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

Charman, T. and Loth, E. and Tillmann, J. and Crawley, D. and Wooldridge, C. and Goyard, D. and Ahmad, J. and Auyeung, B. and Ambrosino, S. and Banaschewski, T. and Baron-Cohen, S. and Baumeister, S. and Beckmann, C. and Bölte, S. and Bourgeron, T. and Bours, C. and Brammer, M. and Brandeis, D. and Brogna, C. and de Bruijn, Y. and Chakrabarti, B. and Cornelissen, I. and Acqua, F.D. and Dumas, G. and Durston, S. and Ecker, C. and Faulkner, J. and Frouin, V. and Garcés, P. and Ham, L. and Hayward, H. and Hipp, J. and Holt, R.J. and Isaksson, J. and Johnson, Mark H. and Jones, Emily J.H. and Kundu, P. and Lai, M.-C. and D’ardhuy, X.L. and Lombardo, M.V. and Lythgoe, D.J. and Mandl, R. and Mason, Luke and Meyer-Lindenberg, A. and Moessnang, C. and Mueller, N. and O’Dwyer, L. and Oldehinkel, M. and Oranje, B. and Pandina, G. and Persico, A.M. and Ruggeri, B. and Ruigrok, A.N.V. and Sabet, J. and Sacco, R. and Cáceres, A.S.J. and Simonoff, E. and Toro, R. and Tost, H. and Waldman, J. and Williams, S.C.R. and Zwiers, M.P. and Spooren, W. and Murphy, D.G.M. and Buitelaar, J.K. (2017) The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation. Molecular Autism 8 (1), ISSN 2040-2392.

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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