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 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.
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: prefrontal, 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.
Introduction
Attention deficit-hyperactivity disorder (ADHD) is a common developmental disorder afflicting 3–7% of school-age children. It is characterized by overactivity, impulsivity, and inattentiveness, which lead to negative academic and social consequences ( ). In the past, these children were considered to have minimal brain dysfunction, but so far the etiology and pathophysiology are mostly unknown.
Magnetic resonance (MR)-based techniques have provided useful information and clues about the areas of the brain that are supposedly involved in this disorder. The majority of studies agree that the reduced volumes underlay in areas involved in attentional and executive functions (prefrontal-striatal areas). However, there are inconsistencies across the studies, especially in relation to right/left predominance of decreased brain volumes and other changes.
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Patients and methods
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Results
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Table 1
Mean Apparent Diffusion Coefficients (ADC) by Every Area
Area Examined Mean ADC of patients ( n = 24) Mean ADC of controls ( n = 8) Right prefrontal 6.6993 E-10 6.9925 E-10 NS Left prefrontal 6.8423 E-10 6.7462 E-10 NS Right striatum 5.8381 E-10 5.7475 E-10 NS Left striatum 5.8195 E-10 5.79 E-10 NS Right cingulate 7.3568 E-10 7.2112 E-10 NS Left cingulate 7.1395 E-10 7.1287 E-10 NS Right centrum semiovale 6.1618 E-10 6.1925 E-10 NS Left centrum semiovale 5.8192 E-10 5.8685 E-10 NS
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Table 2
Mean and SD Values of the Metabolites Relative to Cr
Left Centrum Semiovale Metabolite Ratio to Cr ADHD Children ( n = 24) Controls ( n = 8) Significance NAA/Cr 2.02 (SD 0.13) 1.79 (SD 0.13)P = .0003 Ch/Cr 1.15 (SD 0.12) 1.13 (SD 0.2)P = .6 mI/Cr 0.67 (SD 0.09) 0.67 (SD 0.07)P = .8 Right Prefrontal Region Metabolite Ratio to Cr ADHD Children ( n = 24) Controls ( n = 8) Significance NAA/Cr 1.58 (SD 0.09) 1.47 (SD 0.08)P = .01 Ch/Cr 0.87 (SD 0.13) 0.84 (SD 0.07)P = .07 mI/Cr 0.73 (SD 0.06) 0.72 (SD 0.07)P = .6
Note.—Cr = creatine; ADHD = attention deficit hyperactivity disorder; NAA = N-acetyl-aspartate/creatine; Ch = choline; mI = myo-Inositol
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Discussion
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