title: Methylphenidate-elicited dopamine increases in ventral striatum are associated with long-term symptom improvement in adults with attention deficit hyperactivity disorder.
abstract: Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and [(11)C]raclopride (D(2)/D(3) receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners' Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D(2)/D(3) receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.
authors.affiliation: National Institute on Drug Abuse, Bethesda, Maryland 20892, USA. nvolkow@nida.nih.gov
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Dardo
authors.initials: D
authors.lastname: Tomasi
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kollins
authors.forename: Tim L
authors.initials: TL
authors.lastname: Wigal
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Newcorn
authors.forename: Frank W
authors.initials: FW
authors.lastname: Telang
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Jean
authors.initials: J
authors.lastname: Logan
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Wong
authors.forename: James M
authors.initials: JM
authors.lastname: Swanson
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000097:blood / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D020891:Raclopride / Q000493:pharmacokinetics; D011954:Receptors, Dopamine / Q000378:metabolism; D013223:Statistics as Topic
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D011954:Receptors, Dopamine; D008774:Methylphenidate; D020891:Raclopride; D004298:Dopamine