title: The impact of study design and diagnostic approach in a large multi-centre ADHD study. Part 1: ADHD symptom patterns.
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.
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Zurich, Switzerland. u.c.mueller@bluewin.ch
authors.forename: Ueli C
authors.initials: UC
authors.lastname: Müller
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.forename: Richard P
authors.initials: RP
authors.lastname: Ebstein
authors.forename: Jaques
authors.initials: J
authors.lastname: Eisenberg
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Iris
authors.initials: I
authors.lastname: Manor
authors.forename: Ana
authors.initials: A
authors.lastname: Miranda
authors.forename: Robert D
authors.initials: RD
authors.lastname: Oades
authors.forename: Herbert
authors.initials: H
authors.lastname: Roeyers
authors.forename: Aribert
authors.initials: A
authors.lastname: Rothenberger
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sergeant
authors.forename: Edmund J S
authors.initials: EJ
authors.lastname: Sonuga-Barke
authors.forename: Margaret
authors.initials: M
authors.lastname: Thompson
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Steinhausen
mesh_terms: D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D002648:Child; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005060:Europe; D005260:Female; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D010290:Parents / Q000523:psychology; D011569:Psychiatric Status Rating Scales; D011594:Psychometrics / Q000379:methods; D012107:Research Design; D012737:Sex Factors; D035781:Siblings / Q000523:psychology; D011795:Surveys and Questionnaires