In vivo brain frontal and occipital glutathione levels are unchanged in autistic adults

Abstract

Background The neurobiological underpinnings of Autism Spectrum Disorder (ASD) are diverse and likely multifactorial. One possible mechanism is increased oxidative stress leading to altered neurodevelopment and brain function. However, this hypothesis has mostly been tested in post-mortem studies. So far, available in vivo studies in autistic individuals have reported no differences in glutathione (GSH) levels in frontal, occipital, and subcortical regions. However, these studies were limited by the technically challenging quantification of GSH, the main brain antioxidant molecule. This study aimed to overcome previous studies limitations by using GSH-tailored spectroscopy sequences and optimised quantification methodology to provide clarity on GSH levels in autistic adults. Methods We used spectral editing proton-magnetic resonance spectroscopy (1H-MRS) combined with linear combination model fitting to quantify GSH in the dorsomedial prefrontal cortex (DMPFC) and medial occipital cortex (mOCC) of autistic and non-autistic adults (male and female). We compared GSH levels between groups, also considering biological sex effects. We also examined correlations between GSH and current autism symptoms, measured using the Autism Quotient (AQ). Results Data were available from 31 adult autistic participants (24 males, 7 females) and 40 non-autistic participants (21 males, 16 females); the largest sample to date. The GSH levels did not differ between groups in either region. No biological sex-effects or correlations with AQ were observed. Limitations : Our study was limited to two brain regions, but GSH levels may be altered in other regions. Additionally, we do not know if our findings generalise to other cohorts (e.g. those with intellectual disability or epilepsy). Oxidative stress can be captured more comprehensively through the ratio of GSH to glutathione disulphide (GSSG), however GSSG concentration is not detectable with 1H-MRS, thus we cannot rule out the possibility that GSSG levels, and consequently GSH/GSSG ratios were altered in this ASD cohort. Conclusions GSH levels as measured using 1H-MRS are unaltered in the DMPFC and mOCC regions of autistic adults, suggesting that oxidative stress in these cortical regions is not a marked neurobiological signature of ASD.