Striatal neuronal loss or dysfunction and choline rise in children with attention-deficit hyperactivity disorder: A 1H-magnetic resonance spectroscopy study

Peking University, Peping, Beijing, China
Neuroscience Letters (Impact Factor: 2.03). 12/2001; 315(1-2):45-8. DOI: 10.1016/S0304-3940(01)02315-1
Source: PubMed

ABSTRACT Twelve previously untreated boys suffering from attention-deficit hyperactivity disorder (ADHD) were investigated by using proton magnetic resonance spectroscopy (1H MRS) before and after one dose (10 mg) of methylphenidate. Pre- and post-methylphenidate spectra were acquired bilaterally in the globus pallidus. Peaks of N-acetylaspartate (NAA), choline (Cho), myo-inositol, glutamate and creatine (Cr) were measured and the ratios of the peaks were calculated and compared with data from ten matched controls. In children having ADHD, NAA/Cr ratio decreased significantly in the bilateral striatum while Cho/Cr ratio showed a mild unilateral increase. One oral dose of methylphenidate did not affect the ratios significantly. These findings suggest that the striatum was bilaterally involved in pediatric ADHD patients. Approximately 20-25% of neurons may have died or may be severely dysfunctional. There seems to be a mild hyperactivity of the cholinergic system.

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    • "MRS is a noninvasive neuroimaging technique that can detect neurochemical concentrations of N-acetyl-aspartate (NAA), glutamate (Glu), creatine (Cr), choline (Cho), and myo-inositol (mI), which are indirect markers of neurotransmission and brain functioning.27,28) Several previous MRS studies of children with ADHD who were drug naive or treated with methylphenidate hydrochloride showed inconsistent findings in the brain regions studied.28,29,30,31) Therefore the aim of this pilot study was to identify, using MRS, the neurochemical ratios, normalized to Cr, in the amygdala of children with ADHD who were treated with 20 mg long-acting methylphenidate for 12 weeks. "
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    ABSTRACT: Objective Recent pediatric studies have suggested a correlation between decreased amygdala volume and attention deficit and hyperactivity disorder (ADHD) symptoms, including the emotional dysregulation. To investigate the hypothesis that medication treatment of ADHD specifically improves amygdala function, we used 1H magnetic resonance spectroscopy (MRS) to study the effect of 12 weeks of treatment with daily 20 mg long-acting methylphenidate on the Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the amygdala of medication-naïve children with ADHD. Methods This was a prospective study, using a pre- and post-test design, on a single group of 21 children (average age 8.52 years, 17 males and 4 females) diagnosed with ADHD. Low Time Echo MRS scans sampled voxels of interest (1.5×1.5×2.0) from both the right and left amygdala. Results There was significant clinical improvement after 12 weeks of treatment with 20 mg long-acting methylphenidate. On 1H MRS, there were no statistical significant differences of NAA/Cr ratio, Cho/Cr ratio, mI/Cr ratio before and after 12 weeks administration of 20 mg long-acting methylphenidate both in the right and left amygdala. In addition, Glu/Cr ratio decreased 14.1% in the right amygdala (p=0.029) and 11.4% in the left amygdala (p=0.008). Standardized mean effect sizes ranged from 0.14-0.32. Conclusion The findings are consistent with the possibility that hyperglutamatergic processes in the amygdale are related to the hyperactive-impulsive symptoms of ADHD.
    Clinical Psychopharmacology and Neuroscience 08/2014; 12(2):137-41. DOI:10.9758/cpn.2014.12.2.137
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    • "In addition, similar types of studies support involvement of the glutamatergic system in behavioral models related to ADHD. Magnetic resonance spectroscopy showed an increased glutamatergic tone in the frontal and striatal brains of subjects with ADHD [6-8] that normalized with stimulants and atmoxetine [9]. Dysregulated expression of glutamatergic pathway genes has been observed in spontaneously hypertensive rat models [10,11]. "
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    ABSTRACT: Background The purpose of this study was to investigate the association between the ionotropic and glutamate receptors, N-methyl D-asparate 2A (GRIN2A) and 2B (GRIN2B), and the metabotropic glutamate receptor mGluR7 (GRM7) gene polymorphisms and attention-deficit hyperactivity disorder (ADHD) in Korean population. Methods We conducted a case–control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 149 trios, and compared scores from the continuous performance test (CPT), the Children’s Depression Inventory (CDI), and the State-Trait Anxiety Inventory for Children (STAIC) according to the genotype of the glutamate receptor genes. Results There were no significant differences in the genotype or allele frequencies of the GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphisms between the ADHD and control groups. For 148 ADHD trios, the TDT analysis also showed no preferential transmission of the GRIN2A rs8049651 or GRIN2B rs2284411 polymorphisms. However, the TDT analysis of the GRM7 rs3792452 polymorphism showed biased transmission of the G allele (χ2 = 4.67, p = 0.031). In the ADHD probands, the subjects with GG genotype in the GRM7 rs37952452 polymorphism had higher mean T-scores for omission errors on the CPT than did those with the GA or AA genotype (t = 3.38, p = 0.001). In addition, the ADHD subjects who were homozygous for the G allele in the GRM7 rs37952452 polymorphism had higher STAIC-T (t = 5.52, p < 0.001) and STAIC-S (t = 2.74, p = 0.007) scores than did those with the GA or AA genotype. Conclusions These results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population.
    Behavioral and Brain Functions 01/2013; 9(1):1. DOI:10.1186/1744-9081-9-1 · 1.97 Impact Factor
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    • "However, most of the available MRS studies of ADHD were focused on childhood, and only two studies reporting neurometabolites ratios addressed subjects with average age in the adolescent range (Jin et al., 2001; Sun et al., 2005) . In these two studies, single-voxel 1 H-MRS was applied to investigate the basal ganglia of adolescents with ADHD, yielding a decreased NAA/Cr ratio in bilateral striatum (Jin et al., 2001) and right lenticular nucleus (Sun et al., 2005). Given that not all the children with ADHD will be clinically affected as adolescents, one could speculate that adolescents/adult patients with ADHD represent a distinct subpopulation, possibly with a different neurobiological or environmental underpinning . "
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    ABSTRACT: In this study, short echo time (1)H-magnetic resonance spectroscopy (MRS) was applied for quantification of neurometabolites using the LC Model algorithm in Taiwanese adolescents with attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectra were acquired bilaterally on the prefrontal area (part of the anterior cingulate gyrus and part of the medial frontal gyrus) in 15 adolescents with ADHD (average age of 13.88years) and 22 controls (average age of 14.85years). Absolute metabolite levels and ratios relative to creatine plus phosphocreatine (Cr+PCr) were obtained to be compared between groups. Results showed that adolescents with ADHD had significantly lower mean right prefrontal levels of Cr+PCr as compared with the controls. No significant differences between groups were noted in the remainder of the prefrontal metabolites. As for the group comparison of relative ratios, the N-acetylaspartate/Cr+PCr ratio was significantly higher in the right prefrontal regions of ADHD adolescents. This finding provides evidence of a right prefrontal neurochemical alteration in ADHD adolescents, which is consistent with current ADHD theory of prefrontal neuropathology with developmental mechanism. In addition, it highlights the importance of the method in interpretation of MRS findings in the context of ADHD.
    Psychiatry Research 02/2010; 181(3):199-203. DOI:10.1016/j.pscychresns.2009.10.001 · 2.47 Impact Factor
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