Evidence of brain dysfunction in attention deficit-hyperactivity disorder:: a controlled study with proton magnetic resonance spectroscopy

Rationale and Objectives: Attention deficit-hyperactivity disorder (ADHD) is a socially disabling condition whose pathophysiology is mostly unknown. Previous magnetic resonance imaging (MRI)-based reports have shown structural abnormalities in the prefrontal region and the striaturn, but with inconsistencies across the studies with regard to right/left specificity of changes. Our study is aimed at finding evidence of dysfunction with more refined MRI techniques such as diffusion-weighted MRI and spectroscopy. Materials and Methods: We enrolled 22 ADHD children (mean age 9; SD 2.91) and 8 healthy children (mean age 7.5; SD 3). All of them underwent diffusion-weighted MRI in several areas of the brain bilaterally: preftontal, lentiform nucleus, posterior cingulate, and centrum semiovale; and single-voxel proton magnetic resonance spectroscopy in the left centrum semiovale and right prefrontal region. Results: We did not see either apparent structural abnormalities of the brain in conventional MRI or differences in the apparent-diffusion coefficients in any of the areas studied. However, we observed significant differences in the N-acetyl-aspartate/creatine ratios in relation to controls in the right prefrontal corticosubcortical region: 1.58 (SD 0.09) versus 1.47 (0.08) P =.01): and in the left centrum semiovale: 2.02 (0.13) versus 1.79 (0.13), P =.0003. This finding is consistent with a published report on eight ADHD children in whom N-acetyl-aspartate/creatine ratios were also elevated. Conclusions: Given these results, we hypothesize that a biochemical dysfunction might underlie in the brain of ADHD children. The N-acetyl-aspartate/creatine ratio may be regarded as a potential marker of the disease.