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Prediction of heterogeneity in intelligence and adult prognosis by genetic polymorphisms in the dopamine system among children with attention-deficit/hyperactivity disorder: evidence from 2 birth cohorts.

Mill J, Caspi A, Williams BS, Craig I, Taylor A, Polo-Tomas M, Berridge CW, Poulton R, Moffitt TE

Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, England.

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.

Published 4 April 2006 in Arch Gen Psychiatry, 63(4): 462-9.
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