Brain Glutathione and GABA+ levels in autistic children

Song, Y.; Hupfeld, K. E.; Davies-Jenkins, C. W.; Zöllner, H. J.; Murali-Manohar, S.; Abdul-Nashirudeen, M.; Crocetti, D.; Yedavalli, V.; Oeltzschner, G.; Alessi, N.; Batschelett, M. A.; Puts, N. A. J.; Mostofsky, S. H.; Edden, R. A. E.

doi:10.1101/2023.09.28.559718

bioRxiv · 10.1101/2023.09.28.559718

Brain Glutathione and GABA+ levels in autistic children

Song, Y.·Hupfeld, K. E.·Davies-Jenkins, C. W.·Zöllner, H. J.·Murali-Manohar, S.·Abdul-Nashirudeen, M.·Crocetti, D.·Yedavalli, V.·Oeltzschner, G.·Alessi, N.·Batschelett, M. A.·Puts, N. A. J.·Mostofsky, S. H.·Edden, R. A. E.

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Abstract

Autism 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 large 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. Lay summaryAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication challenges and repetitive behaviors. Altered glutathione (GSH, an important antioxidant and neuromodulator) and gamma-aminobutyric acid (GABA, a major inhibitory neurotransmitter) levels have been proposed as potential contributors to the biology underlying ASD. Here, we used advanced edited Magnetic Resonance Spectroscopy (MRS) to measure levels of these low-concentration metabolites in four brain regions of a pediatric cohort. Contrary to our hypothesis, no significant difference was found between ASD and control subjects in either GSH or GABA levels in any brain region.

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Song, Y., Hupfeld, K. E., Davies-Jenkins, C. W., Zöllner, H. J., Murali-Manohar, S., Abdul-Nashirudeen, M., Crocetti, D., Yedavalli, V., Oeltzschner, G., Alessi, N., Batschelett, M. A., Puts, N. A. J., Mostofsky, S. H., Edden, R. A. E.. 2023-09-29. Brain Glutathione and GABA+ levels in autistic children. https://doi.org/10.1101/2023.09.28.559718

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