Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
BMC Psychiatry. 2011 Apr 7;11:55. doi: 10.1186/1471-244X-11-55.
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.
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.
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.
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.
国际多中心 ADHD 遗传学（IMAGE）项目有来自 7 个欧洲国家和以色列的 11 个参与中心，为当前和未来的研究收集了大量行为和遗传数据库。行为数据来自 1068 名 ADHD 先证者和 1446 名未选择的兄弟姐妹。目的是描述和分析所有先证者和兄弟姐妹的问卷数据和智商测量值。特别是，调查年龄、性别、家庭状况（先证者与兄弟姐妹）、信息提供者和中心对心理病理学测量值样本同质性的影响。
采用 Conners 问卷、长处和困难问卷和韦氏智力测验来描述样本的表型。使用稳健的统计多向程序进行数据分析。
除了年龄、性别、信息提供者和中心的主要效应外，问卷数据还存在相当多的交互效应。先证者和兄弟姐妹在家中的差异大于在校中的差异，这可能反映了父母的对比效应。此外，ADHD 症状评定存在显著的性别与状态相互作用，在先证者样本中，女孩的得分比男孩高一个标准差，但在兄弟姐妹样本中，女孩的得分比男孩低。多中心设计是异质性的另一个重要来源，特别是与家庭状况的相互作用。在很大程度上，中心之间的差异与先证者和兄弟姐妹分数之间的差异有关。
当使用固定症状计数诊断 ADHD 先证者时，先证者样本中疾病的严重程度在男孩和女孩以及不同年龄之间可能有显著差异，尤其是在样本年龄范围较大的情况下。多中心设计存在中心之间存在显著表型差异的风险，因此即使使用标准化诊断程序，样本的异质性也会增加。这些可能的方差源应通过使用年龄和性别调整的诊断程序和区域常模数据来抵消，或者通过使用协变量统计数据、消除异常值或其他适合减少异质性的方法来调整设计因素。
