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NEUROSCIENCE OF ATTENTION-DEFICIT/HYPERACTIVITY DISORDER: THE SEARCH FOR ENDOPHENOTYPES
F. Xavier Castellanos* and Rosemary Tannock
Research on attention-deficit/hyperactivity disorder (ADHD), a highly prevalent and controversial condition, has, for the most part, been descriptive and atheoretical. The imperative to discover the genetic and environmental risk factors for ADHD is motivating the search for quantifiable intermediate constructs, termed endophenotypes. In this selective review, we conclude that such endophenotypes should be solidly grounded in the neurosciences. We propose that three such endophenotypes a specific abnormality in reward-related circuitry that leads to shortened delay gradients, deficits in temporal processing that result in high intrasubject intertrial variability, and deficits in working memory are most amenable to integrative collaborative approaches that aim to uncover the causes of ADHD.
Attention-deficit/hyperactivity disorder (ADHD) is one of many labels for one of the most prevalent conditions in child psychiatry, and, undoubtedly, the most controversial. ADHD is conservatively estimated to occur in3.07.5% of school-age children1, but more permissive criteria yield estimates of up to 17% (REF. 2), and up to
20% of boys in some school systems receive psycho-stimulants for the treatment of ADHD3. Despite the absence of controlled studies in pre-school-age children, and concern about potential long-term adverse effects4, stimulant medications are increasingly being administered to children as young as two years of age5.
The initial phase of research into ADHD has been descriptive by design, but it has also been driven by adult-based models from psychiatry, psychology and neuroscience. Our purpose here is to highlight the crucial studies and perspectives that have guided clinical investigations of ADHD, which form the basis for new integrative and multidisciplinary approaches that incorporate a developmental perspective. We argue that the field is now poised to build on the insights gleaned from descriptive symptom-based approaches by developing endophenotypes of ADHD that are grounded in neuro-science. Endophenotypes are heritable quantitative
traits that index an individuals liability to develop or manifest a given disease, and they are thought to be more directly related than dichotomous diagnostic categories to aetiological factors6,7.
Research into ADHD has been hampered by confusion over nomenclature and diagnostic criteria. The many terms that have been applied to ADHD include attention-deficit disorder (ADD), hyperactivity, hyperkinesis, hyperkinetic syndrome, minimal brain dysfunction and minimal brain damage8. The current criteria...