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Journal of Autism and Developmental Disorders

, Volume 48, Issue 5, pp 1467–1482 | Cite as

Medial Frontal Lobe Neurochemistry in Autism Spectrum Disorder is Marked by Reduced N-Acetylaspartate and Unchanged Gamma-Aminobutyric Acid and Glutamate + Glutamine Levels

  • Andreia Carvalho Pereira
  • Inês R. Violante
  • Susana Mouga
  • Guiomar Oliveira
  • Miguel Castelo-Branco
Original Paper

Abstract

The nature of neurochemical changes in autism spectrum disorder (ASD) remains controversial. We compared medial prefrontal cortex (mPFC) neurochemistry of twenty high-functioning children and adolescents with ASD without associated comorbidities and fourteen controls. We observed reduced total N-acetylaspartate (tNAA) and total creatine, increased Glx/tNAA but unchanged glutamate + glutamine (Glx) and unchanged absolute or relative gamma-aminobutyric acid (GABA+) in the ASD group. Importantly, both smaller absolute and relative GABA+ levels were associated with worse communication skills and developmental delay scores assessed by the autism diagnostic interview—revised (ADI-R). We conclude that tNAA is reduced in the mPFC in ASD and that glutamatergic metabolism may be altered due to unbalanced Glx/tNAA. Moreover, GABA+ is related to autistic symptoms assessed by the ADI-R.

Keywords

Autism spectrum disorder N-acetylaspartate Gamma-aminobutyric acid Glutamate + glutamine Creatine Autism diagnostic interview—revised 

Notes

Acknowledgments

The authors thank all participants and their families for their willingness to participate in this study. The authors thank Dr. Inês Bernardino for support in the neuropsychological evaluation of control participants and Dr. João Castelhano for creating Matlab scripts for MEGA-PRESS combined spectra visualization. The authors are also grateful to the staff of the Institute of Nuclear Sciences Applied to Health (ICNAS, http://www.uc.pt/en/icnas) for their technical assistance with the magnetic resonance scanning, particularly to Mr. Carlos Ferreira, Mr. João Marques and Ms. Sónia Afonso. This research was supported by the Portuguese Foundation for Science and Technology grants: BIGDATIMAGE, CENTRO-01-0145-FEDER-000016 financed by Centro 2020 FEDER, COMPETE, FLAD Life Sciences Ed 2 2016, COMPETE, POCI-01-0145-FEDER-007440, FCT. UID/NEU/04539/2013–2020, PAC – MEDPERSYST POCI-01-0145-FEDER-016428; IRV is funded by is funded by the Wellcome Trust (103045/Z/13/Z), SM is funded by Portuguese Foundation for Science and Technology (individual scholarship: SFRH/BD/102779/2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author Contributions

Conceived and designed the study: ACP IRV MC-B and GO. Acquired data: ACP and SM. Analysed the data: ACP and IRV. Interpreted the data ACP and MC-B. Wrote original draft: ACP and MC-B. All authors reviewed and edited the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors have declared that no competing interests exist.

Supplementary material

10803_2017_3406_MOESM1_ESM.docx (185 kb)
Figure 1S. MEGA-PRESS mean fit (red line) and standard deviation (shaded red) of the difference spectra for each group. Abbreviations: Glx, glutamate+glutamine; GABA+, gamma-aminobutyric acid + lipids and macromolecules; tNAA, N-acetylaspartate + N-acetylaspartylglutamate; MM. macromolecules; ppm, parts per million. (DOCX 184 KB)
10803_2017_3406_MOESM2_ESM.docx (68 kb)
Supplementary material 2 (DOCX 67 KB)

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© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Faculty of MedicineUniversity of CoimbraCoimbraPortugal
  2. 2.Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and NeuroscienceKing’s College LondonLondonUK
  3. 3.The Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of MedicineImperial College LondonLondonUK
  4. 4.Unidade de Neurodesenvolvimento e Autismo do Serviço do Centro de Desenvolvimento da Criança, Pediatric HospitalCentro Hospitalar e Universitário de CoimbraCoimbraPortugal
  5. 5.Centro de Investigação e Formação ClínicaHospital Pediátrico – Centro Hospitalar e Universitário de CoimbraCoimbraPortugal
  6. 6.University Clinic of Pediatrics, Faculty of MedicineUniversity of CoimbraCoimbraPortugal
  7. 7.Institute of Nuclear Sciences Applied to Health (ICNAS), CiBIT, Brain Imaging Network of PortugalUniversity of CoimbraCoimbraPortugal

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