Molecular Autism (Jun 2017)
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
Affiliations
- Tony Charman
- Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Eva Loth
- Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Julian Tillmann
- Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Daisy Crawley
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Caroline Wooldridge
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- David Goyard
- Neurospin Centre CEA
- Jumana Ahmad
- Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Bonnie Auyeung
- Autism Research Centre, Department of Psychiatry, University of Cambridge
- Sara Ambrosino
- Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht
- Tobias Banaschewski
- Child and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg
- Simon Baron-Cohen
- Autism Research Centre, Department of Psychiatry, University of Cambridge
- Sarah Baumeister
- Child and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg
- Christian Beckmann
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
- Sven Bölte
- Center for Neurodevelopmental Disorders at Karolinska Institutet (KIND)
- Thomas Bourgeron
- Institut Pasteur, Human Genetics and Cognitive Functions Unit
- Carsten Bours
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
- Michael Brammer
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Daniel Brandeis
- Child and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg
- Claudia Brogna
- University Campus Bio-Medico
- Yvette de Bruijn
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
- Bhismadev Chakrabarti
- Autism Research Centre, Department of Psychiatry, University of Cambridge
- Ineke Cornelissen
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
- Flavio Dell’ Acqua
- Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Guillaume Dumas
- Institut Pasteur, Human Genetics and Cognitive Functions Unit
- Sarah Durston
- Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht
- Christine Ecker
- Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Jessica Faulkner
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Vincent Frouin
- Neurospin Centre CEA
- Pilar Garcés
- Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel
- Lindsay Ham
- Regulatory Affairs, Pharmaceutical Development, F. Hoffmann-La Roche Pharmaceuticals
- Hannah Hayward
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Joerg Hipp
- Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel
- Rosemary J. Holt
- Autism Research Centre, Department of Psychiatry, University of Cambridge
- Johan Isaksson
- Center for Neurodevelopmental Disorders at Karolinska Institutet (KIND)
- Mark H. Johnson
- Centre for Brain and Cognitive Development, Birkbeck, University of London
- Emily J. H. Jones
- Centre for Brain and Cognitive Development, Birkbeck, University of London
- Prantik Kundu
- Department of Radiology, Icahn School of Medicine at Mount Sinai
- Meng-Chuan Lai
- Autism Research Centre, Department of Psychiatry, University of Cambridge
- Xavier Liogier D’ardhuy
- Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel
- Michael V. Lombardo
- Autism Research Centre, Department of Psychiatry, University of Cambridge
- David J Lythgoe
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- René Mandl
- Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht
- Luke Mason
- Centre for Brain and Cognitive Development, Birkbeck, University of London
- Andreas Meyer-Lindenberg
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Carolin Moessnang
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Nico Mueller
- Child and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg
- Laurence O’Dwyer
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
- Marianne Oldehinkel
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
- Bob Oranje
- Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht
- Gahan Pandina
- Janssen Research & Development
- Antonio M. Persico
- University Campus Bio-Medico
- Barbara Ruggeri
- Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Amber N. V. Ruigrok
- Autism Research Centre, Department of Psychiatry, University of Cambridge
- Jessica Sabet
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Roberto Sacco
- University Campus Bio-Medico
- Antonia San Jóse Cáceres
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Emily Simonoff
- Department of Child and Adolescent Psychiatry, Institute of Psychology, Psychiatry and Neuroscience, King’s College London
- Roberto Toro
- Institut Pasteur, Human Genetics and Cognitive Functions Unit
- Heike Tost
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Jack Waldman
- Autism Research Centre, Department of Psychiatry, University of Cambridge
- Steve C. R. Williams
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Marcel P. Zwiers
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
- Will Spooren
- Roche Pharmaceutical Research and Early Development, NORD Discovery and Translational Area, Roche Innovation Center Basel
- Declan G. M. Murphy
- Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Jan K. Buitelaar
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre
- DOI
- https://doi.org/10.1186/s13229-017-0145-9
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 21
Abstract
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.
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