title: Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder.
abstract: OBJECTIVE
  Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated.
  
  
  METHODS
  We used positron emission tomography and [(11)C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands.
  
  
  RESULTS
  Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005).
  
  
  CONCLUSIONS
  Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.
authors.affiliation: Department of Radiology, Stony Brook University, Stony Brook, New York, USA. gjwang@bnl.gov
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Timothy
authors.initials: T
authors.lastname: Wigal
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kollins
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Newcorn
authors.forename: Frank
authors.initials: F
authors.lastname: Telang
authors.forename: Jean
authors.initials: J
authors.lastname: Logan
authors.forename: Millard
authors.initials: M
authors.lastname: Jayne
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Wong
authors.forename: Hao
authors.initials: H
authors.lastname: Han
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: James M
authors.initials: JM
authors.lastname: Swanson
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D003042:Cocaine / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects*; D059906:Neuroimaging; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D008774:Methylphenidate; D003042:Cocaine