Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD)

Poor control of attention-related and motor processes, often associated with behavioural or cognitive impulsivity, are typical features of children and adults with attention-deficit hyperactivity disorder (ADHD). Until recently clinicians have observed little need to improve on or add to the catecholaminergic model for explaining the features of ADHD. Recent genetic and neuroimaging studies however provide evidence for separate contributions of altered dopamine (DA) and serotonin (5-HT) function in this disorder. Genetic studies imply that for both DA and 5-HT systems variants may frequently occur in ADHD for neurotransmitter uptake, synthesis and breakdown functions. The separate distributions in the brain of mesolimbic DA transporter and mesocortical DA D4 binding sites, both strongly implicated in ADHD, draws attention to potentially differential contributions from the 5-HT system. However, the evidence here points less towards an anatomical differentiation, as towards one in terms of inhibitory/facilitatory pre/post-synaptic location of receptors in the 5-HT(1) and 5-HT(2) families. While the monoamine metabolite levels excreted in ADHD are often correlated, this may well flow from a starting point where 5-HT activity is anomalously higher or lower than the generally lower than normal levels for DA. It appears that perhaps both situations may arise reflecting different diagnostic subgroups of ADHD, and where impulsive characteristics of the subjects reflect externalizing behaviour or cognitive impulsivity. For these features there is clear evidence that DA and 5-HT neuronal systems can and do interact anomalously in ADHD at the level of the soma, the terminals and at a distance. Interactions mediated by macroglia are also likely. However, it remains difficult to ascribe specific mechanisms to their effects (in potentially different subgroups of patients) from this relatively new field of study that has as yet produced rather heterogeneous results.