Evidence of Brain Dysfunction in Attention Deficit-Hyperactivity Disorder: a Controlled Study with Proton Magnetic Resonance Spectroscopy

Abstract

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 striatum, 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. 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: prefrontal, lentiform nucleus, posterior cingulate, and centrum semiovale; and single-voxel proton magnetic resonance spectroscopy in the left centrum semiovale and right prefrontal region. 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. 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.