High midbrain [F-18]DOPA accumulation in children with attention deficit hyperactivity disorder

Objective: Attention deficit hyperactivity disorder (ADHD) is a highly prev alent childhood psychiatric disorder characterized by impaired attention, e xcessive motor activity, and impulsivity. Despite extensive investigation o f the neuropathophysiology of ADHD by a wide array of methodologies, the ne urobiochemical substrate of this disorder is still unknown. Converging evid ence, however, suggests a primary role of the dopaminergic system. Method: This study examined the integrity of presynaptic dopaminergic function in c hildren with ADHD through use of positron emission tomography and the trace r [F-18]fluorodopa ([F-18]DOPA). Accumulation of [F-18]DOPA in synaptic ter minals, a measure of dopa decarboxylase activity, was quantified in regions rich in dopaminergic innervation, including caudate nucleus, putamen, fron tal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum). Re sults: Accumulation of [F-18]DOPA in the right midbrain was higher by 48% i n 10 children with ADHD than in 10 normal children. Despite its magnitude, this difference would not have reached statistical significance if correcte d by the Bonferroni test for multiple comparisons. However, [F-18]DOPA in t he right midbrain was correlated with symptom severity. No other dopamine-r ich regions significantly differed between groups. Conclusions: These findi ngs are suggestive of dopaminergic dysfunction at the level of the dopamine rgic nuclei in children with ADHD. Abnormality in dopa decarboxylase activi ty may be primary or secondary to deficits in other functional units of the dopamine pathway (e.g., receptor, uptake transporter, vesicular transporte r, degradation enzymes). Efforts toward defining the origin of this abnorma lity should help delineate mechanisms of midbrain control of attention and motor behavior important for the understanding of the causes and treatment of ADHD.