Open Access Research article

The impact of study design and diagnostic approach in a large multi-centre ADHD study. Part 1: ADHD symptom patterns

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, Switzerland

2 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, 11:54  doi:10.1186/1471-244X-11-54

Published: 7 April 2011



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 the combined type of attention deficit/hyperactivity disorder (ADHD-CT) and 1446 'unselected' siblings. The aim was to analyse the IMAGE sample with respect to demographic features (gender, age, family status, and recruiting centres) and psychopathological characteristics (diagnostic subtype, symptom frequencies, age at symptom detection, and comorbidities). A particular focus was on the effects of the study design and the diagnostic procedure on the homogeneity of the sample in terms of symptom-based behavioural data, and potential consequences for further analyses based on these data.


Diagnosis was based on the Parental Account of Childhood Symptoms (PACS) interview and the DSM-IV items of the Conners' teacher questionnaire. Demographics of the full sample and the homogeneity of a subsample (all probands) were analysed by using robust statistical procedures which were adjusted for unequal sample sizes and skewed distributions. These procedures included multi-way analyses based on trimmed means and winsorised variances as well as bootstrapping.


Age and proband/sibling ratios differed between participating centres. There was no significant difference in the distribution of gender between centres. There was a significant interaction between age and centre for number of inattentive, but not number of hyperactive symptoms. Higher ADHD symptom frequencies were reported by parents than teachers. The diagnostic symptoms differed from each other in their frequencies. The face-to-face interview was more sensitive than the questionnaire. The differentiation between ADHD-CT probands and unaffected siblings was mainly due to differences in hyperactive/impulsive symptoms.


Despite a symptom-based standardized inclusion procedure according to DSM-IV criteria with defined symptom thresholds, centres may differ markedly in probands' ADHD symptom frequencies. Both the diagnostic procedure and the multi-centre design influence the behavioural characteristics of a sample and, thus, may bias statistical analyses, particularly in genetic or neurobehavioral studies.

ADHD; multi-centre study; sibling design; ADHD; informant effects; centre effects