Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder of childhood onset that can include elements of inattention, hyperactivity and impulsive behavior. It is often treated with stimulant medications such as methylphenidate hydrochloride (MPH). The neurobiology of ADHD is not well understood, but there is converging evidence of the involvement of the catecholamine rich frontal-striatal circuitry. A prominent theory of ADHD is that there is a dysregulation of dopamine neurotransmission in this circuitry. Given support to this theory is the observation from human imaging studies that MPH blocks the dopamine transporter (DAT), the main mechanism for removing dopamine from the synapse; thereby increasing extracellular dopamine levels in the striatum. Genetic and molecular studies have also demonstrated an association between dopamine related genes (e.g., DAT, dopamine D4 and D5 receptors) and ADHD.
Development: Studies using positron emission tomography (PET) and single photon emission tomography indicate alterations in dopamine markers in ADHD. The majority of the existing studies have reported increased DAT binding (ranging between 17 and 70%) in the striatum of both children and adults with ADHD, while a new PET study reported lower DAT binding in the midbrain (where the dopaminergic neurons of the substantia nigra and ventral tegmental area are located) of adolescents with ADHD. Studies using [18F]fluorodopa to assess dopamine synthesis and metabolism have demonstrated abnormalities in presynaptic activity in patients with ADHD; however the nature of these changes appears to be age-dependent. Some limited data also indicate potential alterations in dopamine D2 receptor availability in children with ADHD.
Conclusions: The results from the human brain imaging studies are still not definitive because of discrepancies in the findings. There is a great need to replicate and expand these findings in treatment-naïve patients with ADHD, taking into consideration potential variables such as drug and smoking history, ethnicity, and presence of comorbidity.