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Evidence From 2 Birth Cohorts

Jonathan Mill, PhD; Avshalom Caspi, PhD; Benjamin S. Williams, BA; Ian Craig, PhD; Alan Taylor, MSc; Monica Polo-Tomas, MSc; Craig W. Berridge, PhD; Richie Poulton, PhD; Terrie E. Moffitt, PhD

Arch Gen Psychiatry. 2006;63:462-469.

Context  The study and treatment of psychiatric disorders is made difficult by the fact that patients with identical symptoms often differ markedly in their clinical features and presumably in their etiology. A principal aim of genetic research is to provide new information that can resolve such clinical heterogeneity and that can be incorporated into diagnostic practice.

Objective  To test the hypothesis that the DRD4 seven-repeat allele and DAT1 ten-repeat allele would prove useful in identifying a subset of children with attention-deficit/hyperactivity disorder (ADHD) who have compromised intellectual functions.

Design  Longitudinal epidemiologic investigation of 2 independent birth cohorts.

Setting  Britain and New Zealand.

Participants  The first cohort was born in Britain in 1994-1995 and includes 2232 children; the second cohort was born in New Zealand in 1972-1973 and includes 1037 children.

Main Outcome Measures  Evaluation of ADHD, IQ, and adult psychosocial adjustment.

Results  We present replicated evidence that polymorphisms in the DRD4 and DAT1 genes were associated with variation in intellectual functioning among children diagnosed as having ADHD, apart from severity of their symptoms. We further show longitudinal evidence that these polymorphisms predicted which children with ADHD were at greatest risk for poor adult prognosis.

Conclusion  The findings indicate that genetic information of this nature may prove useful for etiology-based psychiatric nosologies.

Author Affiliations: Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, England (Drs Mill, Caspi, Craig, and Moffitt, Messrs Williams and Taylor, and Ms Polo-Tomas); Department of Psychology, University of Wisconsin, Madison (Drs Caspi, Moffitt, and Berridge); and Dunedin School of Medicine, University of Otago, Dunedin, New Zealand (Dr Poulton).

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