Evidence map›Paper›PMID 28649312›Full record

Observational studyMolecular autism2017

The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.

Eva Loth, Tony Charman, Luke Mason, Julian Tillmann, Emily J H Jones, Caroline Wooldridge, Jumana Ahmad, Bonnie Auyeung, Claudia Brogna, Sara Ambrosino and 55 more

Registry-linked trialOpen 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. It is linked to trial NCT06817746 (Fostering Infant Responsivity and Reciprocity - Support to Thrive. A Multisite Randomized Control Trial of a Preemptive Telehealth Intervention for Infants With Early Signs of Autism Spectrum Disorders), which is not on this map. Cited by 137 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
137citing papers in PubMed, 3 pooled it
14.8field-weighted citation impact, top 1% 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.

NCT06817746 narecruitingnot on this mapstarted 2024, after this paper: background citation

Fostering Infant Responsivity and Reciprocity - Support to Thrive. A Multisite Randomized Control Trial of a Preemptive Telehealth Intervention for Infants With Early Signs of Autism Spectrum Disorders

TypeinterventionalSponsorIRCCS Fondazione Stella MarisRan2024 to 2027Enrolled132ConditionsAutism Spectrum Disorder (ASD)ArmsFIRRST, Parent Education
3 · Its place in the literature

Who cites it

137 citing papers in PubMed, 3 syntheses or guidelines pooled it, 305 citations in OpenAlex.

  1. Pooled it
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  3. Cortical thickness abnormalities in autism spectrum disorder.European child & adolescent psychiatry · 2024
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  13. Novel therapeutics in autism spectrum disorder.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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77 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 18 institutions in 11 countries.

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.ORCID 0000-0001-9458-9167
Tony CharmanClinical Child Psychology, Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Luke MasonCentre for Brain and Cognitive Development, Birkbeck, University of London, Henry Wellcome Building, Malet Street, London, WC1E 7HX UK.
Julian TillmannClinical Child Psychology, Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Emily J H JonesCentre for Brain and Cognitive Development, Birkbeck, University of London, Henry Wellcome Building, Malet Street, London, WC1E 7HX UK.
Caroline WooldridgeDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
Jumana AhmadDepartment of Forensic and Neurodevelopmental Sciences, 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.
Claudia BrognaUniversity Campus Bio-Medico, via Álvaro del Portillo, 21, Rome, Italy.
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, Medical Faculty Mannheim, University of Heidelberg, 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, Medical Faculty Mannheim, University of Heidelberg, J5, 68159 Mannheim, Germany.
Christian BeckmannDonders 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, Medical Faculty Mannheim, University of Heidelberg, J5, 68159 Mannheim, Germany.
Sven BölteCenter for Neurodevelopmental Disorders at Karolinska Institutet (KIND), Stockholm, Sweden.
Thomas BourgeronHuman Genetics and Cognitive Functions Unit, Institut Pasteur, 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.
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.
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.
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 DumasHuman Genetics and Cognitive Functions Unit, Institut Pasteur, 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 EckerSackler Institute for Translational Neurodevelopment, 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 GarcesRoche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Grenzacherstrasse 124, B.001 N.667, CH-4070 Basel, Switzerland.
David GoyardNeurospin Centre CEA, Saclay, 91191 Gif sur Yvette, France.
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.
Lindsay M HamRegulatory Affairs, Product Development, F. Hoffmann-La Roche Pharmaceuticals, Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
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.
Mark H JohnsonCentre for Brain and Cognitive Development, Birkbeck, University of London, Henry Wellcome Building, Malet Street, London, WC1E 7HX UK.
Johan IsakssonCenter for Neurodevelopmental Disorders at Karolinska Institutet (KIND), Stockholm, Sweden.
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.
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, Medical Faculty Mannheim, University of Heidelberg, 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.
Amber N V RuigrokAutism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
Barbara RuggeriSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, 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 José 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 8AF UK.
Roberto ToroHuman Genetics and Cognitive Functions Unit, Institut Pasteur, 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 Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Grenzacherstrasse 124, B.001 N.667, 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 · NLUniversity of Cambridge · GBHeidelberg University · DERoche (Switzerland) · CHUniversity Medical Center Utrecht · NLBirkbeck, University of London · GBInstitut Pasteur · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRUniversità Campus Bio-Medico · ITCentre for Addiction and Mental Health · CAGoethe University Frankfurt · DEIcahn School of Medicine at Mount Sinai · USJanssen (United States) · USKarolinska Institutet · SEUniversity of Messina · ITUniversity of Zurich · CHUppsala University · SE

Funding

Medical Research Council G1100359Medical Research Council MR/N026063/1Medical Research Council MR/P023894/1
6 · The paper itself

Abstract

backgroundThe tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD.

methodsLEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability.

resultsHere, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted).

conclusionWe expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.

Indexed as

Eye Movement MeasurementsGenetic HeterogeneityAdultAutism Spectrum DisorderBiomarkersBrainChildFemaleHairHumansIndividualityLongitudinal StudiesMagnetic Resonance ImagingMaleNeuroimagingPatient SelectionBiomarkersBiomarkersCognitionEEGEye-trackingGeneticsMRINeuroimaging

Identifiers

PMID28649312
PMCPMC5481887
OpenAlexW2625516444

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Registered trials

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.