. ELLEGOOD, Auteur ; A. CARUSO, Auteur ; C. MICHETTI, Auteur ; O. BROCK, Auteur ; R. EVANS, Auteur ; F. RUDARI, Auteur ; A. DELOGU, Auteur ; M. L. SCATTONI, Auteur ; J. P. LERCH, Auteur ; C. FERNANDES, Auteur ; M. A. BASSON, Auteur . - 16 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 16 p. Mots-clés : Animals  Animals, Newborn  Autistic Disorder/genetics  Behavior, Animal  Brain/diagnostic imaging/embryology/growth & development  Cell Proliferation  DNA-Binding Proteins/deficiency/genetics  Disease Models, Animal  Female  Gene Expression Regulation, Developmental  Mice, Transgenic  Phenotype  Pregnancy  Stem Cells  Tumor Suppressor Protein p53/genetics  Apoptosis  Autism  Chd8  Chromatin  Conditional knockout  Cortex  Gene expression  Hypomorph  Intermediate progenitor  Mouse  Neural progenitor  Proliferation  Tbr2  p53  Pathways plc. This work is unrelated to COMPASS Pathways plc. No other competing  interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: CHD8 haploinsufficiency causes autism and macrocephaly with high penetrance in the human population. Chd8 heterozygous mice exhibit relatively subtle brain overgrowth and little gene expression changes in the embryonic neocortex. The purpose of this study was to generate new, sub-haploinsufficient Chd8 mouse models to allow us to identify and study the functions of CHD8 during embryonic cortical development. METHODS: To examine the possibility that certain phenotypes may only appear at sub-heterozygous Chd8 levels in the mouse, we created an allelic series of Chd8-deficient mice to reduce CHD8 protein levels to approximately 35% (mild hypomorph), 10% (severe hypomorph) and 0% (neural-specific conditional knockout) of wildtype levels. We used RNA sequencing to compare transcriptional dysregulation, structural MRI and brain weight to investigate effects on brain size, and cell proliferation, differentiation and apoptosis markers in immunostaining assays to quantify changes in neural progenitor fate. RESULTS: Mild Chd8 hypomorphs displayed significant postnatal lethality, with surviving animals exhibiting more pronounced brain hyperplasia than heterozygotes. Over 2000 genes were dysregulated in mild hypomorphs, including autism-associated neurodevelopmental and cell cycle genes. We identify increased proliferation of non-ventricular zone TBR2+ intermediate progenitors as one potential cause of brain hyperplasia in these mutants. Severe Chd8 hypomorphs displayed even greater transcriptional dysregulation, including evidence for p53 pathway upregulation. In contrast to mild hypomorphs, these mice displayed reduced brain size and increased apoptosis in the embryonic neocortex. Homozygous, conditional deletion of Chd8 in early neuronal progenitors resulted in pronounced brain hypoplasia, partly caused by p53 target gene derepression and apoptosis in the embryonic neocortex. Limitations Our findings identify an important role for the autism-associated factor CHD8 in controlling the proliferation of intermediate progenitors in the mouse neocortex. We propose that CHD8 has a similar function in human brain development, but studies on human cells are required to confirm this. Because many of our mouse mutants with reduced CHD8 function die shortly after birth, it is not possible to fully determine to what extent reduced CHD8 function results in autism-associated behaviours in mice. CONCLUSIONS: Together, these findings identify important, dosage-sensitive functions for CHD8 in p53 pathway repression, neurodevelopmental gene expression and neural progenitor fate in the embryonic neocortex. We conclude that brain development is acutely sensitive to reduced CHD8 expression and that the varying sensitivities of different progenitor populations and cellular processes to CHD8 dosage result in non-linear effects on gene transcription and brain growth. Shaun Hurley, Conor Mohan and Philipp Suetterlin have contributed equally to this work. En ligne : http://dx.doi.org/10.1186/s13229-020-00409-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile / G. AGAR in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 18 p. Titre : Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile Type de document : Texte imprimé et/ou numérique Auteurs : G. AGAR, Auteur ; C. BROWN, Auteur ; D. SUTHERLAND, Auteur ; S. COULBORN, Auteur ; C. OLIVER, Auteur ; C. RICHARDS, Auteur Article en page(s) : 18 p. Langues : Anglais (eng) Mots-clés : Congenital Abnormalities/epidemiology  Humans  Prevalence  Sleep Wake Disorders/epidemiology  Syndrome  Genetic syndromes  Intellectual disability  Meta-analysis  Sleep disorders  Sleep profile Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disorders are common in people with intellectual disability (ID) and autism, with growing evidence of diverse sleep profiles across ID associated genetic syndromes. Documenting the prevalence and profile of specific sleep disorders in syndromes will quantify syndrome-driven 'risk', inform prognosis and enhance understanding of aetiology of sleep disorders. METHOD: Following PRISMA guidelines for meta-analysis, we searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, Web of Science and PubMed Central with use of syndrome-specific keywords and 60 sleep-related search terms. We screened and extracted papers that reported sleep disorder prevalence data for five or more individuals within a genetic syndrome, and applied quality criteria to produce a quality-effects prevalence model of six types of sleep disorder across nineteen syndromes. Relative risk estimates were calculated for the prevalence of each sleep disorder in each syndrome. RESULTS: Two hundred and seventy three papers were identified, generating 463 prevalence estimates for Angelman, CHARGE, Cornelia de Lange, Down, fragile X, Prader-Willi, Rett, Smith-Magenis and Williams syndromes, mucopolysaccharidoses (MPS disorders), neurofibromatosis and tuberous sclerosis complex. Prevalence estimates were higher in genetic syndromes than published equivalents for typically developing individuals, with few exceptions. Between-syndrome differences for some disorders were evident; sleep-disordered breathing was most prevalent in MPS disorders (72-77%), while excessive daytime sleepiness was highest in Smith-Magenis syndrome (60%). Conversely, insomnia, which was reported at a higher rate than TD estimates in all syndromes except fragile X, was not associated with specific genetic risk. This suggests insomnia could emerge because of the individual's environment or associated developmental delay, rather than any specific genetic syndromes. LIMITATIONS: Due to the broad scope of the meta-analysis, only syndromes previously identified as reporting preliminary sleep research were included. Other syndromes may also experience elevated prevalence rates of specific types of sleep disorder. Only English language papers were included. CONCLUSIONS: Differing prevalence rates between types of sleep disorder suggest differing causal mechanisms, such as cranio-facial morphology in Down and Prader-Willi syndromes and the build-up of mucopolysaccharides in MPS disorders. Priorities for clinical assessment and intervention for sleep disorders are discussed. En ligne : http://dx.doi.org/10.1186/s13229-021-00426-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile [Texte imprimé et/ou numérique] / G. AGAR, Auteur ; C. BROWN, Auteur ; D. SUTHERLAND, Auteur ; S. COULBORN, Auteur ; C. OLIVER, Auteur ; C. RICHARDS, Auteur . - 18 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 18 p. Mots-clés : Congenital Abnormalities/epidemiology  Humans  Prevalence  Sleep Wake Disorders/epidemiology  Syndrome  Genetic syndromes  Intellectual disability  Meta-analysis  Sleep disorders  Sleep profile Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disorders are common in people with intellectual disability (ID) and autism, with growing evidence of diverse sleep profiles across ID associated genetic syndromes. Documenting the prevalence and profile of specific sleep disorders in syndromes will quantify syndrome-driven 'risk', inform prognosis and enhance understanding of aetiology of sleep disorders. METHOD: Following PRISMA guidelines for meta-analysis, we searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, Web of Science and PubMed Central with use of syndrome-specific keywords and 60 sleep-related search terms. We screened and extracted papers that reported sleep disorder prevalence data for five or more individuals within a genetic syndrome, and applied quality criteria to produce a quality-effects prevalence model of six types of sleep disorder across nineteen syndromes. Relative risk estimates were calculated for the prevalence of each sleep disorder in each syndrome. RESULTS: Two hundred and seventy three papers were identified, generating 463 prevalence estimates for Angelman, CHARGE, Cornelia de Lange, Down, fragile X, Prader-Willi, Rett, Smith-Magenis and Williams syndromes, mucopolysaccharidoses (MPS disorders), neurofibromatosis and tuberous sclerosis complex. Prevalence estimates were higher in genetic syndromes than published equivalents for typically developing individuals, with few exceptions. Between-syndrome differences for some disorders were evident; sleep-disordered breathing was most prevalent in MPS disorders (72-77%), while excessive daytime sleepiness was highest in Smith-Magenis syndrome (60%). Conversely, insomnia, which was reported at a higher rate than TD estimates in all syndromes except fragile X, was not associated with specific genetic risk. This suggests insomnia could emerge because of the individual's environment or associated developmental delay, rather than any specific genetic syndromes. LIMITATIONS: Due to the broad scope of the meta-analysis, only syndromes previously identified as reporting preliminary sleep research were included. Other syndromes may also experience elevated prevalence rates of specific types of sleep disorder. Only English language papers were included. CONCLUSIONS: Differing prevalence rates between types of sleep disorder suggest differing causal mechanisms, such as cranio-facial morphology in Down and Prader-Willi syndromes and the build-up of mucopolysaccharides in MPS disorders. Priorities for clinical assessment and intervention for sleep disorders are discussed. En ligne : http://dx.doi.org/10.1186/s13229-021-00426-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Increased aperiodic gamma power in young boys with Fragile X Syndrome is associated with better language ability / C. L. WILKINSON in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 17 p. Titre : Increased aperiodic gamma power in young boys with Fragile X Syndrome is associated with better language ability Type de document : Texte imprimé et/ou numérique Auteurs : C. L. WILKINSON, Auteur ; C. A. NELSON, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Brain/physiopathology  Child  Child Language  Child, Preschool  Electroencephalography  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/genetics/physiopathology/psychology  Humans  Male  Biomarker  E:I ratio  Fragile X Syndrome  Gamma  Language  Outcome measures Index. décimale : PER Périodiques Résumé : BACKGROUND: The lack of robust and reliable clinical biomarkers in Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, has limited the successful translation of bench-to-bedside therapeutics. While numerous drugs have shown promise in reversing synaptic and behavioral phenotypes in mouse models of FXS, none have demonstrated clinical efficacy in humans. Electroencephalographic (EEG) measures have been identified as candidate biomarkers as EEG recordings of both adults with FXS and mouse models of FXS consistently exhibit alterations in resting state and task-related activity. However, the developmental timing of these EEG differences is not known as thus far EEG studies have not focused on young children with FXS. Further, understanding how EEG differences are associated with core symptoms of FXS is crucial to successful use of EEG as a biomarker, and may improve our understanding of the disorder. METHODS: Resting-state EEG was collected from FXS boys with full mutation of Fmr1 (2.5-7 years old, n?=?11) and compared with both age-matched (n?=?12) and cognitive-matched (n?=?12) typically developing boys. Power spectra (including aperiodic and periodic components) were compared using non-parametric cluster-based permutation testing. Associations between 30 and 50 Hz gamma power and cognitive, language, and behavioral measures were evaluated using Pearson correlation and linear regression with age as a covariate. RESULTS: FXS participants showed increased power in the beta/gamma range (~?25-50 Hz) across multiple brain regions. Both a reduction in the aperiodic (1/f) slope and increase in beta/gamma periodic activity contributed to the significant increase in high-frequency power. Increased gamma power, driven by the aperiodic component, was associated with better language ability in the FXS group. No association was observed between gamma power and parent report measures of behavioral challenges, sensory hypersensitivities, or adaptive behaviors. LIMITATIONS: The study sample size was small, although comparable to other human studies in rare-genetic disorders. Findings are also limited to males in the age range studied. CONCLUSIONS: Resting-state EEG measures from this study in young boys with FXS identified similar increases in gamma power previously reported in adults and mouse models. The observed positive association between resting state aperiodic gamma power and language development supports hypotheses that alterations in some EEG measures may reflect ongoing compensatory mechanisms. En ligne : http://dx.doi.org/10.1186/s13229-021-00425-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Increased aperiodic gamma power in young boys with Fragile X Syndrome is associated with better language ability [Texte imprimé et/ou numérique] / C. L. WILKINSON, Auteur ; C. A. NELSON, Auteur . - 17 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 17 p. Mots-clés : Brain/physiopathology  Child  Child Language  Child, Preschool  Electroencephalography  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/genetics/physiopathology/psychology  Humans  Male  Biomarker  E:I ratio  Fragile X Syndrome  Gamma  Language  Outcome measures Index. décimale : PER Périodiques Résumé : BACKGROUND: The lack of robust and reliable clinical biomarkers in Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, has limited the successful translation of bench-to-bedside therapeutics. While numerous drugs have shown promise in reversing synaptic and behavioral phenotypes in mouse models of FXS, none have demonstrated clinical efficacy in humans. Electroencephalographic (EEG) measures have been identified as candidate biomarkers as EEG recordings of both adults with FXS and mouse models of FXS consistently exhibit alterations in resting state and task-related activity. However, the developmental timing of these EEG differences is not known as thus far EEG studies have not focused on young children with FXS. Further, understanding how EEG differences are associated with core symptoms of FXS is crucial to successful use of EEG as a biomarker, and may improve our understanding of the disorder. METHODS: Resting-state EEG was collected from FXS boys with full mutation of Fmr1 (2.5-7 years old, n?=?11) and compared with both age-matched (n?=?12) and cognitive-matched (n?=?12) typically developing boys. Power spectra (including aperiodic and periodic components) were compared using non-parametric cluster-based permutation testing. Associations between 30 and 50 Hz gamma power and cognitive, language, and behavioral measures were evaluated using Pearson correlation and linear regression with age as a covariate. RESULTS: FXS participants showed increased power in the beta/gamma range (~?25-50 Hz) across multiple brain regions. Both a reduction in the aperiodic (1/f) slope and increase in beta/gamma periodic activity contributed to the significant increase in high-frequency power. Increased gamma power, driven by the aperiodic component, was associated with better language ability in the FXS group. No association was observed between gamma power and parent report measures of behavioral challenges, sensory hypersensitivities, or adaptive behaviors. LIMITATIONS: The study sample size was small, although comparable to other human studies in rare-genetic disorders. Findings are also limited to males in the age range studied. CONCLUSIONS: Resting-state EEG measures from this study in young boys with FXS identified similar increases in gamma power previously reported in adults and mouse models. The observed positive association between resting state aperiodic gamma power and language development supports hypotheses that alterations in some EEG measures may reflect ongoing compensatory mechanisms. En ligne : http://dx.doi.org/10.1186/s13229-021-00425-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Towards robust and replicable sex differences in the intrinsic brain function of autism / D. L. FLORIS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 19 p. Titre : Towards robust and replicable sex differences in the intrinsic brain function of autism Type de document : Texte imprimé et/ou numérique Auteurs : D. L. FLORIS, Auteur ; J. O. A. FILHO, Auteur ; Meng-Chuan LAI, Auteur ; S. GIAVASIS, Auteur ; M. OLDEHINKEL, Auteur ; M. MENNES, Auteur ; Tony CHARMAN, Auteur ; J. TILLMANN, Auteur ; G. DUMAS, Auteur ; C. ECKER, Auteur ; F. DELL'ACQUA, Auteur ; Tobias BANASCHEWSKI, Auteur ; C. MOESSNANG, Auteur ; Simon BARON-COHEN, Auteur ; S. DURSTON, Auteur ; E. LOTH, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; M. P. MILHAM, Auteur ; A. DI MARTINO, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Adolescent  Autistic Disorder/diagnostic imaging/physiopathology  Brain/diagnostic imaging/physiopathology  Child  Female  Humans  Magnetic Resonance Imaging  Male  Sex Characteristics  Autism spectrum disorder  Replication  Resting-state functional connectivity  Robustness  Sex differences  Voxel-mirrored homotopic connectivity  Responsiveness Scale—Child Version by Organization Speciali, Italy. JKB has been a  consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice,  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. CFB is director and  shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and  received book royalties from Guildford Press and Sage. DM has been a consultant to,  and advisory board member, for Roche and Servier. He is not an employee of any of  these companies, and not a stock shareholder of any of these companies. TB served in  an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals,  Oberberg GmbH, Shire, and Infectopharm. He received conference support or speaker’s  fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP  Medien, Oxford University Press  the present work is unrelated to these  relationships. JT is a consultant to Roche. The remaining authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. METHODS: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z?>?3.1, cluster-level P? En ligne : http://dx.doi.org/10.1186/s13229-021-00415-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Towards robust and replicable sex differences in the intrinsic brain function of autism [Texte imprimé et/ou numérique] / D. L. FLORIS, Auteur ; J. O. A. FILHO, Auteur ; Meng-Chuan LAI, Auteur ; S. GIAVASIS, Auteur ; M. OLDEHINKEL, Auteur ; M. MENNES, Auteur ; Tony CHARMAN, Auteur ; J. TILLMANN, Auteur ; G. DUMAS, Auteur ; C. ECKER, Auteur ; F. DELL'ACQUA, Auteur ; Tobias BANASCHEWSKI, Auteur ; C. MOESSNANG, Auteur ; Simon BARON-COHEN, Auteur ; S. DURSTON, Auteur ; E. LOTH, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; M. P. MILHAM, Auteur ; A. DI MARTINO, Auteur . - 19 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 19 p. Mots-clés : Adolescent  Autistic Disorder/diagnostic imaging/physiopathology  Brain/diagnostic imaging/physiopathology  Child  Female  Humans  Magnetic Resonance Imaging  Male  Sex Characteristics  Autism spectrum disorder  Replication  Resting-state functional connectivity  Robustness  Sex differences  Voxel-mirrored homotopic connectivity  Responsiveness Scale—Child Version by Organization Speciali, Italy. JKB has been a  consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice,  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. CFB is director and  shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and  received book royalties from Guildford Press and Sage. DM has been a consultant to,  and advisory board member, for Roche and Servier. He is not an employee of any of  these companies, and not a stock shareholder of any of these companies. TB served in  an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals,  Oberberg GmbH, Shire, and Infectopharm. He received conference support or speaker’s  fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP  Medien, Oxford University Press  the present work is unrelated to these  relationships. JT is a consultant to Roche. The remaining authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. METHODS: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z?>?3.1, cluster-level P? En ligne : http://dx.doi.org/10.1186/s13229-021-00415-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Improving the measurement of alexithymia in autistic adults: a psychometric investigation and refinement of the twenty-item Toronto Alexithymia Scale / Z. J. WILLIAMS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 20 p. Titre : Improving the measurement of alexithymia in autistic adults: a psychometric investigation and refinement of the twenty-item Toronto Alexithymia Scale Type de document : Texte imprimé et/ou numérique Auteurs : Z. J. WILLIAMS, Auteur ; K. O. GOTHAM, Auteur Article en page(s) : 20 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Affective Symptoms/diagnosis  Autistic Disorder/psychology  Factor Analysis, Statistical  Female  Humans  Male  Psychiatric Status Rating Scales  Psychometrics  Reproducibility of Results  Surveys and Questionnaires  Young Adult  Alexithymia  Autism  Bayesian statistics  Differential item functioning  Emotion  Factor analysis  Item response theory  Measurement  Psychometric  Reliability  Validity  Network Vanderbilt site and the autistic researcher review board of the Autism  Intervention Network for Physical Health (AIR-P). ZJW also serves as a consultant to  Roche. KOG has no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Alexithymia, a personality trait characterized by difficulties interpreting one's own emotional states, is commonly elevated in autistic adults, and a growing body of literature suggests that this trait underlies a number of cognitive and emotional differences previously attributed to autism, such as difficulties in facial emotion recognition and reduced empathy. Although questionnaires such as the twenty-item Toronto Alexithymia Scale (TAS-20) are frequently used to measure alexithymia in the autistic population, few studies have attempted to determine the psychometric properties of these questionnaires in autistic adults, including whether differential item functioning (I-DIF) exists between autistic and general population adults. METHODS: We conducted an in-depth psychometric analysis of the TAS-20 in a large sample of 743 verbal autistic adults recruited from the Simons Foundation SPARK participant pool and 721 general population controls enrolled in a large international psychological study (the Human Penguin Project). The factor structure of the TAS-20 was examined using confirmatory factor analysis, and item response theory was used to further refine the scale based on local model misfit and I-DIF between the groups. Correlations between alexithymia and other clinical outcomes such as autistic traits, anxiety, and quality-of-life were used to assess the nomological validity of the revised alexithymia scale in the SPARK sample. RESULTS: The TAS-20 did not exhibit adequate global model fit in either the autistic or general population samples. Empirically driven item reduction was undertaken, resulting in an eight-item unidimensional scale (TAS-8) with sound psychometric properties and practically ignorable I-DIF between diagnostic groups. Correlational analyses indicated that TAS-8 scores meaningfully predict autistic trait levels, anxiety and depression symptoms, and quality of life, even after controlling for trait neuroticism. LIMITATIONS: Limitations of the current study include a sample of autistic adults that was overwhelmingly female, later-diagnosed, and well-educated; clinical and control groups drawn from different studies with variable measures; and an inability to test several other important psychometric characteristics of the TAS-8, including sensitivity to change and I-DIF across multiple administrations. CONCLUSIONS: These results indicate the potential of the TAS-8 as a psychometrically robust tool to measure alexithymia in both autistic and non-autistic adults. A free online score calculator has been created to facilitate the use of norm-referenced TAS-8 latent trait scores in research applications (available at http://asdmeasures.shinyapps.io/TAS8_Score ). En ligne : http://dx.doi.org/10.1186/s13229-021-00427-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Improving the measurement of alexithymia in autistic adults: a psychometric investigation and refinement of the twenty-item Toronto Alexithymia Scale [Texte imprimé et/ou numérique] / Z. J. WILLIAMS, Auteur ; K. O. GOTHAM, Auteur . - 20 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 20 p. Mots-clés : Adolescent  Adult  Affective Symptoms/diagnosis  Autistic Disorder/psychology  Factor Analysis, Statistical  Female  Humans  Male  Psychiatric Status Rating Scales  Psychometrics  Reproducibility of Results  Surveys and Questionnaires  Young Adult  Alexithymia  Autism  Bayesian statistics  Differential item functioning  Emotion  Factor analysis  Item response theory  Measurement  Psychometric  Reliability  Validity  Network Vanderbilt site and the autistic researcher review board of the Autism  Intervention Network for Physical Health (AIR-P). ZJW also serves as a consultant to  Roche. KOG has no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Alexithymia, a personality trait characterized by difficulties interpreting one's own emotional states, is commonly elevated in autistic adults, and a growing body of literature suggests that this trait underlies a number of cognitive and emotional differences previously attributed to autism, such as difficulties in facial emotion recognition and reduced empathy. Although questionnaires such as the twenty-item Toronto Alexithymia Scale (TAS-20) are frequently used to measure alexithymia in the autistic population, few studies have attempted to determine the psychometric properties of these questionnaires in autistic adults, including whether differential item functioning (I-DIF) exists between autistic and general population adults. METHODS: We conducted an in-depth psychometric analysis of the TAS-20 in a large sample of 743 verbal autistic adults recruited from the Simons Foundation SPARK participant pool and 721 general population controls enrolled in a large international psychological study (the Human Penguin Project). The factor structure of the TAS-20 was examined using confirmatory factor analysis, and item response theory was used to further refine the scale based on local model misfit and I-DIF between the groups. Correlations between alexithymia and other clinical outcomes such as autistic traits, anxiety, and quality-of-life were used to assess the nomological validity of the revised alexithymia scale in the SPARK sample. RESULTS: The TAS-20 did not exhibit adequate global model fit in either the autistic or general population samples. Empirically driven item reduction was undertaken, resulting in an eight-item unidimensional scale (TAS-8) with sound psychometric properties and practically ignorable I-DIF between diagnostic groups. Correlational analyses indicated that TAS-8 scores meaningfully predict autistic trait levels, anxiety and depression symptoms, and quality of life, even after controlling for trait neuroticism. LIMITATIONS: Limitations of the current study include a sample of autistic adults that was overwhelmingly female, later-diagnosed, and well-educated; clinical and control groups drawn from different studies with variable measures; and an inability to test several other important psychometric characteristics of the TAS-8, including sensitivity to change and I-DIF across multiple administrations. CONCLUSIONS: These results indicate the potential of the TAS-8 as a psychometrically robust tool to measure alexithymia in both autistic and non-autistic adults. A free online score calculator has been created to facilitate the use of norm-referenced TAS-8 latent trait scores in research applications (available at http://asdmeasures.shinyapps.io/TAS8_Score ). En ligne : http://dx.doi.org/10.1186/s13229-021-00427-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Evaluating the latent structure of the non-social domain of autism in autistic adults / R. GROVE in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 22 p. Titre : Evaluating the latent structure of the non-social domain of autism in autistic adults Type de document : Texte imprimé et/ou numérique Auteurs : R. GROVE, Auteur ; Sander BEGEER, Auteur ; Anke M. SCHEEREN, Auteur ; R. F. WEILAND, Auteur ; R. A. HOEKSTRA, Auteur Article en page(s) : 22 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Aged  Aged, 80 and over  Autistic Disorder/psychology  Female  Humans  Male  Middle Aged  Psychiatric Status Rating Scales  Young Adult  Adults  Autism  Non-social autistic traits  Repetitive behaviours Index. décimale : PER Périodiques Résumé : BACKGROUND: The social domain of autism has been studied in depth, but the relationship between the non-social traits of autism has received less attention. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) outlines four criteria that make up the non-social domain including repetitive motor movements, insistence on sameness, restricted interests and sensory sensitivity. There is a lack of research into the relationship between these four criteria. This study aimed to evaluate the relationship between the non-social traits of autism in a large sample of autistic adults. It explored whether these traits are best conceptualised as four distinct factors, or exist along a single dimension. METHODS: Participants included autistic adults from the Netherlands Autism Register. The four components identified within the DSM-5 non-social domain were measured by items from the Adult Routines Inventory, the Autism Spectrum Quotient short and the Sensory Perception Quotient short. Confirmatory factor analysis, as well as exploratory factor analysis and exploratory structural equation modelling, was implemented to examine the relationship between these four criteria. RESULTS: Results indicated that a four-factor model provided the best fit, mapping onto the DSM-5 criteria. These four factors were moderately correlated, suggesting that four distinct, yet related factors best describe the non-social domain of autism. The one-factor model did not provide a good fit, highlighting that the non-social domain of autism is not a unitary construct. LIMITATIONS: The study included autistic adults who were cognitively able to complete the self-report measures. This may limit the generalisability of the findings to those who are less able to do so. CONCLUSIONS: This study provided evidence for the multidimensional nature of the non-social domain of autism. Given only two of the four criteria within the non-social domain need to be endorsed for a diagnosis of autism, there is room for substantial variation across individuals, who will have a unique profile within the non-social domain. The results have implications for our understanding of the heterogeneous nature of autistic traits, as well as for how we conceptualise autism as a diagnostic category. This is important for the provision of diagnosis and support within research and clinical practice. En ligne : http://dx.doi.org/10.1186/s13229-020-00401-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Evaluating the latent structure of the non-social domain of autism in autistic adults [Texte imprimé et/ou numérique] / R. GROVE, Auteur ; Sander BEGEER, Auteur ; Anke M. SCHEEREN, Auteur ; R. F. WEILAND, Auteur ; R. A. HOEKSTRA, Auteur . - 22 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 22 p. Mots-clés : Adolescent  Adult  Aged  Aged, 80 and over  Autistic Disorder/psychology  Female  Humans  Male  Middle Aged  Psychiatric Status Rating Scales  Young Adult  Adults  Autism  Non-social autistic traits  Repetitive behaviours Index. décimale : PER Périodiques Résumé : BACKGROUND: The social domain of autism has been studied in depth, but the relationship between the non-social traits of autism has received less attention. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) outlines four criteria that make up the non-social domain including repetitive motor movements, insistence on sameness, restricted interests and sensory sensitivity. There is a lack of research into the relationship between these four criteria. This study aimed to evaluate the relationship between the non-social traits of autism in a large sample of autistic adults. It explored whether these traits are best conceptualised as four distinct factors, or exist along a single dimension. METHODS: Participants included autistic adults from the Netherlands Autism Register. The four components identified within the DSM-5 non-social domain were measured by items from the Adult Routines Inventory, the Autism Spectrum Quotient short and the Sensory Perception Quotient short. Confirmatory factor analysis, as well as exploratory factor analysis and exploratory structural equation modelling, was implemented to examine the relationship between these four criteria. RESULTS: Results indicated that a four-factor model provided the best fit, mapping onto the DSM-5 criteria. These four factors were moderately correlated, suggesting that four distinct, yet related factors best describe the non-social domain of autism. The one-factor model did not provide a good fit, highlighting that the non-social domain of autism is not a unitary construct. LIMITATIONS: The study included autistic adults who were cognitively able to complete the self-report measures. This may limit the generalisability of the findings to those who are less able to do so. CONCLUSIONS: This study provided evidence for the multidimensional nature of the non-social domain of autism. Given only two of the four criteria within the non-social domain need to be endorsed for a diagnosis of autism, there is room for substantial variation across individuals, who will have a unique profile within the non-social domain. The results have implications for our understanding of the heterogeneous nature of autistic traits, as well as for how we conceptualise autism as a diagnostic category. This is important for the provision of diagnosis and support within research and clinical practice. En ligne : http://dx.doi.org/10.1186/s13229-020-00401-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

