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  Garces; 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 Cacéres; 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 Garces, 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 Cacéres , Emily Simonoff, Roberto Toro, Heike Tost, Jack Waldman, Steve C R Williams, Marcel P Zwiers, Will Spooren, Declan G M Murphy, Jan K Buitelaar

Research output: Contribution to journal › Article › peer-review

Abstract

The EU-AIMS Longitudinal European Autism Project (LEAP) is the to-date 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 and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers (Loth et al., under review).

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 phenotyping including IQ and a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. We examined whether there are sex, age, and IQ differences in the severity of ASD symptoms and 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 interview and observational 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 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 females than males (in adults only). Scores on ASD symptom measures were moderately negatively associated with IQ. Males with ASD had higher levels of Inattentive ADHD symptoms than females and both Inattentive and Hyperactive/Impulsive ADHD symptoms were lower in adults than children and adolescents.

Conclusions: The well-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, IQ – and whether clinician, parent or self-reported. The accelerated longitudinal design of the LEAP cohort will enable us to track trajectories of the ASD phenotype and co-occurring conditions over development and relate these to the wide range of candidate biomarkers also tested in the sample.

Original language	English
Pages (from-to)	1-21
Number of pages	21
Journal	Molecular Autism
Volume	8
Issue number	27
Early online date	23 Jun 2017
DOIs	https://doi.org/10.1186/s13229-017-0145-9
Publication status	E-pub ahead of print - 23 Jun 2017

Keywords

autism
autism spectrum disorder
phenotype
behaviours
heterogeneity
sex
age
IQ

Access to Document

10.1186/s13229-017-0145-9

CharmanEtalMA2017TheEU-AIMSLongitudinalEuropeanAutismProject(LEAP)Final published version, 1.06 MBLicence: Creative Commons: Attribution (CC-BY)
Supplementary Table 1 Predicted effect of age and IQ on ADOS Calibrated Severity ScoresFinal published version, 180 KBLicence: Creative Commons: Attribution (CC-BY)
Supplementary Table 2 Predicted effect of age and IQ on parent-and self-report ASD measuresFinal published version, 215 KBLicence: Creative Commons: Attribution (CC-BY)
Supplementary Table 3Final published version, 312 KBLicence: Creative Commons: Attribution (CC-BY)

Cite this

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(27), 1-21. https://doi.org/10.1186/s13229-017-0145-9

@article{cf4a6b1ee58f4e28a4942ef2f2c12c43,

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

abstract = "The EU-AIMS Longitudinal European Autism Project (LEAP) is the to-date 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 and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers (Loth et al., under review).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 phenotyping including IQ and a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. We examined whether there are sex, age, and IQ differences in the severity of ASD symptoms and 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 interview and observational 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 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 females than males (in adults only). Scores on ASD symptom measures were moderately negatively associated with IQ. Males with ASD had higher levels of Inattentive ADHD symptoms than females and both Inattentive and Hyperactive/Impulsive ADHD symptoms were lower in adults than children and adolescents. Conclusions: The well-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, IQ – and whether clinician, parent or self-reported. The accelerated longitudinal design of the LEAP cohort will enable us to track trajectories of the ASD phenotype and co-occurring conditions over development and relate these to the wide range of candidate biomarkers also tested in the sample.",

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

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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, Bruijn, YD, Chakrabarti, B, Cornelissen, I, Dell’ Acqua, F, Dumas, G, Durston, S, Ecker, C, Faulkner, J, Frouin, V, Garces, P, Ham, L, Hayward, H, Hipp, J, Holt, RJ, Isaksson, J, Johnson, MH, Jones , EJH, Kundu, P, Lai, M-C, Liogier D’ardhuy, X, 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, San Jóse Cacéres , A, 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. 27, pp. 1-21. 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 - Bruijn, Yvette de

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 - Garces, 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 - Liogier D’ardhuy, Xavier

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 - San Jóse Cacéres , Antonia

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

N1 - ROUTE2

PY - 2017/6/23

Y1 - 2017/6/23

N2 - The EU-AIMS Longitudinal European Autism Project (LEAP) is the to-date 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 and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers (Loth et al., under review).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 phenotyping including IQ and a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. We examined whether there are sex, age, and IQ differences in the severity of ASD symptoms and 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 interview and observational 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 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 females than males (in adults only). Scores on ASD symptom measures were moderately negatively associated with IQ. Males with ASD had higher levels of Inattentive ADHD symptoms than females and both Inattentive and Hyperactive/Impulsive ADHD symptoms were lower in adults than children and adolescents. Conclusions: The well-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, IQ – and whether clinician, parent or self-reported. The accelerated longitudinal design of the LEAP cohort will enable us to track trajectories of the ASD phenotype and co-occurring conditions over development and relate these to the wide range of candidate biomarkers also tested in the sample.

AB - The EU-AIMS Longitudinal European Autism Project (LEAP) is the to-date 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 and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers (Loth et al., under review).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 phenotyping including IQ and a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. We examined whether there are sex, age, and IQ differences in the severity of ASD symptoms and 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 interview and observational 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 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 females than males (in adults only). Scores on ASD symptom measures were moderately negatively associated with IQ. Males with ASD had higher levels of Inattentive ADHD symptoms than females and both Inattentive and Hyperactive/Impulsive ADHD symptoms were lower in adults than children and adolescents. Conclusions: The well-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, IQ – and whether clinician, parent or self-reported. The accelerated longitudinal design of the LEAP cohort will enable us to track trajectories of the ASD phenotype and co-occurring conditions over development and relate these to the wide range of candidate biomarkers also tested in the sample.

KW - autism

KW - autism spectrum disorder

KW - phenotype

KW - behaviours

KW - heterogeneity

KW - sex

KW - age

KW - IQ

U2 - 10.1186/s13229-017-0145-9

DO - 10.1186/s13229-017-0145-9

M3 - Article

VL - 8

SP - 1

EP - 21

JO - Molecular Autism

JF - Molecular Autism

SN - 2040-2392

IS - 27

ER -

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

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