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

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-017-0145-9) contains supplementary material, which is available to authorized users.

Investigating the factors underlying adaptive functioning in autism in the EU‐AIMS Longitudinal European Autism Project

“…The sample consists of 417 participants with ASD ranging in age from 6 to 31 years ( M = 16.9, SD = 5.95, IQR = 9.12) recruited as part of LEAP. Details of the study procedure, protocol, as well as inclusion/exclusion criteria and demographic and clinical characteristics of the cohort have been described elsewhere [Charman et al, ; Loth et al, ]. Descriptive statistics for the sample are listed in Table .…”

“…To overcome some of these previous limitations, we tested unique predictors of adaptive functioning as measured by the VABS and the discrepancy between IQ and adaptive functioning in a well‐characterized sample of individuals with ASD as part of the EU‐AIMS Longitudinal European Autism Project (LEAP) cohort [Charman et al, ; Loth et al, ]. LEAP includes participants across a broad age range from young children to adults and of different intellectual functioning.…”

Sex Differences in Autism Spectrum Disorder: a Review

“…This discrepancy between self-report and clinician observation has important implications for both diagnostic and self-report measures, and also indicates that societal expectations may lead to more self-criticism in females than in males. Besides discrepancies with self-reports, clinicians often find less sex differences in ASD presentation than represented by parent reports, on which much of the literature is based [203–206]. Hiller et al [201] interestingly point out that parent and teacher reports of behavior often conflict with each other as well, with the parent reports often describing more impairments than teacher reports, particularly for females.…”

Atypical brain asymmetry in autism – a candidate for clinically meaningful stratification

“…Handedness was assessed with the short version of the Edinburgh Handedness Inventory (37). For further details on all cognitive measures, see SI and (33).…”