Recent studies on the neurobiology of attention-deficit/hyperactivity disorder (ADHD) have suggested that there is dysregulation of dopamine-mediated neurotransmission, particularly in the prefrontal cortex and basal ganglia, and that treatment with methylphenidate reverses this dysregulation. Using methodology similar to previous studies involving putative markers of brain functioning, we used 1H magnetic resonance spectroscopy to study the effect of 12-week treatment with daily 20-mg long-acting methylphenidate on the glutamate/creatine, N-acetyl-aspartate/creatine, choline/creatine, and myoinositol/creatine ratios in the prefrontal cortices of medication-naive children with ADHD.
This was a prospective study, using a pretest and posttest design, on a single group of 21 children (mean age, 8.52 years; 17 males and 4 females) with a diagnosis of ADHD. A low time echo (TE) magnetic resonance spectroscopic scans sampled voxels of interest (1.5 × 1.5 × 2.0) from both the right and left prefrontal cortices.
After treatment, the N-acetyl-aspartate/creatine ratio increased 18.8% in the right prefrontal cortex (P = 0.001) and 10% in the left prefrontal cortex (P = 0.007); the glutamate/creatine ratio decreased 15% in the right prefrontal cortex (P = 0.005) and 14.1% in the left prefrontal cortex (P = 0.005); the choline/creatine ratio decreased 12.4% in the right prefrontal cortex (P = 0.037) and 16% in the left prefrontal cortex (P = 0.006); and the myoinositol/creatine ratio decreased 14.7% in the left prefrontal cortex (P = 0.011) and 7.7% in the right prefrontal cortex (P = 0.129).
Notwithstanding the limitations of this pilot study, we found, after stimulant treatment, significant neurochemical changes (thought to reflect functional improvement and improved neuroplasticity) in the prefrontal cortices of children with ADHD.