The EU-AIMS Longitudinal European Autism Project (LEAP): Clinical characterisation

Tony Charman; Eva Loth; Julian Tillmann; Daisy Crawley; Caroline Wooldridge; David Goyard; Jumana Ahmad; Bonnie Auyeung; Sara Ambrosino; Tobias Banaschewski; Simon Baron-Cohen; Sarah Baumeister; Christian Beckmann; Sven Bölte; Thomas Bourgeron; Carsten Bours; Michael Brammer; Daniel Brandeis; Claudia Brogna; Yvette De Bruijn; Bhismadev Chakrabarti; Ineke Cornelissen; Flavio Dell' Acqua; Guillaume Dumas; Sarah Durston; Christine Ecker; Jessica Faulkner; Vincent Frouin; Pilar Garcés; Lindsay Ham; Hannah Hayward; Joerg Hipp; Rosemary J. Holt; Johan Isaksson; Mark H. Johnson; Emily J. H. Jones; Prantik Kundu; Meng Chuan Lai; Xavier Liogier D'ardhuy; Michael V. Lombardo; David J. Lythgoe; René Mandl; Luke Mason; Andreas Meyer-Lindenberg; Carolin Moessnang; Nico Mueller; Laurence O'Dwyer; Marianne Oldehinkel; Bob Oranje; Gahan Pandina; Antonio M. Persico; Barbara Ruggeri; Amber N. V. Ruigrok; Jessica Sabet; Roberto Sacco; Antonia San Jóse Cáceres; Emily Simonoff; Roberto Toro; Heike Tost; Jack Waldman; Steve C. R. Williams; Marcel P. Zwiers; Will Spooren; Declan G. M. Murphy; Jan K. Buitelaar

doi:10.1186/s13229-017-0145-9

The EU-AIMS Longitudinal European Autism Project (LEAP): Clinical characterisation

Tony Charman^*, Eva Loth, Julian Tillmann, Daisy Crawley, Caroline Wooldridge, David Goyard, Jumana Ahmad, Bonnie Auyeung, Sara Ambrosino, Tobias Banaschewski, Simon Baron-Cohen, Sarah Baumeister, Christian Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette De BruijnBhismadev Chakrabarti, Ineke Cornelissen, Flavio Dell' Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Jessica Faulkner, Vincent Frouin, Pilar Garcés, Lindsay Ham, Hannah Hayward, Joerg Hipp, Rosemary J. Holt, Johan Isaksson, Mark H. Johnson, Emily J. H. Jones, Prantik Kundu, Meng Chuan Lai, Xavier Liogier D'ardhuy, Michael V. Lombardo, David J. Lythgoe, René Mandl, Luke Mason, Andreas Meyer-Lindenberg, Carolin Moessnang, Nico Mueller, Laurence O'Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M. Persico, Barbara Ruggeri, Amber N. V. Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San Jóse Cáceres, Emily Simonoff, Roberto Toro, Heike Tost, Jack Waldman, Steve C. R. Williams, Marcel P. Zwiers, Will Spooren, Declan G. M. Murphy, Jan K. Buitelaar

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	27
Journal	Molecular Autism
Volume	8
Issue number	1
DOIs	https://doi.org/10.1186/s13229-017-0145-9
Publication status	Published - 23 Jun 2017

Keywords

Age
Autism
Autism spectrum disorder
Behaviours
Heterogeneity
IQ
Phenotype
Sex

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Charman, T., Loth, E., Tillmann, J., Crawley, D., Wooldridge, C., Goyard, D., Ahmad, J., Auyeung, B., Ambrosino, S., Banaschewski, T., Baron-Cohen, S., Baumeister, S., Beckmann, C., Bölte, S., Bourgeron, T., Bours, C., Brammer, M., Brandeis, D., Brogna, C., ... Buitelaar, J. K. (2017). The EU-AIMS Longitudinal European Autism Project (LEAP): Clinical characterisation. Molecular Autism, 8(1), Article 27. https://doi.org/10.1186/s13229-017-0145-9

@article{a47f24d20a3241ebadc0260bd243ffa8,

title = "The EU-AIMS Longitudinal European Autism Project (LEAP): Clinical characterisation",

abstract = "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.",

keywords = "Age, Autism, Autism spectrum disorder, Behaviours, Heterogeneity, IQ, Phenotype, Sex",

author = "Tony Charman and Eva Loth and Julian Tillmann and Daisy Crawley and Caroline Wooldridge and David Goyard and Jumana Ahmad and Bonnie Auyeung and Sara Ambrosino and Tobias Banaschewski and Simon Baron-Cohen and Sarah Baumeister and Christian Beckmann and Sven B{\"o}lte and Thomas Bourgeron and Carsten Bours and Michael Brammer and Daniel Brandeis and Claudia Brogna and {De Bruijn}, Yvette and Bhismadev Chakrabarti and Ineke Cornelissen and {Dell' Acqua}, Flavio and Guillaume Dumas and Sarah Durston and Christine Ecker and Jessica Faulkner and Vincent Frouin and Pilar Garc{\'e}s and Lindsay Ham and Hannah Hayward and Joerg Hipp and Holt, {Rosemary J.} and Johan Isaksson and Johnson, {Mark H.} and Jones, {Emily J. H.} and Prantik Kundu and Lai, {Meng Chuan} and D'ardhuy, {Xavier Liogier} and Lombardo, {Michael V.} and Lythgoe, {David J.} and Ren{\'e} Mandl and Luke Mason and Andreas Meyer-Lindenberg and Carolin Moessnang and Nico Mueller and Laurence O'Dwyer and Marianne Oldehinkel and Bob Oranje and Gahan Pandina and Persico, {Antonio M.} and Barbara Ruggeri and Ruigrok, {Amber N. V.} and Jessica Sabet and Roberto Sacco and C{\'a}ceres, {Antonia San J{\'o}se} and Emily Simonoff and Roberto Toro and Heike Tost and Jack Waldman and Williams, {Steve C. R.} and Zwiers, {Marcel P.} and Will Spooren and Murphy, {Declan G. M.} and Buitelaar, {Jan K.}",

