The effect of low neonatal cerebral blood flow (CBF) on dopaminergic neurotransmission was studied in 6 genetically susceptible high-risk, preterm neonates followed with attention deficit hyperactivity disorder (ADHD) at Aarhus University Hospital, Denmark, and tested at 12-14 years of age. The authors hypothesized that cerebral ischemia at birth might contribute to deficient dopaminergic neurotransmission, which is considered to be the basis for ADHD. Dopamine receptor binding in the striatum was examined with positron emission tomography (PET), and inattention and impulsiveness were measured by continuous reaction times (RT) and RT variability determined by a computerized test of variables (TOVA). In 6 adolescents (12-14 years of age; 5 boys) with CBF measurements at preterm birth and a subsequent diagnosis of ADHD, high striatal dopamine receptor availability (’empty receptors’) was correlated with increased RT and RT variability, findings that supported a dopaminergic role in ADHD symptomatology. The link demonstrated between high dopamine receptor availability with low neonatal CBF supports the hypothesis of cerebral ischemia as a risk factor for ADHD. 
COMMENT. These results support the long held theory that some cases of ADHD may be a consequence of prematurity and low cerebral blood flow (CBF) with perinatal hypoxic-ischemic encephalopathy. The low neonatal CBF predisposes to dopamine depletion in the prefrontal-striatal-limbic system that, in genetically susceptible individuals, leads to ADHD. The beneficial effect of methylphenidate is further convincing evidence that dopaminergic systems are implicated in the pathogenesis of ADHD.