Catecholamine dysfunction in attention-deficit/hyperactivity disorder: an update

J Clin Psychopharmacol. 2008 Jun;28(3 Suppl 2):S39-45. doi: 10.1097/JCP.0b013e318174f92a.


Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disease that affects children, adolescents, and adults. Genetic research has confirmed that there is a large hereditary component to this condition and has helped identify some of the genes associated with it. Among these are several genes associated with the catecholaminergic system including the dopamine receptor genes (DRD4 and DRD5), the dopamine transporter gene, and the gene for dopamine beta-hydroxylase, which catalyzes conversion of dopamine to norepinephrine. Attention-deficit/hyperactivity disorder is believed to be a result of abnormalities in the frontal regions of the brain, particularly the prefrontal cortex and associated subcortical structures and circuits. Underpinning these abnormalities are disturbances of catecholamine neurotransmission. Studies have demonstrated that patients with ADHD have depleted levels of dopamine and norepinephrine thought to be largely the result of dysfunction of their respective transporter systems. The efficacy of stimulant agents confirms that the neurotransmitter abnormalities seen in ADHD are primarily catecholaminergic in origin. This article focuses on the catecholaminergic networks of higher cognitive functions such as attention and focus and of motor functions that may be associated with such networks, reviewing both the physiology of such functions and the pathophysiology of ADHD. Researchers are currently investigating whether other neurotransmitter systems may be partially involved and are investigating whether agents that affect these other systems will prove complementary to currently used treatments.

Publication types

  • Review

MeSH terms

  • Attention / drug effects
  • Attention / physiology
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Central Nervous System Stimulants / therapeutic use
  • Child
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiopathology
  • Dopamine / metabolism*
  • Frontal Lobe / drug effects
  • Frontal Lobe / physiopathology*
  • Humans
  • Methylphenidate / therapeutic use
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nerve Net / drug effects
  • Nerve Net / physiopathology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Norepinephrine / metabolism*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Central Nervous System Stimulants
  • Methylphenidate
  • Dopamine
  • Norepinephrine