Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis / Pilar GARCES in Molecular Autism, 13 (2022)  

Public ISBD [article]  inMolecular Autism > 13 (2022) . - 22 p. Titre : Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis Type de document : texte imprimé Auteurs : Pilar GARCES, Auteur ; Sarah BAUMEISTER, Auteur ; Luke MASON, Auteur ; Christopher H. CHATHAM, Auteur ; Stefan HOLIGA, Auteur ; Juergen DUKART, Auteur ; Emily J.H. JONES, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sven BÖLTE, Auteur ; Jan K. BUITELAAR, Auteur ; Sarah DURSTON, Auteur ; Bob ORANJE, Auteur ; Antonio M. PERSICO, Auteur ; Christian F. BECKMANN, Auteur ; Thomas BOURGERON, Auteur ; Flavio DELL'ACQUA, Auteur ; Christine ECKER, Auteur ; Carolin MOESSNANG, Auteur ; Tony CHARMAN, Auteur ; Julian TILLMANN, Auteur ; Declan G.M. MURPHY, Auteur ; Mark H. JOHNSON, Auteur ; Eva LOTH, Auteur ; Daniel BRANDEIS, Auteur ; Joerg F. HIPP, Auteur Article en page(s) : 22 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/diagnosis  Autistic Disorder  Brain/diagnostic imaging  Brain Mapping/methods  Child  Cross-Sectional Studies  Electroencephalography/methods  Humans  Magnetic Resonance Imaging/methods  Reproducibility of Results  Autism spectrum disorder  Eeg  Functional connectivity  Power spectrum  Resting state Index. décimale : PER Périodiques Résumé : BACKGROUND: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. METHODS: We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2-32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n=212 ASD, n=199 neurotypicals [NT], all with IQ?> 75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%-30% split). RESULTS: In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p=.042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52-0.62, specificity 0.59-0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. LIMITATIONS: The statistical power to detect weak effects-of the magnitude of those found in the training dataset-in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects. CONCLUSIONS: This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects. En ligne : http://dx.doi.org/10.1186/s13229-022-00500-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477 [article] Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis [texte imprimé] / Pilar GARCES, Auteur ; Sarah BAUMEISTER, Auteur ; Luke MASON, Auteur ; Christopher H. CHATHAM, Auteur ; Stefan HOLIGA, Auteur ; Juergen DUKART, Auteur ; Emily J.H. JONES, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sven BÖLTE, Auteur ; Jan K. BUITELAAR, Auteur ; Sarah DURSTON, Auteur ; Bob ORANJE, Auteur ; Antonio M. PERSICO, Auteur ; Christian F. BECKMANN, Auteur ; Thomas BOURGERON, Auteur ; Flavio DELL'ACQUA, Auteur ; Christine ECKER, Auteur ; Carolin MOESSNANG, Auteur ; Tony CHARMAN, Auteur ; Julian TILLMANN, Auteur ; Declan G.M. MURPHY, Auteur ; Mark H. JOHNSON, Auteur ; Eva LOTH, Auteur ; Daniel BRANDEIS, Auteur ; Joerg F. HIPP, Auteur . - 22 p. Langues : Anglais (eng) in Molecular Autism > 13 (2022) . - 22 p. Mots-clés : Adolescent  Adult  Autism Spectrum Disorder/diagnosis  Autistic Disorder  Brain/diagnostic imaging  Brain Mapping/methods  Child  Cross-Sectional Studies  Electroencephalography/methods  Humans  Magnetic Resonance Imaging/methods  Reproducibility of Results  Autism spectrum disorder  Eeg  Functional connectivity  Power spectrum  Resting state Index. décimale : PER Périodiques Résumé : BACKGROUND: Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. METHODS: We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2-32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n=212 ASD, n=199 neurotypicals [NT], all with IQ?