The psychological impact of the COVID-19 pandemic on adults with autism: a survey study across three countries / D. OOMEN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 21 p. Titre : The psychological impact of the COVID-19 pandemic on adults with autism: a survey study across three countries Type de document : Texte imprimé et/ou numérique Auteurs : D. OOMEN, Auteur ; A. D. NIJHOF, Auteur ; Jan R. WIERSEMA, Auteur Article en page(s) : 21 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Aged  Anxiety/epidemiology  Autistic Disorder/psychology  Belgium/epidemiology  COVID-19/psychology  Depression/epidemiology  Female  Humans  Male  Middle Aged  Netherlands/epidemiology  SARS-CoV-2  Social Interaction  Stress, Psychological/epidemiology  Surveys and Questionnaires  United Kingdom/epidemiology  Young Adult  Autism  Covid-19  Mental health  Pandemic Index. décimale : PER Périodiques Résumé : BACKGROUND: Previous studies have reported a negative psychological and mental health impact of the COVID-19 pandemic. This impact is likely to be stronger for people with autism as they are at heightened risk of mental health problems and because the pandemic directly affects social functioning and everyday routines. We therefore examined COVID-19 pandemic-related changes in mental health, the impact of the pandemic on their social life and routines, satisfaction with pandemic-related information and tips, and participants' wishes for guidance. METHODS: We used a mixed-method approach, collecting quantitative and qualitative survey data from adults with and without autism across three European countries: Belgium, the Netherlands, and the UK (N?=?1044). RESULTS: We found an increase in depression and anxiety symptoms in response to the pandemic for both the non-autism and the autism group, which was greater for adults with autism. Furthermore, adults with autism showed a greater increase in worries about their pets, work, getting medication and food, and their own safety/security. They felt more relieved from social stress, yet experienced the loss of social contact as difficult. Adults with autism also felt more stressed about the loss of routines. Pleasant changes noted by adults with autism were the increase in solidarity and reduced sensory and social overload. Adults with autism frequently reported problems with cancellation of guidance due to the pandemic and expressed their wish for (more) autism-specific information and advice. LIMITATIONS: Our sample is likely to reflect some degree of selection bias, and longitudinal studies are needed to determine long-term effects. CONCLUSIONS: Results highlight the psychological burden of the pandemic on adults with autism and shed light on how to support them during this COVID-19 pandemic, which is especially important now that the pandemic is likely to have a prolonged course. There is a need for accessible, affordable (continued) support from health services. Guidance may focus on the maintenance of a social network, and adjusting routines to the rapid ongoing changes. Finally, we may learn from the COVID-19 pandemic-related changes experienced as pleasant by adults with autism to build a more autism-friendly society post-pandemic. En ligne : http://dx.doi.org/10.1186/s13229-021-00424-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] The psychological impact of the COVID-19 pandemic on adults with autism: a survey study across three countries [Texte imprimé et/ou numérique] / D. OOMEN, Auteur ; A. D. NIJHOF, Auteur ; Jan R. WIERSEMA, Auteur . - 21 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 21 p. Mots-clés : Adolescent  Adult  Aged  Anxiety/epidemiology  Autistic Disorder/psychology  Belgium/epidemiology  COVID-19/psychology  Depression/epidemiology  Female  Humans  Male  Middle Aged  Netherlands/epidemiology  SARS-CoV-2  Social Interaction  Stress, Psychological/epidemiology  Surveys and Questionnaires  United Kingdom/epidemiology  Young Adult  Autism  Covid-19  Mental health  Pandemic Index. décimale : PER Périodiques Résumé : BACKGROUND: Previous studies have reported a negative psychological and mental health impact of the COVID-19 pandemic. This impact is likely to be stronger for people with autism as they are at heightened risk of mental health problems and because the pandemic directly affects social functioning and everyday routines. We therefore examined COVID-19 pandemic-related changes in mental health, the impact of the pandemic on their social life and routines, satisfaction with pandemic-related information and tips, and participants' wishes for guidance. METHODS: We used a mixed-method approach, collecting quantitative and qualitative survey data from adults with and without autism across three European countries: Belgium, the Netherlands, and the UK (N?=?1044). RESULTS: We found an increase in depression and anxiety symptoms in response to the pandemic for both the non-autism and the autism group, which was greater for adults with autism. Furthermore, adults with autism showed a greater increase in worries about their pets, work, getting medication and food, and their own safety/security. They felt more relieved from social stress, yet experienced the loss of social contact as difficult. Adults with autism also felt more stressed about the loss of routines. Pleasant changes noted by adults with autism were the increase in solidarity and reduced sensory and social overload. Adults with autism frequently reported problems with cancellation of guidance due to the pandemic and expressed their wish for (more) autism-specific information and advice. LIMITATIONS: Our sample is likely to reflect some degree of selection bias, and longitudinal studies are needed to determine long-term effects. CONCLUSIONS: Results highlight the psychological burden of the pandemic on adults with autism and shed light on how to support them during this COVID-19 pandemic, which is especially important now that the pandemic is likely to have a prolonged course. There is a need for accessible, affordable (continued) support from health services. Guidance may focus on the maintenance of a social network, and adjusting routines to the rapid ongoing changes. Finally, we may learn from the COVID-19 pandemic-related changes experienced as pleasant by adults with autism to build a more autism-friendly society post-pandemic. En ligne : http://dx.doi.org/10.1186/s13229-021-00424-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Hippocampal neurons isolated from rats subjected to the valproic acid model mimic in vivo synaptic pattern: evidence of neuronal priming during early development in autism spectrum disorders / M. E. TRAETTA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 23 p. Titre : Hippocampal neurons isolated from rats subjected to the valproic acid model mimic in vivo synaptic pattern: evidence of neuronal priming during early development in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : M. E. TRAETTA, Auteur ; M. G. CODAGNONE, Auteur ; N. A. UCCELLI, Auteur ; A. J. RAMOS, Auteur ; S. ZÁRATE, Auteur ; A. REINÉS, Auteur Article en page(s) : 23 p. Langues : Anglais (eng) Mots-clés : Animals  Anticonvulsants  Autism Spectrum Disorder/chemically induced/metabolism  Behavior, Animal/drug effects  Cells, Cultured  Disease Models, Animal  Female  Hippocampus/drug effects/metabolism/ultrastructure  Male  Microglia/drug effects  Neural Cell Adhesion Molecules/metabolism  Neuronal Plasticity/drug effects  Neurons/drug effects/metabolism/ultrastructure  Phosphoprotein Phosphatases/metabolism  Pregnancy  Rats, Wistar  Synapses/drug effects  Valproic Acid  Adhesion molecules  Autism spectrum disorders  Hippocampus  Ncam  Synapse  VPA model Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are synaptopathies characterized by area-specific synaptic alterations and neuroinflammation. Structural and adhesive features of hippocampal synapses have been described in the valproic acid (VPA) model. However, neuronal and microglial contribution to hippocampal synaptic pattern and its time-course of appearance is still unknown. METHODS: Male pups born from pregnant rats injected at embryonic day 10.5 with VPA (450 mg/kg, i.p.) or saline (control) were used. Maturation, exploratory activity and social interaction were assessed as autistic-like traits. Synaptic, cell adhesion and microglial markers were evaluated in the CA3 hippocampal region at postnatal day (PND) 3 and 35. Primary cultures of hippocampal neurons from control and VPA animals were used to study synaptic features and glutamate-induced structural remodeling. Basal and stimuli-mediated reactivity was assessed on microglia primary cultures isolated from control and VPA animals. RESULTS: At PND3, before VPA behavioral deficits were evident, synaptophysin immunoreactivity and the balance between the neuronal cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) were preserved in the hippocampus of VPA animals along with the absence of microgliosis. At PND35, concomitantly with the establishment of behavioral deficits, the hippocampus of VPA rats showed fewer excitatory synapses and increased NCAM/PSA-NCAM balance without microgliosis. Hippocampal neurons from VPA animals in culture exhibited a preserved synaptic puncta number at the beginning of the synaptogenic period in vitro but showed fewer excitatory synapses as well as increased NCAM/PSA-NCAM balance and resistance to glutamate-induced structural synaptic remodeling after active synaptogenesis. Microglial cells isolated from VPA animals and cultured in the absence of neurons showed similar basal and stimuli-induced reactivity to the control group. Results indicate that in the absence of glia, hippocampal neurons from VPA animals mirrored the in vivo synaptic pattern and suggest that while neurons are primed during the prenatal period, hippocampal microglia are not intrinsically altered. CONCLUSIONS: Our study suggests microglial role is not determinant for developing neuronal alterations or counteracting neuronal outcome in the hippocampus and highlights the crucial role of hippocampal neurons and structural plasticity in the establishment of the synaptic alterations in the VPA rat model. En ligne : http://dx.doi.org/10.1186/s13229-021-00428-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Hippocampal neurons isolated from rats subjected to the valproic acid model mimic in vivo synaptic pattern: evidence of neuronal priming during early development in autism spectrum disorders [Texte imprimé et/ou numérique] / M. E. TRAETTA, Auteur ; M. G. CODAGNONE, Auteur ; N. A. UCCELLI, Auteur ; A. J. RAMOS, Auteur ; S. ZÁRATE, Auteur ; A. REINÉS, Auteur . - 23 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 23 p. Mots-clés : Animals  Anticonvulsants  Autism Spectrum Disorder/chemically induced/metabolism  Behavior, Animal/drug effects  Cells, Cultured  Disease Models, Animal  Female  Hippocampus/drug effects/metabolism/ultrastructure  Male  Microglia/drug effects  Neural Cell Adhesion Molecules/metabolism  Neuronal Plasticity/drug effects  Neurons/drug effects/metabolism/ultrastructure  Phosphoprotein Phosphatases/metabolism  Pregnancy  Rats, Wistar  Synapses/drug effects  Valproic Acid  Adhesion molecules  Autism spectrum disorders  Hippocampus  Ncam  Synapse  VPA model Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are synaptopathies characterized by area-specific synaptic alterations and neuroinflammation. Structural and adhesive features of hippocampal synapses have been described in the valproic acid (VPA) model. However, neuronal and microglial contribution to hippocampal synaptic pattern and its time-course of appearance is still unknown. METHODS: Male pups born from pregnant rats injected at embryonic day 10.5 with VPA (450 mg/kg, i.p.) or saline (control) were used. Maturation, exploratory activity and social interaction were assessed as autistic-like traits. Synaptic, cell adhesion and microglial markers were evaluated in the CA3 hippocampal region at postnatal day (PND) 3 and 35. Primary cultures of hippocampal neurons from control and VPA animals were used to study synaptic features and glutamate-induced structural remodeling. Basal and stimuli-mediated reactivity was assessed on microglia primary cultures isolated from control and VPA animals. RESULTS: At PND3, before VPA behavioral deficits were evident, synaptophysin immunoreactivity and the balance between the neuronal cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) were preserved in the hippocampus of VPA animals along with the absence of microgliosis. At PND35, concomitantly with the establishment of behavioral deficits, the hippocampus of VPA rats showed fewer excitatory synapses and increased NCAM/PSA-NCAM balance without microgliosis. Hippocampal neurons from VPA animals in culture exhibited a preserved synaptic puncta number at the beginning of the synaptogenic period in vitro but showed fewer excitatory synapses as well as increased NCAM/PSA-NCAM balance and resistance to glutamate-induced structural synaptic remodeling after active synaptogenesis. Microglial cells isolated from VPA animals and cultured in the absence of neurons showed similar basal and stimuli-induced reactivity to the control group. Results indicate that in the absence of glia, hippocampal neurons from VPA animals mirrored the in vivo synaptic pattern and suggest that while neurons are primed during the prenatal period, hippocampal microglia are not intrinsically altered. CONCLUSIONS: Our study suggests microglial role is not determinant for developing neuronal alterations or counteracting neuronal outcome in the hippocampus and highlights the crucial role of hippocampal neurons and structural plasticity in the establishment of the synaptic alterations in the VPA rat model. En ligne : http://dx.doi.org/10.1186/s13229-021-00428-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California / K. LYALL in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 24 p. Titre : A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California Type de document : Texte imprimé et/ou numérique Auteurs : K. LYALL, Auteur ; Jennifer L. AMES, Auteur ; M. PEARL, Auteur ; M. TRAGLIA, Auteur ; L. A. WEISS, Auteur ; G. C. WINDHAM, Auteur ; M. KHARRAZI, Auteur ; C. K. YOSHIDA, Auteur ; R. YOLKEN, Auteur ; Heather E. VOLK, Auteur ; Paul ASHWOOD, Auteur ; J. VAN DE WATER, Auteur ; Lisa A. CROEN, Auteur Article en page(s) : 24 p. Langues : Anglais (eng) Mots-clés : Adult  Autistic Disorder/blood/epidemiology/immunology  Biomarkers/blood  California/epidemiology  Case-Control Studies  Child  Cytokines/immunology  Endocrine Disruptors  Environmental Exposure  Environmental Pollutants  Female  Humans  Male  Pregnancy/immunology  Thyroid Hormones/blood  Vitamin D/blood  Young Adult  Autism  Early Markers for Autism  Immune response  Risk factors Index. décimale : PER Périodiques Résumé : BACKGROUND: The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD. METHODS: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n?=?629) and intellectual disability without ASD (ID, n?=?230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n?=?599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. RESULTS: EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. LIMITATIONS: Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. CONCLUSIONS: Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures. En ligne : http://dx.doi.org/10.1186/s13229-021-00429-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case-control study in California [Texte imprimé et/ou numérique] / K. LYALL, Auteur ; Jennifer L. AMES, Auteur ; M. PEARL, Auteur ; M. TRAGLIA, Auteur ; L. A. WEISS, Auteur ; G. C. WINDHAM, Auteur ; M. KHARRAZI, Auteur ; C. K. YOSHIDA, Auteur ; R. YOLKEN, Auteur ; Heather E. VOLK, Auteur ; Paul ASHWOOD, Auteur ; J. VAN DE WATER, Auteur ; Lisa A. CROEN, Auteur . - 24 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 24 p. Mots-clés : Adult  Autistic Disorder/blood/epidemiology/immunology  Biomarkers/blood  California/epidemiology  Case-Control Studies  Child  Cytokines/immunology  Endocrine Disruptors  Environmental Exposure  Environmental Pollutants  Female  Humans  Male  Pregnancy/immunology  Thyroid Hormones/blood  Vitamin D/blood  Young Adult  Autism  Early Markers for Autism  Immune response  Risk factors Index. décimale : PER Périodiques Résumé : BACKGROUND: The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD. METHODS: Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n?=?629) and intellectual disability without ASD (ID, n?=?230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n?=?599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. RESULTS: EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. LIMITATIONS: Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. CONCLUSIONS: Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures. En ligne : http://dx.doi.org/10.1186/s13229-021-00429-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development / J. ELLEGOOD in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 25 p. Titre : Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development Type de document : Texte imprimé et/ou numérique Auteurs : J. ELLEGOOD, Auteur ; S. P. PETKOVA, Auteur ; A. KINMAN, Auteur ; L. R. QIU, Auteur ; A. ADHIKARI, Auteur ; A. A. WADE, Auteur ; D. FERNANDES, Auteur ; Z. LINDENMAIER, Auteur ; A. CREIGHTON, Auteur ; L. M. J. NUTTER, Auteur ; A. S. NORD, Auteur ; J. L. SILVERMAN, Auteur ; J. P. LERCH, Auteur Article en page(s) : 25 p. Langues : Anglais (eng) Mots-clés : Animals  Behavior, Animal  Brain/diagnostic imaging/growth & development  Exploratory Behavior  Fear  Female  Gait  Haploinsufficiency  Learning  Magnetic Resonance Imaging  Male  Mice, Mutant Strains  Motor Skills  Neurodevelopmental Disorders/diagnostic imaging/psychology  Recognition, Psychology  Social Behavior  Transcription Factors/genetics/metabolism  Vocalization, Animal  Arid1b  Autism  Behavior  Coffin–Siris syndrome  Magnetic resonance imaging  Mouse Index. décimale : PER Périodiques Résumé : BACKGROUND: One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. METHODS: A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. RESULTS: We validated decreased Arid1b mRNA and protein in Arid1b(+/-) mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b(+/-) cerebellum. During neonatal development, Arid1b(+/-) mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b(+/-) mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b(+/-) mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b(+/-) mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. LIMITATIONS: The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. CONCLUSIONS: This study represents a full validation and investigation of a novel model of Arid1b(+/-) haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs. En ligne : http://dx.doi.org/10.1186/s13229-021-00432-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development [Texte imprimé et/ou numérique] / J. ELLEGOOD, Auteur ; S. P. PETKOVA, Auteur ; A. KINMAN, Auteur ; L. R. QIU, Auteur ; A. ADHIKARI, Auteur ; A. A. WADE, Auteur ; D. FERNANDES, Auteur ; Z. LINDENMAIER, Auteur ; A. CREIGHTON, Auteur ; L. M. J. NUTTER, Auteur ; A. S. NORD, Auteur ; J. L. SILVERMAN, Auteur ; J. P. LERCH, Auteur . - 25 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 25 p. Mots-clés : Animals  Behavior, Animal  Brain/diagnostic imaging/growth & development  Exploratory Behavior  Fear  Female  Gait  Haploinsufficiency  Learning  Magnetic Resonance Imaging  Male  Mice, Mutant Strains  Motor Skills  Neurodevelopmental Disorders/diagnostic imaging/psychology  Recognition, Psychology  Social Behavior  Transcription Factors/genetics/metabolism  Vocalization, Animal  Arid1b  Autism  Behavior  Coffin–Siris syndrome  Magnetic resonance imaging  Mouse Index. décimale : PER Périodiques Résumé : BACKGROUND: One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. METHODS: A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. RESULTS: We validated decreased Arid1b mRNA and protein in Arid1b(+/-) mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b(+/-) cerebellum. During neonatal development, Arid1b(+/-) mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b(+/-) mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b(+/-) mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b(+/-) mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. LIMITATIONS: The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. CONCLUSIONS: This study represents a full validation and investigation of a novel model of Arid1b(+/-) haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs. En ligne : http://dx.doi.org/10.1186/s13229-021-00432-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Tactile cortical responses and association with tactile reactivity in young children on the autism spectrum / S. ESPENHAHN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 26 p. Titre : Tactile cortical responses and association with tactile reactivity in young children on the autism spectrum Type de document : Texte imprimé et/ou numérique Auteurs : S. ESPENHAHN, Auteur ; K. J. GODFREY, Auteur ; S. KAUR, Auteur ; M. ROSS, Auteur ; N. NATH, Auteur ; O. DMITRIEVA, Auteur ; C. MCMORRIS, Auteur ; F. CORTESE, Auteur ; C. WRIGHT, Auteur ; K. MURIAS, Auteur ; D. DEWEY, Auteur ; A. B. PROTZNER, Auteur ; A. MCCRIMMON, Auteur ; S. BRAY, Auteur ; A. D. HARRIS, Auteur Article en page(s) : 26 p. Langues : Anglais (eng) Mots-clés : Autistic Disorder/physiopathology  Child  Child, Preschool  Electroencephalography  Evoked Potentials, Somatosensory  Female  Humans  Male  Somatosensory Cortex/physiopathology  Touch  Adaptation  Autism  Children  Eeg  Erp  Somatosensory-evoked potentials  Tactile sensitivities  Tactile stimulation Index. décimale : PER Périodiques Résumé : BACKGROUND: Unusual behavioral reactions to sensory stimuli are frequently reported in individuals on the autism spectrum (AS). Despite the early emergence of sensory features ( En ligne : http://dx.doi.org/10.1186/s13229-021-00435-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Tactile cortical responses and association with tactile reactivity in young children on the autism spectrum [Texte imprimé et/ou numérique] / S. ESPENHAHN, Auteur ; K. J. GODFREY, Auteur ; S. KAUR, Auteur ; M. ROSS, Auteur ; N. NATH, Auteur ; O. DMITRIEVA, Auteur ; C. MCMORRIS, Auteur ; F. CORTESE, Auteur ; C. WRIGHT, Auteur ; K. MURIAS, Auteur ; D. DEWEY, Auteur ; A. B. PROTZNER, Auteur ; A. MCCRIMMON, Auteur ; S. BRAY, Auteur ; A. D. HARRIS, Auteur . - 26 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 26 p. Mots-clés : Autistic Disorder/physiopathology  Child  Child, Preschool  Electroencephalography  Evoked Potentials, Somatosensory  Female  Humans  Male  Somatosensory Cortex/physiopathology  Touch  Adaptation  Autism  Children  Eeg  Erp  Somatosensory-evoked potentials  Tactile sensitivities  Tactile stimulation Index. décimale : PER Périodiques Résumé : BACKGROUND: Unusual behavioral reactions to sensory stimuli are frequently reported in individuals on the autism spectrum (AS). Despite the early emergence of sensory features ( En ligne : http://dx.doi.org/10.1186/s13229-021-00435-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Imitation and recognition of facial emotions in autism: a computer vision approach / H. DRIMALLA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 27 p. Titre : Imitation and recognition of facial emotions in autism: a computer vision approach Type de document : Texte imprimé et/ou numérique Auteurs : H. DRIMALLA, Auteur ; Irina BASKOW, Auteur ; B. BEHNIA, Auteur ; S. ROEPKE, Auteur ; I. DZIOBEK, Auteur Article en page(s) : 27 p. Langues : Anglais (eng) Mots-clés : Adult  Autistic Disorder/psychology  Emotions  Facial Expression  Female  Humans  Imitative Behavior  Male  Middle Aged  Recognition, Psychology  Signal Processing, Computer-Assisted  Young Adult  Autism  Automated analysis  Emotion recognition  Imitation Index. décimale : PER Périodiques Résumé : BACKGROUND: Imitation of facial expressions plays an important role in social functioning. However, little is known about the quality of facial imitation in individuals with autism and its relationship with defining difficulties in emotion recognition. METHODS: We investigated imitation and recognition of facial expressions in 37 individuals with autism spectrum conditions and 43 neurotypical controls. Using a novel computer-based face analysis, we measured instructed imitation of facial emotional expressions and related it to emotion recognition abilities. RESULTS: Individuals with autism imitated facial expressions if instructed to do so, but their imitation was both slower and less precise than that of neurotypical individuals. In both groups, a more precise imitation scaled positively with participants' accuracy of emotion recognition. LIMITATIONS: Given the study's focus on adults with autism without intellectual impairment, it is unclear whether the results generalize to children with autism or individuals with intellectual disability. Further, the new automated facial analysis, despite being less intrusive than electromyography, might be less sensitive. CONCLUSIONS: Group differences in emotion recognition, imitation and their interrelationships highlight potential for treatment of social interaction problems in individuals with autism. En ligne : http://dx.doi.org/10.1186/s13229-021-00430-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Imitation and recognition of facial emotions in autism: a computer vision approach [Texte imprimé et/ou numérique] / H. DRIMALLA, Auteur ; Irina BASKOW, Auteur ; B. BEHNIA, Auteur ; S. ROEPKE, Auteur ; I. DZIOBEK, Auteur . - 27 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 27 p. Mots-clés : Adult  Autistic Disorder/psychology  Emotions  Facial Expression  Female  Humans  Imitative Behavior  Male  Middle Aged  Recognition, Psychology  Signal Processing, Computer-Assisted  Young Adult  Autism  Automated analysis  Emotion recognition  Imitation Index. décimale : PER Périodiques Résumé : BACKGROUND: Imitation of facial expressions plays an important role in social functioning. However, little is known about the quality of facial imitation in individuals with autism and its relationship with defining difficulties in emotion recognition. METHODS: We investigated imitation and recognition of facial expressions in 37 individuals with autism spectrum conditions and 43 neurotypical controls. Using a novel computer-based face analysis, we measured instructed imitation of facial emotional expressions and related it to emotion recognition abilities. RESULTS: Individuals with autism imitated facial expressions if instructed to do so, but their imitation was both slower and less precise than that of neurotypical individuals. In both groups, a more precise imitation scaled positively with participants' accuracy of emotion recognition. LIMITATIONS: Given the study's focus on adults with autism without intellectual impairment, it is unclear whether the results generalize to children with autism or individuals with intellectual disability. Further, the new automated facial analysis, despite being less intrusive than electromyography, might be less sensitive. CONCLUSIONS: Group differences in emotion recognition, imitation and their interrelationships highlight potential for treatment of social interaction problems in individuals with autism. En ligne : http://dx.doi.org/10.1186/s13229-021-00430-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

