SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder

Abnormalities of frontostriatal circuits, which are modulated by dopamine, have been found by brain imaging studies in patients with attention-deficit/hyperactivity disorder (ADHD). With special radiolabeled ligands selective imaging of the dopamine transporter (DAT), which has a key function in dopamine metabolism, can be performed by SPECT and PET. Most of the studies showed a higher DAT availability in untreated patients with ADHD compared with controls. The relationship between DAT availability and a polymorphism of DAT1 gene in patients with ADHD is not clear and the results are controversial. It has been shown that methylphenidate lowers DAT availability very effectively in normal people and in patients with ADHD. First results seem to indicate that nonresponders to methylphenidate among ADHD patients have a low primary DAT availability, whereas patients with a good response to the drug have high DAT. Nicotine seems to lower DAT availability such as stimulant medication; this may explain the high percentage of smokers among patients with ADHD. Zinc is a DAT inhibitor and seems to have a positive therapeutic effect on ADHD symptoms. This article reviews the function and structure of the DAT, the results of DAT imaging with SPECT and PET, the relations between DAT availability and the DAT1 gene polymorphism, the influence of stimulants on DAT and the significance of DAT for therapeutic response, nicotine, zinc and psychotic symptoms in patients with ADHD.