Abstract
Introduction: 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. We present data showing that genetic information may help to refine heterogeneity and predict prognosis among children diagnosed with attention-deficit hyperactivity (ADHD) disorder. Methods: We report data from two independent birth cohorts in Britain and New Zealand. These cohorts faithfully represent heterogeneity within controls and also within cases. Results: We present replicated evidence that polymorphisms in the DRD4 and DAT1 genes were associated with variation in intellectual functioning among ADHD-diagnosed children, 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. Conclusions: The findings indicate genetic information of this nature may prove useful for etiology-based psychiatric nosologies.