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

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.

The ontogeny of limbs movements towards midline in healthy infants born at term.

BACKGROUND: Movements towards midline are part of the age-adequate motor repertoire of infants. They develop contemporaneously to general movements, changing from occasional simple contact to proper midline motor patterns. AIM: The aim of this study is to describe the ontogeny of movements towards midline in full term healthy infants. STUDY DESIGN: Parents were asked to record their infant every second week, from term age to 22 weeks post-term. SUBJECTS: 25 healthy full-term infants. RESULTS: Three main epochs of development were detected: in the first one, between birth and 4 weeks post-term, movements towards midline were occasional, apparently due to the dominant flexed posture of elbow and knees and the adducted posture of shoulders and hips. In the second epoch, from 4 to 8 weeks, the limbs movements towards midline markedly decreased. In the third one, after 8 weeks, movements towards midline increased again in frequency, first appearing in lower limbs then in upper limbs, first solely as contact and thereafter as manipulation. A temporal overlapping with the occurrence of intermittent or continual fidgety movements was detected. CONCLUSIONS: Movements towards midline progressively change, through a defined timeline, in full term healthy infants. The increased knowledge about the normal age-adequate motor repertoire can help physicians in clinical assessment of high risk infants.