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Open Access Research article

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

Ueli C Müller12*, Philip Asherson3, Tobias Banaschewski124, Jan K Buitelaar5, Richard P Ebstein6, Jaques Eisenberg6, Michael Gill7, Iris Manor8, Ana Miranda9, Robert D Oades10, Herbert Roeyers11, Aribert Rothenberger12, Joseph A Sergeant13, Edmund JS Sonuga-Barke1114, Margaret Thompson14, Stephen V Faraone15 and Hans-Christoph Steinhausen11617

Author Affiliations

1 Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland

2 Departement Pädagogisch-Therapeutische Berufe, Hochschule für Heilpädagogik, Zurich, Switzerland

3 MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, London, UK

4 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, J 5, Mannheim, Germany

5 Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

6 Department of Psychology, Hebrew University, Jerusalem, Israel

7 Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland

8 Geha MHC, Petach-Tikva, Israel

9 Department of Developmental and Educational Psychology, University of Valencia, Valencia, Spain

10 Clinic for Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany

11 Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium

12 Department of Child and Adolescent Psychiatry, University of Göttingen, Göttingen, Germany

13 Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands

14 School of Psychology, University of Southampton, Southampton, UK

15 Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA

16 Aalborg Psychiatric Hospital, Aarhus University Hospital, Aalborg, Denmark

17 Clinical Psychology and Epidemiology, Institute of Psychology, University of Basel, Basel, Switzerland

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BMC Psychiatry 2011, 11:55  doi:10.1186/1471-244X-11-55

Published: 7 April 2011

Abstract

Background

The 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.

Methods

Conners' 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.

Results

Besides 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.

Conclusions

When 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.

Keywords:
ADHD; multi-centre study; sibling design; centre effects