Evidence map›Paper›PMID 28649313›Full record

Observational studyMolecular autism2017

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 and 55 more

Open access · goldAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Molecular autism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 3 pooled it
8.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 3 syntheses or guidelines pooled it, 196 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

65 authors at 20 institutions in 10 countries.

Tony CharmanDepartment of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Eva LothSackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Julian TillmannDepartment of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Daisy CrawleyDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Caroline WooldridgeDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
David GoyardNeurospin Centre CEA, Saclay, 91191 Gif sur Yvette France.
Jumana AhmadSackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Bonnie AuyeungAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
Sara AmbrosinoDepartment of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Tobias BanaschewskiChild and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, J5, 68159 Mannheim, Germany.
Simon Baron-CohenAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
Sarah BaumeisterChild and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, J5, 68159 Mannheim, Germany.
Christian BeckmannDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
Sven BölteCenter for Neurodevelopmental Disorders at Karolinska Institutet (KIND), Stockholm, Sweden.
Thomas BourgeronInstitut Pasteur, Human Genetics and Cognitive Functions Unit, 25 Rue du Docteur Roux, Paris, Cedex 15 France.
Carsten BoursDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
Michael BrammerDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Daniel BrandeisChild and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, J5, 68159 Mannheim, Germany.
Claudia BrognaUniversity Campus Bio-Medico, Via Álvaro del Portillo, 21, Rome, Italy.
Yvette de BruijnDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
Bhismadev ChakrabartiAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
Ineke CornelissenDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
Flavio Dell' AcquaSackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Guillaume DumasInstitut Pasteur, Human Genetics and Cognitive Functions Unit, 25 Rue du Docteur Roux, Paris, Cedex 15 France.
Sarah DurstonDepartment of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Christine EckerDepartment of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Jessica FaulknerDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Vincent FrouinNeurospin Centre CEA, Saclay, 91191 Gif sur Yvette France.
Pilar GarcésRoche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Grenzacherstrasse 124, B.001 N.667, CH-4070 Basel, Switzerland.
Lindsay HamRegulatory Affairs, Pharmaceutical Development, F. Hoffmann-La Roche Pharmaceuticals, Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
Hannah HaywardDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Joerg HippRoche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Grenzacherstrasse 124, B.001 N.667, CH-4070 Basel, Switzerland.
Rosemary J HoltAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
Johan IsakssonCenter for Neurodevelopmental Disorders at Karolinska Institutet (KIND), Stockholm, Sweden.
Mark H JohnsonCentre for Brain and Cognitive Development, Birkbeck, University of London, 32 Torrington Square, London, WC1E 7JL UK.
Emily J H JonesCentre for Brain and Cognitive Development, Birkbeck, University of London, 32 Torrington Square, London, WC1E 7JL UK.
Prantik KunduDepartment of Radiology, Icahn School of Medicine at Mount Sinai, NY, USA.
Meng-Chuan LaiAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
Xavier Liogier D'ardhuyRoche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Grenzacherstrasse 124, B.001 N.667, CH-4070 Basel, Switzerland.
Michael V LombardoAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
David J LythgoeDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
René MandlDepartment of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Luke MasonCentre for Brain and Cognitive Development, Birkbeck, University of London, 32 Torrington Square, London, WC1E 7JL UK.
Andreas Meyer-LindenbergDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
Carolin MoessnangDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
Nico MuellerChild and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, J5, 68159 Mannheim, Germany.
Laurence O'DwyerDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
Marianne OldehinkelDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
Bob OranjeDepartment of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
Gahan PandinaJanssen Research & Development, 1125 Trenton Harbourton Road, Titusville, NJ 08560 USA.
Antonio M PersicoUniversity Campus Bio-Medico, Via Álvaro del Portillo, 21, Rome, Italy.
Barbara RuggeriSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, UK.
Amber N V RuigrokAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
Jessica SabetDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Roberto SaccoUniversity Campus Bio-Medico, Via Álvaro del Portillo, 21, Rome, Italy.
Antonia San Jóse CáceresDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Emily SimonoffDepartment of Child and Adolescent Psychiatry, Institute of Psychology, Psychiatry and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8LF UK.
Roberto ToroInstitut Pasteur, Human Genetics and Cognitive Functions Unit, 25 Rue du Docteur Roux, Paris, Cedex 15 France.
Heike TostDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
Jack WaldmanAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
Steve C R WilliamsDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Marcel P ZwiersDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
Will SpoorenRoche Pharmaceutical Research and Early Development, NORD Discovery and Translational Area, Roche Innovation Center Basel, Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
Declan G M MurphySackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Jan K BuitelaarDonders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
King's College London · GBRadboud University Nijmegen · NLRoche (Switzerland) · CHUniversity of Cambridge · GBUniversity Medical Center Utrecht · NLBirkbeck, University of London · GBCentral Institute of Mental Health · DEHeidelberg University · DEInstitut Pasteur · FRRadboud University Medical Center · NLUniversità Campus Bio-Medico · ITCEA Paris-Saclay · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRGoethe University Frankfurt · DEIcahn School of Medicine at Mount Sinai · USJanssen (United States) · USStockholm County Council · SEUniversity Hospital Heidelberg · DEUniversity of Cyprus · CYUniversity of Edinburgh · GB

Funding

Medical Research Council G1100359Medical Research Council MR/N026063/1
6 · The paper itself

Abstract

backgroundThe 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.

methodsFrom 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.

resultsThe 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.

conclusionsThe 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.

Indexed as

Genetic HeterogeneityImpulsive BehaviorIndividualityAdolescentAdultAge FactorsAutism Spectrum DisorderBiomarkersChildFemaleHumansLongitudinal StudiesMaleParentsPhenotypeSelf ReportBiomarkersAgeAutismAutism spectrum disorderBehavioursHeterogeneityIQPhenotypeSex

Identifiers

PMID28649313
PMCPMC5481972
OpenAlexW2616029603

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.