Role of the serotonin system in ADHD: treatment implications

Expert Rev Neurother. 2007 Oct;7(10):1357-74. doi: 10.1586/14737175.7.10.1357.


A limited number of studies have considered whether the activity of serotonin (5-hydroxytryptamine [5-HT]) contributes to the problems experienced by youngsters with attention-deficit/hyperactivity disorder (ADHD). The aim of this article is to review this work and propose interpretations. Peripheral measures of 5-HT and its metabolite do not point to a widespread association with the diagnosis. However, separate consideration of the major domains of dysfunction (motor activity, inattention and impulsivity) support a more differentiated assessment. The marked innervation of motor regions of the brain by 5-HT projections and the clear involvement of 5-HT systems in the control of locomotion in animals suggests a likely node for dysfunction in ADHD. The few relevant studies do not show evidence of this, but more attention should be accorded to the issue. The situation is different for attention-related processes; here, there are deficiencies in perceptual sensitivity and the appropriate designation of saliency to stimulation. These are attributable, in part, to altered 5-HT activity. Marked and opposite changes of 5-HT responsivity are associated with behavioral and cognitive impulsivity. There is also a growing series of studies demonstrating preferential transmission of various genetic markers for 5-HT receptors that are expressed in ADHD. Currently, the heterogeneity of methods in this young discipline restricts the possibilities of definition of these markers and the types of ADHD in which they are expressed.

Publication types

  • Review

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / diagnosis*
  • Attention Deficit Disorder with Hyperactivity / metabolism*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Humans
  • Receptors, Serotonin / physiology*
  • Serotonin / physiology*


  • Receptors, Serotonin
  • Serotonin