Smaller volumes of caudate nuclei in prepubertal children with ADHD: impact of age.

OBJECTIVE: Age-related abnormalities in caudate volumes have been reported to differ across the periods of childhood and puberty in children with ADHD. This study assessed caudate volumetric abnormalities across two narrow age clusters within the childhood period. METHOD: Three-dimensional manual tracings of the head and body of the caudate nucleus and of the cerebrum were acquired from 26 medication-naïve boys with a diagnosis of ADHD (ages 5.9-10.8 years), and 24 age-matched normal controls. RESULTS: Boys with ADHD had smaller total caudate volumes relative to controls, F(1,48)=4.29, p=0.04. Adjustment of caudate volumes with respect to age demonstrated that this group difference was driven solely by participants in the 5.9-7.3 year range, F(1, 46)=5.64, p=0.022, with an effect size of d=0.69. No Group effect was found in older participants, F(1, 46)=0.82, p=0.37. CONCLUSIONS: These novel findings suggest a different pattern of caudate volume abnormalities across narrow age clusters prior to puberty in boys with ADHD. Anatomical differences in brain structures related to ADHD in prepubertal children should be evaluated with respect to the changing developmental trajectory of brain regions within this period of rapid brain growth.

Metabolite changes resulting from treatment in children with ADHD: a 1H-MRS study.

Previously the authors noted an increase in glutamatergic tone in children with attention deficit hyperactivity disorder compared with age- and gender-matched control subjects. In this study they examine the effect of treatment on metabolite concentrations. Fourteen children with attention deficit hyperactivity disorder were investigated medication free and after treatment, using proton magnetic resonance spectroscopy. In the prefrontal cortex and striatum, metabolite peaks of N-acetyl-aspartate, glutamate/glutamine/gamma-aminobutyric acid, creatine/phosphocreatine, and choline compounds were measured, and ratios of the peaks were calculated and compared before and after treatment. The glutamate/glutamine/gamma-aminobutyric acid-to-creatine/phosphocreatine ratio decreased significantly in the striatum. No other metabolites demonstrated any change in response to medication. These findings suggest that glutamate may be involved in treatment response in attention deficit hyperactivity disorder, especially in the striatum.

Proton spectroscopy in medication-free pediatric attention-deficit/hyperactivity disorder.

BACKGROUND: The frontal-striatal pathway has been previously implicated in the neuropathology of attention-deficit/hyperactivity disorder (ADHD). Hence, we used proton magnetic resonance spectroscopy (1H-MRS) to examine metabolite levels in the prefrontal cortex of children with ADHD. METHODS: Nine age- and gender-matched case-control pairs were examined, ages 7 to 16 years. A long-echo 1H-MRS scan was acquired from the right prefrontal cortex and left striatum in all subjects. Compounds that can be visualized with 1H-MRS include N-acetyl-aspartate (NAA), glutamate/glutamine/gamma-aminobutyric acid (Glx), creatine/phosphocreatine (Cr), and choline compounds (Cho). RESULTS: Frontal-striatal glutamatergic resonances were elevated in the children with ADHD as compared to healthy control subjects. No differences were noted in NAA, Cho, or Cr metabolite ratios. CONCLUSIONS: These findings suggest that frontal-striatal Glx resonances may be increased in children with ADHD in comparison with healthy control subjects.

Glutamatergic changes with treatment in attention deficit hyperactivity disorder: a preliminary case series.

Magnetic resonance spectroscopy, a noninvasive neuroimaging method, is a technique with the potential to measure in vivo neurochemical changes to different medication treatments. Symptoms of attention deficit hyperactivity disorder (ADHD) improved in two children treated with methylphenidate and two children treated with atomoxetine, for whom pre- and posttreatment proton magnetic resonance spectroscopy examinations were obtained to assess the relation between the neurochemical profiles in the striatum and prefrontal cortex among symptom severity and response to treatment. In the striatum, a striking decrease in the glutamate/creatine ratio (mean change 56.1%) was observed between 14 and 18 weeks of therapy in all four children with ADHD. In the prefrontal cortex, however, changes in the glutamate/creatine ratio were noted only in subjects receiving atomoxetine, not in those receiving methylphenidate. These data suggest that in vivo magnetic resonance spectroscopy measurement has the potential to assess response to psychopharmacological treatment in children with ADHD.