Dissecting the phenotypic heterogeneity in sensory features in autism spectrum disorder: a factor mixture modelling approach / J. TILLMANN in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 67 p. Titre : Dissecting the phenotypic heterogeneity in sensory features in autism spectrum disorder: a factor mixture modelling approach Type de document : Texte imprimé et/ou numérique Auteurs : J. TILLMANN, Auteur ; M. ULJAREVIC, Auteur ; D. CRAWLEY, Auteur ; G. DUMAS, Auteur ; E. LOTH, Auteur ; D. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Tony CHARMAN, Auteur Article en page(s) : 67 p. Langues : Anglais (eng) Mots-clés : Anxiety  Autism spectrum disorder  Heterogeneity  Phenotype  Sensory features  Social-communication symptoms  of/and/or speaker for Takeda/Shire, Roche, Medice, Servier and Angelini. 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 and royalties. Julian Tillmann is a consultant to F. Hoffmann-La  Roche. Index. décimale : PER Périodiques Résumé : BACKGROUND: Heterogeneity in the phenotypic presentation of autism spectrum disorder (ASD) is apparent in the profile and the severity of sensory features. Here, we applied factor mixture modelling (FMM) to test a multidimensional factor model of sensory processing in ASD. We aimed to identify homogeneous sensory subgroups in ASD that differ intrinsically in their severity along continuous factor scores. We also investigated sensory subgroups in relation to clinical variables: sex, age, IQ, social-communication symptoms, restricted and repetitive behaviours, adaptive functioning and symptoms of anxiety and attention-deficit/hyperactivity disorder. METHODS: Three hundred thirty-two children and adults with ASD between the ages of 6 and 30?years with IQs varying between 40 and 148 were included. First, three different confirmatory factor models were fit to the 38 items of the Short Sensory Profile (SSP). Then, latent class models (with two-to-six subgroups) were evaluated. The best performing factor model, the 7-factor structure, was subsequently used in two FMMs that varied in the number of subgroups: a two-subgroup, seven-factor model and a three-subgroup and seven-factor model. RESULTS: The 'three-subgroup/seven-factor' FMM was superior to all other models based on different fit criteria. Identified subgroups differed in sensory severity from severe, moderate to low. Accounting for the potential confounding effects of age and IQ, participants in these sensory subgroups had different levels of social-communicative symptoms, restricted and repetitive behaviours, adaptive functioning skills and symptoms of inattention and anxiety. LIMITATIONS: Results were derived using a single parent-report measure of sensory features, the SSP, which limits the generalisability of findings. CONCLUSION: Sensory features can be best described by three homogeneous sensory subgroups that differ in sensory severity gradients along seven continuous factor scores. Identified sensory subgroups were further differentiated by the severity of core and co-occurring symptoms, and level of adaptive functioning, providing novel evidence on the associated clinical correlates of sensory subgroups. These sensory subgroups provide a platform to further interrogate the neurobiological and genetic correlates of altered sensory processing in ASD. En ligne : http://dx.doi.org/10.1186/s13229-020-00367-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433 [article] Dissecting the phenotypic heterogeneity in sensory features in autism spectrum disorder: a factor mixture modelling approach [Texte imprimé et/ou numérique] / J. TILLMANN, Auteur ; M. ULJAREVIC, Auteur ; D. CRAWLEY, Auteur ; G. DUMAS, Auteur ; E. LOTH, Auteur ; D. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Tony CHARMAN, Auteur . - 67 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 67 p. Mots-clés : Anxiety  Autism spectrum disorder  Heterogeneity  Phenotype  Sensory features  Social-communication symptoms  of/and/or speaker for Takeda/Shire, Roche, Medice, Servier and Angelini. 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 and royalties. Julian Tillmann is a consultant to F. Hoffmann-La  Roche. Index. décimale : PER Périodiques Résumé : BACKGROUND: Heterogeneity in the phenotypic presentation of autism spectrum disorder (ASD) is apparent in the profile and the severity of sensory features. Here, we applied factor mixture modelling (FMM) to test a multidimensional factor model of sensory processing in ASD. We aimed to identify homogeneous sensory subgroups in ASD that differ intrinsically in their severity along continuous factor scores. We also investigated sensory subgroups in relation to clinical variables: sex, age, IQ, social-communication symptoms, restricted and repetitive behaviours, adaptive functioning and symptoms of anxiety and