New guidance to seekers of autism biomarkers: an update from studies of identical twins / John N. CONSTANTINO in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 28 p. Titre : New guidance to seekers of autism biomarkers: an update from studies of identical twins Type de document : Texte imprimé et/ou numérique Auteurs : John N. CONSTANTINO, Auteur Article en page(s) : 28 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: The autism spectrum disorders (ASD) are common neuropsychiatric conditions of childhood for which the vast proportion of population risk is attributable to inheritance, and for which there exist few if any replicated biomarkers. MAIN BODY: This commentary summarizes a set of recent studies involving identical (monozygotic, MZ) twins which, taken together, have significant implications for the search for biomarkers of inherited susceptibility to autism. A first is that variation-in-severity of the condition (above the threshold for clinical diagnosis) appears more strongly influenced by stochastic/non-shared environmental influences than by heredity. Second is that there exist disparate early behavioral predictors of the familial recurrence of autism, which are themselves strongly genetically influenced but largely independent from one another. The nature of these postnatal predictors is that they are trait-like, continuously distributed in the general population, and largely independent from variation in general cognition, thereby reflecting a developmental substructure for familial autism. A corollary of these findings is that autism may arise as a developmental consequence of an allostatic load of earlier-occurring liabilities, indexed by early behavioral endophenotypes, in varying permutations and combinations. The clinical threshold can be viewed as a "tipping point" at which stochastic influences and/or other non-shared environmental influences assert much stronger influence on variation-in-severity (a) than do the genetic factors which contributed to the condition in the first place, and (b) than is observed in typical development. CONCLUSION: Biomarkers identified on the basis of association with clinical symptom severity in ASD may reflect effects rather than causes of autism. The search for biomarkers of pathogenesis may benefit from a greater focus on traits that predict autism recurrence, among both clinical and general populations. In case-control studies, salient developmental liabilities should be systematically measured in both cases and controls, to avoid the erosion in statistical power (i.e., to detect differences) that can occur if control subjects carry sub-clinical aggregations of the same unmeasured traits that exert causal influences on the development of autism. En ligne : http://dx.doi.org/10.1186/s13229-021-00434-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] New guidance to seekers of autism biomarkers: an update from studies of identical twins [Texte imprimé et/ou numérique] / John N. CONSTANTINO, Auteur . - 28 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 28 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: The autism spectrum disorders (ASD) are common neuropsychiatric conditions of childhood for which the vast proportion of population risk is attributable to inheritance, and for which there exist few if any replicated biomarkers. MAIN BODY: This commentary summarizes a set of recent studies involving identical (monozygotic, MZ) twins which, taken together, have significant implications for the search for biomarkers of inherited susceptibility to autism. A first is that variation-in-severity of the condition (above the threshold for clinical diagnosis) appears more strongly influenced by stochastic/non-shared environmental influences than by heredity. Second is that there exist disparate early behavioral predictors of the familial recurrence of autism, which are themselves strongly genetically influenced but largely independent from one another. The nature of these postnatal predictors is that they are trait-like, continuously distributed in the general population, and largely independent from variation in general cognition, thereby reflecting a developmental substructure for familial autism. A corollary of these findings is that autism may arise as a developmental consequence of an allostatic load of earlier-occurring liabilities, indexed by early behavioral endophenotypes, in varying permutations and combinations. The clinical threshold can be viewed as a "tipping point" at which stochastic influences and/or other non-shared environmental influences assert much stronger influence on variation-in-severity (a) than do the genetic factors which contributed to the condition in the first place, and (b) than is observed in typical development. CONCLUSION: Biomarkers identified on the basis of association with clinical symptom severity in ASD may reflect effects rather than causes of autism. The search for biomarkers of pathogenesis may benefit from a greater focus on traits that predict autism recurrence, among both clinical and general populations. In case-control studies, salient developmental liabilities should be systematically measured in both cases and controls, to avoid the erosion in statistical power (i.e., to detect differences) that can occur if control subjects carry sub-clinical aggregations of the same unmeasured traits that exert causal influences on the development of autism. En ligne : http://dx.doi.org/10.1186/s13229-021-00434-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome / M. G. MARISCAL in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 29 p. Titre : Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : M. G. MARISCAL, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; L. E. ETHRIDGE, Auteur ; R. FILIP-DHIMA, Auteur ; J. H. FOSS-FEIG, Auteur ; A. KOLEVZON, Auteur ; M. E. MODI, Auteur ; M. W. MOSCONI, Auteur ; C. A. NELSON, Auteur ; C. M. POWELL, Auteur ; P. M. SIPER, Auteur ; L. SOORYA, Auteur ; A. THALIATH, Auteur ; A. THURM, Auteur ; B. ZHANG, Auteur ; M. SAHIN, Auteur ; A. R. LEVIN, Auteur Article en page(s) : 29 p. Langues : Anglais (eng) Mots-clés : Cross-frequency coupling  Eeg  Phase bias  Phelan-McDermid syndrome  Power Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. METHODS: Here, we analyze EEG data collected across multiple sites in individuals with PMS (n?=?26) and typically developing individuals (n?=?15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. RESULTS: We find individuals with PMS display increased alpha-gamma phase bias (U?=?3.841, p? En ligne : http://dx.doi.org/10.1186/s13229-020-00411-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / M. G. MARISCAL, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; L. E. ETHRIDGE, Auteur ; R. FILIP-DHIMA, Auteur ; J. H. FOSS-FEIG, Auteur ; A. KOLEVZON, Auteur ; M. E. MODI, Auteur ; M. W. MOSCONI, Auteur ; C. A. NELSON, Auteur ; C. M. POWELL, Auteur ; P. M. SIPER, Auteur ; L. SOORYA, Auteur ; A. THALIATH, Auteur ; A. THURM, Auteur ; B. ZHANG, Auteur ; M. SAHIN, Auteur ; A. R. LEVIN, Auteur . - 29 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 29 p. Mots-clés : Cross-frequency coupling  Eeg  Phase bias  Phelan-McDermid syndrome  Power Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. METHODS: Here, we analyze EEG data collected across multiple sites in individuals with PMS (n?=?26) and typically developing individuals (n?=?15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. RESULTS: We find individuals with PMS display increased alpha-gamma phase bias (U?=?3.841, p? En ligne : http://dx.doi.org/10.1186/s13229-020-00411-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Extremely preterm birth and autistic traits in young adulthood: the EPICure study / H. O'REILLY in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 30 p. Titre : Extremely preterm birth and autistic traits in young adulthood: the EPICure study Type de document : Texte imprimé et/ou numérique Auteurs : H. O'REILLY, Auteur ; Y. NI, Auteur ; S. JOHNSON, Auteur ; D. WOLKE, Auteur ; N. MARLOW, Auteur Article en page(s) : 30 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Autistic traits  Broader autism phenotype  Preterm birth  The authors have no conflicts of interest relevant to this article to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: A high prevalence of autism spectrum disorder is reported in children born extremely preterm (EP), but an even larger proportion of survivors are affected by subclinical difficulties than meet diagnostic criteria. The aims of this study were to investigate autistic traits associated with the broader autism phenotype in a cohort of young adults born EP, and explore how these traits relate to emotion recognition, empathy and autism symptom presentation in childhood. The prevalence of autism diagnoses was also investigated. METHODS: One hundred and twenty-nine young adults born before 26 weeks of gestation and 65 term-born controls participated in the 19-year follow-up phase of the EPICure studies. In addition to a clinical interview, participants completed the Broader Autism Phenotype Questionnaire (BAPQ), the Empathy Quotient questionnaire, and the Frankfurt Test and Training of Facial Affect Recognition. The Social Communication Questionnaire (SCQ) was completed by the participants' parents at age 11 years. RESULTS: EP born young adults scored significantly higher on the BAPQ in comparison with their term-born peers, indicating greater autistic traits. Among EP participants, BAPQ scores were correlated with SCQ scores in childhood (r?=?0.484, p? En ligne : http://dx.doi.org/10.1186/s13229-021-00414-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Extremely preterm birth and autistic traits in young adulthood: the EPICure study [Texte imprimé et/ou numérique] / H. O'REILLY, Auteur ; Y. NI, Auteur ; S. JOHNSON, Auteur ; D. WOLKE, Auteur ; N. MARLOW, Auteur . - 30 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 30 p. Mots-clés : Autism spectrum disorder  Autistic traits  Broader autism phenotype  Preterm birth  The authors have no conflicts of interest relevant to this article to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: A high prevalence of autism spectrum disorder is reported in children born extremely preterm (EP), but an even larger proportion of survivors are affected by subclinical difficulties than meet diagnostic criteria. The aims of this study were to investigate autistic traits associated with the broader autism phenotype in a cohort of young adults born EP, and explore how these traits relate to emotion recognition, empathy and autism symptom presentation in childhood. The prevalence of autism diagnoses was also investigated. METHODS: One hundred and twenty-nine young adults born before 26 weeks of gestation and 65 term-born controls participated in the 19-year follow-up phase of the EPICure studies. In addition to a clinical interview, participants completed the Broader Autism Phenotype Questionnaire (BAPQ), the Empathy Quotient questionnaire, and the Frankfurt Test and Training of Facial Affect Recognition. The Social Communication Questionnaire (SCQ) was completed by the participants' parents at age 11 years. RESULTS: EP born young adults scored significantly higher on the BAPQ in comparison with their term-born peers, indicating greater autistic traits. Among EP participants, BAPQ scores were correlated with SCQ scores in childhood (r?=?0.484, p? En ligne : http://dx.doi.org/10.1186/s13229-021-00414-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Correction to: Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life / J. A. JIMÉNEZ in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 33 p. Titre : Correction to: Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life Type de document : Texte imprimé et/ou numérique Auteurs : J. A. JIMÉNEZ, Auteur ; T. S. PTACEK, Auteur ; A. H. TUTTLE, Auteur ; R. S. SCHMID, Auteur ; S. S. MOY, Auteur ; J. M. SIMON, Auteur ; M. J. ZYLKA, Auteur Article en page(s) : 33 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00438-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Correction to: Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life [Texte imprimé et/ou numérique] / J. A. JIMÉNEZ, Auteur ; T. S. PTACEK, Auteur ; A. H. TUTTLE, Auteur ; R. S. SCHMID, Auteur ; S. S. MOY, Auteur ; J. M. SIMON, Auteur ; M. J. ZYLKA, Auteur . - 33 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 33 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00438-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Examining a stepped-care telehealth program for parents of young children with autism: a proof-of-concept trial / Allison L. WAINER in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 32 p. Titre : Examining a stepped-care telehealth program for parents of young children with autism: a proof-of-concept trial Type de document : Texte imprimé et/ou numérique Auteurs : Allison L. WAINER, Auteur ; Z. E. ARNOLD, Auteur ; C. LEONCZYK, Auteur ; L. VALLURIPALLI SOORYA, Auteur Article en page(s) : 32 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Digital intervention  Online RIT  Reciprocal imitation training  Stepped-care  Telehealth  ZA, and LS declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intervention during the first years of life for children with autism spectrum disorder (ASD) may have the strongest impact on long-term brain development and functioning. Yet, barriers such as a shortage of trained professionals contribute to significant delays in service. The goal of this proof-of-concept study was to explore strategies that support timely and equitable deployment of ASD-specific interventions. METHODS: This 15-week, randomized proof-of-concept study explored the acceptability of a digital parent mediated intervention online reciprocal imitation training (RIT; a naturalistic developmental behavioral intervention) and compared it to a treatment as usual (TAU) control on parent and child outcomes. Eligible children were between 18 and 60 months, met the cutoff for ASD on the Autism Diagnostic Observation Schedule-2nd Edition and demonstrate significant social imitation deficits. Primary outcomes include the acceptability of RIT (Scale of Treatment Perceptions) and the feasibility of the Online RIT digital intervention (online RIT attributes). Secondary outcomes included parent fidelity (RIT parent fidelity form) and parental self-efficacy (Early Intervention Parenting Self-Efficacy Scale). Exploratory outcome measures included child social communication (Social Communication Checklist), child imitation skills (Unstructured Imitation Assessment), and family quality of life (Beach Center Family Quality of Life Scale). RESULTS: Twenty participants were randomized in a 1:1 fashion. The acceptability and feasibility of RIT and the Online RIT digital intervention were rated highly. Among the secondary outcomes, there were significant group differences in parent fidelity (p? En ligne : http://dx.doi.org/10.1186/s13229-021-00443-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Examining a stepped-care telehealth program for parents of young children with autism: a proof-of-concept trial [Texte imprimé et/ou numérique] / Allison L. WAINER, Auteur ; Z. E. ARNOLD, Auteur ; C. LEONCZYK, Auteur ; L. VALLURIPALLI SOORYA, Auteur . - 32 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 32 p. Mots-clés : Autism spectrum disorder  Digital intervention  Online RIT  Reciprocal imitation training  Stepped-care  Telehealth  ZA, and LS declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intervention during the first years of life for children with autism spectrum disorder (ASD) may have the strongest impact on long-term brain development and functioning. Yet, barriers such as a shortage of trained professionals contribute to significant delays in service. The goal of this proof-of-concept study was to explore strategies that support timely and equitable deployment of ASD-specific interventions. METHODS: This 15-week, randomized proof-of-concept study explored the acceptability of a digital parent mediated intervention online reciprocal imitation training (RIT; a naturalistic developmental behavioral intervention) and compared it to a treatment as usual (TAU) control on parent and child outcomes. Eligible children were between 18 and 60 months, met the cutoff for ASD on the Autism Diagnostic Observation Schedule-2nd Edition and demonstrate significant social imitation deficits. Primary outcomes include the acceptability of RIT (Scale of Treatment Perceptions) and the feasibility of the Online RIT digital intervention (online RIT attributes). Secondary outcomes included parent fidelity (RIT parent fidelity form) and parental self-efficacy (Early Intervention Parenting Self-Efficacy Scale). Exploratory outcome measures included child social communication (Social Communication Checklist), child imitation skills (Unstructured Imitation Assessment), and family quality of life (Beach Center Family Quality of Life Scale). RESULTS: Twenty participants were randomized in a 1:1 fashion. The acceptability and feasibility of RIT and the Online RIT digital intervention were rated highly. Among the secondary outcomes, there were significant group differences in parent fidelity (p? En ligne : http://dx.doi.org/10.1186/s13229-021-00443-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults / E. WEIR in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 31 p. Titre : An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults Type de document : Texte imprimé et/ou numérique Auteurs : E. WEIR, Auteur ; Carrie ALLISON, Auteur ; K. K. ONG, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 31 p. Langues : Anglais (eng) Mots-clés : Adult outcomes  Comorbidities  Exercise  Healthcare  Nutrition  Physical health  Sleep Index. décimale : PER Périodiques Résumé : BACKGROUND: Studies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history. METHODS: We administered an anonymized, online survey to n?=?2386 adults (n?=?1183 autistic) aged 16-90 years of age. We employed Fisher's exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults. RESULTS: Autistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history. LIMITATIONS: Our sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships. CONCLUSIONS: Autistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep-and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep. En ligne : http://dx.doi.org/10.1186/s13229-021-00441-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults [Texte imprimé et/ou numérique] / E. WEIR, Auteur ; Carrie ALLISON, Auteur ; K. K. ONG, Auteur ; Simon BARON-COHEN, Auteur . - 31 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 31 p. Mots-clés : Adult outcomes  Comorbidities  Exercise  Healthcare  Nutrition  Physical health  Sleep Index. décimale : PER Périodiques Résumé : BACKGROUND: Studies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history. METHODS: We administered an anonymized, online survey to n?=?2386 adults (n?=?1183 autistic) aged 16-90 years of age. We employed Fisher's exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults. RESULTS: Autistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history. LIMITATIONS: Our sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships. CONCLUSIONS: Autistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep-and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep. En ligne : http://dx.doi.org/10.1186/s13229-021-00441-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Single-participant structural similarity matrices lead to greater accuracy in classification of participants than function in autism in MRI / M. J. LEMING in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 34 p. Titre : Single-participant structural similarity matrices lead to greater accuracy in classification of participants than function in autism in MRI Type de document : Texte imprimé et/ou numérique Auteurs : M. J. LEMING, Auteur ; Simon BARON-COHEN, Auteur ; J. SUCKLING, Auteur Article en page(s) : 34 p. Langues : Anglais (eng) Mots-clés : Autism  Deep learning  Functional connectivity  Structural similarity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism has previously been characterized by both structural and functional differences in brain connectivity. However, while the literature on single-subject derivations of functional connectivity is extensively developed, similar methods of structural connectivity or similarity derivation from T1 MRI are less studied. METHODS: We introduce a technique of deriving symmetric similarity matrices from regional histograms of grey matter volumes estimated from T1-weighted MRIs. We then validated the technique by inputting the similarity matrices into a convolutional neural network (CNN) to classify between participants with autism and age-, motion-, and intracranial-volume-matched controls from six different databases (29,288 total connectomes, mean age = 30.72, range 0.42-78.00, including 1555 subjects with autism). We compared this method to similar classifications of the same participants using fMRI connectivity matrices as well as univariate estimates of grey matter volumes. We further applied graph-theoretical metrics on output class activation maps to identify areas of the matrices that the CNN preferentially used to make the classification, focusing particularly on hubs. LIMITATIONS: While this study used a large sample size, the majority of data was from a young age group; furthermore, to make a viable machine learning study, we treated autism, a highly heterogeneous condition, as a binary label. Thus, these results are not necessarily generalizable to all subtypes and age groups in autism. RESULTS: Our models gave AUROCs of 0.7298 (69.71% accuracy) when classifying by only structural similarity, 0.6964 (67.72% accuracy) when classifying by only functional connectivity, and 0.7037 (66.43% accuracy) when classifying by univariate grey matter volumes. Combining structural similarity and functional connectivity gave an AUROC of 0.7354 (69.40% accuracy). Analysis of classification performance across age revealed the greatest accuracy in adolescents, in which most data were present. Graph analysis of class activation maps revealed no distinguishable network patterns for functional inputs, but did reveal localized differences between groups in bilateral Heschl's gyrus and upper vermis for structural similarity. CONCLUSION: This study provides a simple means of feature extraction for inputting large numbers of structural MRIs into machine learning models. Our methods revealed a unique emphasis of the deep learning model on the structure of the bilateral Heschl's gyrus when characterizing autism. En ligne : http://dx.doi.org/10.1186/s13229-021-00439-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Single-participant structural similarity matrices lead to greater accuracy in classification of participants than function in autism in MRI [Texte imprimé et/ou numérique] / M. J. LEMING, Auteur ; Simon BARON-COHEN, Auteur ; J. SUCKLING, Auteur . - 34 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 34 p. Mots-clés : Autism  Deep learning  Functional connectivity  Structural similarity Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism has previously been characterized by both structural and functional differences in brain connectivity. However, while the literature on single-subject derivations of functional connectivity is extensively developed, similar methods of structural connectivity or similarity derivation from T1 MRI are less studied. METHODS: We introduce a technique of deriving symmetric similarity matrices from regional histograms of grey matter volumes estimated from T1-weighted MRIs. We then validated the technique by inputting the similarity matrices into a convolutional neural network (CNN) to classify between participants with autism and age-, motion-, and intracranial-volume-matched controls from six different databases (29,288 total connectomes, mean age = 30.72, range 0.42-78.00, including 1555 subjects with autism). We compared this method to similar classifications of the same participants using fMRI connectivity matrices as well as univariate estimates of grey matter volumes. We further applied graph-theoretical metrics on output class activation maps to identify areas of the matrices that the CNN preferentially used to make the classification, focusing particularly on hubs. LIMITATIONS: While this study used a large sample size, the majority of data was from a young age group; furthermore, to make a viable machine learning study, we treated autism, a highly heterogeneous condition, as a binary label. Thus, these results are not necessarily generalizable to all subtypes and age groups in autism. RESULTS: Our models gave AUROCs of 0.7298 (69.71% accuracy) when classifying by only structural similarity, 0.6964 (67.72% accuracy) when classifying by only functional connectivity, and 0.7037 (66.43% accuracy) when classifying by univariate grey matter volumes. Combining structural similarity and functional connectivity gave an AUROC of 0.7354 (69.40% accuracy). Analysis of classification performance across age revealed the greatest accuracy in adolescents, in which most data were present. Graph analysis of class activation maps revealed no distinguishable network patterns for functional inputs, but did reveal localized differences between groups in bilateral Heschl's gyrus and upper vermis for structural similarity. CONCLUSION: This study provides a simple means of feature extraction for inputting large numbers of structural MRIs into machine learning models. Our methods revealed a unique emphasis of the deep learning model on the structure of the bilateral Heschl's gyrus when characterizing autism. En ligne : http://dx.doi.org/10.1186/s13229-021-00439-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Bayonet-shaped language development in autism with regression: a retrospective study / D. GAGNON in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 35 p. Titre : Bayonet-shaped language development in autism with regression: a retrospective study Type de document : Texte imprimé et/ou numérique Auteurs : D. GAGNON, Auteur ; A. ZERIBI, Auteur ; É DOUARD, Auteur ; V. COURCHESNE, Auteur ; B. RODRÍGUEZ-HERREROS, Auteur ; G. HUGUET, Auteur ; S. JACQUEMONT, Auteur ; M. A. LOUM, Auteur ; L. MOTTRON, Auteur Article en page(s) : 35 p. Langues : Anglais (eng) Mots-clés : Autism  Heterogeneity  Language  Regression  Speech Index. décimale : PER Périodiques Résumé : BACKGROUND: Language delay is one of the major referral criteria for an autism evaluation. Once an autism spectrum diagnosis is established, the language prognosis is among the main parental concerns. Early language regression (ELR) is observed by 10-50% of parents but its relevance to late language level and socio-communicative ability is uncertain. This study aimed to establish the predictive value of ELR on the progression of language development and socio-communicative outcomes to guide clinicians in addressing parents' concerns at the time of diagnosis. METHODS: We used socio-communicative, language, and cognitive data of 2,047 autism spectrum participants from the Simons Simplex Collection, aged 4-18 years (mean?=?9 years; SD?=?3.6). Cox proportional hazard and logistic regression models were used to evaluate the effect of ELR on language milestones and the probability of using complex and flexible language, as defined by the choice of ADOS module at enrollment. Linear models were then used to evaluate the relationship of ELR and non-verbal IQ with socio-communicative and language levels. RESULTS: ELR is associated with earlier language milestones but delayed attainment of fluent, complex, and flexible language. However, this language outcome can be expected for almost all autistic children without intellectual disability at 18 years of age. It is mostly influenced by non-verbal IQ, not ELR. The language and socio-communicative level of participants with flexible language, as measured by the Vineland and ADOS socio-communicative subscales, was not affected by ELR. LIMITATIONS: This study is based on a relatively coarse measure of ultimate language level and relies on retrospective reporting of early language milestones and ELR. It does not prospectively document the age at which language catches up, the relationship between ELR and other behavioral areas of regression, nor the effects of intervention. CONCLUSIONS: For autistic individuals with ELR and a normal level of non-verbal intelligence, language development follows a "bayonet shape" trajectory: early first words followed by regression, a plateau with limited progress, and then language catch up. En ligne : http://dx.doi.org/10.1186/s13229-021-00444-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Bayonet-shaped language development in autism with regression: a retrospective study [Texte imprimé et/ou numérique] / D. GAGNON, Auteur ; A. ZERIBI, Auteur ; É DOUARD, Auteur ; V. COURCHESNE, Auteur ; B. RODRÍGUEZ-HERREROS, Auteur ; G. HUGUET, Auteur ; S. JACQUEMONT, Auteur ; M. A. LOUM, Auteur ; L. MOTTRON, Auteur . - 35 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 35 p. Mots-clés : Autism  Heterogeneity  Language  Regression  Speech Index. décimale : PER Périodiques Résumé : BACKGROUND: Language delay is one of the major referral criteria for an autism evaluation. Once an autism spectrum diagnosis is established, the language prognosis is among the main parental concerns. Early language regression (ELR) is observed by 10-50% of parents but its relevance to late language level and socio-communicative ability is uncertain. This study aimed to establish the predictive value of ELR on the progression of language development and socio-communicative outcomes to guide clinicians in addressing parents' concerns at the time of diagnosis. METHODS: We used socio-communicative, language, and cognitive data of 2,047 autism spectrum participants from the Simons Simplex Collection, aged 4-18 years (mean?