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BMC Psychiatry. 2011; 11: 54.
Published online Apr 7, 2011. doi:  10.1186/1471-244X-11-54
PMCID: PMC3082291
The impact of study design and diagnostic approach in a large multi-centre ADHD study. Part 1: ADHD symptom patterns
Ueli C Müller,corresponding author1,2 Philip Asherson,3 Tobias Banaschewski,4,12 Jan K Buitelaar,5 Richard P Ebstein,6 Jaques Eisenberg,6 Michael Gill,7 Iris Manor,8 Ana Miranda,9 Robert D Oades,10 Herbert Roeyers,11 Aribert Rothenberger,12 Joseph A Sergeant,13 Edmund JS Sonuga-Barke,11,14 Margaret Thompson,14 Stephen V Faraone,15 and Hans-Christoph Steinhausen1,16,17
1Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland
2Hochschule für Heilpädagogik, Zurich, Switzerland
3MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, London, UK
4Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, J 5, Mannheim, Germany
5Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
6Department of Psychology, Hebrew University, Jerusalem, Israel
7Department of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland
8Geha MHC, Petach-Tikva, Israel
9Department of Developmental and Educational Psychology, University of Valencia, Valencia, Spain
10Clinic for Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany
11Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium
12Department of Child and Adolescent Psychiatry, University of Göttingen, Göttingen, Germany
13Department of Clinical Neuropsychology, Vrije Universiteit, Amsterdam, The Netherlands
14School of Psychology, University of Southampton, Southampton, UK
15Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA
16Aalborg Psychiatric Hospital, Aarhus University Hospital, Aalborg, Denmark
17Clinical Psychology and Epidemiology, Institute of Psychology, University of Basel, Basel, Switzerland
corresponding authorCorresponding author.
Ueli C Müller: u.c.mueller/at/bluewin.ch; Philip Asherson: Philip.Asherson/at/iop.kcl.ac.uk; Tobias Banaschewski: tobias.banaschewski/at/zi-mannheim.de; Jan K Buitelaar: J.Buitelaar/at/psy.umcn.nl; Richard P Ebstein: Ebstein/at/netvision.net.il; Jaques Eisenberg: Jaques/at/cc.huji.ac.il; Michael Gill: mgill/at/tcd.ie; Iris Manor: Imanor/at/clalit.org.il; Ana Miranda: Ana.Miranda/at/uv.es; Robert D Oades: robert.oades/at/uni-due.de; Herbert Roeyers: Herbert.Roeyers/at/UGent.be; Aribert Rothenberger: arothen/at/gwdg.de; Joseph A Sergeant: JA.Sergeant/at/psy.vu.nl; Edmund JS Sonuga-Barke: ejb3/at/soton.ac.uk; Margaret Thompson: M.Thompson/at/soton.ac.uk; Stephen V Faraone: sfaraone/at/childpsychresearch.org; Hans-Christoph Steinhausen: steinh/at/kjpd.uzh.ch
Received May 13, 2010; Accepted April 7, 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 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.
Methods
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.
Results
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.
Conclusions
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.
Keywords: ADHD, multi-centre study, sibling design, ADHD, informant effects, centre effects
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