Format

Send to

Choose Destination
Mol Autism. 2017 Jun 23;8:27. doi: 10.1186/s13229-017-0145-9. eCollection 2017.

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

Author information

1
Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
2
Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
3
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
4
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF UK.
5
Neurospin Centre CEA, Saclay, 91191 Gif sur Yvette France.
6
Autism Research Centre, Department of Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge, CB2 8AH UK.
7
The School of Philosophy, Psychology, and Language Sciences, University of Edinburgh, Dugald Stewart Building, 3 Charles Street, Edinburgh, EH8 9AD UK.
8
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands.
9
Child and Adolescent Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, J5, 68159 Mannheim, Germany.
10
Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
11
Center for Neurodevelopmental Disorders at Karolinska Institutet (KIND), Stockholm, Sweden.
12
Child and Adolescent Psychiatry, Center of Psychiatry Research, Stockholm County Council, Stockholm, Sweden.
13
Institut Pasteur, Human Genetics and Cognitive Functions Unit, 25 Rue du Docteur Roux, Paris, Cedex 15 France.
14
University Campus Bio-Medico, Via Álvaro del Portillo, 21, Rome, Italy.
15
School of Psychology and Clinical Language Sciences, University of Reading, Whiteknights, Reading, RG6 6AL UK.
16
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt am Main, Goethe University, Deutschordenstrasse 50, 60528 Frankfurt, Germany.
17
Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, Grenzacherstrasse 124, B.001 N.667, CH-4070 Basel, Switzerland.
18
Regulatory Affairs, Pharmaceutical Development, F. Hoffmann-La Roche Pharmaceuticals, Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
19
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
20
Centre for Brain and Cognitive Development, Birkbeck, University of London, 32 Torrington Square, London, WC1E 7JL UK.
21
Department of Radiology, Icahn School of Medicine at Mount Sinai, NY, USA.
22
Child and Youth Mental Health Collaborative, Centre for Addiction and Mental Health and The Hospital for Sick Children, Department of Psychiatry, University of Toronto, 80 Workman Way, Toronto, ON M6J 1H4 Canada.
23
Center for Applied Neuroscience, Department of Psychology, University of Cyprus, PO Box 20537, 1678 Nicosia, Cyprus.
24
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
25
Janssen Research & Development, 1125 Trenton Harbourton Road, Titusville, NJ 08560 USA.
26
Child and Adolescent Neuropsychiatry Unit, "Gaetano Martino" University Hospital, University of Messina, via Consolare Valeria 1, I-98125 Messina, Italy.
27
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Denmark Hill, London, UK.
28
Department of Child and Adolescent Psychiatry, Institute of Psychology, Psychiatry and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8LF UK.
29
Roche Pharmaceutical Research and Early Development, NORD Discovery and Translational Area, Roche Innovation Center Basel, Grenzacherstrasse 124, CH-4070 Basel, Switzerland.

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:

Age; Autism; Autism spectrum disorder; Behaviours; Heterogeneity; IQ; Phenotype; Sex

PMID:
28649313
PMCID:
PMC5481972
DOI:
10.1186/s13229-017-0145-9
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center