=?9 years; SD?=?3.6). Cox proportional hazard and logistic regression models were used to evaluate the effect of ELR on language milestones and the probability of using complex and flexible language, as defined by the choice of ADOS module at enrollment. Linear models were then used to evaluate the relationship of ELR and non-verbal IQ with socio-communicative and language levels. RESULTS: ELR is associated with earlier language milestones but delayed attainment of fluent, complex, and flexible language. However, this language outcome can be expected for almost all autistic children without intellectual disability at 18 years of age. It is mostly influenced by non-verbal IQ, not ELR. The language and socio-communicative level of participants with flexible language, as measured by the Vineland and ADOS socio-communicative subscales, was not affected by ELR. LIMITATIONS: This study is based on a relatively coarse measure of ultimate language level and relies on retrospective reporting of early language milestones and ELR. It does not prospectively document the age at which language catches up, the relationship between ELR and other behavioral areas of regression, nor the effects of intervention. CONCLUSIONS: For autistic individuals with ELR and a normal level of non-verbal intelligence, language development follows a "bayonet shape" trajectory: early first words followed by regression, a plateau with limited progress, and then language catch up. En ligne : http://dx.doi.org/10.1186/s13229-021-00444-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Prospective and detailed behavioral phenotyping in DDX3X syndrome / L. TANG in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 36 p. Titre : Prospective and detailed behavioral phenotyping in DDX3X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : L. TANG, Auteur ; T. LEVY, Auteur ; S. GUILLORY, Auteur ; Danielle B. HALPERN, Auteur ; J. ZWEIFACH, Auteur ; I. GISERMAN-KISS, Auteur ; J. H. FOSS-FEIG, Auteur ; Y. FRANK, Auteur ; R. LOZANO, Auteur ; P. BELANI, Auteur ; C. LAYTON, Auteur ; B. LERMAN, Auteur ; E. FROWNER, Auteur ; Michael S. BREEN, Auteur ; S. DE RUBEIS, Auteur ; A. KOSTIC, Auteur ; A. KOLEVZON, Auteur ; Joseph D. BUXBAUM, Auteur ; P. M. SIPER, Auteur ; D. E. GRICE, Auteur Article en page(s) : 36 p. Langues : Anglais (eng) Mots-clés : Autism  DDX3X syndrome  Developmental delay  Genotype–phenotype correlation  Intellectual disability  Therapeutics, Acadia, and Sema4. PMS is the inventor of the SAND, which is licensed  by Mount Sinai to Stoelting Co. No other competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: DDX3X syndrome is a recently identified genetic disorder that accounts for 1-3% of cases of unexplained developmental delay and/or intellectual disability (ID) in females, and is associated with motor and language delays, and autism spectrum disorder (ASD). To date, the published phenotypic characterization of this syndrome has primarily relied on medical record review; in addition, the behavioral dimensions of the syndrome have not been fully explored. METHODS: We carried out multi-day, prospective, detailed phenotyping of DDX3X syndrome in 14 females and 1 male, focusing on behavioral, psychological, and neurological measures. Three participants in this cohort were previously reported with limited phenotype information and were re-evaluated for this study. We compared results against population norms and contrasted phenotypes between individuals harboring either (1) protein-truncating variants or (2) missense variants or in-frame deletions. RESULTS: Eighty percent (80%) of individuals met criteria for ID, 60% for ASD and 53% for attention-deficit/hyperactivity disorder (ADHD). Motor and language delays were common as were sensory processing abnormalities. The cohort included 5 missense, 3 intronic/splice-site, 2 nonsense, 2 frameshift, 2 in-frame deletions, and one initiation codon variant. Genotype-phenotype correlations indicated that, on average, missense variants/in-frame deletions were associated with more severe language, motor, and adaptive deficits in comparison to protein-truncating variants. LIMITATIONS: Sample size is modest, however, DDX3X syndrome is a rare and underdiagnosed disorder. CONCLUSION: This study, representing a first, prospective, detailed characterization of DDX3X syndrome, extends our understanding of the neurobehavioral phenotype. Gold-standard diagnostic approaches demonstrated high rates of ID, ASD, and ADHD. In addition, sensory deficits were observed to be a key part of the syndrome. Even with a modest sample, we observe evidence for genotype-phenotype correlations with missense variants/in-frame deletions generally associated with more severe phenotypes. En ligne : http://dx.doi.org/10.1186/s13229-021-00431-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Prospective and detailed behavioral phenotyping in DDX3X syndrome [Texte imprimé et/ou numérique] / L. TANG, Auteur ; T. LEVY, Auteur ; S. GUILLORY, Auteur ; Danielle B. HALPERN, Auteur ; J. ZWEIFACH, Auteur ; I. GISERMAN-KISS, Auteur ; J. H. FOSS-FEIG, Auteur ; Y. FRANK, Auteur ; R. LOZANO, Auteur ; P. BELANI, Auteur ; C. LAYTON, Auteur ; B. LERMAN, Auteur ; E. FROWNER, Auteur ; Michael S. BREEN, Auteur ; S. DE RUBEIS, Auteur ; A. KOSTIC, Auteur ; A. KOLEVZON, Auteur ; Joseph D. BUXBAUM, Auteur ; P. M. SIPER, Auteur ; D. E. GRICE, Auteur . - 36 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 36 p. Mots-clés : Autism  DDX3X syndrome  Developmental delay  Genotype–phenotype correlation  Intellectual disability  Therapeutics, Acadia, and Sema4. PMS is the inventor of the SAND, which is licensed  by Mount Sinai to Stoelting Co. No other competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: DDX3X syndrome is a recently identified genetic disorder that accounts for 1-3% of cases of unexplained developmental delay and/or intellectual disability (ID) in females, and is associated with motor and language delays, and autism spectrum disorder (ASD). To date, the published phenotypic characterization of this syndrome has primarily relied on medical record review; in addition, the behavioral dimensions of the syndrome have not been fully explored. METHODS: We carried out multi-day, prospective, detailed phenotyping of DDX3X syndrome in 14 females and 1 male, focusing on behavioral, psychological, and neurological measures. Three participants in this cohort were previously reported with limited phenotype information and were re-evaluated for this study. We compared results against population norms and contrasted phenotypes between individuals harboring either (1) protein-truncating variants or (2) missense variants or in-frame deletions. RESULTS: Eighty percent (80%) of individuals met criteria for ID, 60% for ASD and 53% for attention-deficit/hyperactivity disorder (ADHD). Motor and language delays were common as were sensory processing abnormalities. The cohort included 5 missense, 3 intronic/splice-site, 2 nonsense, 2 frameshift, 2 in-frame deletions, and one initiation codon variant. Genotype-phenotype correlations indicated that, on average, missense variants/in-frame deletions were associated with more severe language, motor, and adaptive deficits in comparison to protein-truncating variants. LIMITATIONS: Sample size is modest, however, DDX3X syndrome is a rare and underdiagnosed disorder. CONCLUSION: This study, representing a first, prospective, detailed characterization of DDX3X syndrome, extends our understanding of the neurobehavioral phenotype. Gold-standard diagnostic approaches demonstrated high rates of ID, ASD, and ADHD. In addition, sensory deficits were observed to be a key part of the syndrome. Even with a modest sample, we observe evidence for genotype-phenotype correlations with missense variants/in-frame deletions generally associated with more severe phenotypes. En ligne : http://dx.doi.org/10.1186/s13229-021-00431-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

The Comprehensive Autistic Trait Inventory (CATI): development and validation of a new measure of autistic traits in the general population / M. C. W. ENGLISH in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 37 p. Titre : The Comprehensive Autistic Trait Inventory (CATI): development and validation of a new measure of autistic traits in the general population Type de document : Texte imprimé et/ou numérique Auteurs : M. C. W. ENGLISH, Auteur ; G. E. GIGNAC, Auteur ; Troy A. W. VISSER, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; J. T. ENNS, Auteur ; M. T. MAYBERY, Auteur Article en page(s) : 37 p. Langues : Anglais (eng) Mots-clés : Autism  Autistic traits  Broader autism spectrum  Factor analysis  General population  Questionnaire  Self-report  Subscales Index. décimale : PER Périodiques Résumé : BACKGROUND: Traits and characteristics qualitatively similar to those seen in diagnosed autism spectrum disorder can be found to varying degrees in the general population. To measure these traits and facilitate their use in autism research, several questionnaires have been developed that provide broad measures of autistic traits [e.g. Autism-Spectrum Quotient (AQ), Broad Autism Phenotype Questionnaire (BAPQ)]. However, since their development, our understanding of autism has grown considerably, and it is arguable that existing measures do not provide an ideal representation of the trait dimensions currently associated with autism. Our aim was to create a new measure of autistic traits that reflects our current understanding of autism, the Comprehensive Autism Trait Inventory (CATI). METHODS: In Study 1, 107 pilot items were administered to 1119 individuals in the general population and exploratory factor analysis of responses used to create the 42-item CATI comprising six subscales: Social Interactions, Communication, Social Camouflage, Repetitive Behaviours, Cognitive Rigidity, and Sensory Sensitivity. In Study 2, the CATI was administered to 1068 new individuals and confirmatory factor analysis used to verify the factor structure. The AQ and BAPQ were administered to validate the CATI, and additional autistic participants were recruited to compare the predictive ability of the measures. In Study 3, to validate the CATI subscales, the CATI was administered to 195 new individuals along with existing valid measures qualitatively similar to each CATI subscale. RESULTS: The CATI showed convergent validity at both the total-scale (r???.79) and subscale level (r???.68). The CATI also showed superior internal reliability for total-scale scores (??=?.95) relative to the AQ (??=?.90) and BAPQ (??=?.94), consistently high reliability for subscales (??>?.81), greater predictive ability for classifying autism (Youden's Index?=?.62 vs .56-.59), and demonstrated measurement invariance for sex. LIMITATIONS: Analyses of predictive ability for classifying autism depended upon self-reported diagnosis or identification of autism. The autistic sample was not large enough to test measurement invariance of autism diagnosis. CONCLUSIONS: The CATI is a reliable and economical new measure that provides observations across a wide range of trait dimensions associated with autism, potentially precluding the need to administer multiple measures, and to our knowledge, the CATI is also the first broad measure of autistic traits to have dedicated subscales for social camouflage and sensory sensitivity. En ligne : http://dx.doi.org/10.1186/s13229-021-00445-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] The Comprehensive Autistic Trait Inventory (CATI): development and validation of a new measure of autistic traits in the general population [Texte imprimé et/ou numérique] / M. C. W. ENGLISH, Auteur ; G. E. GIGNAC, Auteur ; Troy A. W. VISSER, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; J. T. ENNS, Auteur ; M. T. MAYBERY, Auteur . - 37 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 37 p. Mots-clés : Autism  Autistic traits  Broader autism spectrum  Factor analysis  General population  Questionnaire  Self-report  Subscales Index. décimale : PER Périodiques Résumé : BACKGROUND: Traits and characteristics qualitatively similar to those seen in diagnosed autism spectrum disorder can be found to varying degrees in the general population. To measure these traits and facilitate their use in autism research, several questionnaires have been developed that provide broad measures of autistic traits [e.g. Autism-Spectrum Quotient (AQ), Broad Autism Phenotype Questionnaire (BAPQ)]. However, since their development, our understanding of autism has grown considerably, and it is arguable that existing measures do not provide an ideal representation of the trait dimensions currently associated with autism. Our aim was to create a new measure of autistic traits that reflects our current understanding of autism, the Comprehensive Autism Trait Inventory (CATI). METHODS: In Study 1, 107 pilot items were administered to 1119 individuals in the general population and exploratory factor analysis of responses used to create the 42-item CATI comprising six subscales: Social Interactions, Communication, Social Camouflage, Repetitive Behaviours, Cognitive Rigidity, and Sensory Sensitivity. In Study 2, the CATI was administered to 1068 new individuals and confirmatory factor analysis used to verify the factor structure. The AQ and BAPQ were administered to validate the CATI, and additional autistic participants were recruited to compare the predictive ability of the measures. In Study 3, to validate the CATI subscales, the CATI was administered to 195 new individuals along with existing valid measures qualitatively similar to each CATI subscale. RESULTS: The CATI showed convergent validity at both the total-scale (r???.79) and subscale level (r???.68). The CATI also showed superior internal reliability for total-scale scores (??=?.95) relative to the AQ (??=?.90) and BAPQ (??=?.94), consistently high reliability for subscales (??>?.81), greater predictive ability for classifying autism (Youden's Index?=?.62 vs .56-.59), and demonstrated measurement invariance for sex. LIMITATIONS: Analyses of predictive ability for classifying autism depended upon self-reported diagnosis or identification of autism. The autistic sample was not large enough to test measurement invariance of autism diagnosis. CONCLUSIONS: The CATI is a reliable and economical new measure that provides observations across a wide range of trait dimensions associated with autism, potentially precluding the need to administer multiple measures, and to our knowledge, the CATI is also the first broad measure of autistic traits to have dedicated subscales for social camouflage and sensory sensitivity. En ligne : http://dx.doi.org/10.1186/s13229-021-00445-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder / Andrew W. ZIMMERMAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 38 p. Titre : Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Andrew W. ZIMMERMAN, Auteur ; K. SINGH, Auteur ; S. L. CONNORS, Auteur ; H. LIU, Auteur ; Anita A PANJWANI, Auteur ; L. C. LEE, Auteur ; E. DIGGINS, Auteur ; A. FOLEY, Auteur ; S. MELNYK, Auteur ; I. N. SINGH, Auteur ; S. J. JAMES, Auteur ; R. E. FRYE, Auteur ; J. W. FAHEY, Auteur Article en page(s) : 38 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Biomarkers  Clinical trial  Placebo effects  Sulforaphane  defendants in matters related to pediatric neurology and Autism Spectrum Disorder.  JWF retired from the full-time faculty at Johns Hopkins in mid-2020, and now serves  as a scientific advisor to Brassica Protection Products LLC (Baltimore, MD, USA),  which produces a glucoraphanin-rich broccoli seed extract that it supplies to the  supplement industry. AWZ is named on a patent on the use of sulforaphane for the  treatment of autism that has been assigned to Johns Hopkins University. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. METHODS: We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3-12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. RESULTS: Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen's d 0.21; 95% CI -?0.46, 0.88 and 0.10; 95% CI -?0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen's d -?0.96; 95% CI -?1.73, -?0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p? En ligne : http://dx.doi.org/10.1186/s13229-021-00447-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Andrew W. ZIMMERMAN, Auteur ; K. SINGH, Auteur ; S. L. CONNORS, Auteur ; H. LIU, Auteur ; Anita A PANJWANI, Auteur ; L. C. LEE, Auteur ; E. DIGGINS, Auteur ; A. FOLEY, Auteur ; S. MELNYK, Auteur ; I. N. SINGH, Auteur ; S. J. JAMES, Auteur ; R. E. FRYE, Auteur ; J. W. FAHEY, Auteur . - 38 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 38 p. Mots-clés : Autism spectrum disorder (ASD)  Biomarkers  Clinical trial  Placebo effects  Sulforaphane  defendants in matters related to pediatric neurology and Autism Spectrum Disorder.  JWF retired from the full-time faculty at Johns Hopkins in mid-2020, and now serves  as a scientific advisor to Brassica Protection Products LLC (Baltimore, MD, USA),  which produces a glucoraphanin-rich broccoli seed extract that it supplies to the  supplement industry. AWZ is named on a patent on the use of sulforaphane for the  treatment of autism that has been assigned to Johns Hopkins University. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. METHODS: We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3-12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. RESULTS: Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen's d 0.21; 95% CI -?0.46, 0.88 and 0.10; 95% CI -?0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen's d -?0.96; 95% CI -?1.73, -?0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p? En ligne : http://dx.doi.org/10.1186/s13229-021-00447-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Using the big data approach to clarify the structure of restricted and repetitive behaviors across the most commonly used autism spectrum disorder measures / M. ULJAREVIC in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 39 p. Titre : Using the big data approach to clarify the structure of restricted and repetitive behaviors across the most commonly used autism spectrum disorder measures Type de document : Texte imprimé et/ou numérique Auteurs : M. ULJAREVIC, Auteur ; B. JO, Auteur ; T. W. FRAZIER, Auteur ; Lawrence SCAHILL, Auteur ; Eric A. YOUNGSTROM, Auteur ; A. Y. HARDAN, Auteur Article en page(s) : 39 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Circumscribed interest  Factor analysis  Insistence of sameness  Repetitive motor behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviors (RRB) in autism spectrum disorder (ASD) encompass several distinct domains. However, commonly used general ASD measures provide broad RRB scores rather than assessing separate RRB domains. The main objective of the current investigation was to conduct a psychometric evaluation of the ability of the Social Responsiveness Scale (SRS-2), the Social Communication Questionnaire (SCQ), the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) to capture different RRB constructs. METHODS: Exploratory Structural Equation Modeling (ESEM) was conducted using individual item-level data from the SRS-2, SCQ, ADI-R and the ADOS. Data were obtained from five existing publicly available databases. For the SRS-2, the final sample consisted of N?=?16,761 individuals (M(age)?=?9.43, SD?=?3.73; 18.5% female); for the SCQ, of N?=?15,840 (M(age)?=?7.99, SD?=?4.06; 18.1% female); for the ADI-R, of N?=?8985 (M(age)?=?8.86, SD?=?4.68; 19.4% female); and for the ADOS, of N?=?6314 (M(age)?=?12.29, SD?=?6.79; 17.7% female). RESULTS: The three-factor structure provided the most optimal and interpretable fit to data for all measures (comparative fit index???.983, Tucker Lewis index???.966, root mean square error of approximation???.028). Repetitive-motor behaviors, insistence on sameness and unusual or circumscribed interests factors emerged across all instruments. No acceptable fit was identified for the ADOS. LIMITATIONS: The five datasets used here afforded a large as well as wide distribution of the RRB item scores. However, measures used for establishing convergent and divergent validity were only available for a portion of the sample. CONCLUSIONS: Reported findings offer promise for capturing important RRB domains using general ASD measures and highlight the need for measurement development. En ligne : http://dx.doi.org/10.1186/s13229-021-00419-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Using the big data approach to clarify the structure of restricted and repetitive behaviors across the most commonly used autism spectrum disorder measures [Texte imprimé et/ou numérique] / M. ULJAREVIC, Auteur ; B. JO, Auteur ; T. W. FRAZIER, Auteur ; Lawrence SCAHILL, Auteur ; Eric A. YOUNGSTROM, Auteur ; A. Y. HARDAN, Auteur . - 39 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 39 p. Mots-clés : Autism spectrum disorder  Circumscribed interest  Factor analysis  Insistence of sameness  Repetitive motor behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behaviors (RRB) in autism spectrum disorder (ASD) encompass several distinct domains. However, commonly used general ASD measures provide broad RRB scores rather than assessing separate RRB domains. The main objective of the current investigation was to conduct a psychometric evaluation of the ability of the Social Responsiveness Scale (SRS-2), the Social Communication Questionnaire (SCQ), the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) to capture different RRB constructs. METHODS: Exploratory Structural Equation Modeling (ESEM) was conducted using individual item-level data from the SRS-2, SCQ, ADI-R and the ADOS. Data were obtained from five existing publicly available databases. For the SRS-2, the final sample consisted of N?=?16,761 individuals (M(age)?=?9.43, SD?=?3.73; 18.5% female); for the SCQ, of N?=?15,840 (M(age)?=?7.99, SD?=?4.06; 18.1% female); for the ADI-R, of N?=?8985 (M(age)?=?8.86, SD?=?4.68; 19.4% female); and for the ADOS, of N?=?6314 (M(age)?=?12.29, SD?=?6.79; 17.7% female). RESULTS: The three-factor structure provided the most optimal and interpretable fit to data for all measures (comparative fit index???.983, Tucker Lewis index???.966, root mean square error of approximation???.028). Repetitive-motor behaviors, insistence on sameness and unusual or circumscribed interests factors emerged across all instruments. No acceptable fit was identified for the ADOS. LIMITATIONS: The five datasets used here afforded a large as well as wide distribution of the RRB item scores. However, measures used for establishing convergent and divergent validity were only available for a portion of the sample. CONCLUSIONS: Reported findings offer promise for capturing important RRB domains using general ASD measures and highlight the need for measurement development. En ligne : http://dx.doi.org/10.1186/s13229-021-00419-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Retraction Note to: Improving the measurement of alexithymia in autistic adults: a psychometric investigation and refinement of the twenty-item Toronto Alexithymia Scale / Z. J. WILLIAMS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 40 p. Titre : Retraction Note to: Improving the measurement of alexithymia in autistic adults: a psychometric investigation and refinement of the twenty-item Toronto Alexithymia Scale Type de document : Texte imprimé et/ou numérique Auteurs : Z. J. WILLIAMS, Auteur ; K. O. GOTHAM, Auteur Article en page(s) : 40 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00446-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Retraction Note to: Improving the measurement of alexithymia in autistic adults: a psychometric investigation and refinement of the twenty-item Toronto Alexithymia Scale [Texte imprimé et/ou numérique] / Z. J. WILLIAMS, Auteur ; K. O. GOTHAM, Auteur . - 40 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 40 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00446-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity / N. SARN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 41 p. Titre : Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity Type de document : Texte imprimé et/ou numérique Auteurs : N. SARN, Auteur ; S. THACKER, Auteur ; H. LEE, Auteur ; C. ENG, Auteur Article en page(s) : 41 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Complement  Microglia  Mouse model  Neurodegeneration  Neuroinflammation  Oxytocin  PTEN mutation  Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) has a strong genetic etiology. Germline mutation in the tumor suppressor gene PTEN is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific Pten loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior. As such, there is a growing need to understand more about how various aspects of PTEN activity and cell-compartment-specific functions, contribute to certain neurological or behavior phenotypes. METHODS: To understand more about the relationship between Pten localization and downstream effects on neurophenotypes, we generated the nuclear-predominant Pten(Y68H/+) mouse, which is identical to the genotype of some PTEN-ASD individuals. We subjected the Pten(Y68H/+) mouse to morphological and behavioral phenotyping, including the three-chamber sociability, open field, rotarod, and marble burying tests. We subsequently performed in vivo and in vitro cellular phenotyping and concluded the work with a transcriptomic survey of the Pten(Y68H/+) cortex, which profiled gene expression. RESULTS: We observe a significant increase in P-Akt downstream of canonical Pten signaling, macrocephaly, decreased sociability, decreased preference for novel social stimuli, increased repetitive behavior, and increased thigmotaxis in Pten(Y68H/+) six-week-old (P40) mice. In addition, we found significant microglial activation with increased expression of complement and neuroinflammatory proteins in vivo and in vitro accompanied by enhanced phagocytosis. These observations were subsequently validated with RNA-seq and qRT-PCR, which revealed overexpression of many genes involved in neuroinflammation and neuronal function, including oxytocin. Oxytocin transcript was fivefold overexpressed (P?=?0.0018), and oxytocin protein was strongly overexpressed in the Pten(Y68H/+) hypothalamus. CONCLUSIONS: The nuclear-predominant Pten(Y68H/+) model has clarified that Pten dysfunction links to microglial pathology and this associates with increased Akt signaling. We also demonstrate that Pten dysfunction associates with changes in the oxytocin system, an important connection between a prominent ASD risk gene and a potent neuroendocrine regulator of social behavior. These cellular and molecular pathologies may related to the observed changes in social behavior. Ultimately, the findings from this work may reveal important biomarkers and/or novel therapeutic modalities that could be explored in individuals with germline mutations in PTEN with ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00448-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity [Texte imprimé et/ou numérique] / N. SARN, Auteur ; S. THACKER, Auteur ; H. LEE, Auteur ; C. ENG, Auteur . - 41 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 41 p. Mots-clés : Autism spectrum disorder  Complement  Microglia  Mouse model  Neurodegeneration  Neuroinflammation  Oxytocin  PTEN mutation  Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) has a strong genetic etiology. Germline mutation in the tumor suppressor gene PTEN is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific Pten loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior. As such, there is a growing need to understand more about how various aspects of PTEN activity and cell-compartment-specific functions, contribute to certain neurological or behavior phenotypes. METHODS: To understand more about the relationship between Pten localization and downstream effects on neurophenotypes, we generated the nuclear-predominant Pten(Y68H/+) mouse, which is identical to the genotype of some PTEN-ASD individuals. We subjected the Pten(Y68H/+) mouse to morphological and behavioral phenotyping, including the three-chamber sociability, open field, rotarod, and marble burying tests. We subsequently performed in vivo and in vitro cellular phenotyping and concluded the work with a transcriptomic survey of the Pten(Y68H/+) cortex, which profiled gene expression. RESULTS: We observe a significant increase in P-Akt downstream of canonical Pten signaling, macrocephaly, decreased sociability, decreased preference for novel social stimuli, increased repetitive behavior, and increased thigmotaxis in Pten(Y68H/+) six-week-old (P40) mice. In addition, we found significant microglial activation with increased expression of complement and neuroinflammatory proteins in vivo and in vitro accompanied by enhanced phagocytosis. These observations were subsequently validated with RNA-seq and qRT-PCR, which revealed overexpression of many genes involved in neuroinflammation and neuronal function, including oxytocin. Oxytocin transcript was fivefold overexpressed (P?