attention-deficit/hyperactivity disorder. METHODS: Three hundred thirty-two children and adults with ASD between the ages of 6 and 30?years with IQs varying between 40 and 148 were included. First, three different confirmatory factor models were fit to the 38 items of the Short Sensory Profile (SSP). Then, latent class models (with two-to-six subgroups) were evaluated. The best performing factor model, the 7-factor structure, was subsequently used in two FMMs that varied in the number of subgroups: a two-subgroup, seven-factor model and a three-subgroup and seven-factor model. RESULTS: The 'three-subgroup/seven-factor' FMM was superior to all other models based on different fit criteria. Identified subgroups differed in sensory severity from severe, moderate to low. Accounting for the potential confounding effects of age and IQ, participants in these sensory subgroups had different levels of social-communicative symptoms, restricted and repetitive behaviours, adaptive functioning skills and symptoms of inattention and anxiety. LIMITATIONS: Results were derived using a single parent-report measure of sensory features, the SSP, which limits the generalisability of findings. CONCLUSION: Sensory features can be best described by three homogeneous sensory subgroups that differ in sensory severity gradients along seven continuous factor scores. Identified sensory subgroups were further differentiated by the severity of core and co-occurring symptoms, and level of adaptive functioning, providing novel evidence on the associated clinical correlates of sensory subgroups. These sensory subgroups provide a platform to further interrogate the neurobiological and genetic correlates of altered sensory processing in ASD. En ligne : http://dx.doi.org/10.1186/s13229-020-00367-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433

The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation / Tony CHARMAN in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 27p. Titre : The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation Type de document : Texte imprimé et/ou numérique Auteurs : Tony CHARMAN, Auteur ; E. LOTH, Auteur ; J. TILLMANN, Auteur ; D. CRAWLEY, Auteur ; C. WOOLDRIDGE, Auteur ; D. GOYARD, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; S. AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; C. BECKMANN, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; C. BROGNA, Auteur ; Y. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; I. CORNELISSEN, Auteur ; F. D. ACQUA, Auteur ; G. DUMAS, Auteur ; S. DURSTON, Auteur ; C. ECKER, Auteur ; J. FAULKNER, Auteur ; V. FROUIN, Auteur ; P. GARCES, Auteur ; L. HAM, Auteur ; H. HAYWARD, Auteur ; J. HIPP, Auteur ; R. J. HOLT, Auteur ; J. ISAKSSON, Auteur ; M. H. JOHNSON, Auteur ; E. J. H. JONES, Auteur ; P. KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; L. D'ARDHUY X, Auteur ; M. V. LOMBARDO, Auteur ; D. J. LYTHGOE, Auteur ; R. MANDL, Auteur ; L. MASON, Auteur ; A. MEYER-LINDENBERG, Auteur ; C. MOESSNANG, Auteur ; N. MUELLER, Auteur ; L. O'DWYER, Auteur ; M. OLDEHINKEL, Auteur ; B. ORANJE, Auteur ; Gahan PANDINA, Auteur ; A. M. PERSICO, Auteur ; B. RUGGERI, Auteur ; A. N. V. RUIGROK, Auteur ; J. SABET, Auteur ; R. SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; E. SIMONOFF, Auteur ; R. TORO, Auteur ; H. TOST, Auteur ; J. WALDMAN, Auteur ; S. C. R. WILLIAMS, Auteur ; M. P. ZWIERS, Auteur ; W. SPOOREN, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur Article en page(s) : 27p. Langues : Anglais (eng) Mots-clés : Age  Autism  Autism spectrum disorder  Behaviours  Heterogeneity  Iq  Phenotype  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers. METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females. CONCLUSIONS: The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-017-0145-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation [Texte imprimé et/ou numérique] / Tony CHARMAN, Auteur ; E. LOTH, Auteur ; J. TILLMANN, Auteur ; D. CRAWLEY, Auteur ; C. WOOLDRIDGE, Auteur ; D. GOYARD, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; S. AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; C. BECKMANN, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; C. BROGNA, Auteur ; Y. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; I. CORNELISSEN, Auteur ; F. D. ACQUA, Auteur ; G. DUMAS, Auteur ; S. DURSTON, Auteur ; C. ECKER, Auteur ; J. FAULKNER, Auteur ; V. FROUIN, Auteur ; P. GARCES, Auteur ; L. HAM, Auteur ; H. HAYWARD, Auteur ; J. HIPP, Auteur ; R. J. HOLT, Auteur ; J. ISAKSSON, Auteur ; M. H. JOHNSON, Auteur ; E. J. H. JONES, Auteur ; P. KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; L. D'ARDHUY X, Auteur ; M. V. LOMBARDO, Auteur ; D. J. LYTHGOE, Auteur ; R. MANDL, Auteur ; L. MASON, Auteur ; A. MEYER-LINDENBERG, Auteur ; C. MOESSNANG, Auteur ; N. MUELLER, Auteur ; L. O'DWYER, Auteur ; M. OLDEHINKEL, Auteur ; B. ORANJE, Auteur ; Gahan PANDINA, Auteur ; A. M. PERSICO, Auteur ; B. RUGGERI, Auteur ; A. N. V. RUIGROK, Auteur ; J. SABET, Auteur ; R. SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; E. SIMONOFF, Auteur ; R. TORO, Auteur ; H. TOST, Auteur ; J. WALDMAN, Auteur ; S. C. R. WILLIAMS, Auteur ; M. P. ZWIERS, Auteur ; W. SPOOREN, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur . - 27p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 27p. Mots-clés : Age  Autism  Autism spectrum disorder  Behaviours  Heterogeneity  Iq  Phenotype  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers. METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females. CONCLUSIONS: The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-017-0145-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders / E. LOTH in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 24p. Titre : The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : E. LOTH, Auteur ; Tony CHARMAN, Auteur ; L. MASON, Auteur ; J. TILLMANN, Auteur ; E. J. H. JONES, Auteur ; C. WOOLDRIDGE, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; C. BROGNA, Auteur ; S. AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; C. BECKMANN, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Y. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; D. CRAWLEY, Auteur ; I. CORNELISSEN, Auteur ; F. D. ACQUA, Auteur ; G. DUMAS, Auteur ; S. DURSTON, Auteur ; C. ECKER, Auteur ; J. FAULKNER, Auteur ; V. FROUIN, Auteur ; P. GARCES, Auteur ; D. GOYARD, Auteur ; H. HAYWARD, Auteur ; L. M. HAM, Auteur ; J. HIPP, Auteur ; R. J. HOLT, Auteur ; M. H. JOHNSON, Auteur ; J. ISAKSSON, Auteur ; P. KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; L. D'ARDHUY X, Auteur ; M. V. LOMBARDO, Auteur ; D. J. LYTHGOE, Auteur ; R. MANDL, Auteur ; A. MEYER-LINDENBERG, Auteur ; C. MOESSNANG, Auteur ; N. MUELLER, Auteur ; L. O'DWYER, Auteur ; M. OLDEHINKEL, Auteur ; B. ORANJE, Auteur ; Gahan PANDINA, Auteur ; A. M. PERSICO, Auteur ; A. N. V. RUIGROK, Auteur ; B. RUGGERI, Auteur ; J. SABET, Auteur ; R. SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; E. SIMONOFF, Auteur ; R. TORO, Auteur ; H. TOST, Auteur ; J. WALDMAN, Auteur ; S. C. R. WILLIAMS, Auteur ; M. P. ZWIERS, Auteur ; W. SPOOREN, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur Article en page(s) : 24p. Langues : Anglais (eng) Mots-clés : Biomarkers  Cognition  Eeg  Eye-tracking  Genetics  Mri  Neuroimaging Index. décimale : PER Périodiques Résumé : BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). CONCLUSION: We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. En ligne : http://dx.doi.org/10.1186/s13229-017-0146-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders [Texte imprimé et/ou numérique] / E. LOTH, Auteur ; Tony CHARMAN, Auteur ; L. MASON, Auteur ; J. TILLMANN, Auteur ; E. J. H. JONES, Auteur ; C. WOOLDRIDGE, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; C. BROGNA, Auteur ; S. AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; C. BECKMANN, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Y. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; D. CRAWLEY, Auteur ; I. CORNELISSEN, Auteur ; F. D. ACQUA, Auteur ; G. DUMAS, Auteur ; S. DURSTON, Auteur ; C. ECKER, Auteur ; J. FAULKNER, Auteur ; V. FROUIN, Auteur ; P. GARCES, Auteur ; D. GOYARD, Auteur ; H. HAYWARD, Auteur ; L. M. HAM, Auteur ; J. HIPP, Auteur ; R. J. HOLT, Auteur ; M. H. JOHNSON, Auteur ; J. ISAKSSON, Auteur ; P. KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; L. D'ARDHUY X, Auteur ; M. V. LOMBARDO, Auteur ; D. J. LYTHGOE, Auteur ; R. MANDL, Auteur ; A. MEYER-LINDENBERG, Auteur ; C. MOESSNANG, Auteur ; N. MUELLER, Auteur ; L. O'DWYER, Auteur ; M. OLDEHINKEL, Auteur ; B. ORANJE, Auteur ; Gahan PANDINA, Auteur ; A. M. PERSICO, Auteur ; A. N. V. RUIGROK, Auteur ; B. RUGGERI, Auteur ; J. SABET, Auteur ; R. SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; E. SIMONOFF, Auteur ; R. TORO, Auteur ; H. TOST, Auteur ; J. WALDMAN, Auteur ; S. C. R. WILLIAMS, Auteur ; M. P. ZWIERS, Auteur ; W. SPOOREN, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur . - 24p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 24p. Mots-clés : Biomarkers  Cognition  Eeg  Eye-tracking  Genetics  Mri  Neuroimaging Index. décimale : PER Périodiques Résumé : BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). CONCLUSION: We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. En ligne : http://dx.doi.org/10.1186/s13229-017-0146-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

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 ; Adriana 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 ; Adriana 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

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