Metabolic Brain Disease

, Volume 33, Issue 3, pp 843–854 | Cite as

Relationship between absolute and relative ratios of glutamate, glutamine and GABA and severity of autism spectrum disorder

  • Hanoof Al-Otaish
  • Laila Al-Ayadhi
  • Geir Bjørklund
  • Salvatore Chirumbolo
  • Mauricio A. Urbina
  • Afaf El-Ansary
Original Article


Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by an impairment in social interaction, communication difficulties, and repetitive behaviors. Glutamate signaling abnormalities are thought to be considered as major etiological mechanisms leading to ASD. The search for amino-acidic catabolytes related to glutamate in patients with different levels of ASD might help current research to clarify the mechanisms underlying glutamate signaling and its disorders, particularly in relation to ASD. In the present study, plasma levels of the amino acids and their derivatives glutamate, glutamine, and γ-aminobutyric acid (GABA), associated with their relative ratios, were evaluated using an enzyme-linked immunosorbent assay (ELISA) technique in 40 male children with ASD and in 38 age- and gender-matched neurotypical health controls. The Social Responsiveness Scale (SRS) was used to evaluate social cognition, and the Childhood Autism Rating Scale (CARS) was used to assess subjects’ behaviors. Children with ASD exhibited a significant elevation of plasma GABA and glutamate/glutamine ratio, as well as significantly lower levels of plasma glutamine and glutamate/GABA ratios compared to controls. No significant correlation was found between glutamate levels and the severity of autism, measured by CARS and SRS. In receiver operating characteristic (ROC) curve analysis, the area under the curve for GABA compared to other parameters was close to one, indicating its potential use as a biomarker. Glutamine appeared as the best predictive prognostic markers in the present study. The results of the present study indicate a disturbed balance between GABAergic and glutamatergic neurotransmission in ASD. The study also indicates that an increased plasma level of GABA can be potentially used as an early diagnostic biomarker for ASD.


autism neurotransmitter glutamate excitotoxicity gamma-aminobutyric acid glutamine childhood autism rating scale 



This research project was supported by a grant from the research center of the Center for Female Scientific and Medical Colleges at King Saud University.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Biochemistry Department, Science CollegeKing Saud UniversityRiyadhSaudi Arabia
  2. 2.Autism Research and Treatment CenterRiyadhSaudi Arabia
  3. 3.Shaik AL-Amodi Autism Research ChairKing Saud UniversityRiyadhSaudi Arabia
  4. 4.Department of Physiology, Faculty of MedicineKing Saud UniversityRiyadhSaudi Arabia
  5. 5.Council for Nutritional and Environmental MedicineMo i RanaNorway
  6. 6.Department of Neurological and Movement SciencesUniversity of VeronaVeronaItaly
  7. 7.Department of ZoologyUniversity of ConcepcionConcepciónChile
  8. 8.Central Laboratory, Female Center for Medical Studies and Scientific SectionKing Saud UniversityRiyadhSaudi Arabia
  9. 9.Medicinal Chemistry DepartmentNational Research CentreCairoEgypt

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