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The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence

The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence
The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence
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 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.

Methods: 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.

Results: 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.

Conclusions: 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 4 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.

1471-244X
55
Muller, Ueli C.
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Asherson, Philip
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Banaschewski, Tobias
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Buitelaar, Jan K.
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Epstein, Richard P.
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Eisenberg, Jaques
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Gill, Michael
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Manor, Iris
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Miranda, Ana
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Oades, Robert D.
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Roeyers, Herbert
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Rothenberger, Aribert
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Sergeant, Joseph A.
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Sonuga-Barke, Edmund J.S.
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Thompson, Margaret
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Faraone, Stephen V.
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Steinhausen, Hans-Christoph
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Muller, Ueli C.
bfdacc4e-2640-4b43-8873-f47f7a95ea4c
Asherson, Philip
a734c1f6-f31a-450b-81c3-ba7bb373e147
Banaschewski, Tobias
4627c589-04cc-4f5b-ac2d-05f547f63dfd
Buitelaar, Jan K.
a2e08a14-4de4-419e-9ea8-1e97ebbdddba
Epstein, Richard P.
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Eisenberg, Jaques
4a898cb4-b86d-43d9-970b-240c370e9b6f
Gill, Michael
408d1dfa-5205-4e50-8130-7b26aa8288e8
Manor, Iris
786b2370-0f31-4448-a3b3-484204b3b7e2
Miranda, Ana
e416878c-5ff3-4892-bb8f-17e8de0884ac
Oades, Robert D.
85d7ca21-1a76-458d-a3e3-69d4b13232db
Roeyers, Herbert
3554b6b3-e364-4a6a-9e8b-64f5188a6d60
Rothenberger, Aribert
736981ca-a16d-44b3-8312-2067dc792a6d
Sergeant, Joseph A.
fca17df1-498d-4009-b445-dc6033711ab0
Sonuga-Barke, Edmund J.S.
bc80bf95-6cf9-4c76-a09d-eaaf0b717635
Thompson, Margaret
bfe8522c-b252-4771-8036-744e93357c67
Faraone, Stephen V.
bd307516-e8db-4d38-b649-9d7d7caafe93
Steinhausen, Hans-Christoph
991ad7f9-c5d1-4c61-8118-3d4895d2706d

Muller, Ueli C., Asherson, Philip, Banaschewski, Tobias, Buitelaar, Jan K., Epstein, Richard P., Eisenberg, Jaques, Gill, Michael, Manor, Iris, Miranda, Ana, Oades, Robert D., Roeyers, Herbert, Rothenberger, Aribert, Sergeant, Joseph A., Sonuga-Barke, Edmund J.S., Thompson, Margaret, Faraone, Stephen V. and Steinhausen, Hans-Christoph (2011) The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence. BMC Psychiatry, 11 (1), 55. (doi:10.1186/1471-244X-11-55). (PMID:21473746)

Record type: Article

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 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.

Methods: 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.

Results: 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.

Conclusions: 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 4 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.

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Published date: 7 April 2011

Identifiers

Local EPrints ID: 180617
URI: http://eprints.soton.ac.uk/id/eprint/180617
ISSN: 1471-244X
PURE UUID: 01525842-0c57-4aab-a60a-bdcba10540e8

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Date deposited: 12 Apr 2011 08:32
Last modified: 14 Mar 2024 02:52

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Contributors

Author: Ueli C. Muller
Author: Philip Asherson
Author: Tobias Banaschewski
Author: Jan K. Buitelaar
Author: Richard P. Epstein
Author: Jaques Eisenberg
Author: Michael Gill
Author: Iris Manor
Author: Ana Miranda
Author: Robert D. Oades
Author: Herbert Roeyers
Author: Aribert Rothenberger
Author: Joseph A. Sergeant
Author: Edmund J.S. Sonuga-Barke
Author: Margaret Thompson
Author: Stephen V. Faraone
Author: Hans-Christoph Steinhausen

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