> 75). We performed analyses in source-space using individual head models derived from the participants' MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%-30% split). RESULTS: In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p=.042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52-0.62, specificity 0.59-0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. LIMITATIONS: The statistical power to detect weak effects-of the magnitude of those found in the training dataset-in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset's effects. CONCLUSIONS: This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects. En ligne : http://dx.doi.org/10.1186/s13229-022-00500-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=477

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 Auteurs : Tony CHARMAN, Auteur ; Eva LOTH, Auteur ; Julian TILLMANN, Auteur ; Daisy CRAWLEY, Auteur ; Caroline WOOLDRIDGE, Auteur ; David GOYARD, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; Sara AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; Christian F. BECKMANN, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; Claudia BROGNA, Auteur ; Yvette G.E. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Ineke CORNELISSEN, Auteur ; Flavio DELL'ACQUA, Auteur ; Guillaume DUMAS, Auteur ; Sarah DURSTON, Auteur ; Christine ECKER, Auteur ; Jessica FAULKNER, Auteur ; Vincent FROUIN, Auteur ; Pilar GARCES, Auteur ; Lindsay HAM, Auteur ; Hannah HAYWARD, Auteur ; Joerg F. HIPP, Auteur ; Rosemary J. HOLT, Auteur ; Johan ISAKSSON, Auteur ; Mark Henry JOHNSON, Auteur ; Emily Jane Harrison JONES, Auteur ; Prantik KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; X. Liogier D'ARDHUY, Auteur ; Michael V. LOMBARDO, Auteur ; David J. LYTHGOE, Auteur ; René MANDL, Auteur ; Luke MASON, Auteur ; Andreas MEYER-LINDENBERG, Auteur ; Carolin MOESSNANG, Auteur ; Nico MUELLER, Auteur ; Laurence O'DWYER, Auteur ; Marianne OLDEHINKEL, Auteur ; Bob ORANJE, Auteur ; Gahan PANDINA, Auteur ; Antonio M. PERSICO, Auteur ; Barbara RUGGERI, Auteur ; Amber N.V. RUIGROK, Auteur ; Jessica SABET, Auteur ; Roberto SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Emily SIMONOFF, Auteur ; Roberto TORO, Auteur ; Heike TOST, Auteur ; Jack WALDMAN, Auteur ; Steven C.R. WILLIAMS, Auteur ; Marcel P. ZWIERS, Auteur ; Will SPOOREN, Auteur ; Declan 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] / Tony CHARMAN, Auteur ; Eva LOTH, Auteur ; Julian TILLMANN, Auteur ; Daisy CRAWLEY, Auteur ; Caroline WOOLDRIDGE, Auteur ; David GOYARD, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; Sara AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; Christian F. BECKMANN, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; Claudia BROGNA, Auteur ; Yvette G.E. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Ineke CORNELISSEN, Auteur ; Flavio DELL'ACQUA, Auteur ; Guillaume DUMAS, Auteur ; Sarah DURSTON, Auteur ; Christine ECKER, Auteur ; Jessica FAULKNER, Auteur ; Vincent FROUIN, Auteur ; Pilar GARCES, Auteur ; Lindsay HAM, Auteur ; Hannah HAYWARD, Auteur ; Joerg F. HIPP, Auteur ; Rosemary J. HOLT, Auteur ; Johan ISAKSSON, Auteur ; Mark Henry JOHNSON, Auteur ; Emily Jane Harrison JONES, Auteur ; Prantik KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; X. Liogier D'ARDHUY, Auteur ; Michael V. LOMBARDO, Auteur ; David J. LYTHGOE, Auteur ; René MANDL, Auteur ; Luke MASON, Auteur ; Andreas MEYER-LINDENBERG, Auteur ; Carolin MOESSNANG, Auteur ; Nico MUELLER, Auteur ; Laurence O'DWYER, Auteur ; Marianne OLDEHINKEL, Auteur ; Bob ORANJE, Auteur ; Gahan PANDINA, Auteur ; Antonio M. PERSICO, Auteur ; Barbara RUGGERI, Auteur ; Amber N.V. RUIGROK, Auteur ; Jessica SABET, Auteur ; Roberto SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Emily SIMONOFF, Auteur ; Roberto TORO, Auteur ; Heike TOST, Auteur ; Jack WALDMAN, Auteur ; Steven C.R. WILLIAMS, Auteur ; Marcel P. ZWIERS, Auteur ; Will SPOOREN, Auteur ; Declan 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 / Eva 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 Auteurs : Eva LOTH, Auteur ; Tony CHARMAN, Auteur ; Luke MASON, Auteur ; Julian TILLMANN, Auteur ; Emily Jane Harrison JONES, Auteur ; Caroline WOOLDRIDGE, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; Claudia BROGNA, Auteur ; Sara AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; Christian F. BECKMANN, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Yvette G.E. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Daisy CRAWLEY, Auteur ; Ineke CORNELISSEN, Auteur ; Flavio DELL'ACQUA, Auteur ; Guillaume DUMAS, Auteur ; Sarah DURSTON, Auteur ; Christine ECKER, Auteur ; Jessica FAULKNER, Auteur ; Vincent FROUIN, Auteur ; Pilar GARCES, Auteur ; David GOYARD, Auteur ; Hannah HAYWARD, Auteur ; Lindsay M. HAM, Auteur ; Joerg F. HIPP, Auteur ; Rosemary J. HOLT, Auteur ; Mark Henry JOHNSON, Auteur ; Johan ISAKSSON, Auteur ; Prantik KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; X. Liogier D'ARDHUY, Auteur ; Michael V. LOMBARDO, Auteur ; David J. LYTHGOE, Auteur ; René MANDL, Auteur ; Andreas MEYER-LINDENBERG, Auteur ; Carolin MOESSNANG, Auteur ; Nico MUELLER, Auteur ; Laurence O'DWYER, Auteur ; Marianne OLDEHINKEL, Auteur ; Bob ORANJE, Auteur ; Gahan PANDINA, Auteur ; Antonio M. PERSICO, Auteur ; Amber N.V. RUIGROK, Auteur ; Barbara RUGGERI, Auteur ; Jessica SABET, Auteur ; Roberto SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Emily SIMONOFF, Auteur ; Roberto TORO, Auteur ; Heike TOST, Auteur ; Jack WALDMAN, Auteur ; Steven C.R. WILLIAMS, Auteur ; Marcel P. ZWIERS, Auteur ; Will SPOOREN, Auteur ; Declan 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] / Eva LOTH, Auteur ; Tony CHARMAN, Auteur ; Luke MASON, Auteur ; Julian TILLMANN, Auteur ; Emily Jane Harrison JONES, Auteur ; Caroline WOOLDRIDGE, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; Claudia BROGNA, Auteur ; Sara AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; Christian F. BECKMANN, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Yvette G.E. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Daisy CRAWLEY, Auteur ; Ineke CORNELISSEN, Auteur ; Flavio DELL'ACQUA, Auteur ; Guillaume DUMAS, Auteur ; Sarah DURSTON, Auteur ; Christine ECKER, Auteur ; Jessica FAULKNER, Auteur ; Vincent FROUIN, Auteur ; Pilar GARCES, Auteur ; David GOYARD, Auteur ; Hannah HAYWARD, Auteur ; Lindsay M. HAM, Auteur ; Joerg F. HIPP, Auteur ; Rosemary J. HOLT, Auteur ; Mark Henry JOHNSON, Auteur ; Johan ISAKSSON, Auteur ; Prantik KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; X. Liogier D'ARDHUY, Auteur ; Michael V. LOMBARDO, Auteur ; David J. LYTHGOE, Auteur ; René MANDL, Auteur ; Andreas MEYER-LINDENBERG, Auteur ; Carolin MOESSNANG, Auteur ; Nico MUELLER, Auteur ; Laurence O'DWYER, Auteur ; Marianne OLDEHINKEL, Auteur ; Bob ORANJE, Auteur ; Gahan PANDINA, Auteur ; Antonio M. PERSICO, Auteur ; Amber N.V. RUIGROK, Auteur ; Barbara RUGGERI, Auteur ; Jessica SABET, Auteur ; Roberto SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Emily SIMONOFF, Auteur ; Roberto TORO, Auteur ; Heike TOST, Auteur ; Jack WALDMAN, Auteur ; Steven C.R. WILLIAMS, Auteur ; Marcel P. ZWIERS, Auteur ; Will SPOOREN, Auteur ; Declan 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

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