Brain glutathione and GABA+ levels in autistic children

Author:

Song Yulu12ORCID,Hupfeld Kathleen E.12,Davies‐Jenkins Christopher W.12,Zöllner Helge J.12,Murali‐Manohar Saipavitra12,Mumuni Abdul Nashirudeen3ORCID,Crocetti Deana4,Yedavalli Vivek1,Oeltzschner Georg12,Alessi Natalie4,Batschelett Mitchell A.4,Puts Nicolaas A. J.56,Mostofsky Stewart H.478,Edden Richard A. E.12

Affiliation:

1. The Russel H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore Maryland USA

2. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute Baltimore Maryland USA

3. Department of Medical Imaging University for Development Studies Tamale Ghana

4. Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute Baltimore Maryland USA

5. Department of Forensic and Neurodevelopmental Sciences Institute of Psychiatry, Psychology, and Neuroscience, King's College London London UK

6. MRC Center for Neurodevelopmental Disorders, King's College London London UK

7. Department of Neurology The Johns Hopkins University School of Medicine Baltimore Maryland USA

8. Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore Maryland USA

Abstract

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Altered neurometabolite levels, including glutathione (GSH) and gamma‐aminobutyric acid (GABA), have been proposed as potential contributors to the biology underlying ASD. This study investigated whether cerebral GSH or GABA levels differ between a cohort of children aged 8–12 years with ASD (n = 52) and typically developing children (TDC, n = 49). A comprehensive analysis of GSH and GABA levels in multiple brain regions, including the primary motor cortex (SM1), thalamus (Thal), medial prefrontal cortex (mPFC), and supplementary motor area (SMA), was conducted using single‐voxel HERMES MR spectroscopy at 3T. The results revealed no significant differences in cerebral GSH or GABA levels between the ASD and TDC groups across all examined regions. These findings suggest that the concentrations of GSH (an important antioxidant and neuromodulator) and GABA (a major inhibitory neurotransmitter) do not exhibit marked alterations in children with ASD compared to TDC. A statistically significant positive correlation was observed between GABA levels in the SM1 and Thal regions with ADHD inattention scores. No significant correlation was found between metabolite levels and hyper/impulsive scores of ADHD, measures of core ASD symptoms (ADOS‐2, SRS‐P) or adaptive behavior (ABAS‐2). While both GSH and GABA have been implicated in various neurological disorders, the current study provides valuable insights into the specific context of ASD and highlights the need for further research to explore other neurochemical alterations that may contribute to the pathophysiology of this complex disorder.

Funder

National Institute of Health Sciences

Publisher

Wiley

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