year = "2017",

month = jun,

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doi = "10.1186/s13229-017-0145-9",

language = "English",

volume = "8",

journal = "Molecular Autism",

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Charman, T , Loth, E , Tillmann, J , Crawley, D, Wooldridge, C, Goyard, D, Ahmad, J, Auyeung, B, Ambrosino, S, Banaschewski, T, Baron-Cohen, S, Baumeister, S, Beckmann, C, Bölte, S, Bourgeron, T, Bours, C, Brammer, M, Brandeis, D, Brogna, C, De Bruijn, Y, Chakrabarti, B, Cornelissen, I, Dell' Acqua, F, Dumas, G, Durston, S, Ecker, C , Faulkner, J, Frouin, V, Garcés, P, Ham, L, Hayward, H, Hipp, J, Holt, RJ, Isaksson, J, Johnson, MH, Jones, EJH, Kundu, P, Lai, MC, D'ardhuy, XL, Lombardo, MV, Lythgoe, DJ, Mandl, R, Mason, L, Meyer-Lindenberg, A, Moessnang, C, Mueller, N, O'Dwyer, L, Oldehinkel, M, Oranje, B, Pandina, G, Persico, AM, Ruggeri, B, Ruigrok, ANV, Sabet, J, Sacco, R, Cáceres, ASJ , Simonoff, E, Toro, R, Tost, H, Waldman, J, Williams, SCR, Zwiers, MP, Spooren, W, Murphy, DGM & Buitelaar, JK 2017, 'The EU-AIMS Longitudinal European Autism Project (LEAP): Clinical characterisation', Molecular Autism, vol. 8, no. 1, 27. https://doi.org/10.1186/s13229-017-0145-9

TY - JOUR

T1 - The EU-AIMS Longitudinal European Autism Project (LEAP)

T2 - Clinical characterisation

AU - Charman, Tony

AU - Loth, Eva

AU - Tillmann, Julian

AU - Crawley, Daisy

AU - Wooldridge, Caroline

AU - Goyard, David

AU - Ahmad, Jumana

AU - Auyeung, Bonnie

AU - Ambrosino, Sara

AU - Banaschewski, Tobias

AU - Baron-Cohen, Simon

AU - Baumeister, Sarah

AU - Beckmann, Christian

AU - Bölte, Sven

AU - Bourgeron, Thomas

AU - Bours, Carsten

AU - Brammer, Michael

AU - Brandeis, Daniel

AU - Brogna, Claudia

AU - De Bruijn, Yvette

AU - Chakrabarti, Bhismadev

AU - Cornelissen, Ineke

AU - Dell' Acqua, Flavio

AU - Dumas, Guillaume

AU - Durston, Sarah

AU - Ecker, Christine

AU - Faulkner, Jessica

AU - Frouin, Vincent

AU - Garcés, Pilar

AU - Ham, Lindsay

AU - Hayward, Hannah

AU - Hipp, Joerg

AU - Holt, Rosemary J.

AU - Isaksson, Johan

AU - Johnson, Mark H.

AU - Jones, Emily J. H.

AU - Kundu, Prantik

AU - Lai, Meng Chuan

AU - D'ardhuy, Xavier Liogier

AU - Lombardo, Michael V.

AU - Lythgoe, David J.

AU - Mandl, René

AU - Mason, Luke

AU - Meyer-Lindenberg, Andreas

AU - Moessnang, Carolin

AU - Mueller, Nico

AU - O'Dwyer, Laurence

AU - Oldehinkel, Marianne

AU - Oranje, Bob

AU - Pandina, Gahan

AU - Persico, Antonio M.

AU - Ruggeri, Barbara

AU - Ruigrok, Amber N. V.

AU - Sabet, Jessica

AU - Sacco, Roberto

AU - Cáceres, Antonia San Jóse

AU - Simonoff, Emily

AU - Toro, Roberto

AU - Tost, Heike

AU - Waldman, Jack

AU - Williams, Steve C. R.

AU - Zwiers, Marcel P.

AU - Spooren, Will

AU - Murphy, Declan G. M.

AU - Buitelaar, Jan K.

PY - 2017/6/23

Y1 - 2017/6/23

N2 - 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.

AB - 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.

KW - Age

KW - Autism

KW - Autism spectrum disorder

KW - Behaviours

KW - Heterogeneity

KW - IQ

KW - Phenotype

KW - Sex

UR - http://www.scopus.com/inward/record.url?scp=85021142828&partnerID=8YFLogxK

U2 - 10.1186/s13229-017-0145-9

DO - 10.1186/s13229-017-0145-9

M3 - Article

AN - SCOPUS:85021142828

SN - 2040-2392

VL - 8

JO - Molecular Autism

JF - Molecular Autism

IS - 1

M1 - 27

ER -

The EU-AIMS Longitudinal European Autism Project (LEAP): Clinical characterisation

Abstract

Keywords

UN SDGs

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