: Attention Deficit/Hyperactivity Disorder (ADHD) is a prevalent syndrome with onset in early childhood characterized by problems with attention span, distractibility, hyperactivity and impulsiveness. A variety of studies have documented that ADHD is associated with academic failure, poor peer relationships and family dysfunction. ADHD has also been associated with increases in injuries, visits to emergency rooms, traffic violations, tobacco, alcohol and drug use. A variety of family, twin and adoption studies have demonstrated that ADHD is highly heritable. The long-term goal of this application is to identify specific genetic elements predisposing to ADHD. The identification of such elements would enhance diagnosis and, potentially, the treatment of children with this disorder. A variety of imaging, neurochemical, behavioral and drug response studies implicate pre-frontal catecholamine pathways as being involved in the etiology and treatment response of ADHD. In particular, dopamine-related pathways appear critical to problems with inattention. We propose in this study to screen 75 genes related to pre-frontal cortical development, neuronal activity dependent energy metabolism and catecholamine pathway function for coding region allelic variations associated with subtypes of ADHD. As phenotypes for analysis, we will use both DSM-IV defined subtypes, as well as refined categories derived through the use of latent class analysis. Groups of previously identified children will be screened for allelic variation in dopamine pathway genes using Denaturing High-Performance Liquid Chromatography (DHPLC). The presence of allelic variation identified using DHPLC will be confirmed by genomic DNA sequencing. Whether specific alleles are associated with subtypes of ADHD will be tested using the Transmission Disequilibrium Test (TDT).
