Proton MR Spectroscopy: Higher Right Anterior Cingulate N-Acetylaspartate/Choline Ratio in Asperger Syndrome Compared with Healthy Controls

Öner, Özgür; Devrimci-Özgüven, Halise; Öktem, Ferhunde; Yağmurlu, Banu; Başkak, Bora; Münir, Kerim

doi:10.3174/ajnr.a0625

Cited by 29 publications

(35 citation statements)

References 27 publications

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“…While the reason for the discrepancy between the present results of decreased ACC and frontal neurometabolites in AS and prior studies that reported elevations of the same metabolites in similar brain regions could be methodological or due to differences in AS cohort characteristics, the difference in age may be the primary reason for the discrepancy: in the present study we have investigated only children with AS where prior studies had investigated only adults [12,13] or a mixture of children and adults [14]. In fact, to our knowledge, the present study is the first to use 1 H MRS to assess the neurometabolic characteristics of children with AS, and age-dependent metabolic differences have been reported, albeit in different regions [10, 13].…”

Section: Discussioncontrasting

confidence: 98%

“…These results are in disagreement with the results of two prior studies in adults with AS, which reported elevations of ACC and frontal lobe NAA compared to controls [12,14]. A third prior study had measured levels of metabolites in amygdala-hippocampal complex in 10–50 years old AS, and found no significant difference compared to controls although it reported report a significant age-related reduction in NAA, NAA/Cr, and tCho in the AS group [13], suggesting potential differences in these metabolites between adults and children (vide infra). With respect to the levels of the other metabolites, one of the prior studies, reported elevations of prefrontal tCr and tCho [12], which were also in disagreement with the results of the present study.…”

Section: Discussioncontrasting

confidence: 63%

“…In fact, to our knowledge, the present study is the first to use 1 H MRS to assess the neurometabolic characteristics of children with AS, and age-dependent metabolic differences have been reported, albeit in different regions [10, 13]. …”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis of 1 H MRS data from the ACC of children with ASD found significant decreases in the levels of the putative neuronal marker, N-acetylaspartate (NAA), compared to controls [10]. By contrast, levels of frontal lobe NAA were found to be higher in AS than in controls in the two prior studies [12,13]. Despite these discrepant NAA findings in ASD and AS, we hypothesized that, as in the two prior studies in AS, NAA would be increased in the disorder compared to controls, while no differences would be observed in the cerebellum.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS)

et al. 2017

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PurposeProton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger’s syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder.MethodsStudy participants consisted of 34 children with AS (2–12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2–11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum.ResultsIn the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions.ConclusionThe finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls.

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Section: Discussioncontrasting

confidence: 98%

Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS)

et al. 2017

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“…Cochran et al [33] found higher glutamine (Gln) levels and lower GABA/Cre levels in ASD, supporting the idea of an excitatory (Glu)/inhibitory (GABA) imbalance hypothesis. Anterior cingulate NAA, t-Cho, Cre, and mI signals were also found to be altered in some earlier studies [9, 10, 31, 34–37]. In the left dorsolateral prefrontal cortex (DLPFC), low NAA/Cre levels were found in the study by Fujii and colleagues [36], but no significant differences were found in two other studies [34, 38].…”

Section: Introductionmentioning

confidence: 74%

Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study

et al. 2017

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BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism.MethodsUsing the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions.ResultsWe did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks’ lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076).ConclusionsWe were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed.

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Atypical Developmental Patterns of Brain Chemistry in Children With Autism Spectrum Disorder

et al. 2013

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IMPORTANCE Autism spectrum disorder (ASD) is a neurodevelopmental disorder with symptoms emerging during early childhood. The pathophysiology underlying the disorder remains incompletely understood. OBJECTIVE To examine cross-sectional and longitudinal patterns of brain chemical concentrations in children with ASD or idiopathic developmental delay (DD) from 3 different age points, beginning early in the clinical course. DESIGN Proton magnetic resonance spectroscopic imaging data were acquired longitudinally for children with ASD or DD, and primarily cross-sectionally for children with typical development (TD), at 3 to 4, 6 to 7, and 9 to 10 years of age. SETTING Recruitment, diagnostic assessments, and magnetic resonance imaging were performed at the University of Washington in Seattle. PARTICIPANTS Seventy-three children (45 with ASD, 14 with DD, and 14 with TD) at 3 to 4 years of age; 69 children (35 with ASD, 14 with DD, and 20 with TD) at 6 to 7 years of age; and 77 children (29 with ASD, 15 with DD, and 33 with TD) at 9 to 10 years of age. MAIN OUTCOMES AND MEASURES Concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mI), and glutamine plus glutamate (Glx) in cerebral gray matter (GM) and white matter (WM) at 3 to 4, 6 to 7, and 9 to 10 years of age, and calculation of rates of change of these chemicals between 3 and 10 years of age. RESULTS At 3 to 4 years of age, the ASD group exhibited lower NAA, Cho, and Cr concentrations than did the TD group in both GM and WM, alterations that largely were not observed at 9 to 10 years of age. The DD group exhibited reduced GM and WM NAA concentrations at 3 to 4 years of age; GM NAA concentrations remained reduced at 9 to 10 years of age compared with the TD group. There were distinct differences between the ASD and DD groups in the rates of GM NAA, Cho, and Cr changes between 3 and 10 years of age. CONCLUSIONS AND RELEVANCE The GM chemical changes between 3 and 10 years of age differentiated the children with ASD from those with DD. Most notably, a dynamic reversal of GM NAA reductions was observed in the children with ASD. By contrast, persistent GM NAA reductions in the children with DD suggest a different, more static, underlying developmental process.

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Proton MR Spectroscopy: Higher Right Anterior Cingulate N-Acetylaspartate/Choline Ratio in Asperger Syndrome Compared with Healthy Controls

Cited by 29 publications

References 27 publications

Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS)

Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS)

Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study

Atypical Developmental Patterns of Brain Chemistry in Children With Autism Spectrum Disorder

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