Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder.
Abnormal central dopamine (DA) neurotransmission has been implicated in the impulsivity, inattention, and hyperactivity of attention deficit hyperactivity disorder (ADHD). We hypothesized that a pharmacological challenge with methylphenidate (MP) at a therapeutic dose increases extracellular DA concentrations in proportion to the severity of these specific ADHD symptoms. To test this hypothesis, we measured by PET the effect of acute challenge with MP on the availability of striatal binding sites for [11C]raclopride (pB), an index of altered interstitial DA concentration, in nine unmedicated adolescents (1 female, 8 males; age 13.7 +/- 1.8 years) with a current diagnosis of ADHD. We estimated the pB of [11C]raclopride for brain dopamine D2/3 receptors first in a baseline resting condition, and again after an acute challenge with MP (0.3 mg/kg, p.o.), and calculated the percentage change in (%DeltapB) in left and right striatum. On another day, measurements of impulsivity and inattention were performed using a computerized continuous performance test. There was a significant correlation between the magnitude of %DeltapB in the right striatum and the severity of inattention and impulsivity. MP-evoked %DeltapB correlated with standard scores for impulse control (r = 0.68; P = 0.02), attention (r = 0.81; P = 0.005), information processing (r = 0.66; P = 0.02), and consistency of attention, or variability (r = 0.60; P = 0.04). In conclusion, the results link inattention and impulsivity with sensitivity of brain DA receptor availability to an MP challenge, corroborating the hypothesis that MP serves to potentiate decreased DA neurotransmission in ADHD.
Rosa-Neto
Pedro
P
Center for Functionally Integrative Neuroscience, Aarhus University and PET Center, Aarhus University Hospitals, 44 Nørrebrogade, Building 10, Aarhus C 8000, Denmark.
Lou
Hans C
HC
Cumming
Paul
P
Pryds
Ole
O
Karrebaek
Hanne
H
Lunding
Jytte
J
Gjedde
Albert
A
D000293:Adolescent; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging* / Q000188:drug therapy; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002648:Child; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects*; D004292:Dominance, Cerebral / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007175:Impulsive Behavior / Q000000981:diagnostic imaging* / Q000188:drug therapy; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use; D009483:Neuropsychological Tests; D010364:Pattern Recognition, Visual / Q000187:drug effects; D049268:Positron-Emission Tomography; D011597:Psychomotor Performance / Q000187:drug effects; D020891:Raclopride; D011869:Radioligand Assay; D011930:Reaction Time / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3; D013223:Statistics as Topic; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D008774:Methylphenidate; D020891:Raclopride; D004298:Dopamine