=?0.0018), and oxytocin protein was strongly overexpressed in the Pten(Y68H/+) hypothalamus. CONCLUSIONS: The nuclear-predominant Pten(Y68H/+) model has clarified that Pten dysfunction links to microglial pathology and this associates with increased Akt signaling. We also demonstrate that Pten dysfunction associates with changes in the oxytocin system, an important connection between a prominent ASD risk gene and a potent neuroendocrine regulator of social behavior. These cellular and molecular pathologies may related to the observed changes in social behavior. Ultimately, the findings from this work may reveal important biomarkers and/or novel therapeutic modalities that could be explored in individuals with germline mutations in PTEN with ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00448-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Psychometric validation and refinement of the Interoception Sensory Questionnaire (ISQ) in adolescents and adults on the autism spectrum / E. SUZMAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 42 p. Titre : Psychometric validation and refinement of the Interoception Sensory Questionnaire (ISQ) in adolescents and adults on the autism spectrum Type de document : Texte imprimé et/ou numérique Auteurs : E. SUZMAN, Auteur ; Z. J. WILLIAMS, Auteur ; J. I. FELDMAN, Auteur ; M. FAILLA, Auteur ; Carissa J. CASCIO, Auteur ; Mark T. WALLACE, Auteur ; M. NIARCHOU, Auteur ; J. S. SUTCLIFFE, Auteur ; E. WODKA, Auteur ; Tiffany G. WOYNAROSKI, Auteur Article en page(s) : 42 p. Langues : Anglais (eng) Mots-clés : Autism  Interoception  Item response theory  Measurement  Psychometric  Reliability  Sensory  Validity  Network Vanderbilt site. ZJW also serves as a consultant to Roche. The other authors  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals on the autism spectrum are reported to display alterations in interoception, the sense of the internal state of the body. The Interoception Sensory Questionnaire (ISQ) is a 20-item self-report measure of interoception specifically intended to measure this construct in autistic people. The psychometrics of the ISQ, however, have not previously been evaluated in a large sample of autistic individuals. METHODS: Using confirmatory factor analysis, we evaluated the latent structure of the ISQ in a large online sample of adults on the autism spectrum and found that the unidimensional model fit the data poorly. Using misspecification analysis to identify areas of local misfit and item response theory to investigate the appropriateness of the seven-point response scale, we removed redundant items and collapsed the response options to put forth a novel eight-item, five-response choice ISQ. RESULTS: The revised, five-response choice ISQ (ISQ-8) showed much improved fit while maintaining high internal reliability. Differential item functioning (DIF) analyses indicated that the items of the ISQ-8 were answered in comparable ways by autistic adolescents and adults and across multiple other sociodemographic groups. LIMITATIONS: Our results were limited by the fact that we did not collect data for typically developing controls, preventing the analysis of DIF by diagnostic status. Additionally, while this study proposes a new 5-response scale for the ISQ-8, our data were not collected using this method; thus, the psychometric properties for the revised version of this instrument require further investigation. CONCLUSION: The ISQ-8 shows promise as a reliable and valid measure of interoception in adolescents and adults on the autism spectrum, but additional work is needed to examine its psychometrics in this population. A free online score calculator has been created to facilitate the use of ISQ-8 latent trait scores for further studies of autistic adolescents and adults (available at https://asdmeasures.shinyapps.io/ISQ_score/ ). En ligne : http://dx.doi.org/10.1186/s13229-021-00440-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Psychometric validation and refinement of the Interoception Sensory Questionnaire (ISQ) in adolescents and adults on the autism spectrum [Texte imprimé et/ou numérique] / E. SUZMAN, Auteur ; Z. J. WILLIAMS, Auteur ; J. I. FELDMAN, Auteur ; M. FAILLA, Auteur ; Carissa J. CASCIO, Auteur ; Mark T. WALLACE, Auteur ; M. NIARCHOU, Auteur ; J. S. SUTCLIFFE, Auteur ; E. WODKA, Auteur ; Tiffany G. WOYNAROSKI, Auteur . - 42 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 42 p. Mots-clés : Autism  Interoception  Item response theory  Measurement  Psychometric  Reliability  Sensory  Validity  Network Vanderbilt site. ZJW also serves as a consultant to Roche. The other authors  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals on the autism spectrum are reported to display alterations in interoception, the sense of the internal state of the body. The Interoception Sensory Questionnaire (ISQ) is a 20-item self-report measure of interoception specifically intended to measure this construct in autistic people. The psychometrics of the ISQ, however, have not previously been evaluated in a large sample of autistic individuals. METHODS: Using confirmatory factor analysis, we evaluated the latent structure of the ISQ in a large online sample of adults on the autism spectrum and found that the unidimensional model fit the data poorly. Using misspecification analysis to identify areas of local misfit and item response theory to investigate the appropriateness of the seven-point response scale, we removed redundant items and collapsed the response options to put forth a novel eight-item, five-response choice ISQ. RESULTS: The revised, five-response choice ISQ (ISQ-8) showed much improved fit while maintaining high internal reliability. Differential item functioning (DIF) analyses indicated that the items of the ISQ-8 were answered in comparable ways by autistic adolescents and adults and across multiple other sociodemographic groups. LIMITATIONS: Our results were limited by the fact that we did not collect data for typically developing controls, preventing the analysis of DIF by diagnostic status. Additionally, while this study proposes a new 5-response scale for the ISQ-8, our data were not collected using this method; thus, the psychometric properties for the revised version of this instrument require further investigation. CONCLUSION: The ISQ-8 shows promise as a reliable and valid measure of interoception in adolescents and adults on the autism spectrum, but additional work is needed to examine its psychometrics in this population. A free online score calculator has been created to facilitate the use of ISQ-8 latent trait scores for further studies of autistic adolescents and adults (available at https://asdmeasures.shinyapps.io/ISQ_score/ ). En ligne : http://dx.doi.org/10.1186/s13229-021-00440-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts / B. G. MCKENNA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 43 p. Titre : Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts Type de document : Texte imprimé et/ou numérique Auteurs : B. G. MCKENNA, Auteur ; Y. HUANG, Auteur ; K. VERVIER, Auteur ; D. HOFAMMANN, Auteur ; M. CAFFERATA, Auteur ; S. AL-MOMANI, Auteur ; F. LOWENTHAL, Auteur ; A. ZHANG, Auteur ; J. Y. KOH, Auteur ; S. THENUWARA, Auteur ; L. BRUEGGEMAN, Auteur ; E. BAHL, Auteur ; T. KOOMAR, Auteur ; N. POTTSCHMIDT, Auteur ; T. KALMUS, Auteur ; L. CASTEN, Auteur ; T. R. THOMAS, Auteur ; J. J. MICHAELSON, Auteur Article en page(s) : 43 p. Langues : Anglais (eng) Mots-clés : Androgen exposure  Autism spectrum disorder  Masculinity  Neurodevelopment  Social functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear. METHODS: Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores. RESULTS: We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all [Formula: see text]), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text], respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ([Formula: see text], [Formula: see text]), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ([Formula: see text], [Formula: see text]). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ([Formula: see text], [Formula: see text], and [Formula: see text], [Formula: see text] for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: [Formula: see text]; testosterone: [Formula: see text] from 0.1%-ile to 99.9%-ile; SHBG: [Formula: see text] from 0.1%-ile to 99.9%-ile). LIMITATIONS: In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules. CONCLUSIONS: These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females. En ligne : http://dx.doi.org/10.1186/s13229-021-00450-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts [Texte imprimé et/ou numérique] / B. G. MCKENNA, Auteur ; Y. HUANG, Auteur ; K. VERVIER, Auteur ; D. HOFAMMANN, Auteur ; M. CAFFERATA, Auteur ; S. AL-MOMANI, Auteur ; F. LOWENTHAL, Auteur ; A. ZHANG, Auteur ; J. Y. KOH, Auteur ; S. THENUWARA, Auteur ; L. BRUEGGEMAN, Auteur ; E. BAHL, Auteur ; T. KOOMAR, Auteur ; N. POTTSCHMIDT, Auteur ; T. KALMUS, Auteur ; L. CASTEN, Auteur ; T. R. THOMAS, Auteur ; J. J. MICHAELSON, Auteur . - 43 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 43 p. Mots-clés : Androgen exposure  Autism spectrum disorder  Masculinity  Neurodevelopment  Social functioning Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear. METHODS: Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores. RESULTS: We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all [Formula: see text]), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text], respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ([Formula: see text], [Formula: see text]), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ([Formula: see text], [Formula: see text]). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ([Formula: see text], [Formula: see text], and [Formula: see text], [Formula: see text] for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: [Formula: see text]; testosterone: [Formula: see text] from 0.1%-ile to 99.9%-ile; SHBG: [Formula: see text] from 0.1%-ile to 99.9%-ile). LIMITATIONS: In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules. CONCLUSIONS: These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females. En ligne : http://dx.doi.org/10.1186/s13229-021-00450-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder / Andrew W. ZIMMERMAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 44 p. Titre : Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Andrew W. ZIMMERMAN, Auteur ; K. SINGH, Auteur ; S. L. CONNORS, Auteur ; H. LIU, Auteur ; Anita A PANJWANI, Auteur ; L. C. LEE, Auteur ; E. DIGGINS, Auteur ; A. FOLEY, Auteur ; S. MELNYK, Auteur ; I. N. SINGH, Auteur ; S. JILL JAMES, Auteur ; R. E. FRYE, Auteur ; J. W. FAHEY, Auteur Article en page(s) : 44 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00451-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Andrew W. ZIMMERMAN, Auteur ; K. SINGH, Auteur ; S. L. CONNORS, Auteur ; H. LIU, Auteur ; Anita A PANJWANI, Auteur ; L. C. LEE, Auteur ; E. DIGGINS, Auteur ; A. FOLEY, Auteur ; S. MELNYK, Auteur ; I. N. SINGH, Auteur ; S. JILL JAMES, Auteur ; R. E. FRYE, Auteur ; J. W. FAHEY, Auteur . - 44 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 44 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00451-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Development and validation of the suicidal behaviours questionnaire - autism spectrum conditions in a community sample of autistic, possibly autistic and non-autistic adults / Sarah A. CASSIDY in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 46 p. Titre : Development and validation of the suicidal behaviours questionnaire - autism spectrum conditions in a community sample of autistic, possibly autistic and non-autistic adults Type de document : Texte imprimé et/ou numérique Auteurs : Sarah A. CASSIDY, Auteur ; Louise BRADLEY, Auteur ; Heather COGGER-WARD, Auteur ; J. RODGERS, Auteur Article en page(s) : 46 p. Langues : Anglais (eng) Mots-clés : Autism spectrum conditions  Autistic traits  Measurement invariance  Measurement properties  Suicidal behaviours questionnaire  Suicidality Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic people and those with high autistic traits are at high risk of experiencing suicidality. Yet, there are no suicidality assessment tools developed or validated for these groups. METHODS: A widely used and validated suicidality assessment tool developed for the general population (SBQ-R), was adapted using feedback from autistic adults, to create the Suicidal Behaviours Questionnaire-Autism Spectrum Conditions (SBQ-ASC). The adapted tool was refined through nine interviews, and an online survey with 251 autistic adults, to establish clarity and relevance of the items. Subsequently, 308 autistic, 113 possibly autistic, and 268 non-autistic adults completed the adapted tool online, alongside self-report measures of autistic traits (AQ), camouflaging autistic traits (CAT-Q), depression (PHQ-9), anxiety (ASA-A), thwarted belongingness and perceived burdensomeness (INQ-15), lifetime non-suicidal self-injury, and the original version of the suicidality assessment tool (SBQ-R). Analyses explored the appropriateness and measurement properties of the adapted tool between the groups. RESULTS: There was evidence in support of content validity, structural validity, internal consistency, convergent and divergent validity, test-retest validity, sensitivity and specificity (for distinguishing those with or without lifetime experience of suicide attempt), and hypothesis testing of the adapted tool (SBQ-ASC) in each group. The structure of the SBQ-ASC was equivalent between autistic and possibly autistic adults, regardless of gender, or use of visual aids to help quantify abstract rating scales. LIMITATIONS: The samples involved in the development and validation of the adapted tool were largely female, and largely diagnosed as autistic in adulthood, which limits the generalisability of results to the wider autistic population. The SBQ-ASC has been developed for use in research and is not recommended to assess risk of future suicide attempts and/or self-harm. The SBQ-ASC has been designed with and for autistic and possibly autistic adults, and is not appropriate to compare to non-autistic adults given measurement differences between these groups. CONCLUSIONS: The SBQ-ASC is a brief self-report suicidality assessment tool, developed and validated with and for autistic adults, without co-occurring intellectual disability. The SBQ-ASC is appropriate for use in research to identify suicidal thoughts and behaviours in autistic and possibly autistic people, and model associations with risk and protective factors. En ligne : http://dx.doi.org/10.1186/s13229-021-00449-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Development and validation of the suicidal behaviours questionnaire - autism spectrum conditions in a community sample of autistic, possibly autistic and non-autistic adults [Texte imprimé et/ou numérique] / Sarah A. CASSIDY, Auteur ; Louise BRADLEY, Auteur ; Heather COGGER-WARD, Auteur ; J. RODGERS, Auteur . - 46 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 46 p. Mots-clés : Autism spectrum conditions  Autistic traits  Measurement invariance  Measurement properties  Suicidal behaviours questionnaire  Suicidality Index. décimale : PER Périodiques Résumé : BACKGROUND: Autistic people and those with high autistic traits are at high risk of experiencing suicidality. Yet, there are no suicidality assessment tools developed or validated for these groups. METHODS: A widely used and validated suicidality assessment tool developed for the general population (SBQ-R), was adapted using feedback from autistic adults, to create the Suicidal Behaviours Questionnaire-Autism Spectrum Conditions (SBQ-ASC). The adapted tool was refined through nine interviews, and an online survey with 251 autistic adults, to establish clarity and relevance of the items. Subsequently, 308 autistic, 113 possibly autistic, and 268 non-autistic adults completed the adapted tool online, alongside self-report measures of autistic traits (AQ), camouflaging autistic traits (CAT-Q), depression (PHQ-9), anxiety (ASA-A), thwarted belongingness and perceived burdensomeness (INQ-15), lifetime non-suicidal self-injury, and the original version of the suicidality assessment tool (SBQ-R). Analyses explored the appropriateness and measurement properties of the adapted tool between the groups. RESULTS: There was evidence in support of content validity, structural validity, internal consistency, convergent and divergent validity, test-retest validity, sensitivity and specificity (for distinguishing those with or without lifetime experience of suicide attempt), and hypothesis testing of the adapted tool (SBQ-ASC) in each group. The structure of the SBQ-ASC was equivalent between autistic and possibly autistic adults, regardless of gender, or use of visual aids to help quantify abstract rating scales. LIMITATIONS: The samples involved in the development and validation of the adapted tool were largely female, and largely diagnosed as autistic in adulthood, which limits the generalisability of results to the wider autistic population. The SBQ-ASC has been developed for use in research and is not recommended to assess risk of future suicide attempts and/or self-harm. The SBQ-ASC has been designed with and for autistic and possibly autistic adults, and is not appropriate to compare to non-autistic adults given measurement differences between these groups. CONCLUSIONS: The SBQ-ASC is a brief self-report suicidality assessment tool, developed and validated with and for autistic adults, without co-occurring intellectual disability. The SBQ-ASC is appropriate for use in research to identify suicidal thoughts and behaviours in autistic and possibly autistic people, and model associations with risk and protective factors. En ligne : http://dx.doi.org/10.1186/s13229-021-00449-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Correction to: Hans Asperger, National Socialism, and "race hygiene" in Nazi-era Vienna / H. CZECH in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 45 p. Titre : Correction to: Hans Asperger, National Socialism, and "race hygiene" in Nazi-era Vienna Type de document : Texte imprimé et/ou numérique Auteurs : H. CZECH, Auteur Article en page(s) : 45 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00433-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Correction to: Hans Asperger, National Socialism, and "race hygiene" in Nazi-era Vienna [Texte imprimé et/ou numérique] / H. CZECH, Auteur . - 45 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 45 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00433-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Neurite orientation dispersion and density imaging reveals white matter microstructural alterations in adults with autism / C. ANDICA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 48 p. Titre : Neurite orientation dispersion and density imaging reveals white matter microstructural alterations in adults with autism Type de document : Texte imprimé et/ou numérique Auteurs : C. ANDICA, Auteur ; K. KAMAGATA, Auteur ; E. KIRINO, Auteur ; W. UCHIDA, Auteur ; R. IRIE, Auteur ; S. MURATA, Auteur ; S. AOKI, Auteur Article en page(s) : 48 p. Langues : Anglais (eng) Mots-clés : Autism  Diffusion tensor imaging  Linear discriminant analysis  Neurite orientation dispersion and density imaging  Neuroinflammation  Neuronal loss  Region-of-interest  Tract-based spatial statistics  White matter microstructure Index. décimale : PER Périodiques Résumé : BACKGROUND: Evidences suggesting the association between behavioral anomalies in autism and white matter (WM) microstructural alterations are increasing. Diffusion tensor imaging (DTI) is widely used to infer tissue microstructure. However, due to its lack of specificity, the underlying pathology of reported differences in DTI measures in autism remains poorly understood. Herein, we applied neurite orientation dispersion and density imaging (NODDI) to quantify and define more specific causes of WM microstructural changes associated with autism in adults. METHODS: NODDI (neurite density index [NDI], orientation dispersion index, and isotropic volume fraction [ISOVF]) and DTI (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity [RD]) measures were compared between autism (N?=?26; 19 males and 7 females; 32.93?±?9.24 years old) and age- and sex-matched typically developing (TD; N?=?25; 17 males and 8 females; 34.43?±?9.02 years old) groups using tract-based spatial statistics and region-of-interest analyses. Linear discriminant analysis using leave-one-out cross-validation (LDA-LOOCV) was also performed to assess the discriminative power of diffusion measures in autism and TD. RESULTS: Significantly lower NDI and higher ISOVF, suggestive of decreased neurite density and increased extracellular free-water, respectively, were demonstrated in the autism group compared with the TD group, mainly in commissural and long-range association tracts, but with distinct predominant sides. Consistent with previous reports, the autism group showed lower FA and higher MD and RD when compared with TD group. Notably, LDA-LOOCV suggests that NDI and ISOVF have relatively higher accuracy (82%) and specificity (NDI, 84%; ISOVF, 88%) compared with that of FA, MD, and RD (accuracy, 67-73%; specificity, 68-80%). LIMITATIONS: The absence of histopathological confirmation limit the interpretation of our findings. CONCLUSIONS: Our results suggest that NODDI measures might be useful as imaging biomarkers to diagnose autism in adults and assess its behavioral characteristics. Furthermore, NODDI allows interpretation of previous findings on changes in WM diffusion tensor metrics in individuals with autism. En ligne : http://dx.doi.org/10.1186/s13229-021-00456-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Neurite orientation dispersion and density imaging reveals white matter microstructural alterations in adults with autism [Texte imprimé et/ou numérique] / C. ANDICA, Auteur ; K. KAMAGATA, Auteur ; E. KIRINO, Auteur ; W. UCHIDA, Auteur ; R. IRIE, Auteur ; S. MURATA, Auteur ; S. AOKI, Auteur . - 48 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 48 p. Mots-clés : Autism  Diffusion tensor imaging  Linear discriminant analysis  Neurite orientation dispersion and density imaging  Neuroinflammation  Neuronal loss  Region-of-interest  Tract-based spatial statistics  White matter microstructure Index. décimale : PER Périodiques Résumé : BACKGROUND: Evidences suggesting the association between behavioral anomalies in autism and white matter (WM) microstructural alterations are increasing. Diffusion tensor imaging (DTI) is widely used to infer tissue microstructure. However, due to its lack of specificity, the underlying pathology of reported differences in DTI measures in autism remains poorly understood. Herein, we applied neurite orientation dispersion and density imaging (NODDI) to quantify and define more specific causes of WM microstructural changes associated with autism in adults. METHODS: NODDI (neurite density index [NDI], orientation dispersion index, and isotropic volume fraction [ISOVF]) and DTI (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity [RD]) measures were compared between autism (N?=?26; 19 males and 7 females; 32.93?±?9.24 years old) and age- and sex-matched typically developing (TD; N?=?25; 17 males and 8 females; 34.43?±?9.02 years old) groups using tract-based spatial statistics and region-of-interest analyses. Linear discriminant analysis using leave-one-out cross-validation (LDA-LOOCV) was also performed to assess the discriminative power of diffusion measures in autism and TD. RESULTS: Significantly lower NDI and higher ISOVF, suggestive of decreased neurite density and increased extracellular free-water, respectively, were demonstrated in the autism group compared with the TD group, mainly in commissural and long-range association tracts, but with distinct predominant sides. Consistent with previous reports, the autism group showed lower FA and higher MD and RD when compared with TD group. Notably, LDA-LOOCV suggests that NDI and ISOVF have relatively higher accuracy (82%) and specificity (NDI, 84%; ISOVF, 88%) compared with that of FA, MD, and RD (accuracy, 67-73%; specificity, 68-80%). LIMITATIONS: The absence of histopathological confirmation limit the interpretation of our findings. CONCLUSIONS: Our results suggest that NODDI measures might be useful as imaging biomarkers to diagnose autism in adults and assess its behavioral characteristics. Furthermore, NODDI allows interpretation of previous findings on changes in WM diffusion tensor metrics in individuals with autism. En ligne : http://dx.doi.org/10.1186/s13229-021-00456-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Autism symptoms in anorexia nervosa: a comparative study with females with autism spectrum disorder / J. KERR-GAFFNEY in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 47 p. Titre : Autism symptoms in anorexia nervosa: a comparative study with females with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : J. KERR-GAFFNEY, Auteur ; H. HAYWARD, Auteur ; E. J. H. JONES, Auteur ; D. HALLS, Auteur ; D. MURPHY, Auteur ; K. TCHANTURIA, Auteur Article en page(s) : 47 p. Langues : Anglais (eng) Mots-clés : Anorexia nervosa  Autism diagnostic observation schedule  Autism spectrum disorder  Comorbidity  Diagnosis  Screening Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent research suggests a link between autism spectrum disorder (ASD) and anorexia nervosa (AN). Individuals with AN show high scores on measures of ASD symptoms, relative to individuals without AN, however, there are currently no studies directly comparing women with AN to women with ASD. The aim of the current study was to examine profiles of ASD symptoms in young women in the acute and recovered stages of AN, women with ASD, and typically developing controls (TD), on both self-report and clinical interview measures. METHODS: Four groups of participants aged 12-30 years were included (n?=?218): AN, recovered AN (REC), ASD, and TD. Group differences on the Social Responsiveness Scale, 2nd edition (SRS-2), 10-item Autism Quotient (AQ-10), and the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) were examined. To explore similarities and differences in specific symptom profiles associated with AN and ASD, individual item endorsement on the ADOS-2 was also examined in AN, REC, and ASD. RESULTS: Across measures, women with ASD showed the highest scores, and TDs the lowest. Generally, individuals with AN and REC showed intermediate levels of ASD symptoms, scoring between the other two groups. However, AN and ASD did not differ on restricted interests and repetitive behaviour subscales. The ADOS-2 item 'quality of social response' adequately discriminated between ASD and non-ASD participants. LIMITATIONS: A full diagnostic assessment for ASD was not provided for participants with AN/REC, nor were eating disorders assessed in the ASD group. Therefore, some diagnostic overlap between groups is possible. The cross-sectional design is another limitation. CONCLUSIONS: The results suggest similarities in scores on both self-report and clinical interview measures in AN and ASD. However, individual ADOS-2 item analyses also revealed subtle differences, particularly in reciprocal social interaction. ASD symptoms may be a combination of both state and trait features in AN. En ligne : http://dx.doi.org/10.1186/s13229-021-00455-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Autism symptoms in anorexia nervosa: a comparative study with females with autism spectrum disorder [Texte imprimé et/ou numérique] / J. KERR-GAFFNEY, Auteur ; H. HAYWARD, Auteur ; E. J. H. JONES, Auteur ; D. HALLS, Auteur ; D. MURPHY, Auteur ; K. TCHANTURIA, Auteur . - 47 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 47 p. Mots-clés : Anorexia nervosa  Autism diagnostic observation schedule  Autism spectrum disorder  Comorbidity  Diagnosis  Screening Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent research suggests a link between autism spectrum disorder (ASD) and anorexia nervosa (AN). Individuals with AN show high scores on measures of ASD symptoms, relative to individuals without AN, however, there are currently no studies directly comparing women with AN to women with ASD. The aim of the current study was to examine profiles of ASD symptoms in young women in the acute and recovered stages of AN, women with ASD, and typically developing controls (TD), on both self-report and clinical interview measures. METHODS: Four groups of participants aged 12-30 years were included (n?