6533b828fe1ef96bd128867c

RESEARCH PRODUCT

1H-NMR-Based Metabolomics in Autism Spectrum Disorder and Pediatric Acute-Onset Neuropsychiatric Syndrome

Antonella GaglianoFederica MurgiaAgata Maria CapodiferroMarcello Giuseppe TancaAran HendrenStella Giulia FalquiMichela ArestiMartina CominiSara CarucciEleonora Cocco 2Lorena LoreficeMichele RoccellaLuigi VetriStefano SotgiuAlessandro ZuddasLuigi Atzori

subject

autism spectrum disorderGeneral Medicinebiomarkers’ evaluationpediatric acute-onset neuropsychiatric syndromepathways analysisSettore MED/39 - Neuropsichiatria Infantileautism spectrum disorder; pediatric acute-onset neuropsychiatric syndrome; metabolomics; biomarkers’ evaluation; pathways analysismetabolomic

description

We recently described a unique plasma metabolite profile in subjects with pediatric acute-onset neuropsychiatric syndrome (PANS), suggesting pathogenic models involving specific patterns of neurotransmission, neuroinflammation, and oxidative stress. Here, we extend the analysis to a group of patients with autism spectrum disorder (ASD), as a consensus has recently emerged around its immune-mediated pathophysiology with a widespread involvement of brain networks. This observational case-control study enrolled patients referred for PANS and ASD from June 2019 to May 2020, as well as neurotypical age and gender-matched control subjects. Thirty-four PANS outpatients, fifteen ASD outpatients, and twenty-five neurotypical subjects underwent physical and neuropsychiatric evaluations, alongside serum metabolomic analysis with 1H-NMR. In supervised models, the metabolomic profile of ASD was significantly different from controls (p = 0.0001), with skewed concentrations of asparagine, aspartate, betaine, glycine, lactate, glucose, and pyruvate. Metabolomic separation was also observed between PANS and ASD subjects (p = 0.02), with differences in the concentrations of arginine, aspartate, betaine, choline, creatine phosphate, glycine, pyruvate, and tryptophan. We confirmed a unique serum metabolomic profile of PANS compared with both ASD and neurotypical subjects, distinguishing PANS as a pathophysiological entity per se. Tryptophan and glycine appear as neuroinflammatory fingerprints of PANS and ASD, respectively. In particular, a reduction in glycine would primarily affect NMDA-R excitatory tone, overall impairing downstream glutamatergic, dopaminergic, and GABAergic transmissions. Nonetheless, we found metabolomic similarities between PANS and ASD that suggest a putative role of N-methyl-D-aspartate receptor (NMDA-R) dysfunction in both disorders. Metabolomics-based approaches could contribute to the identification of novel ASD and PANS biomarkers.

10.3390/jcm11216493https://dx.doi.org/10.3390/jcm11216493