Timing, space and ADHD: The dopamine theory revisited

Objective: The objective of this study was to review the dopamine theory of attention deficit hyperactivity disorder (ADHD) in terms of advances made over the last decade. Method: 'Hyper' and 'hypo' dopaminergic theories are discussed, as well as noradrenergic and neuropsychological findings in ADHD. A model incorporating both anterior and posterior attention systems, involved in orienting, inhibition, vigilance and working memory, is described. Neuropsychological studies of covert orienting are reviewed. Results: The dopamine theory is supported by neuroimaging, genetic and stimulant medication studies, which confirm an inhibitory dopaminergic effect at striatal/prefrontal level. Work in rodents and primates, as well as humans has shown that noradrenergic systems are also important in prefrontal regulation, in particular α_2A noradrenergic agonists have a beneficial effect on cognitive tasks. Neuropsychological studies implicate posterior parietal mechanisms in the orienting of attention. Working memory may require integration of spatial and temporal information, involving anterior and posterior systems. Conclusions: Anterior and posterior attention systems are involved in inhibition, working memory and orientation. Attention deficit hyperactivity disorder symptoms and subtypes are likely to reflect deficits in both inhibition and working memory, and may be heterogenous. While the dopamine theory is supported by genetic and stimulant medication studies, the work of Arnsten and colleagues suggests a potential role for α₂ noradrenergic agonists such as guanfacine.