Aberrant local striatal functional connectivity in attention-deficit/hyperactivity disorder / Daniel VON RHEIN in Journal of Child Psychology and Psychiatry, 57-6 (June 2016)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 57-6 (June 2016) . - p.697-705 Titre : Aberrant local striatal functional connectivity in attention-deficit/hyperactivity disorder Type de document : texte imprimé Auteurs : Daniel VON RHEIN, Auteur ; Marianne OLDEHINKEL, Auteur ; Christian F. BECKMANN, Auteur ; Jaap OOSTERLAAN, Auteur ; Dirk J. HESLENFELD, Auteur ; Catharina A. HARTMAN, Auteur ; Pieter J. HOEKSTRA, Auteur ; Barbara FRANKE, Auteur ; Roshan COOLS, Auteur ; Jan K. BUITELAAR, Auteur ; Maarten MENNES, Auteur Article en page(s) : p.697-705 Langues : Anglais (eng) Mots-clés : Resting-state fMRI  functional connectivity  attention-deficit/hyperactivity disorder  cortico-striatal networks  striatum  putamen Index. décimale : PER Périodiques Résumé : Background Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global cortico-striatal functional architecture, or whether ADHD-related alterations are limited to local, intrastriatal functional connections. Methods We included a cohort of adolescents with ADHD (N = 181) and healthy controls (N = 140) and assessed functional connectivity of nucleus accumbens, caudate nucleus, anterior putamen, and posterior putamen. To assess global cortico-striatal functional architecture we computed whole-brain functional connectivity by including all regions of interest in one multivariate analysis. We assessed local striatal functional connectivity using partial correlations between the time series of the striatal regions. Results Diagnostic status did not influence global cortico-striatal functional architecture. However, compared to controls, participants with ADHD exhibited significantly increased local functional connectivity between anterior and posterior putamen (p = .0003; ADHD: z = .30, controls: z = .24). Results were not affected by medication use or comorbid oppositional defiant disorder and conduct disorder. Conclusions Our results do not support hypotheses that ADHD is associated with alterations in cortico-striatal networks, but suggest changes in local striatal functional connectivity. We interpret our findings as aberrant development of local functional connectivity of the putamen, potentially leading to decreased functional segregation between anterior and posterior putamen in ADHD. En ligne : http://dx.doi.org/10.1111/jcpp.12529 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=289 [article] Aberrant local striatal functional connectivity in attention-deficit/hyperactivity disorder [texte imprimé] / Daniel VON RHEIN, Auteur ; Marianne OLDEHINKEL, Auteur ; Christian F. BECKMANN, Auteur ; Jaap OOSTERLAAN, Auteur ; Dirk J. HESLENFELD, Auteur ; Catharina A. HARTMAN, Auteur ; Pieter J. HOEKSTRA, Auteur ; Barbara FRANKE, Auteur ; Roshan COOLS, Auteur ; Jan K. BUITELAAR, Auteur ; Maarten MENNES, Auteur . - p.697-705. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 57-6 (June 2016) . - p.697-705 Mots-clés : Resting-state fMRI  functional connectivity  attention-deficit/hyperactivity disorder  cortico-striatal networks  striatum  putamen Index. décimale : PER Périodiques Résumé : Background Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global cortico-striatal functional architecture, or whether ADHD-related alterations are limited to local, intrastriatal functional connections. Methods We included a cohort of adolescents with ADHD (N = 181) and healthy controls (N = 140) and assessed functional connectivity of nucleus accumbens, caudate nucleus, anterior putamen, and posterior putamen. To assess global cortico-striatal functional architecture we computed whole-brain functional connectivity by including all regions of interest in one multivariate analysis. We assessed local striatal functional connectivity using partial correlations between the time series of the striatal regions. Results Diagnostic status did not influence global cortico-striatal functional architecture. However, compared to controls, participants with ADHD exhibited significantly increased local functional connectivity between anterior and posterior putamen (p = .0003; ADHD: z = .30, controls: z = .24). Results were not affected by medication use or comorbid oppositional defiant disorder and conduct disorder. Conclusions Our results do not support hypotheses that ADHD is associated with alterations in cortico-striatal networks, but suggest changes in local striatal functional connectivity. We interpret our findings as aberrant development of local functional connectivity of the putamen, potentially leading to decreased functional segregation between anterior and posterior putamen in ADHD. En ligne : http://dx.doi.org/10.1111/jcpp.12529 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=289

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

Towards robust and replicable sex differences in the intrinsic brain function of autism / Dorothea 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 Auteurs : Dorothea L. FLORIS, Auteur ; José O. A. FILHO, Auteur ; Meng-Chuan LAI, Auteur ; Steve GIAVASIS, Auteur ; Marianne OLDEHINKEL, Auteur ; Maarten MENNES, Auteur ; Tony CHARMAN, Auteur ; Julian TILLMANN, Auteur ; Guillaume DUMAS, Auteur ; Christine ECKER, Auteur ; Flavio DELL'ACQUA, Auteur ; Tobias BANASCHEWSKI, Auteur ; Carolin MOESSNANG, Auteur ; Simon BARON-COHEN, Auteur ; Sarah DURSTON, Auteur ; Eva LOTH, Auteur ; Declan G.M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; Michael 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 < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research. RESULTS: Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples-EU-AIMS LEAP. LIMITATIONS: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability. CONCLUSIONS: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies. 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] / Dorothea L. FLORIS, Auteur ; José O. A. FILHO, Auteur ; Meng-Chuan LAI, Auteur ; Steve GIAVASIS, Auteur ; Marianne OLDEHINKEL, Auteur ; Maarten MENNES, Auteur ; Tony CHARMAN, Auteur ; Julian TILLMANN, Auteur ; Guillaume DUMAS, Auteur ; Christine ECKER, Auteur ; Flavio DELL'ACQUA, Auteur ; Tobias BANASCHEWSKI, Auteur ; Carolin MOESSNANG, Auteur ; Simon BARON-COHEN, Auteur ; Sarah DURSTON, Auteur ; Eva LOTH, Auteur ; Declan G.M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; Michael 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 < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research. RESULTS: Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples-EU-AIMS LEAP. LIMITATIONS: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability. CONCLUSIONS: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies. 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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