Alteration of Plasma Glutamate and Glutamine Levels in Children with High-Functioning Autism
Open accessAbstract
BACKGROUND: It has recently been hypothesized that hyperglutamatergia in the brain is involved in the pathophysiology of autism. However, there is no conclusive evidence of the validity of this hypothesis. As peripheral glutamate/glutamine levels have been reported to be correlated with those of the central nervous system, the authors examined whether the levels of 25 amino acids, including glutamate and glutamine, in the platelet-poor plasma of drug-naïve, male children with high-functioning autism (HFA) would be altered compared with those of normal controls. METHODOLOGY/PRINCIPAL FINDINGS: Plasma levels of 25 amino acids in male children (N = 23) with HFA and normally developed healthy male controls (N = 22) were determined using high-performance liquid chromatography. Multiple testing was allowed for in the analyses. Compared with the normal control group, the HFA group had higher levels of plasma glutamate and lower levels of plasma glutamine. No significant group difference was found in the remaining 23 amino acids. The effect size (Cohen's d) for glutamate and glutamine was large: 1.13 and 1.36, respectively. Using discriminant analysis with logistic regression, the two values of plasma glutamate and glutamine were shown to well-differentiate the HFA group from the control group; the rate of correct classification was 91%. CONCLUSIONS/SIGNIFICANCE: The present study suggests that plasma glutamate and glutamine levels can serve as a diagnostic tool for the early detection of autism, especially normal IQ autism. These findings indicate that glutamatergic abnormalities in the brain may be associated with the pathobiology of autism.
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p-cresol and p-cresyl sulfate are phenolic compounds produced by bacteria such as C. difficile and Bifidobacterium.
“Another metabolite that we could considered is p-cresol and its co-metabolite p-cresyl sulfate, which are phenolic compounds that are produced by bacteria such as C. difficile and Bifidobacterium [185,186,187].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [187]
ASD patients have high levels of free amino acids (FAAs), which are derived from hydrolysis of proteins and peptides; glutamate may be involved in the etiopathogenesis of neurodevelopmental disorders.
“Furthermore, ASD patients have high level of free amino acids (FAAs) [186], which are derived from hydrolysis of proteins and peptides, like glutamate that may be involved in the etiopathogenesis of neurodevelopmental disorders [187].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [187]
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- Authors
- Shimmura, C., Suda, S., Tsuchiya, K. J., Hashimoto, K., Ohno, K., Matsuzaki, H., Iwata, K., Matsumoto, K., Wakuda, T., Kameno, Y., Suzuki, K., Tsujii, M., Nakamura, K., Takei, N., & Mori, N.
- Affiliations
- Hamamatsu University School of Medicine (JP)
- Chiba University (JP)
- Corresponding author
- Suda, Shiro
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-10-05
- Volume
- 6
- Issue
- 10
- Pages
- e25340
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3187770
- OpenAlex
- W1980865555
- Cited by
- 189
- References
- 38
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 11 · 2023: 14 · 2022: 15 · 2021: 18 · 2020: 15 · 2019: 14 · 2018: 17 · 2017: 12 · 2016: 11 · 2015: 14 · 2014: 11 · 2013: 9 · 2012: 6
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- HamaMed-Repository (Hamamatsu University School of Medicine) (submittedVersion, cc-by-nc-nd)
- Funders
- Takeda Science Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (22591260, 22390221, 21200014)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- high-functioning autism, plasma glutamate, plasma glutamine, amino acid levels, autism biomarkers, early diagnosis of autism, children
- MeSH terms
- Adolescent, Autistic Disorder, Child, Chromatography, High Pressure Liquid, Glutamine, Humans, Male, Discriminant Analysis, Case-Control Studies, Glutamic Acid
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