=?218): AN, recovered AN (REC), ASD, and TD. Group differences on the Social Responsiveness Scale, 2nd edition (SRS-2), 10-item Autism Quotient (AQ-10), and the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) were examined. To explore similarities and differences in specific symptom profiles associated with AN and ASD, individual item endorsement on the ADOS-2 was also examined in AN, REC, and ASD. RESULTS: Across measures, women with ASD showed the highest scores, and TDs the lowest. Generally, individuals with AN and REC showed intermediate levels of ASD symptoms, scoring between the other two groups. However, AN and ASD did not differ on restricted interests and repetitive behaviour subscales. The ADOS-2 item 'quality of social response' adequately discriminated between ASD and non-ASD participants. LIMITATIONS: A full diagnostic assessment for ASD was not provided for participants with AN/REC, nor were eating disorders assessed in the ASD group. Therefore, some diagnostic overlap between groups is possible. The cross-sectional design is another limitation. CONCLUSIONS: The results suggest similarities in scores on both self-report and clinical interview measures in AN and ASD. However, individual ADOS-2 item analyses also revealed subtle differences, particularly in reciprocal social interaction. ASD symptoms may be a combination of both state and trait features in AN. En ligne : http://dx.doi.org/10.1186/s13229-021-00455-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin / C. M. PRETZSCH in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 49 p. Titre : Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin Type de document : Texte imprimé et/ou numérique Auteurs : C. M. PRETZSCH, Auteur ; D. L. FLORIS, Auteur ; B. VOINESCU, Auteur ; M. ELSAHIB, Auteur ; M. A. MENDEZ, Auteur ; R. WICHERS, Auteur ; L. AJRAM, Auteur ; G. IVIN, Auteur ; M. HEASMAN, Auteur ; E. PRETZSCH, Auteur ; S. WILLIAMS, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur ; G. M. MCALONAN, Auteur Article en page(s) : 49 p. Langues : Anglais (eng) Mots-clés : Autism spectrum condition  Autism spectrum disorder  Cbdv  Cannabidivarin  Functional connectivity  Striatum Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) has a high cost to affected individuals and society, but treatments for core symptoms are lacking. To expand intervention options, it is crucial to gain a better understanding of potential treatment targets, and their engagement, in the brain. For instance, the striatum (caudate, putamen, and nucleus accumbens) plays a central role during development and its (atypical) functional connectivity (FC) may contribute to multiple ASD symptoms. We have previously shown, in the adult autistic and neurotypical brain, the non-intoxicating cannabinoid cannabidivarin (CBDV) alters the balance of striatal 'excitatory-inhibitory' metabolites, which help regulate FC, but the effects of CBDV on (atypical) striatal FC are unknown. METHODS: To examine this in a small pilot study, we acquired resting state functional magnetic resonance imaging data from 28 men (15 neurotypicals, 13 ASD) on two occasions in a repeated-measures, double-blind, placebo-controlled study. We then used a seed-based approach to (1) compare striatal FC between groups and (2) examine the effect of pharmacological probing (600 mg CBDV/matched placebo) on atypical striatal FC in ASD. Visits were separated by at least 13 days to allow for drug washout. RESULTS: Compared to the neurotypicals, ASD individuals had lower FC between the ventral striatum and frontal and pericentral regions (which have been associated with emotion, motor, and vision processing). Further, they had higher intra-striatal FC and higher putamenal FC with temporal regions involved in speech and language. In ASD, CBDV reduced hyperconnectivity to the neurotypical level. LIMITATIONS: Our findings should be considered in light of several methodological aspects, in particular our participant group (restricted to male adults), which limits the generalizability of our findings to the wider and heterogeneous ASD population. CONCLUSION: In conclusion, here we show atypical striatal FC with regions commonly associated with ASD symptoms. We further provide preliminary proof of concept that, in the adult autistic brain, acute CBDV administration can modulate atypical striatal circuitry towards neurotypical function. Future studies are required to determine whether modulation of striatal FC is associated with a change in ASD symptoms. TRIAL REGISTRATION: clinicaltrials.gov, Identifier: NCT03537950. Registered May 25th, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03537950?term=NCT03537950&draw=2&rank=1 . En ligne : http://dx.doi.org/10.1186/s13229-021-00454-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin [Texte imprimé et/ou numérique] / C. M. PRETZSCH, Auteur ; D. L. FLORIS, Auteur ; B. VOINESCU, Auteur ; M. ELSAHIB, Auteur ; M. A. MENDEZ, Auteur ; R. WICHERS, Auteur ; L. AJRAM, Auteur ; G. IVIN, Auteur ; M. HEASMAN, Auteur ; E. PRETZSCH, Auteur ; S. WILLIAMS, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur ; G. M. MCALONAN, Auteur . - 49 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 49 p. Mots-clés : Autism spectrum condition  Autism spectrum disorder  Cbdv  Cannabidivarin  Functional connectivity  Striatum Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) has a high cost to affected individuals and society, but treatments for core symptoms are lacking. To expand intervention options, it is crucial to gain a better understanding of potential treatment targets, and their engagement, in the brain. For instance, the striatum (caudate, putamen, and nucleus accumbens) plays a central role during development and its (atypical) functional connectivity (FC) may contribute to multiple ASD symptoms. We have previously shown, in the adult autistic and neurotypical brain, the non-intoxicating cannabinoid cannabidivarin (CBDV) alters the balance of striatal 'excitatory-inhibitory' metabolites, which help regulate FC, but the effects of CBDV on (atypical) striatal FC are unknown. METHODS: To examine this in a small pilot study, we acquired resting state functional magnetic resonance imaging data from 28 men (15 neurotypicals, 13 ASD) on two occasions in a repeated-measures, double-blind, placebo-controlled study. We then used a seed-based approach to (1) compare striatal FC between groups and (2) examine the effect of pharmacological probing (600 mg CBDV/matched placebo) on atypical striatal FC in ASD. Visits were separated by at least 13 days to allow for drug washout. RESULTS: Compared to the neurotypicals, ASD individuals had lower FC between the ventral striatum and frontal and pericentral regions (which have been associated with emotion, motor, and vision processing). Further, they had higher intra-striatal FC and higher putamenal FC with temporal regions involved in speech and language. In ASD, CBDV reduced hyperconnectivity to the neurotypical level. LIMITATIONS: Our findings should be considered in light of several methodological aspects, in particular our participant group (restricted to male adults), which limits the generalizability of our findings to the wider and heterogeneous ASD population. CONCLUSION: In conclusion, here we show atypical striatal FC with regions commonly associated with ASD symptoms. We further provide preliminary proof of concept that, in the adult autistic brain, acute CBDV administration can modulate atypical striatal circuitry towards neurotypical function. Future studies are required to determine whether modulation of striatal FC is associated with a change in ASD symptoms. TRIAL REGISTRATION: clinicaltrials.gov, Identifier: NCT03537950. Registered May 25th, 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03537950?term=NCT03537950&draw=2&rank=1 . En ligne : http://dx.doi.org/10.1186/s13229-021-00454-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys / O. OZTAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 50 p. Titre : Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys Type de document : Texte imprimé et/ou numérique Auteurs : O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 50 p. Langues : Anglais (eng) Mots-clés : Arginine vasopressin  Autism spectrum disorder  Biomarker  Cerebrospinal fluid  Kinase signaling pathway  Oxytocin  Rhesus macaque  Social responsiveness scale  Social trait variation  the University of California, San Francisco (UCSF) have filed patent applications  related to biological measures studied herein (Stanford University:  PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism  spectrum disorder”  UCSF: PCT/US2016/014623 “Methods of diagnosing and treating  autism spectrum disorders”). These patents have not been granted or licensed, and no  study author is receiving any financial compensation at this time. EHS serves on the  advisory board for Retrophin Inc. All other authors declare that they have no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N?=?76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n?=?43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n?=?57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n?=?75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys [Texte imprimé et/ou numérique] / O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - 50 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 50 p. Mots-clés : Arginine vasopressin  Autism spectrum disorder  Biomarker  Cerebrospinal fluid  Kinase signaling pathway  Oxytocin  Rhesus macaque  Social responsiveness scale  Social trait variation  the University of California, San Francisco (UCSF) have filed patent applications  related to biological measures studied herein (Stanford University:  PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism  spectrum disorder”  UCSF: PCT/US2016/014623 “Methods of diagnosing and treating  autism spectrum disorders”). These patents have not been granted or licensed, and no  study author is receiving any financial compensation at this time. EHS serves on the  advisory board for Retrophin Inc. All other authors declare that they have no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N?=?76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n?=?43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n?=?57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n?=?75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Maternal steroid levels and the autistic traits of the mother and infant / A. TSOMPANIDIS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 51 p. Titre : Maternal steroid levels and the autistic traits of the mother and infant Type de document : Texte imprimé et/ou numérique Auteurs : A. TSOMPANIDIS, Auteur ; E. AYDIN, Auteur ; E. PADAIGAIT?, Auteur ; G. RICHARDS, Auteur ; Carrie ALLISON, Auteur ; G. HACKETT, Auteur ; T. AUSTIN, Auteur ; R. HOLT, Auteur ; Simon BARON-COHEN, Auteur Article en page(s) : 51 p. Langues : Anglais (eng) Mots-clés : Autism  Autistic Traits  Estradiol  Interaction  Pregnancy  Prenatal  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal sex steroids have been associated with autism in several clinical and epidemiological studies. It is unclear how this relates to the autistic traits of the mother and how early this can be detected during pregnancy and postnatal development. METHODS: Maternal serum was collected from pregnant women (n?=?122) before or during their first ultrasound appointment [mean?=?12.7 (SD?=?0.7) weeks]. Concentrations of the following were measured via immunoassays: testosterone, estradiol, dehydroepiandrosterone sulphate, progesterone; and sex hormone-binding globulin which was used to compute the free fractions of estradiol (FEI) and testosterone (FTI). Standardised human choriogonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) values were obtained from clinical records corresponding to the same serum samples. Mothers completed the Autism Spectrum Quotient (AQ) and for their infants, the Quantitative Checklist for Autism in Toddlers (Q-CHAT) when the infants were between 18 and 20 months old. RESULTS: FEI was positively associated with maternal autistic traits in univariate (n?=?108, Pearson's r?=?0.22, p?=?0.019) and multiple regression models (semipartial r?=?0.19, p?=?0.048) controlling for maternal age and a diagnosis of PCOS. Maternal estradiol levels significantly interacted with fetal sex in predicting infant Q-CHAT scores, with a positive relationship in males but not females (n?=?100, interaction term: semipartial r?=?0.23, p?=?0.036) after controlling for maternal AQ and other covariates. The opposite was found for standardised hCG values and Q-CHAT scores, with a positive association in females but not in males (n?=?151, interaction term: r?=?-0.25, p?=?0.005). LIMITATIONS: Sample size of this cohort was small, with potential ascertainment bias given elective recruitment. Clinical covariates were controlled in multiple regression models, but additional research is needed to confirm the statistically significant findings in larger cohorts. CONCLUSION: Maternal steroid factors during pregnancy are associated with autistic traits in mothers and their infants. En ligne : http://dx.doi.org/10.1186/s13229-021-00453-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Maternal steroid levels and the autistic traits of the mother and infant [Texte imprimé et/ou numérique] / A. TSOMPANIDIS, Auteur ; E. AYDIN, Auteur ; E. PADAIGAIT?, Auteur ; G. RICHARDS, Auteur ; Carrie ALLISON, Auteur ; G. HACKETT, Auteur ; T. AUSTIN, Auteur ; R. HOLT, Auteur ; Simon BARON-COHEN, Auteur . - 51 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 51 p. Mots-clés : Autism  Autistic Traits  Estradiol  Interaction  Pregnancy  Prenatal  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: Prenatal sex steroids have been associated with autism in several clinical and epidemiological studies. It is unclear how this relates to the autistic traits of the mother and how early this can be detected during pregnancy and postnatal development. METHODS: Maternal serum was collected from pregnant women (n?=?122) before or during their first ultrasound appointment [mean?=?12.7 (SD?=?0.7) weeks]. Concentrations of the following were measured via immunoassays: testosterone, estradiol, dehydroepiandrosterone sulphate, progesterone; and sex hormone-binding globulin which was used to compute the free fractions of estradiol (FEI) and testosterone (FTI). Standardised human choriogonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) values were obtained from clinical records corresponding to the same serum samples. Mothers completed the Autism Spectrum Quotient (AQ) and for their infants, the Quantitative Checklist for Autism in Toddlers (Q-CHAT) when the infants were between 18 and 20 months old. RESULTS: FEI was positively associated with maternal autistic traits in univariate (n?=?108, Pearson's r?=?0.22, p?=?0.019) and multiple regression models (semipartial r?=?0.19, p?=?0.048) controlling for maternal age and a diagnosis of PCOS. Maternal estradiol levels significantly interacted with fetal sex in predicting infant Q-CHAT scores, with a positive relationship in males but not females (n?=?100, interaction term: semipartial r?=?0.23, p?=?0.036) after controlling for maternal AQ and other covariates. The opposite was found for standardised hCG values and Q-CHAT scores, with a positive association in females but not in males (n?=?151, interaction term: r?=?-0.25, p?=?0.005). LIMITATIONS: Sample size of this cohort was small, with potential ascertainment bias given elective recruitment. Clinical covariates were controlled in multiple regression models, but additional research is needed to confirm the statistically significant findings in larger cohorts. CONCLUSION: Maternal steroid factors during pregnancy are associated with autistic traits in mothers and their infants. En ligne : http://dx.doi.org/10.1186/s13229-021-00453-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Initial action output and feedback-guided motor behaviors in autism spectrum disorder / K. E. UNRUH in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 52 p. Titre : Initial action output and feedback-guided motor behaviors in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : K. E. UNRUH, Auteur ; W. S. MCKINNEY, Auteur ; E. K. BOJANEK, Auteur ; K. K. FLEMING, Auteur ; J. A. SWEENEY, Auteur ; M. W. MOSCONI, Auteur Article en page(s) : 52 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Eye movement  Lateralization  Precision grip  Sensorimotor Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensorimotor issues are common in autism spectrum disorder (ASD), related to core symptoms, and predictive of worse functional outcomes. Deficits in rapid behaviors supported primarily by feedforward mechanisms, and continuous, feedback-guided motor behaviors each have been reported, but the degrees to which they are distinct or co-segregate within individuals and across development are not well understood. METHODS: We characterized behaviors that varied in their involvement of feedforward control relative to feedback control across skeletomotor (precision grip force) and oculomotor (saccades) control systems in 109 individuals with ASD and 101 age-matched typically developing controls (range: 5-29 years) including 58 individuals with ASD and 57 controls who completed both grip and saccade tests. Grip force was examined across multiple force (15, 45, and 85% MVC) and visual gain levels (low, medium, high). Maximum grip force also was examined. During grip force tests, reaction time, initial force output accuracy, variability, and entropy were examined. For the saccade test, latency, accuracy, and trial-wise variability of latency and accuracy were examined. RESULTS: Relative to controls, individuals with ASD showed similar accuracy of initial grip force but reduced accuracy of saccadic eye movements specific to older ages of our sample. Force variability was greater in ASD relative to controls, but saccade gain variability (across trials) was not different between groups. Force entropy was reduced in ASD, especially at older ages. We also find reduced grip strength in ASD that was more severe in dominant compared to non-dominant hands. LIMITATIONS: Our age-related findings rely on cross-sectional data. Longitudinal studies of sensorimotor behaviors and their associations with ASD symptoms are needed. CONCLUSIONS: We identify reduced accuracy of initial motor output in ASD that was specific to the oculomotor system implicating deficient feedforward control that may be mitigated during slower occurring behaviors executed in the periphery. Individuals with ASD showed increased continuous force variability but similar levels of trial-to-trial saccade accuracy variability suggesting that feedback-guided refinement of motor commands is deficient specifically when adjustments occur rapidly during continuous behavior. We also document reduced lateralization of grip strength in ASD implicating atypical hemispheric specialization. En ligne : http://dx.doi.org/10.1186/s13229-021-00452-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Initial action output and feedback-guided motor behaviors in autism spectrum disorder [Texte imprimé et/ou numérique] / K. E. UNRUH, Auteur ; W. S. MCKINNEY, Auteur ; E. K. BOJANEK, Auteur ; K. K. FLEMING, Auteur ; J. A. SWEENEY, Auteur ; M. W. MOSCONI, Auteur . - 52 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 52 p. Mots-clés : Autism spectrum disorder (ASD)  Eye movement  Lateralization  Precision grip  Sensorimotor Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensorimotor issues are common in autism spectrum disorder (ASD), related to core symptoms, and predictive of worse functional outcomes. Deficits in rapid behaviors supported primarily by feedforward mechanisms, and continuous, feedback-guided motor behaviors each have been reported, but the degrees to which they are distinct or co-segregate within individuals and across development are not well understood. METHODS: We characterized behaviors that varied in their involvement of feedforward control relative to feedback control across skeletomotor (precision grip force) and oculomotor (saccades) control systems in 109 individuals with ASD and 101 age-matched typically developing controls (range: 5-29 years) including 58 individuals with ASD and 57 controls who completed both grip and saccade tests. Grip force was examined across multiple force (15, 45, and 85% MVC) and visual gain levels (low, medium, high). Maximum grip force also was examined. During grip force tests, reaction time, initial force output accuracy, variability, and entropy were examined. For the saccade test, latency, accuracy, and trial-wise variability of latency and accuracy were examined. RESULTS: Relative to controls, individuals with ASD showed similar accuracy of initial grip force but reduced accuracy of saccadic eye movements specific to older ages of our sample. Force variability was greater in ASD relative to controls, but saccade gain variability (across trials) was not different between groups. Force entropy was reduced in ASD, especially at older ages. We also find reduced grip strength in ASD that was more severe in dominant compared to non-dominant hands. LIMITATIONS: Our age-related findings rely on cross-sectional data. Longitudinal studies of sensorimotor behaviors and their associations with ASD symptoms are needed. CONCLUSIONS: We identify reduced accuracy of initial motor output in ASD that was specific to the oculomotor system implicating deficient feedforward control that may be mitigated during slower occurring behaviors executed in the periphery. Individuals with ASD showed increased continuous force variability but similar levels of trial-to-trial saccade accuracy variability suggesting that feedback-guided refinement of motor commands is deficient specifically when adjustments occur rapidly during continuous behavior. We also document reduced lateralization of grip strength in ASD implicating atypical hemispheric specialization. En ligne : http://dx.doi.org/10.1186/s13229-021-00452-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

MEK inhibition ameliorates social behavior phenotypes in a Spred1 knockout mouse model for RASopathy disorders / S. C. BORRIE in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 53 p. Titre : MEK inhibition ameliorates social behavior phenotypes in a Spred1 knockout mouse model for RASopathy disorders Type de document : Texte imprimé et/ou numérique Auteurs : S. C. BORRIE, Auteur ; E. PLASSCHAERT, Auteur ; Z. CALLAERTS-VEGH, Auteur ; A. YOSHIMURA, Auteur ; R. D'HOOGE, Auteur ; Y. ELGERSMA, Auteur ; S. A. KUSHNER, Auteur ; E. LEGIUS, Auteur ; H. BREMS, Auteur Article en page(s) : 53 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Neurofibromatosis type 1  RASopathy  Social dominance  Spred1  Ultrasonic vocalization  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: RASopathies are a group of disorders that result from mutations in genes coding for proteins involved in regulating the Ras-MAPK signaling pathway, and have an increased incidence of autism spectrum disorder (ASD). Legius syndrome is a rare RASopathy caused by loss-of-function mutations in the SPRED1 gene. The patient phenotype is similar to, but milder than, Neurofibromatosis type 1-another RASopathy caused by loss-of-function mutations in the NF1 gene. RASopathies exhibit increased activation of Ras-MAPK signaling and commonly manifest with cognitive impairments and ASD. Here, we investigated if a Spred1-/- mouse model for Legius syndrome recapitulates ASD-like symptoms, and whether targeting the Ras-MAPK pathway has therapeutic potential in this RASopathy mouse model. METHODS: We investigated social and communicative behaviors in Spred1-/- mice and probed therapeutic mechanisms underlying the observed behavioral phenotypes by pharmacological targeting of the Ras-MAPK pathway with the MEK inhibitor PD325901. RESULTS: Spred1-/- mice have robust increases in social dominance in the automated tube test and reduced adult ultrasonic vocalizations during social communication. Neonatal ultrasonic vocalization was also altered, with significant differences in spectral properties. Spred1-/- mice also exhibit impaired nesting behavior. Acute MEK inhibitor treatment in adulthood with PD325901 reversed the enhanced social dominance in Spred1-/- mice to normal levels, and improved nesting behavior in adult Spred1-/- mice. LIMITATIONS: This study used an acute treatment protocol to administer the drug. It is not known what the effects of longer-term treatment would be on behavior. Further studies titrating the lowest dose of this drug that is required to alter Spred1-/- social behavior are still required. Finally, our findings are in a homozygous mouse model, whereas patients carry heterozygous mutations. These factors should be considered before any translational conclusions are drawn. CONCLUSIONS: These results demonstrate for the first time that social behavior phenotypes in a mouse model for RASopathies (Spred1-/-) can be acutely reversed. This highlights a key role for Ras-MAPK dysregulation in mediating social behavior phenotypes in mouse models for ASD, suggesting that proper regulation of Ras-MAPK signaling is important for social behavior. En ligne : http://dx.doi.org/10.1186/s13229-021-00458-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] MEK inhibition ameliorates social behavior phenotypes in a Spred1 knockout mouse model for RASopathy disorders [Texte imprimé et/ou numérique] / S. C. BORRIE, Auteur ; E. PLASSCHAERT, Auteur ; Z. CALLAERTS-VEGH, Auteur ; A. YOSHIMURA, Auteur ; R. D'HOOGE, Auteur ; Y. ELGERSMA, Auteur ; S. A. KUSHNER, Auteur ; E. LEGIUS, Auteur ; H. BREMS, Auteur . - 53 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 53 p. Mots-clés : Autism spectrum disorder  Neurofibromatosis type 1  RASopathy  Social dominance  Spred1  Ultrasonic vocalization  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: RASopathies are a group of disorders that result from mutations in genes coding for proteins involved in regulating the Ras-MAPK signaling pathway, and have an increased incidence of autism spectrum disorder (ASD). Legius syndrome is a rare RASopathy caused by loss-of-function mutations in the SPRED1 gene. The patient phenotype is similar to, but milder than, Neurofibromatosis type 1-another RASopathy caused by loss-of-function mutations in the NF1 gene. RASopathies exhibit increased activation of Ras-MAPK signaling and commonly manifest with cognitive impairments and ASD. Here, we investigated if a Spred1-/- mouse model for Legius syndrome recapitulates ASD-like symptoms, and whether targeting the Ras-MAPK pathway has therapeutic potential in this RASopathy mouse model. METHODS: We investigated social and communicative behaviors in Spred1-/- mice and probed therapeutic mechanisms underlying the observed behavioral phenotypes by pharmacological targeting of the Ras-MAPK pathway with the MEK inhibitor PD325901. RESULTS: Spred1-/- mice have robust increases in social dominance in the automated tube test and reduced adult ultrasonic vocalizations during social communication. Neonatal ultrasonic vocalization was also altered, with significant differences in spectral properties. Spred1-/- mice also exhibit impaired nesting behavior. Acute MEK inhibitor treatment in adulthood with PD325901 reversed the enhanced social dominance in Spred1-/- mice to normal levels, and improved nesting behavior in adult Spred1-/- mice. LIMITATIONS: This study used an acute treatment protocol to administer the drug. It is not known what the effects of longer-term treatment would be on behavior. Further studies titrating the lowest dose of this drug that is required to alter Spred1-/- social behavior are still required. Finally, our findings are in a homozygous mouse model, whereas patients carry heterozygous mutations. These factors should be considered before any translational conclusions are drawn. CONCLUSIONS: These results demonstrate for the first time that social behavior phenotypes in a mouse model for RASopathies (Spred1-/-) can be acutely reversed. This highlights a key role for Ras-MAPK dysregulation in mediating social behavior phenotypes in mouse models for ASD, suggesting that proper regulation of Ras-MAPK signaling is important for social behavior. En ligne : http://dx.doi.org/10.1186/s13229-021-00458-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome / V. SARAVANAPANDIAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 54 p. Titre : Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome Type de document : Texte imprimé et/ou numérique Auteurs : V. SARAVANAPANDIAN, Auteur ; D. NADKARNI, Auteur ; S. H. HSU, Auteur ; S. A. HUSSAIN, Auteur ; K. MASKI, Auteur ; P. GOLSHANI, Auteur ; C. S. COLWELL, Auteur ; S. BALASUBRAMANIAN, Auteur ; A. DIXON, Auteur ; D. H. GESCHWIND, Auteur ; S. S. JESTE, Auteur Article en page(s) : 54 p. Langues : Anglais (eng) Mots-clés : Autism  Biomarkers  Dup15q syndrome  Eeg  Gabaar  Sleep  Slow wave sleep  Spindles  UBE3A  Hoffmann-La Roche Ltd. and Yamo Pharmaceuticals. All the other authors declare that  they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for neurodevelopmental disorders (NDDs) such as intellectual disability and ASD, as well as sleep disturbances. Genes in the 15q region, particularly UBE3A and a cluster of GABA(A) receptor genes, are critical for neural development, synaptic protein synthesis and degradation, and inhibitory neurotransmission. During awake electroencephalography (EEG), children with Dup15q syndrome demonstrate increased beta band oscillations (12-30 Hz) that likely reflect aberrant GABAergic neurotransmission. Healthy sleep rhythms, necessary for robust cognitive development, are also highly dependent on GABAergic neurotransmission. We therefore hypothesized that sleep physiology would be abnormal in children with Dup15q syndrome. METHODS: To test the hypothesis that elevated beta oscillations persist in sleep in Dup15q syndrome and that NREM sleep rhythms would be disrupted, we computed: (1) beta power, (2) spindle density, and (3) percentage of slow-wave sleep (SWS) in overnight sleep EEG recordings from a cohort of children with Dup15q syndrome (n?=?15) and compared them to age-matched neurotypical children (n?=?12). RESULTS: Children with Dup15q syndrome showed abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls. LIMITATIONS: This study relied on clinical EEG where sleep staging was not available. However, considering that clinical polysomnograms are challenging to collect in this population, the ability to quantify these biomarkers on clinical EEG-routinely ordered for epilepsy monitoring-opens the door for larger-scale studies. While comparable to other human studies in rare genetic disorders, a larger sample would allow for examination of the role of seizure severity, medications, and developmental age that may impact sleep physiology. CONCLUSIONS: We have identified three quantitative EEG biomarkers of sleep disruption in Dup15q syndrome, a genetic condition highly penetrant for ASD. Insights from this study not only promote a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome, but also lay the foundation for studies that investigate the association between sleep and cognition. Abnormal sleep physiology may undermine healthy cognitive development and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions. En ligne : http://dx.doi.org/10.1186/s13229-021-00460-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome [Texte imprimé et/ou numérique] / V. SARAVANAPANDIAN, Auteur ; D. NADKARNI, Auteur ; S. H. HSU, Auteur ; S. A. HUSSAIN, Auteur ; K. MASKI, Auteur ; P. GOLSHANI, Auteur ; C. S. COLWELL, Auteur ; S. BALASUBRAMANIAN, Auteur ; A. DIXON, Auteur ; D. H. GESCHWIND, Auteur ; S. S. JESTE, Auteur . - 54 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 54 p. Mots-clés : Autism  Biomarkers  Dup15q syndrome  Eeg  Gabaar  Sleep  Slow wave sleep  Spindles  UBE3A  Hoffmann-La Roche Ltd. and Yamo Pharmaceuticals. All the other authors declare that  they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for neurodevelopmental disorders (NDDs) such as intellectual disability and ASD, as well as sleep disturbances. Genes in the 15q region, particularly UBE3A and a cluster of GABA(A) receptor genes, are critical for neural development, synaptic protein synthesis and degradation, and inhibitory neurotransmission. During awake electroencephalography (EEG), children with Dup15q syndrome demonstrate increased beta band oscillations (12-30 Hz) that likely reflect aberrant GABAergic neurotransmission. Healthy sleep rhythms, necessary for robust cognitive development, are also highly dependent on GABAergic neurotransmission. We therefore hypothesized that sleep physiology would be abnormal in children with Dup15q syndrome. METHODS: To test the hypothesis that elevated beta oscillations persist in sleep in Dup15q syndrome and that NREM sleep rhythms would be disrupted, we computed: (1) beta power, (2) spindle density, and (3) percentage of slow-wave sleep (SWS) in overnight sleep EEG recordings from a cohort of children with Dup15q syndrome (n?=?15) and compared them to age-matched neurotypical children (n?