The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence

Abstract

BackgroundThe International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings. In particular, to investigate the influence of age, gender, family status (proband vs. sibling), informant, and centres on sample homogeneity in psychopathological measures.MethodsConners' Questionnaires, Strengths and Difficulties Questionnaires, and Wechsler Intelligence Scores were used to describe the phenotype of the sample. Data were analysed by use of robust statistical multi-way procedures.ResultsBesides main effects of age, gender, informant, and centre, there were considerable interaction effects on questionnaire data. The larger differences between probands and siblings at home than at school may reflect contrast effects in the parents. Furthermore, there were marked gender by status effects on the ADHD symptom ratings with girls scoring one standard deviation higher than boys in the proband sample but lower than boys in the siblings sample. The multi-centre design is another important source of heterogeneity, particularly in the interaction with the family status. To a large extent the centres differed from each other with regard to differences between proband and sibling scores.ConclusionsWhen ADHD probands are diagnosed by use of fixed symptom counts, the severity of the disorder in the proband sample may markedly differ between boys and girls and across age, particularly in samples with a large age range. A multi-centre design carries the risk of considerable phenotypic differences between centres and, consequently, of additional heterogeneity of the sample even if standardized diagnostic procedures are used. These possible sources of variance should be counteracted in genetic analyses either by using age and gender adjusted diagnostic procedures and regional normative data or by adjusting for design artefacts by use of covariate statistics, by eliminating outliers, or by other methods suitable for reducing heterogeneity.

The behavioural profile of children with attention-deficit/hyperactivity disorder and of their siblings

“…In comparison to teachers, parents have much better and more frequent opportunities to observe also emotional problems in their children so that there was a much better differentiation of the groups regarding behavioural domains other than ADHD by the parents in the present study. These findings differ from those by Müller et al [19,20 ], who found smaller informant effects in emotional problems.…”

“…This study found larger differences between probands and siblings at home than at school in most of the behavioural scores reflecting contrast effects in the parents [19,20].…”

“…Thus, also our third hypothesis on the impact of the informant was also clearly supported. Informant differences have been also detected in the data-set of the IMAGE project [19,20]. They were particularly pronounced in probands, but almost absent in siblings, leading to significant rater effects.…”

“…The detailed diagnostic procedure and algorithm (HYPESCHEME) has been described in an early paper coming from the IMAGE project by Brookes, Xu, Chen, Zhou, Neale, Lowe et al [25]. The present study was in part modelled after the IMAGE project [19,20]. DSM-IV subtypes of siblings were defined according to the HYPESCHEME algorithm, with the exception of three siblings.…”

Thinner Medial Temporal Cortex in Adolescents With Attention-Deficit/Hyperactivity Disorder and the Effects of Stimulants

“…Participants were selected from the Dutch follow-up phase of the International Multicenter ADHD Genetics (IMAGE) study [34][35][36] . ADHD diagnosis, ADHD severity, and presence of comorbid disorders were established using an algorithm based on both the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS 37 ) and Conners' ADHD questionnaires for parents 38 …”