Does sex influence the diagnostic evaluation of autism spectrum disorder in adults? / C. Ellie WILSON in Autism, 20-7 (October 2016)  

Public ISBD [article]  inAutism > 20-7 (October 2016) . - p.808-819 Titre : Does sex influence the diagnostic evaluation of autism spectrum disorder in adults? Type de document : texte imprimé Auteurs : C. Ellie WILSON, Auteur ; Clodagh M. MURPHY, Auteur ; Gráinne M. MCALONAN, Auteur ; Dene ROBERTSON, Auteur ; Debbie SPAIN, Auteur ; Hannah HAYWARD, Auteur ; Emma WOODHOUSE, Auteur ; Quinton DEELEY, Auteur ; Nicola GILLAN, Auteur ; J. Chris OHLSEN, Auteur ; Janneke ZINKSTOK, Auteur ; Vladimira STOENCHEVA, Auteur ; Jessica FAULKNER, Auteur ; Hatice YILDIRAN, Auteur ; Vaughan BELL, Auteur ; Neil HAMMOND, Auteur ; Michael C. CRAIG, Auteur ; Declan G.M. MURPHY, Auteur Article en page(s) : p.808-819 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  diagnosis  females  males  sex differences Index. décimale : PER Périodiques Résumé : It is unknown whether sex influences the diagnostic evaluation of autism spectrum disorder, or whether male and female adults within the spectrum have different symptom profiles. This study reports sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment. Significantly, more males (72%) than females (66%) were diagnosed with an autism spectrum disorder of any subtype (x2 = 4.09; p = 0.04). In high-functioning autism spectrum disorder adults (IQ > 70; N = 827), there were no significant sex differences in severity of socio-communicative domain symptoms. Males had significantly more repetitive behaviours/restricted interests than females (p = 0.001, d = 0.3). A multivariate analysis of variance indicated a significant interaction between autism spectrum disorder subtype (full-autism spectrum disorder/partial-autism spectrum disorder) and sex: in full-autism spectrum disorder, males had more severe socio-communicative symptoms than females; for partial-autism spectrum disorder, the reverse was true. There were no sex differences in prevalence of co-morbid psychopathologies. Sex influenced diagnostic evaluation in a clinical sample of adults with suspected autism spectrum disorder. The sexes may present with different manifestations of the autism spectrum disorder phenotype and differences vary by diagnostic subtype. Understanding and awareness of adult female repetitive behaviours/restricted interests warrant attention and sex-specific diagnostic assessment tools may need to be considered. En ligne : http://dx.doi.org/10.1177/1362361315611381 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=293 [article] Does sex influence the diagnostic evaluation of autism spectrum disorder in adults? [texte imprimé] / C. Ellie WILSON, Auteur ; Clodagh M. MURPHY, Auteur ; Gráinne M. MCALONAN, Auteur ; Dene ROBERTSON, Auteur ; Debbie SPAIN, Auteur ; Hannah HAYWARD, Auteur ; Emma WOODHOUSE, Auteur ; Quinton DEELEY, Auteur ; Nicola GILLAN, Auteur ; J. Chris OHLSEN, Auteur ; Janneke ZINKSTOK, Auteur ; Vladimira STOENCHEVA, Auteur ; Jessica FAULKNER, Auteur ; Hatice YILDIRAN, Auteur ; Vaughan BELL, Auteur ; Neil HAMMOND, Auteur ; Michael C. CRAIG, Auteur ; Declan G.M. MURPHY, Auteur . - p.808-819. Langues : Anglais (eng) in Autism > 20-7 (October 2016) . - p.808-819 Mots-clés : autism spectrum disorder  diagnosis  females  males  sex differences Index. décimale : PER Périodiques Résumé : It is unknown whether sex influences the diagnostic evaluation of autism spectrum disorder, or whether male and female adults within the spectrum have different symptom profiles. This study reports sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment. Significantly, more males (72%) than females (66%) were diagnosed with an autism spectrum disorder of any subtype (x2 = 4.09; p = 0.04). In high-functioning autism spectrum disorder adults (IQ > 70; N = 827), there were no significant sex differences in severity of socio-communicative domain symptoms. Males had significantly more repetitive behaviours/restricted interests than females (p = 0.001, d = 0.3). A multivariate analysis of variance indicated a significant interaction between autism spectrum disorder subtype (full-autism spectrum disorder/partial-autism spectrum disorder) and sex: in full-autism spectrum disorder, males had more severe socio-communicative symptoms than females; for partial-autism spectrum disorder, the reverse was true. There were no sex differences in prevalence of co-morbid psychopathologies. Sex influenced diagnostic evaluation in a clinical sample of adults with suspected autism spectrum disorder. The sexes may present with different manifestations of the autism spectrum disorder phenotype and differences vary by diagnostic subtype. Understanding and awareness of adult female repetitive behaviours/restricted interests warrant attention and sex-specific diagnostic assessment tools may need to be considered. En ligne : http://dx.doi.org/10.1177/1362361315611381 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=293

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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