=?12). RESULTS: Children with Dup15q syndrome showed abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls. LIMITATIONS: This study relied on clinical EEG where sleep staging was not available. However, considering that clinical polysomnograms are challenging to collect in this population, the ability to quantify these biomarkers on clinical EEG-routinely ordered for epilepsy monitoring-opens the door for larger-scale studies. While comparable to other human studies in rare genetic disorders, a larger sample would allow for examination of the role of seizure severity, medications, and developmental age that may impact sleep physiology. CONCLUSIONS: We have identified three quantitative EEG biomarkers of sleep disruption in Dup15q syndrome, a genetic condition highly penetrant for ASD. Insights from this study not only promote a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome, but also lay the foundation for studies that investigate the association between sleep and cognition. Abnormal sleep physiology may undermine healthy cognitive development and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions. En ligne : http://dx.doi.org/10.1186/s13229-021-00460-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project design and methodologies: a dimensional approach to understanding neurobiological and genetic aetiology / R. KNOTT in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 55 p. Titre : The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project design and methodologies: a dimensional approach to understanding neurobiological and genetic aetiology Type de document : Texte imprimé et/ou numérique Auteurs : R. KNOTT, Auteur ; Beth P. JOHNSON, Auteur ; J. TIEGO, Auteur ; O. MELLAHN, Auteur ; A. FINLAY, Auteur ; K. KALLADY, Auteur ; M. KOUSPOS, Auteur ; V. P. MOHANAKUMAR SINDHU, Auteur ; Z. HAWI, Auteur ; A. ARNATKEVICIUTE, Auteur ; T. CHAU, Auteur ; D. MARON, Auteur ; E. C. MERCIECA, Auteur ; K. FURLEY, Auteur ; K. HARRIS, Auteur ; K. WILLIAMS, Auteur ; A. URE, Auteur ; A. FORNITO, Auteur ; K. GRAY, Auteur ; D. COGHILL, Auteur ; A. NICHOLSON, Auteur ; D. PHUNG, Auteur ; E. LOTH, Auteur ; L. MASON, Auteur ; D. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Mark A. BELLGROVE, Auteur Article en page(s) : 55 p. Langues : Anglais (eng) Mots-clés : Adhd  Asd  Cognition  Eye-tracking  Genetics  HiTOP  Neuroimaging  RDoC Index. décimale : PER Périodiques Résumé : BACKGROUND: ASD and ADHD are prevalent neurodevelopmental disorders that frequently co-occur and have strong evidence for a degree of shared genetic aetiology. Behavioural and neurocognitive heterogeneity in ASD and ADHD has hampered attempts to map the underlying genetics and neurobiology, predict intervention response, and improve diagnostic accuracy. Moving away from categorical conceptualisations of psychopathology to a dimensional approach is anticipated to facilitate discovery of data-driven clusters and enhance our understanding of the neurobiological and genetic aetiology of these conditions. The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project is one of the first large-scale, family-based studies to take a truly transdiagnostic approach to ASD and ADHD. Using a comprehensive phenotyping protocol capturing dimensional traits central to ASD and ADHD, the MAGNET project aims to identify data-driven clusters across ADHD-ASD spectra using deep phenotyping of symptoms and behaviours; investigate the degree of familiality for different dimensional ASD-ADHD phenotypes and clusters; and map the neurocognitive, brain imaging, and genetic correlates of these data-driven symptom-based clusters. METHODS: The MAGNET project will recruit 1,200 families with children who are either typically developing, or who display elevated ASD, ADHD, or ASD-ADHD traits, in addition to affected and unaffected biological siblings of probands, and parents. All children will be comprehensively phenotyped for behavioural symptoms, comorbidities, neurocognitive and neuroimaging traits and genetics. CONCLUSION: The MAGNET project will be the first large-scale family study to take a transdiagnostic approach to ASD-ADHD, utilising deep phenotyping across behavioural, neurocognitive, brain imaging and genetic measures. En ligne : http://dx.doi.org/10.1186/s13229-021-00457-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project design and methodologies: a dimensional approach to understanding neurobiological and genetic aetiology [Texte imprimé et/ou numérique] / R. KNOTT, Auteur ; Beth P. JOHNSON, Auteur ; J. TIEGO, Auteur ; O. MELLAHN, Auteur ; A. FINLAY, Auteur ; K. KALLADY, Auteur ; M. KOUSPOS, Auteur ; V. P. MOHANAKUMAR SINDHU, Auteur ; Z. HAWI, Auteur ; A. ARNATKEVICIUTE, Auteur ; T. CHAU, Auteur ; D. MARON, Auteur ; E. C. MERCIECA, Auteur ; K. FURLEY, Auteur ; K. HARRIS, Auteur ; K. WILLIAMS, Auteur ; A. URE, Auteur ; A. FORNITO, Auteur ; K. GRAY, Auteur ; D. COGHILL, Auteur ; A. NICHOLSON, Auteur ; D. PHUNG, Auteur ; E. LOTH, Auteur ; L. MASON, Auteur ; D. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Mark A. BELLGROVE, Auteur . - 55 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 55 p. Mots-clés : Adhd  Asd  Cognition  Eye-tracking  Genetics  HiTOP  Neuroimaging  RDoC Index. décimale : PER Périodiques Résumé : BACKGROUND: ASD and ADHD are prevalent neurodevelopmental disorders that frequently co-occur and have strong evidence for a degree of shared genetic aetiology. Behavioural and neurocognitive heterogeneity in ASD and ADHD has hampered attempts to map the underlying genetics and neurobiology, predict intervention response, and improve diagnostic accuracy. Moving away from categorical conceptualisations of psychopathology to a dimensional approach is anticipated to facilitate discovery of data-driven clusters and enhance our understanding of the neurobiological and genetic aetiology of these conditions. The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project is one of the first large-scale, family-based studies to take a truly transdiagnostic approach to ASD and ADHD. Using a comprehensive phenotyping protocol capturing dimensional traits central to ASD and ADHD, the MAGNET project aims to identify data-driven clusters across ADHD-ASD spectra using deep phenotyping of symptoms and behaviours; investigate the degree of familiality for different dimensional ASD-ADHD phenotypes and clusters; and map the neurocognitive, brain imaging, and genetic correlates of these data-driven symptom-based clusters. METHODS: The MAGNET project will recruit 1,200 families with children who are either typically developing, or who display elevated ASD, ADHD, or ASD-ADHD traits, in addition to affected and unaffected biological siblings of probands, and parents. All children will be comprehensively phenotyped for behavioural symptoms, comorbidities, neurocognitive and neuroimaging traits and genetics. CONCLUSION: The MAGNET project will be the first large-scale family study to take a transdiagnostic approach to ASD-ADHD, utilising deep phenotyping across behavioural, neurocognitive, brain imaging and genetic measures. En ligne : http://dx.doi.org/10.1186/s13229-021-00457-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Improving the measurement of alexithymia in autistic adults: a psychometric investigation of the 20-item Toronto Alexithymia Scale and generation of a general alexithymia factor score using item response theory / Z. J. WILLIAMS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 56 p. Titre : Improving the measurement of alexithymia in autistic adults: a psychometric investigation of the 20-item Toronto Alexithymia Scale and generation of a general alexithymia factor score using item response theory Type de document : Texte imprimé et/ou numérique Auteurs : Z. J. WILLIAMS, Auteur ; K. O. GOTHAM, Auteur Article en page(s) : 56 p. Langues : Anglais (eng) Mots-clés : Alexithymia  Autism  Bayesian statistics  Differential item functioning  Emotion  Factor analysis  Item response theory  Measurement  Psychometric  Reliability  Validity  site and a member of the autistic researcher review board of the Autism Intervention  Network for Physical Health (AIR-P). ZJW also serves as a consultant to Roche. KOG  has no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Alexithymia, a personality trait characterized by difficulties interpreting emotional states, is commonly elevated in autistic adults, and a growing body of literature suggests that this trait underlies several cognitive and emotional differences previously attributed to autism. Although questionnaires such as the 20-item Toronto Alexithymia Scale (TAS-20) are frequently used to measure alexithymia in the autistic population, few studies have investigated the psychometric properties of these questionnaires in autistic adults, including whether differential item functioning (I-DIF) exists between autistic and general population adults. METHODS: This study is a revised version of a previous article that was retracted due to copyright concerns (Williams and Gotham in Mol Autism 12:1-40). We conducted an in-depth psychometric analysis of the TAS-20 in a large sample of 743 cognitively able autistic adults recruited from the Simons Foundation SPARK participant pool and 721 general population controls enrolled in a large international psychological study. The factor structure of the TAS-20 was examined using confirmatory factor analysis, and item response theory was used to generate a subset of the items that were strong indicators of a "general alexithymia" factor. Correlations between alexithymia and other clinical outcomes were used to assess the nomological validity of the new alexithymia score in the SPARK sample. RESULTS: The TAS-20 did not exhibit adequate model fit in either the autistic or general population samples. Empirically driven item reduction was undertaken, resulting in an 8-item general alexithymia factor score (GAFS-8, with "TAS" no longer referenced due to copyright) with sound psychometric properties and practically ignorable I-DIF between diagnostic groups. Correlational analyses indicated that GAFS-8 scores, as derived from the TAS-20, meaningfully predict autistic trait levels, repetitive behaviors, and depression symptoms, even after controlling for trait neuroticism. The GAFS-8 also presented no meaningful decrement in nomological validity over the full TAS-20 in autistic participants. LIMITATIONS: Limitations of the current study include a sample of autistic adults that was majority female, later diagnosed, and well educated; clinical and control groups drawn from different studies with variable measures; only 16 of the TAS-20 items being administered to the non-autistic sample; and an inability to test several other important psychometric characteristics of the GAFS-8, including sensitivity to change and I-DIF across multiple administrations. CONCLUSIONS: These results indicate the potential of the GAFS-8 to robustly measure alexithymia in both autistic and non-autistic adults. A free online score calculator has been created to facilitate the use of norm-referenced GAFS-8 latent trait scores in research applications (available at https://asdmeasures.shinyapps.io/alexithymia ). En ligne : http://dx.doi.org/10.1186/s13229-021-00463-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Improving the measurement of alexithymia in autistic adults: a psychometric investigation of the 20-item Toronto Alexithymia Scale and generation of a general alexithymia factor score using item response theory [Texte imprimé et/ou numérique] / Z. J. WILLIAMS, Auteur ; K. O. GOTHAM, Auteur . - 56 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 56 p. Mots-clés : Alexithymia  Autism  Bayesian statistics  Differential item functioning  Emotion  Factor analysis  Item response theory  Measurement  Psychometric  Reliability  Validity  site and a member of the autistic researcher review board of the Autism Intervention  Network for Physical Health (AIR-P). ZJW also serves as a consultant to Roche. KOG  has no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Alexithymia, a personality trait characterized by difficulties interpreting emotional states, is commonly elevated in autistic adults, and a growing body of literature suggests that this trait underlies several cognitive and emotional differences previously attributed to autism. Although questionnaires such as the 20-item Toronto Alexithymia Scale (TAS-20) are frequently used to measure alexithymia in the autistic population, few studies have investigated the psychometric properties of these questionnaires in autistic adults, including whether differential item functioning (I-DIF) exists between autistic and general population adults. METHODS: This study is a revised version of a previous article that was retracted due to copyright concerns (Williams and Gotham in Mol Autism 12:1-40). We conducted an in-depth psychometric analysis of the TAS-20 in a large sample of 743 cognitively able autistic adults recruited from the Simons Foundation SPARK participant pool and 721 general population controls enrolled in a large international psychological study. The factor structure of the TAS-20 was examined using confirmatory factor analysis, and item response theory was used to generate a subset of the items that were strong indicators of a "general alexithymia" factor. Correlations between alexithymia and other clinical outcomes were used to assess the nomological validity of the new alexithymia score in the SPARK sample. RESULTS: The TAS-20 did not exhibit adequate model fit in either the autistic or general population samples. Empirically driven item reduction was undertaken, resulting in an 8-item general alexithymia factor score (GAFS-8, with "TAS" no longer referenced due to copyright) with sound psychometric properties and practically ignorable I-DIF between diagnostic groups. Correlational analyses indicated that GAFS-8 scores, as derived from the TAS-20, meaningfully predict autistic trait levels, repetitive behaviors, and depression symptoms, even after controlling for trait neuroticism. The GAFS-8 also presented no meaningful decrement in nomological validity over the full TAS-20 in autistic participants. LIMITATIONS: Limitations of the current study include a sample of autistic adults that was majority female, later diagnosed, and well educated; clinical and control groups drawn from different studies with variable measures; only 16 of the TAS-20 items being administered to the non-autistic sample; and an inability to test several other important psychometric characteristics of the GAFS-8, including sensitivity to change and I-DIF across multiple administrations. CONCLUSIONS: These results indicate the potential of the GAFS-8 to robustly measure alexithymia in both autistic and non-autistic adults. A free online score calculator has been created to facilitate the use of norm-referenced GAFS-8 latent trait scores in research applications (available at https://asdmeasures.shinyapps.io/alexithymia ). En ligne : http://dx.doi.org/10.1186/s13229-021-00463-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Non-verbal IQ and change in restricted and repetitive behavior throughout childhood in autism: a longitudinal study using the Autism Diagnostic Interview-Revised / V. COURCHESNE in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 57 p. Titre : Non-verbal IQ and change in restricted and repetitive behavior throughout childhood in autism: a longitudinal study using the Autism Diagnostic Interview-Revised Type de document : Texte imprimé et/ou numérique Auteurs : V. COURCHESNE, Auteur ; Rachael BEDFORD, Auteur ; A. PICKLES, Auteur ; E. DUKU, Auteur ; Connor M. KERNS, Auteur ; P. MIRENDA, Auteur ; Teresa BENNETT, Auteur ; S. GEORGIADES, Auteur ; I. M. SMITH, Auteur ; W. J. UNGAR, Auteur ; T. VAILLANCOURT, Auteur ; A. ZAIDMAN-ZAIT, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; P. SZATMARI, Auteur ; M. ELSABBAGH, Auteur Article en page(s) : 57 p. Langues : Anglais (eng) Mots-clés : Adi-r  Autism  Behaviors  Intelligence  Interest  Longitudinal  Repetitive  Restricted  Wechsler Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behavior (RRB) is one of the characteristic features of Autism Spectrum Disorder. This domain of symptoms includes a broad range of behaviors. There is a need to study each behavior individually to better understand the role of each in the development of autistic children. Moreover, there are currently no longitudinal studies investigating change in these behaviors over development. METHODS: The goal of the present study was to explore the association between age and non-verbal IQ (NVIQ) on 15 RRB symptoms included in the Autism Diagnostic Interview-Revised (ADI-R) over time. A total of 205 children with ASD were assessed using the ADI-R at time of diagnosis, at age 6 years, and at age 11 years, and with the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) at age 8 years. RESULTS: The proportion of children showing each RRB tended to diminish with increasing age, except for sensitivity to noise and circumscribed interests, where the proportion increased over time. Although there was no significant main effect of NVIQ, there was a significant interaction between age and NVIQ. This was mainly driven by Difficulties with change in routine, for which higher NVIQ was associated with the behavior remaining relatively stable with age, while lower NVIQ was associated with the behavior becoming more prevalent with age. LIMITATIONS: The study focused on the presence/absence of each RRB but did not account for potential changes in frequency or severity of the behaviors over development. Furthermore, some limitations are inherent to the measures used. The ADI-R relies on parent report and hence has some level of subjectivity, while the Wechsler intelligence scales can underestimate the intellectual abilities of some autistic children. CONCLUSIONS: These results confirm that specific RRB are differentially linked to age and NVIQ. Studying RRB individually is a promising approach to better understanding how RRB change over the development of autistic children and are linked to other developmental domains. En ligne : http://dx.doi.org/10.1186/s13229-021-00461-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Non-verbal IQ and change in restricted and repetitive behavior throughout childhood in autism: a longitudinal study using the Autism Diagnostic Interview-Revised [Texte imprimé et/ou numérique] / V. COURCHESNE, Auteur ; Rachael BEDFORD, Auteur ; A. PICKLES, Auteur ; E. DUKU, Auteur ; Connor M. KERNS, Auteur ; P. MIRENDA, Auteur ; Teresa BENNETT, Auteur ; S. GEORGIADES, Auteur ; I. M. SMITH, Auteur ; W. J. UNGAR, Auteur ; T. VAILLANCOURT, Auteur ; A. ZAIDMAN-ZAIT, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; P. SZATMARI, Auteur ; M. ELSABBAGH, Auteur . - 57 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 57 p. Mots-clés : Adi-r  Autism  Behaviors  Intelligence  Interest  Longitudinal  Repetitive  Restricted  Wechsler Index. décimale : PER Périodiques Résumé : BACKGROUND: Restricted and repetitive behavior (RRB) is one of the characteristic features of Autism Spectrum Disorder. This domain of symptoms includes a broad range of behaviors. There is a need to study each behavior individually to better understand the role of each in the development of autistic children. Moreover, there are currently no longitudinal studies investigating change in these behaviors over development. METHODS: The goal of the present study was to explore the association between age and non-verbal IQ (NVIQ) on 15 RRB symptoms included in the Autism Diagnostic Interview-Revised (ADI-R) over time. A total of 205 children with ASD were assessed using the ADI-R at time of diagnosis, at age 6 years, and at age 11 years, and with the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) at age 8 years. RESULTS: The proportion of children showing each RRB tended to diminish with increasing age, except for sensitivity to noise and circumscribed interests, where the proportion increased over time. Although there was no significant main effect of NVIQ, there was a significant interaction between age and NVIQ. This was mainly driven by Difficulties with change in routine, for which higher NVIQ was associated with the behavior remaining relatively stable with age, while lower NVIQ was associated with the behavior becoming more prevalent with age. LIMITATIONS: The study focused on the presence/absence of each RRB but did not account for potential changes in frequency or severity of the behaviors over development. Furthermore, some limitations are inherent to the measures used. The ADI-R relies on parent report and hence has some level of subjectivity, while the Wechsler intelligence scales can underestimate the intellectual abilities of some autistic children. CONCLUSIONS: These results confirm that specific RRB are differentially linked to age and NVIQ. Studying RRB individually is a promising approach to better understanding how RRB change over the development of autistic children and are linked to other developmental domains. En ligne : http://dx.doi.org/10.1186/s13229-021-00461-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome / Elizabeth L. BERG in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 59 p. Titre : Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth L. BERG, Auteur ; S. P. PETKOVA, Auteur ; H. A. BORN, Auteur ; A. ADHIKARI, Auteur ; A. E. ANDERSON, Auteur ; J. L. SILVERMAN, Auteur Article en page(s) : 59 p. Langues : Anglais (eng) Mots-clés : Angelman Syndrome  Behavior  Eeg  Igf  Insulin-like growth factor  Mouse model  Rat model  Ube3a  Ubiquitin Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems. METHODS: We used both the Ube3a maternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes. RESULTS: Acute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability; however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition. LIMITATIONS: The generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy. CONCLUSIONS: Despite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mouse or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS. En ligne : http://dx.doi.org/10.1186/s13229-021-00467-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome [Texte imprimé et/ou numérique] / Elizabeth L. BERG, Auteur ; S. P. PETKOVA, Auteur ; H. A. BORN, Auteur ; A. ADHIKARI, Auteur ; A. E. ANDERSON, Auteur ; J. L. SILVERMAN, Auteur . - 59 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 59 p. Mots-clés : Angelman Syndrome  Behavior  Eeg  Igf  Insulin-like growth factor  Mouse model  Rat model  Ube3a  Ubiquitin Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems. METHODS: We used both the Ube3a maternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes. RESULTS: Acute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability; however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition. LIMITATIONS: The generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy. CONCLUSIONS: Despite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mouse or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS. En ligne : http://dx.doi.org/10.1186/s13229-021-00467-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis / S. ANTOUN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 60 p. Titre : Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis Type de document : Texte imprimé et/ou numérique Auteurs : S. ANTOUN, Auteur ; P. ELLUL, Auteur ; H. PEYRE, Auteur ; M. ROSENZWAJG, Auteur ; P. GRESSENS, Auteur ; D. KLATZMANN, Auteur ; R. DELORME, Auteur Article en page(s) : 60 p. Langues : Anglais (eng) Mots-clés : Autism  Children  Immunology  Maternal immune activation Index. décimale : PER Périodiques Résumé : BACKGROUND: Fever during pregnancy is a relatively common and most often trivial event. However, under specific conditions, it could affect significantly fetal brain development. Few studies, with inconsistent results, investigated whether fever, regardless the pathogen, could represent a risk factor for neurodevelopmental disorders (NDD) in the offspring. We aimed to explore further this question by performing a systematic review and meta-analysis. METHODS: Peer-reviewed studies exploring the occurrence of NDD in offspring after a fetal exposure to maternal fever were included. We specifically considered the impact of fever severity and duration, taking into consideration some confounding variables such as the use of antipyretic during pregnancy, the trimester in which the fever arose, the maternal age or smoking at time of gestation. MEDLINE, EMBASE, PsycINFO, Cochrane and Web of Science were searched without language restriction. PRISMA recommendations were followed. Odds ratio (OR) were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using random-effects meta-regression analysis. (PROSPERO CRD42020182801). RESULTS: We finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case-control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12-1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13-95% CI: 1.02-1.26]. LIMITATIONS: We excluded studies that considered infections with no evidence of fever. Another potential limitation may be the possible heterogeneity between study designs (cohorts and case-control). CONCLUSION: Additional evidence supported the association between fever during pregnancy and increased risk for NDD in offspring. Careful monitoring should be considered for children born from mothers with a febrile episode during pregnancy (specifically during the first trimester). En ligne : http://dx.doi.org/10.1186/s13229-021-00464-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis [Texte imprimé et/ou numérique] / S. ANTOUN, Auteur ; P. ELLUL, Auteur ; H. PEYRE, Auteur ; M. ROSENZWAJG, Auteur ; P. GRESSENS, Auteur ; D. KLATZMANN, Auteur ; R. DELORME, Auteur . - 60 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 60 p. Mots-clés : Autism  Children  Immunology  Maternal immune activation Index. décimale : PER Périodiques Résumé : BACKGROUND: Fever during pregnancy is a relatively common and most often trivial event. However, under specific conditions, it could affect significantly fetal brain development. Few studies, with inconsistent results, investigated whether fever, regardless the pathogen, could represent a risk factor for neurodevelopmental disorders (NDD) in the offspring. We aimed to explore further this question by performing a systematic review and meta-analysis. METHODS: Peer-reviewed studies exploring the occurrence of NDD in offspring after a fetal exposure to maternal fever were included. We specifically considered the impact of fever severity and duration, taking into consideration some confounding variables such as the use of antipyretic during pregnancy, the trimester in which the fever arose, the maternal age or smoking at time of gestation. MEDLINE, EMBASE, PsycINFO, Cochrane and Web of Science were searched without language restriction. PRISMA recommendations were followed. Odds ratio (OR) were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using random-effects meta-regression analysis. (PROSPERO CRD42020182801). RESULTS: We finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case-control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12-1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13-95% CI: 1.02-1.26]. LIMITATIONS: We excluded studies that considered infections with no evidence of fever. Another potential limitation may be the possible heterogeneity between study designs (cohorts and case-control). CONCLUSION: Additional evidence supported the association between fever during pregnancy and increased risk for NDD in offspring. Careful monitoring should be considered for children born from mothers with a febrile episode during pregnancy (specifically during the first trimester). En ligne : http://dx.doi.org/10.1186/s13229-021-00464-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Individuals with FOXP1 syndrome present with a complex neurobehavioral profile with high rates of ADHD, anxiety, repetitive behaviors, and sensory symptoms / M. P. TRELLES in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 61 p. Titre : Individuals with FOXP1 syndrome present with a complex neurobehavioral profile with high rates of ADHD, anxiety, repetitive behaviors, and sensory symptoms Type de document : Texte imprimé et/ou numérique Auteurs : M. P. TRELLES, Auteur ; T. LEVY, Auteur ; B. LERMAN, Auteur ; P. SIPER, Auteur ; R. LOZANO, Auteur ; Danielle B. HALPERN, Auteur ; H. WALKER, Auteur ; J. ZWEIFACH, Auteur ; Y. FRANK, Auteur ; J. FOSS-FEIG, Auteur ; A. KOLEVZON, Auteur ; Joseph D. BUXBAUM, Auteur Article en page(s) : 61 p. Langues : Anglais (eng) Mots-clés : Anxiety  Attention-deficit/hyperactivity disorder  Autism spectrum disorder  FOXP1 gene  FOXP1 syndrome  Intellectual disability  Neurodevelopment  Therapeutics, Acadia, Alkermes, Sema4, and Ritrova. PMS and Mount Sinai licensed the  Sensory Assessment for Neurodevelopmental Disorders (SAND) developed by PMS to  Stoelting, Co. No other competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: FOXP1 syndrome is an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, speech and language delays, and externalizing behaviors. We previously evaluated nine children and adolescents with FOXP1 syndrome to better characterize its phenotype. We identified specific areas of interest to be further explored, namely autism spectrum disorder (ASD) and internalizing and externalizing behaviors. METHODS: Here, we assess a prospective cohort of additional 17 individuals to expand our initial analyses and focus on these areas of interest. An interdisciplinary group of clinicians evaluated neurodevelopmental, behavioral, and medical features in participants. We report results from this cohort both alone, and in combination with the previous cohort, where possible. RESULTS: Previous observations of intellectual disability, motor delays, and language deficits were confirmed. In addition, 24% of the cohort met criteria for ASD. Seventy-five percent of individuals met DSM-5 criteria for attention-deficit/hyperactivity disorder and 38% for an anxiety disorder. Repetitive behaviors were almost universally present (95%) even without a diagnosis of ASD. Sensory symptoms, in particular sensory seeking, were common. LIMITATIONS: As FOXP1 syndrome is a rare disorder, sample size is limited. CONCLUSIONS: These findings have important implications for the treatment and care of individuals with FOXP1 syndrome. Notably, standardized testing for ASD showed high sensitivity, but low specificity, when compared to expert consensus diagnosis. Furthermore, many individuals in our cohort who received diagnoses of attention-deficit/hyperactivity disorder or anxiety disorder were not being treated for these symptoms; therefore, our findings suggest that there may be immediate areas for improvements in treatment for some individuals. En ligne : http://dx.doi.org/10.1186/s13229-021-00469-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Individuals with FOXP1 syndrome present with a complex neurobehavioral profile with high rates of ADHD, anxiety, repetitive behaviors, and sensory symptoms [Texte imprimé et/ou numérique] / M. P. TRELLES, Auteur ; T. LEVY, Auteur ; B. LERMAN, Auteur ; P. SIPER, Auteur ; R. LOZANO, Auteur ; Danielle B. HALPERN, Auteur ; H. WALKER, Auteur ; J. ZWEIFACH, Auteur ; Y. FRANK, Auteur ; J. FOSS-FEIG, Auteur ; A. KOLEVZON, Auteur ; Joseph D. BUXBAUM, Auteur . - 61 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 61 p. Mots-clés : Anxiety  Attention-deficit/hyperactivity disorder  Autism spectrum disorder  FOXP1 gene  FOXP1 syndrome  Intellectual disability  Neurodevelopment  Therapeutics, Acadia, Alkermes, Sema4, and Ritrova. PMS and Mount Sinai licensed the  Sensory Assessment for Neurodevelopmental Disorders (SAND) developed by PMS to  Stoelting, Co. No other competing interests to declare. Index. décimale : PER Périodiques Résumé : BACKGROUND: FOXP1 syndrome is an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, speech and language delays, and externalizing behaviors. We previously evaluated nine children and adolescents with FOXP1 syndrome to better characterize its phenotype. We identified specific areas of interest to be further explored, namely autism spectrum disorder (ASD) and internalizing and externalizing behaviors. METHODS: Here, we assess a prospective cohort of additional 17 individuals to expand our initial analyses and focus on these areas of interest. An interdisciplinary group of clinicians evaluated neurodevelopmental, behavioral, and medical features in participants. We report results from this cohort both alone, and in combination with the previous cohort, where possible. RESULTS: Previous observations of intellectual disability, motor delays, and language deficits were confirmed. In addition, 24% of the cohort met criteria for ASD. Seventy-five percent of individuals met DSM-5 criteria for attention-deficit/hyperactivity disorder and 38% for an anxiety disorder. Repetitive behaviors were almost universally present (95%) even without a diagnosis of ASD. Sensory symptoms, in particular sensory seeking, were common. LIMITATIONS: As FOXP1 syndrome is a rare disorder, sample size is limited. CONCLUSIONS: These findings have important implications for the treatment and care of individuals with FOXP1 syndrome. Notably, standardized testing for ASD showed high sensitivity, but low specificity, when compared to expert consensus diagnosis. Furthermore, many individuals in our cohort who received diagnoses of attention-deficit/hyperactivity disorder or anxiety disorder were not being treated for these symptoms; therefore, our findings suggest that there may be immediate areas for improvements in treatment for some individuals. En ligne : http://dx.doi.org/10.1186/s13229-021-00469-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome / J. FASTMAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 62 p. Titre : A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. FASTMAN, Auteur ; J. FOSS-FEIG, Auteur ; Y. FRANK, Auteur ; Danielle B. HALPERN, Auteur ; Hala HARONY-NICOLAS, Auteur ; C. LAYTON, Auteur ; S. SANDIN, Auteur ; P. SIPER, Auteur ; L. TANG, Auteur ; P. TRELLES, Auteur ; J. ZWEIFACH, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur Article en page(s) : 62 p. Langues : Anglais (eng) Mots-clés : Asd  Autism spectrum disorder  Oxytocin  Pms  Phelan-McDermid syndrome  Shank3  Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in  Phelan-McDermid syndrome. No other authors have competing interests to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized by global developmental delays, deficits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory deficits in Shank3-deficient rats, there have been no trials in individuals with PMS. The purpose of this study is to assess the efficacy and safety of intranasal oxytocin as a treatment for the core symptoms of ASD in a cohort of children with PMS. METHODS: Eighteen children aged 5-17 with PMS were enrolled. Participants were randomized to receive intranasal oxytocin or placebo (intranasal saline) and underwent treatment during a 12-week double-blind, parallel group phase, followed by a 12-week open-label extension phase during which all participants received oxytocin. