TY - JOUR
T1 - Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder
AU - Rosa-Neto, Pedro
AU - Lou, Hans C.
AU - Cumming, Paul
AU - Pryds, Ole
AU - Karrebaek, Hanne
AU - Lunding, Jytte
AU - Gjedde, Albert
N1 - Funding Information:
This study was supported by the Lundbeck Foundation, Denmark's Basic Science Foundation (Center for Functionally Integrative Neuroscience), and National Health Research Council.
PY - 2005/4/15
Y1 - 2005/4/15
N2 - 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 (%ΔpB) 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 %ΔpB in the right striatum and the severity of inattention and impulsivity. MP-evoked %ΔpB 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.
AB - 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 (%ΔpB) 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 %ΔpB in the right striatum and the severity of inattention and impulsivity. MP-evoked %ΔpB 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.
KW - Attention deficit/hyperactivity disorder
KW - Dopamine
KW - Methylphenidate
KW - PET
KW - Raclopride
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U2 - 10.1016/j.neuroimage.2004.11.031
DO - 10.1016/j.neuroimage.2004.11.031
M3 - Article
C2 - 15808987
AN - SCOPUS:16244419757
SN - 1053-8119
VL - 25
SP - 868
EP - 876
JO - NeuroImage
JF - NeuroImage
IS - 3
ER -