Differential One-carbon metabolites among children with autism spectrum disorder: A case-control study.

ABSTRACT

BACKGROUND: Driven by the complex multifactorial etiopathogenesis of autism spectrum disorder (ASD), a growing interest surrounds the disturbance in folate-dependent one-carbon metabolism (OCM) in the pathology of ASD, while the evidence remained inconclusive. OBJECTIVE: The study aims to investigate the association of OCM metabolism and ASD and characterize differential OCM metabolites among children with ASD. METHODS: Plasma OCM metabolites were investigated in 59 children with ASD and 40 neurotypical children using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS) technology. Differences (significance level< 0.001) were tested in each OCM metabolite between cases and controls. Multivariable models were also performed after adjusting for covariates. RESULTS: Ten out of 22 examined OCM metabolites were significantly different in children with ASD, compared to neurotypical controls. Specifically, S-adenosylmethionine (SAM), oxidized glutathione (GSSG), and glutathione (GSH) levels were increased, while S-adenosylhomocysteine (SAH), choline, glycine, L-serine, cystathionine, L-cysteine, and taurine levels were significantly decreased. Children with ASD showed significantly higher SAM /SAH ratio (3.87±0.93 vs. 2.00±0.76, p=0.0001) and lower GSH/GSSG ratio (0.58 (0.46, 0.81) vs. 1.71 (0.93, 2.99)) compared with the neurotypical controls. Potential interactive effects between SAM/SAH ratio, taurine, L-serine and gastrointestinal syndromes were further observed. CONCLUSION: OCM disturbance was observed among children with ASD, particularly in methionine methylation and trans-sulfuration pathways. The findings add valuable insights into the mechanisms underlying ASD and the potential of ameliorating OCM as a promising therapeutic of ASD, which warrant further validation.