Testing for Neuropsychological Endophenotypes in Siblings Discordant for Attention-Deficit/Hyperactivity Disorder

Background Neurocognitive deficits associated with attention-deficit/hyperactivity disorder (ADHD) might be useful intermediate endophenotypes for determining specific genetic pathways that contribute to ADHD. Methods This study administered 17 measures from prominent neuropsychological theories of ADHD (executive function, processing speed, arousal regulation and, motivation/delay aversion) in dizygotic (DZ) twin pairs discordant for ADHD and control twin pairs (ages 8–18 years) to compare performance between twins affected with ADHD (n = 266), their unaffected co-twins (n = 228), and control children from twin pairs without ADHD or learning difficulties (n = 332). Results The ADHD subjects show significant impairment on executive function, processing speed, and response variability measures compared with control subjects. Unaffected co-twins of ADHD subjects are significantly impaired on nearly all the same measures as their ADHD siblings, even when subclinical symptoms of ADHD are controlled. Conclusions Executive function, processing speed, and response variability deficits might be useful endophenotypes for genetic studies of ADHD.