Neuroscience of ADHD

Castellanos, F. X. (August 2002). Neuroscience of Attention-Deficit/Hyperactivity Disorder: The Search for Endophenotypes, Nature Reviews. Volume 3.

An endophenotype is an heritable quantitative trait that can be used to index and predict a person's risk of developing a given disease. Research into ADHD has traditionally been hampered by confusion over fuzzy operational definitions and diagnostic criteria. Towards development of an objective diagnostic test, the authors of this article propose three categories of endophenotypes, each grounded in neuroscience.

Abnormality in the reward-related circuitry that leads to shortened delay gradients. Delay aversion tasks can assess a person's intolerance for waiting that can lead to selection of an immediate reward over a larger, delayed reward. Sonuga-Barke argues that fundamental abnormalities in the reward mechanisms of ADHD subjects translate into a faster decline in the effectiveness of reinforcement as the delay between behavior and reward increases.

Deficits in temporal processing. People with ADHD appear to exhibit deficits in time-estimation and time-production, especially time estimation tasks between 2-60 seconds which require cortical mediation and rehearsal in working memory (as opposed to smaller durations which are dependent on the basal ganglia and cerebellum), but not wholesale -- instead, they exhibit variability in performance. This article suggests that this variability itself is a characteristic of the disorder and can be used as a rating.

Deficits in working memory. Working memory controls attention and guides decision-making and behavior. It is mediated by the prefrontal cortex and modulated by the catecholamines dopamine and noradrenaline. Catecholaminergic dysregulation and prefrontal dysfunction are central to the pathophysiology of ADHD. A P300 Component, derived from EEG analysis, provides an index of the attentional and working memory demands of a task and may be fitting for use as an endophenotype. (See also Coherence wave patterns.)

Other candidate endophenotypes were ruled out due to incompleteness of data, potential confounds, or the multiplicity of operational definitions. These include genetic factors, locomotor hyperactivity, and general response inhibition.