Müller, U.C., Asherson, P., Banaschewski, T., Buitelaar, J. K., Ebstein, R. P., Eisenberg, J., Gill, M., Manor, I., Miranda, A., Oades, R. D., Roeyers, H., Rothenberger, A., Sergeant, J. A., Sonuga-Barke, E. J. S., Thompson, M., Faraone, S. V., & Steinhausen, H-C.,

The impact of study design and diagnostic approach in a large multi-centre ADHD study. Part 1: ADHD symptom patterns. . BMC Psychiatry, 11, 54 .
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Introduction: The International Multi-centre ADHD-Genetics (IMAGE) project with 11 participating centres from 7 European countries & Israel has collected a large behavioural & genetic database for present & future research. Behavioural data were collected from 1068 probands with ADHD & 1446 unselected siblings.

Methods: The diagnostic behavioural measures in the probands and 339 siblings suspected to have ADHD were analyzed with respect to effects of age, gender, family status, informant, diagnostic instrument, and centres. Diagnosis was based on the PACS interview (Parental Account of Childrens' Symptoms) & the DSM-IV items of the Conners' teacher questionnaire. Due to pronounced deviations from normal & symmetrical distributions, unequal sample sizes and variances in the data, robust statistical procedures were applied.

1 - There were no differences in gender ratios & in proband / sibling ratios between the participating centres.

2 - The mean age differed between centres, but neither between boys and girls nor between probands and siblings. -- However, there was a significant interaction between age & centres.

3 - Depending on age and centre, the number of positive symptoms and age at symptom onset differed for inattention but not for hyperactivity.

4 - Symptom frequencies were higher at home than at school, differed between centres, and were dependent on the diagnostic instrument with higher frequencies in the interview with respect to the questionnaire.

5 - The differentiation between probands & unaffected siblings was mainly based on hyperactive/impulsive symptoms

Conclusions/Discussion: The number of positive symptoms in ADHD probands is dependent on the informant and the diagnostic instrument. -- Despite a symptom-based standardized inclusion procedure according to DSM-IV criteria with defined symptom thresholds, the participating centres differed up to 11% in ADHD symptom frequencies.

Both the diagnostic procedure and the multi-centre design have an effect on the behavioural characteristics of a sample and, thus, may increase heterogeneity and reduce power in genetic analyses.