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as a number of secondary outcome measures related to the core symptoms of ASD. Safety was monitored throughout the study period. RESULTS: There was no statistically significant improvement with oxytocin as compared to placebo on the ABC-SW (Mann-Whitney U?=?50, p?=?0.055), or on any secondary outcome measures, during either the double-blind or open-label phases. Oxytocin was generally well tolerated, and there were no serious adverse events. LIMITATIONS: The small sample size, potential challenges with drug administration, and expectancy bias due to relying on parent reported outcome measures may all contribute to limitations in interpreting results. CONCLUSION: Our results suggest that intranasal oxytocin is not efficacious in improving the core symptoms of ASD in children with PMS. Trial registration NCT02710084. En ligne : http://dx.doi.org/10.1186/s13229-021-00459-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / J. FASTMAN, Auteur ; J. FOSS-FEIG, Auteur ; Y. FRANK, Auteur ; Danielle B. HALPERN, Auteur ; Hala HARONY-NICOLAS, Auteur ; C. LAYTON, Auteur ; S. SANDIN, Auteur ; P. SIPER, Auteur ; L. TANG, Auteur ; P. TRELLES, Auteur ; J. ZWEIFACH, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur . - 62 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 62 p. Mots-clés : Asd  Autism spectrum disorder  Oxytocin  Pms  Phelan-McDermid syndrome  Shank3  Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in  Phelan-McDermid syndrome. No other authors have competing interests to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized by global developmental delays, deficits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory deficits in Shank3-deficient rats, there have been no trials in individuals with PMS. The purpose of this study is to assess the efficacy and safety of intranasal oxytocin as a treatment for the core symptoms of ASD in a cohort of children with PMS. METHODS: Eighteen children aged 5-17 with PMS were enrolled. Participants were randomized to receive intranasal oxytocin or placebo (intranasal saline) and underwent treatment during a 12-week double-blind, parallel group phase, followed by a 12-week open-label extension phase during which all participants received oxytocin. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as a number of secondary outcome measures related to the core symptoms of ASD. Safety was monitored throughout the study period. RESULTS: There was no statistically significant improvement with oxytocin as compared to placebo on the ABC-SW (Mann-Whitney U?=?50, p?=?0.055), or on any secondary outcome measures, during either the double-blind or open-label phases. Oxytocin was generally well tolerated, and there were no serious adverse events. LIMITATIONS: The small sample size, potential challenges with drug administration, and expectancy bias due to relying on parent reported outcome measures may all contribute to limitations in interpreting results. CONCLUSION: Our results suggest that intranasal oxytocin is not efficacious in improving the core symptoms of ASD in children with PMS. Trial registration NCT02710084. En ligne : http://dx.doi.org/10.1186/s13229-021-00459-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

How rare and common risk variation jointly affect liability for autism spectrum disorder / L. KLEI in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 66 p. Titre : How rare and common risk variation jointly affect liability for autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : L. KLEI, Auteur ; L. L. MCCLAIN, Auteur ; B. MAHJANI, Auteur ; K. PANAYIDOU, Auteur ; S. DE RUBEIS, Auteur ; A. S. GRAHNAT, Auteur ; G. KARLSSON, Auteur ; Y. LU, Auteur ; N. MELHEM, Auteur ; X. XU, Auteur ; A. REICHENBERG, Auteur ; S. SANDIN, Auteur ; C. M. HULTMAN, Auteur ; Joseph D. BUXBAUM, Auteur ; K. ROEDER, Auteur ; B. DEVLIN, Auteur Article en page(s) : 66 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  De novo mutation  Genomic-Best Linear Unbiased Prediction (G-BLUP)  Liability  Polygenic risk score Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic studies have implicated rare and common variations in liability for autism spectrum disorder (ASD). Of the discovered risk variants, those rare in the population invariably have large impact on liability, while common variants have small effects. Yet, collectively, common risk variants account for the majority of population-level variability. How these rare and common risk variants jointly affect liability for individuals requires further study. METHODS: To explore how common and rare variants jointly affect liability, we assessed two cohorts of ASD families characterized for rare and common genetic variations (Simons Simplex Collection and Population-Based Autism Genetics and Environment Study). We analyzed data from 3011 affected subjects, as well as two cohorts of unaffected individuals characterized for common genetic variation: 3011 subjects matched for ancestry to ASD subjects and 11,950 subjects for estimating allele frequencies. We used genetic scores, which assessed the relative burden of common genetic variation affecting risk of ASD (henceforth "burden"), and determined how this burden was distributed among three subpopulations: ASD subjects who carry a potentially damaging variant implicated in risk of ASD ("PDV carriers"); ASD subjects who do not ("non-carriers"); and unaffected subjects who are assumed to be non-carriers. RESULTS: Burden harbored by ASD subjects is stochastically greater than that harbored by control subjects. For PDV carriers, their average burden is intermediate between non-carrier ASD and control subjects. Both carrier and non-carrier ASD subjects have greater burden, on average, than control subjects. The effects of common and rare variants likely combine additively to determine individual-level liability. LIMITATIONS: Only 305 ASD subjects were known PDV carriers. This relatively small subpopulation limits this study to characterizing general patterns of burden, as opposed to effects of specific PDVs or genes. Also, a small fraction of subjects that are categorized as non-carriers could be PDV carriers. CONCLUSIONS: Liability arising from common and rare risk variations likely combines additively to determine risk of any individual diagnosed with ASD. On average, ASD subjects carry a substantial burden of common risk variation, even if they also carry a rare PDV affecting risk. En ligne : http://dx.doi.org/10.1186/s13229-021-00466-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] How rare and common risk variation jointly affect liability for autism spectrum disorder [Texte imprimé et/ou numérique] / L. KLEI, Auteur ; L. L. MCCLAIN, Auteur ; B. MAHJANI, Auteur ; K. PANAYIDOU, Auteur ; S. DE RUBEIS, Auteur ; A. S. GRAHNAT, Auteur ; G. KARLSSON, Auteur ; Y. LU, Auteur ; N. MELHEM, Auteur ; X. XU, Auteur ; A. REICHENBERG, Auteur ; S. SANDIN, Auteur ; C. M. HULTMAN, Auteur ; Joseph D. BUXBAUM, Auteur ; K. ROEDER, Auteur ; B. DEVLIN, Auteur . - 66 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 66 p. Mots-clés : Autism spectrum disorder  De novo mutation  Genomic-Best Linear Unbiased Prediction (G-BLUP)  Liability  Polygenic risk score Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic studies have implicated rare and common variations in liability for autism spectrum disorder (ASD). Of the discovered risk variants, those rare in the population invariably have large impact on liability, while common variants have small effects. Yet, collectively, common risk variants account for the majority of population-level variability. How these rare and common risk variants jointly affect liability for individuals requires further study. METHODS: To explore how common and rare variants jointly affect liability, we assessed two cohorts of ASD families characterized for rare and common genetic variations (Simons Simplex Collection and Population-Based Autism Genetics and Environment Study). We analyzed data from 3011 affected subjects, as well as two cohorts of unaffected individuals characterized for common genetic variation: 3011 subjects matched for ancestry to ASD subjects and 11,950 subjects for estimating allele frequencies. We used genetic scores, which assessed the relative burden of common genetic variation affecting risk of ASD (henceforth "burden"), and determined how this burden was distributed among three subpopulations: ASD subjects who carry a potentially damaging variant implicated in risk of ASD ("PDV carriers"); ASD subjects who do not ("non-carriers"); and unaffected subjects who are assumed to be non-carriers. RESULTS: Burden harbored by ASD subjects is stochastically greater than that harbored by control subjects. For PDV carriers, their average burden is intermediate between non-carrier ASD and control subjects. Both carrier and non-carrier ASD subjects have greater burden, on average, than control subjects. The effects of common and rare variants likely combine additively to determine individual-level liability. LIMITATIONS: Only 305 ASD subjects were known PDV carriers. This relatively small subpopulation limits this study to characterizing general patterns of burden, as opposed to effects of specific PDVs or genes. Also, a small fraction of subjects that are categorized as non-carriers could be PDV carriers. CONCLUSIONS: Liability arising from common and rare risk variations likely combines additively to determine risk of any individual diagnosed with ASD. On average, ASD subjects carry a substantial burden of common risk variation, even if they also carry a rare PDV affecting risk. En ligne : http://dx.doi.org/10.1186/s13229-021-00466-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder / B. MAHJANI in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 65 p. Titre : Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : B. MAHJANI, Auteur ; S. DE RUBEIS, Auteur ; C. GUSTAVSSON MAHJANI, Auteur ; M. MULHERN, Auteur ; X. XU, Auteur ; L. KLEI, Auteur ; F. K. SATTERSTROM, Auteur ; J. FU, Auteur ; Michael E. TALKOWSKI, Auteur ; A. REICHENBERG, Auteur ; S. SANDIN, Auteur ; C. M. HULTMAN, Auteur ; D. E. GRICE, Auteur ; K. ROEDER, Auteur ; B. DEVLIN, Auteur ; Joseph D. BUXBAUM, Auteur Article en page(s) : 65 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Copy number variant  Intellectual disability  Pages  Single nucleotide variant  Whole exome sequencing  that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Autism Sequencing Consortium identified 102 high-confidence autism spectrum disorder (ASD) genes, showing that individuals with ASD and with potentially damaging single nucleotide variation (pdSNV) in these genes had lower cognitive levels and delayed age at walking, when compared to ASD participants without pdSNV. Here, we made use of a Swedish sample of individuals with ASD (called PAGES, for Population-Based Autism Genetics & Environment Study) to evaluate the frequency of pdSNV and their impact on medical and psychiatric phenotypes, using an epidemiological frame and universal health reporting. We then combine findings with those for potentially damaging copy number variation (pdCNV). METHODS: SNV and CNV calls were generated from whole-exome sequencing and chromosome microarray data, respectively. Birth and medical register data were used to collect phenotypes. RESULTS: Of 808 individuals assessed by sequencing, 69 (9%) had pdSNV in the 102 ASC genes, and 144 (18%) had pdSNV in the 102 ASC genes or in a larger set of curated neurodevelopmental genes (from the Deciphering Developmental Disorders study, the gene2phenotype database, and the Radboud University gene lists). Three or more individuals had pdSNV in GRIN2B, POGZ, SATB1, DYNC1H1, SCN8A, or CREBBP. In comparison, out of the 996 individuals from whom CNV were called, 105 (11%) carried one or more pdCNV, including four or more individuals with CNV in the recurrent 15q11q13, 22q11.2, and 16p11.2 loci. Carriers of pdSNV were more likely to have intellectual disability (ID) and epilepsy, while carriers of pdCNV showed increased rates of congenital anomalies and scholastic skill disorders. Carriers of either pdSNV or pdCNV were more likely to have ID, scholastic skill disorders, and epilepsy. LIMITATIONS: The cohort only included individuals with autistic disorder, the more severe form of ASD, and phenotypes are defined from medical registers. Not all genes studied are definitively ASD genes, and we did not have de novo information to aid in classification. CONCLUSIONS: In this epidemiological sample, rare pdSNV were more common than pdCNV and the combined yield of potentially damaging variation was substantial at 27%. The results provide compelling rationale for the use of high-throughout sequencing as part of routine clinical workup for ASD and support the development of precision medicine in ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00465-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder [Texte imprimé et/ou numérique] / B. MAHJANI, Auteur ; S. DE RUBEIS, Auteur ; C. GUSTAVSSON MAHJANI, Auteur ; M. MULHERN, Auteur ; X. XU, Auteur ; L. KLEI, Auteur ; F. K. SATTERSTROM, Auteur ; J. FU, Auteur ; Michael E. TALKOWSKI, Auteur ; A. REICHENBERG, Auteur ; S. SANDIN, Auteur ; C. M. HULTMAN, Auteur ; D. E. GRICE, Auteur ; K. ROEDER, Auteur ; B. DEVLIN, Auteur ; Joseph D. BUXBAUM, Auteur . - 65 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 65 p. Mots-clés : Autism spectrum disorder  Copy number variant  Intellectual disability  Pages  Single nucleotide variant  Whole exome sequencing  that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: The Autism Sequencing Consortium identified 102 high-confidence autism spectrum disorder (ASD) genes, showing that individuals with ASD and with potentially damaging single nucleotide variation (pdSNV) in these genes had lower cognitive levels and delayed age at walking, when compared to ASD participants without pdSNV. Here, we made use of a Swedish sample of individuals with ASD (called PAGES, for Population-Based Autism Genetics & Environment Study) to evaluate the frequency of pdSNV and their impact on medical and psychiatric phenotypes, using an epidemiological frame and universal health reporting. We then combine findings with those for potentially damaging copy number variation (pdCNV). METHODS: SNV and CNV calls were generated from whole-exome sequencing and chromosome microarray data, respectively. Birth and medical register data were used to collect phenotypes. RESULTS: Of 808 individuals assessed by sequencing, 69 (9%) had pdSNV in the 102 ASC genes, and 144 (18%) had pdSNV in the 102 ASC genes or in a larger set of curated neurodevelopmental genes (from the Deciphering Developmental Disorders study, the gene2phenotype database, and the Radboud University gene lists). Three or more individuals had pdSNV in GRIN2B, POGZ, SATB1, DYNC1H1, SCN8A, or CREBBP. In comparison, out of the 996 individuals from whom CNV were called, 105 (11%) carried one or more pdCNV, including four or more individuals with CNV in the recurrent 15q11q13, 22q11.2, and 16p11.2 loci. Carriers of pdSNV were more likely to have intellectual disability (ID) and epilepsy, while carriers of pdCNV showed increased rates of congenital anomalies and scholastic skill disorders. Carriers of either pdSNV or pdCNV were more likely to have ID, scholastic skill disorders, and epilepsy. LIMITATIONS: The cohort only included individuals with autistic disorder, the more severe form of ASD, and phenotypes are defined from medical registers. Not all genes studied are definitively ASD genes, and we did not have de novo information to aid in classification. CONCLUSIONS: In this epidemiological sample, rare pdSNV were more common than pdCNV and the combined yield of potentially damaging variation was substantial at 27%. The results provide compelling rationale for the use of high-throughout sequencing as part of routine clinical workup for ASD and support the development of precision medicine in ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00465-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Affect and gaze responses during an Emotion-Evoking Task in infants at an increased likelihood for autism spectrum disorder / Lori-Ann R. SACREY in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 63 p. Titre : Affect and gaze responses during an Emotion-Evoking Task in infants at an increased likelihood for autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Lori-Ann R. SACREY, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Jessica BRIAN, Auteur ; I. M. SMITH, Auteur ; V. ARMSTRONG, Auteur ; S. RAZA, Auteur ; T. VAILLANCOURT, Auteur ; Louis A. SCHMIDT, Auteur Article en page(s) : 63 p. Langues : Anglais (eng) Mots-clés : Affect  Autism  Emotion regulation  Gaze  Increased likelihood cohort  Temperament Index. décimale : PER Périodiques Résumé : BACKGROUND: The majority of research examining emotional difficulties in autism spectrum disorder (ASD) prior to age 2 relies on parent report. METHODS: We examined behavioral responses (affect and gaze) during emotionally salient tasks designed to elicit mildly positive and negative emotional states in infants. At 12 and 18 months, infants at an increased likelihood for an ASD diagnosis (IL; have an older sibling with ASD; n = 60) and low likelihood (LL; no family history of ASD; n = 21) completed the Emotion-Evoking (EE) Task and parents completed the Infant Behavior Questionnaire-Revised (IBQ-R). All children received an Autism Diagnostic Observation Scale-second Edition assessment for ASD symptomatology at 24 months. RESULTS: The main findings were (1) the IL group displayed higher rates of negative affect and spent less time looking at the task objects compared to the LL group, and (2) affect and gaze scores at 12 and 18 months, but not scores on the IBQ-R, predicted ASD symptoms at 24 months. LIMITATIONS: The data were drawn from an IL sample and may not be generalizable to the general ASD population, and the children were not followed to determine a diagnosis of ASD. CONCLUSION: These results suggest that behavioral responses can provide important information that complements parent reports of emotional regulation in IL infants as early as 12 months of age. En ligne : http://dx.doi.org/10.1186/s13229-021-00468-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Affect and gaze responses during an Emotion-Evoking Task in infants at an increased likelihood for autism spectrum disorder [Texte imprimé et/ou numérique] / Lori-Ann R. SACREY, Auteur ; Lonnie ZWAIGENBAUM, Auteur ; Jessica BRIAN, Auteur ; I. M. SMITH, Auteur ; V. ARMSTRONG, Auteur ; S. RAZA, Auteur ; T. VAILLANCOURT, Auteur ; Louis A. SCHMIDT, Auteur . - 63 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 63 p. Mots-clés : Affect  Autism  Emotion regulation  Gaze  Increased likelihood cohort  Temperament Index. décimale : PER Périodiques Résumé : BACKGROUND: The majority of research examining emotional difficulties in autism spectrum disorder (ASD) prior to age 2 relies on parent report. METHODS: We examined behavioral responses (affect and gaze) during emotionally salient tasks designed to elicit mildly positive and negative emotional states in infants. At 12 and 18 months, infants at an increased likelihood for an ASD diagnosis (IL; have an older sibling with ASD; n = 60) and low likelihood (LL; no family history of ASD; n = 21) completed the Emotion-Evoking (EE) Task and parents completed the Infant Behavior Questionnaire-Revised (IBQ-R). All children received an Autism Diagnostic Observation Scale-second Edition assessment for ASD symptomatology at 24 months. RESULTS: The main findings were (1) the IL group displayed higher rates of negative affect and spent less time looking at the task objects compared to the LL group, and (2) affect and gaze scores at 12 and 18 months, but not scores on the IBQ-R, predicted ASD symptoms at 24 months. LIMITATIONS: The data were drawn from an IL sample and may not be generalizable to the general ASD population, and the children were not followed to determine a diagnosis of ASD. CONCLUSION: These results suggest that behavioral responses can provide important information that complements parent reports of emotional regulation in IL infants as early as 12 months of age. En ligne : http://dx.doi.org/10.1186/s13229-021-00468-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Prediction learning in adults with autism and its molecular correlates / L. A. SAPEY-TRIOMPHE in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 64 p. Titre : Prediction learning in adults with autism and its molecular correlates Type de document : Texte imprimé et/ou numérique Auteurs : L. A. SAPEY-TRIOMPHE, Auteur ; J. TEMMERMAN, Auteur ; N. A. J. PUTS, Auteur ; J. WAGEMANS, Auteur Article en page(s) : 64 p. Langues : Anglais (eng) Mots-clés : Asd  Gaba  Glutamate  Glutathione  Magnetic resonance spectroscopy  Prediction  Prior  Probabilistic learning  Uncertainty  Volatility Index. décimale : PER Périodiques Résumé : BACKGROUND: According to Bayesian hypotheses, individuals with Autism Spectrum Disorder (ASD) have difficulties making accurate predictions about their environment. In particular, the mechanisms by which they assign precision to predictions or sensory inputs would be suboptimal in ASD. These mechanisms are thought to be mostly mediated by glutamate and GABA. Here, we aimed to shed light on prediction learning in ASD and on its neurobiological correlates. METHODS: Twenty-six neurotypical and 26 autistic adults participated in an associative learning task where they had to learn a probabilistic association between a tone and the rotation direction of two dots, in a volatile context. They also took part in magnetic resonance spectroscopy (MRS) measurements to quantify Glx (glutamate and glutamine), GABA?+?and glutathione in a low-level perceptual region (occipital cortex) and in a higher-level region involved in prediction learning (inferior frontal gyrus). RESULTS: Neurotypical and autistic adults had their percepts biased by their expectations, and this bias was smaller for individuals with a more atypical sensory sensitivity. Both groups were able to learn the association and to update their beliefs after a change in contingency. Interestingly, the percentage of correct predictions was correlated with the Glx/GABA?+?ratio in the occipital cortex (positive correlation) and in the right inferior frontal gyrus (negative correlation). In this region, MRS results also showed an increased concentration of Glx in the ASD group compared to the neurotypical group. LIMITATIONS: We used a quite restrictive approach to select the MR spectra showing a good fit, which led to the exclusion of some MRS datasets and therefore to the reduction of the sample size for certain metabolites/regions. CONCLUSIONS: Autistic adults appeared to have intact abilities to make predictions in this task, in contrast with the Bayesian hypotheses of ASD. Yet, higher ratios of Glx/GABA?+?in a frontal region were associated with decreased predictive abilities, and ASD individuals tended to have more Glx in this region. This neurobiological difference might contribute to suboptimal predictive mechanisms in ASD in certain contexts. En ligne : http://dx.doi.org/10.1186/s13229-021-00470-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Prediction learning in adults with autism and its molecular correlates [Texte imprimé et/ou numérique] / L. A. SAPEY-TRIOMPHE, Auteur ; J. TEMMERMAN, Auteur ; N. A. J. PUTS, Auteur ; J. WAGEMANS, Auteur . - 64 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 64 p. Mots-clés : Asd  Gaba  Glutamate  Glutathione  Magnetic resonance spectroscopy  Prediction  Prior  Probabilistic learning  Uncertainty  Volatility Index. décimale : PER Périodiques Résumé : BACKGROUND: According to Bayesian hypotheses, individuals with Autism Spectrum Disorder (ASD) have difficulties making accurate predictions about their environment. In particular, the mechanisms by which they assign precision to predictions or sensory inputs would be suboptimal in ASD. These mechanisms are thought to be mostly mediated by glutamate and GABA. Here, we aimed to shed light on prediction learning in ASD and on its neurobiological correlates. METHODS: Twenty-six neurotypical and 26 autistic adults participated in an associative learning task where they had to learn a probabilistic association between a tone and the rotation direction of two dots, in a volatile context. They also took part in magnetic resonance spectroscopy (MRS) measurements to quantify Glx (glutamate and glutamine), GABA?+?and glutathione in a low-level perceptual region (occipital cortex) and in a higher-level region involved in prediction learning (inferior frontal gyrus). RESULTS: Neurotypical and autistic adults had their percepts biased by their expectations, and this bias was smaller for individuals with a more atypical sensory sensitivity. Both groups were able to learn the association and to update their beliefs after a change in contingency. Interestingly, the percentage of correct predictions was correlated with the Glx/GABA?+?ratio in the occipital cortex (positive correlation) and in the right inferior frontal gyrus (negative correlation). In this region, MRS results also showed an increased concentration of Glx in the ASD group compared to the neurotypical group. LIMITATIONS: We used a quite restrictive approach to select the MR spectra showing a good fit, which led to the exclusion of some MRS datasets and therefore to the reduction of the sample size for certain metabolites/regions. CONCLUSIONS: Autistic adults appeared to have intact abilities to make predictions in this task, in contrast with the Bayesian hypotheses of ASD. Yet, higher ratios of Glx/GABA?+?in a frontal region were associated with decreased predictive abilities, and ASD individuals tended to have more Glx in this region. This neurobiological difference might contribute to suboptimal predictive mechanisms in ASD in certain contexts. En ligne : http://dx.doi.org/10.1186/s13229-021-00470-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis / P. ELLUL in Molecular Autism, 12 (2021)  

Public ISBD [article]  Titre : Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis Type de document : Texte imprimé et/ou numérique Auteurs : P. ELLUL, Auteur ; M. ROSENZWAJG, Auteur ; H. PEYRE, Auteur ; G. FOURCADE, Auteur ; E. MARIOTTI-FERRANDIZ, Auteur ; V. TREBOSSEN, Auteur ; D. KLATZMANN, Auteur ; R. DELORME, Auteur Article en page(s) : 68 p. Langues : Anglais (eng) Mots-clés : Asd  Immunology  Peripheral blood  Regulatory T lymphocyte  Th17 lymphocytes Index. décimale : PER Périodiques Résumé : BACKGROUND: Immune system dysfunction has been proposed to play a critical role in the pathophysiology of autism spectrum disorders (ASD). Conflicting reports of lymphocyte subpopulation abnormalities have been described in numerous studies of patients with ASD. To