Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects / C. LINTAS in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.18 Titre : Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects Type de document : Texte imprimé et/ou numérique Auteurs : C. LINTAS, Auteur ; R. SACCO, Auteur ; A. M. PERSICO, Auteur Article en page(s) : p.18 Langues : Anglais (eng) Mots-clés : Autism  DNA methylation  Epigenetics  Post-mortem brains  Reelin Index. décimale : PER Périodiques Résumé : BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. METHODS: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. RESULTS: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. CONCLUSIONS: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression. En ligne : http://dx.doi.org/10.1186/s11689-016-9151-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects [Texte imprimé et/ou numérique] / C. LINTAS, Auteur ; R. SACCO, Auteur ; A. M. PERSICO, Auteur . - p.18. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.18 Mots-clés : Autism  DNA methylation  Epigenetics  Post-mortem brains  Reelin Index. décimale : PER Périodiques Résumé : BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. METHODS: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. RESULTS: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. CONCLUSIONS: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression. En ligne : http://dx.doi.org/10.1186/s11689-016-9151-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder / J. TILLMANN in Journal of Autism and Developmental Disorders, 48-7 (July 2018)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 48-7 (July 2018) . - p.2490-2505 Titre : Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : J. TILLMANN, Auteur ; K. ASHWOOD, Auteur ; M. ABSOUD, Auteur ; Sven BÖLTE, Auteur ; Frédérique BONNET-BRILHAULT, Auteur ; Jan K. BUITELAAR, Auteur ; Sara CALDERONI, Auteur ; R. CALVO, Auteur ; Ricardo CANAL-BEDIA, Auteur ; Roberto CANITANO, Auteur ; Annelies A. DE BILDT, Auteur ; Marie GOMOT, Auteur ; P. J. HOEKSTRA, Auteur ; A. KAALE, Auteur ; H. MCCONACHIE, Auteur ; D. G. MURPHY, Auteur ; A. NARZISI, Auteur ; I. OOSTERLING, Auteur ; M. PEJOVIC-MILOVANCEVIC, Auteur ; A. M. PERSICO, Auteur ; O. PUIG, Auteur ; H. ROEYERS, Auteur ; Nanda N. ROMMELSE, Auteur ; R. SACCO, Auteur ; V. SCANDURRA, Auteur ; A. C. STANFIELD, Auteur ; E. ZANDER, Auteur ; Tony CHARMAN, Auteur Article en page(s) : p.2490-2505 Langues : Anglais (eng) Mots-clés : Age  Autism Spectrum Disorder  Phenotype  Sex  Symptom severity Index. décimale : PER Périodiques Résumé : Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology. En ligne : http://dx.doi.org/10.1007/s10803-018-3510-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=367 [article] Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / J. TILLMANN, Auteur ; K. ASHWOOD, Auteur ; M. ABSOUD, Auteur ; Sven BÖLTE, Auteur ; Frédérique BONNET-BRILHAULT, Auteur ; Jan K. BUITELAAR, Auteur ; Sara CALDERONI, Auteur ; R. CALVO, Auteur ; Ricardo CANAL-BEDIA, Auteur ; Roberto CANITANO, Auteur ; Annelies A. DE BILDT, Auteur ; Marie GOMOT, Auteur ; P. J. HOEKSTRA, Auteur ; A. KAALE, Auteur ; H. MCCONACHIE, Auteur ; D. G. MURPHY, Auteur ; A. NARZISI, Auteur ; I. OOSTERLING, Auteur ; M. PEJOVIC-MILOVANCEVIC, Auteur ; A. M. PERSICO, Auteur ; O. PUIG, Auteur ; H. ROEYERS, Auteur ; Nanda N. ROMMELSE, Auteur ; R. SACCO, Auteur ; V. SCANDURRA, Auteur ; A. C. STANFIELD, Auteur ; E. ZANDER, Auteur ; Tony CHARMAN, Auteur . - p.2490-2505. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 48-7 (July 2018) . - p.2490-2505 Mots-clés : Age  Autism Spectrum Disorder  Phenotype  Sex  Symptom severity Index. décimale : PER Périodiques Résumé : Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology. En ligne : http://dx.doi.org/10.1007/s10803-018-3510-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=367

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

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