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 [C-11]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 [C-11]raclopride for brain dopamine D-2/3 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 (%Delta pB) 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 %Delta pB in the right striatum and the severity of inattention and impulsivity. NIP-evoked %Delta pB 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. (c) 2004 Elsevier Inc. All rights reserved.