Effect of 12-week administration of 20-mg long-acting methylphenidate on Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the prefrontal cortices of school-age children in Indonesia: a study using 1H magnetic resonance spectroscopy (MRS).
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Child and Adolescent Psychiatry Division, Department of Psychiatry, University of Indonesia, Jakarta, Indonesia. twiga00@yahoo.com
Tjhin
T
Wiguna
Anthony P S
AP
Guerrero
Sasanto
S
Wibisono
Sudigdo
S
Sastroasmoro
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D002648:Child; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D011446:Prospective Studies; D011522:Protons; D013997:Time Factors
D011522:Protons; D008774:Methylphenidate; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline