Brain dopamine transporter levels in treatment and drug naïve adults with ADHD.
Attention deficit hyperactivity disorder (ADHD) is the most frequent psychiatric disorder in children, yet data are sparse on its pathophysiology. Particularly relevant are the dopamine transporters since these are the main targets of stimulant medications used for ADHD treatment. Though some imaging studies have shown increases in dopamine transporters in ADHD others have not and their role in the neurobiology of ADHD remains unclear. Here we investigate dopamine transporters in ADHD subjects with control of potentially confounding factors (previous medication and/or drug histories, comorbidity) and their association with clinical symptoms. Positron emission tomography and [11C]cocaine were used to measure dopamine transporters in 20 never medicated adults with ADHD and 25 controls. Dopamine transporters were lower in left caudate (13%, p < 0.05) and in left nucleus accumbens (p < 0.005) in ADHD subjects than in controls. In putamen dopamine transporters did not differ between groups but were associated with scores of inattention (Conners Adult Attention Rating Scale) both in ADHD subjects (p < 0.005) and in controls (p < 0.005). Thus, for a given transporter level the scores for inattention were on average five times greater in ADHD subjects than in controls. These results do not corroborate increases in dopamine transporters in ADHD subjects and show that in some they are reduced. It also provides evidence that dopamine transporter levels modulate attention but suggest that additional pathology (e.g., prefrontal or cingulostriatal pathways, noradrenergic neurotransmission) is necessary to account for the large differences in inattention observed between controls and ADHD subjects.
Volkow
Nora D
ND
National Institute on Drug Abuse, Bethesda, MD 20892, USA. nvolkow@nida.nih.gov
Wang
Gene-Jack
GJ
Newcorn
Jeffrey
J
Fowler
Joanna S
JS
Telang
Frank
F
Solanto
Mary V
MV
Logan
Jean
J
Wong
Christopher
C
Ma
Yeming
Y
Swanson
James M
JM
Schulz
Kurt
K
Pradhan
Kith
K
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003042:Cocaine / Q000493:pharmacokinetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000187:drug effects
D002250:Carbon Radioisotopes; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D003042:Cocaine