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

Tony Charman 1, * Eva Loth 1 Julian Tillmann 1 Daisy Crawley 1 Caroline Wooldridge 1 David Goyard 2 Jumana Ahmad 1 Bonnie Auyeung 3, 4 Sara Ambrosino 5 Tobias Banaschewski 6 Simon Baron-Cohen 4 Sarah Baumeister 7 Christian Beckmann 8 Sven Bölte 9, 10 Thomas Bourgeron 11 Carsten Bours 8 Michael Brammer 1 Daniel Brandeis 7 Claudia Brogna 12 Yvette de Bruijn 8 Bhismadev Chakrabarti 13, 4 Ineke Cornelissen 8 Flavio Dell'Acqua 1 Guillaume Dumas 11 Sarah Durston 5 Christine Ecker 14, 1 Jessica Faulkner 1 Vincent Frouin 2 Pilar Garcés 15 Lindsay Ham 16 Hannah Hayward 1 Joerg Hipp 15 Rosemary Holt 4 Johan Isaksson 17, 9 Mark Johnson 18 Emily Jones 18 Prantik Kundu 19 Meng-Chuan Lai 20, 4 Xavier D’ardhuy 15 Michael Lombardo 4, 21 David Lythgoe 1 René Mandl 5 Luke Mason 22 Andreas Meyer-Lindenberg 7 Carolin Moessnang 7 Nico Mueller 7 Laurence O’dwyer 8 Marianne Oldehinkel 8 Bob Oranje 5 Gahan Pandina 23 Antonio Persico 12, 24 Barbara Ruggeri 1 Amber Ruigrok 4 Jessica Sabet 1 Roberto Sacco 12 Antonia Cáceres 1 Emily Simonoff 1 Roberto Toro 11 Heike Tost 7 Jack Waldman 4 Steve Williams 1 Marcel Zwiers 25 Will Spooren 15 Declan Murphy 1 Jan Buitelaar 25
* Corresponding author
1 Institute of Psychiatry, Psychology & Neuroscience, King's College London
2 NEUROSPIN - Service NEUROSPIN
3 University of Edinburgh
4 CAM - University of Cambridge [UK]
5 University Medical Center [Utrecht]
6 Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim]
7 Universität Heidelberg [Heidelberg]
8 Radboud University Medical Center [Nijmegen]
9 Karolinska Institutet [Stockholm]
10 Stockholm County Council
11 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
12 UCBM - Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome
13 UOR - University of Reading
14 Universitätsklinikum Frankfurt
15 pRED - Roche Pharma Research and Early Development [Basel]
16 F. Hoffmann-La Roche [Basel]
17 Uppsala University
18 University of London [London]
19 MSSM - Icahn School of Medicine at Mount Sinai [New York]
20 University of Toronto
21 University of Cyprus [Nicosia]
22 Centre for Brain and Cognitive Development [Birkbeck College]
23 Janssen Research & Development
24 University of Messina
25 Donders Institute for Brain, Cognition and Behaviour
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 : Sex IQ Phenotype Age Autism Autism spectrum disorder Behaviours Heterogeneity
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Tony Charman, Eva Loth, Julian Tillmann, Daisy Crawley, Caroline Wooldridge, et al.. The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation. Molecular Autism, BioMed Central, 2017, 8, pp.27. ⟨10.1186/s13229-017-0145-9⟩. ⟨pasteur-01967230⟩

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