Urinary Metabolomic Study in a Healthy Children Population and Metabolic Biomarker Discovery of Attention-Deficit/Hyperactivity Disorder (ADHD)

Abstract

ObjectivesKnowledge of the urinary metabolomic profiles of healthy children and adolescents plays a promising role in the field of pediatrics. Metabolomics has also been used to diagnose disease, discover novel biomarkers, and elucidate pathophysiological pathways. Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in childhood. However, large-sample urinary metabolomic studies in children with ADHD are relatively rare. In this study, we aimed to identify specific biomarkers for ADHD diagnosis in children and adolescents by urinary metabolomic profiling.MethodsWe explored the urine metabolome in 363 healthy children aged 1–18 years and 76 patients with ADHD using high-resolution mass spectrometry.ResultsMetabolic pathways, such as arachidonic acid metabolism, steroid hormone biosynthesis, and catecholamine biosynthesis, were found to be related to sex and age in healthy children. The urinary metabolites displaying the largest differences between patients with ADHD and healthy controls belonged to the tyrosine, leucine, and fatty acid metabolic pathways. A metabolite panel consisting of FAPy-adenine, 3-methylazelaic acid, and phenylacetylglutamine was discovered to have good predictive ability for ADHD, with a receiver operating characteristic area under the curve (ROC–AUC) of 0.918. A panel of FAPy-adenine, N-acetylaspartylglutamic acid, dopamine 4-sulfate, aminocaproic acid, and asparaginyl-leucine was used to establish a robust model for ADHD comorbid tic disorders and controls with an AUC of 0.918.

Serum metabolome indicators of early childhood development in the Brazilian National Survey on Child Nutrition (ENANI-2019)

“…The age-dependent associations observed in our study are consistent with the age-related changes in metabolic profile reported by previous studies (Chiu et al, 2016; Gu et al, 2009; Psihogios et al, 2008; Tian et al, 2022). Increased urinary TMAO and betaine levels were found in children aged six months, whereas creatine and Crtn levels increased significantly after six months (Chiu et al, 2016).…”

“…As circulating concentrations of the essential amino acid, phenylalanine, were not directly associated with DQ in our study, this suggests that differences in gut microbiome composition impacting PAG formation among children are likely a major determinant of DQ rather than dietary protein intake. Similarly to our findings, a previous study involving 76 patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and 363 healthy children aged 1–18 years identified an inverse relationship between urinary PAG and ADHD (Tian et al, 2022). While the specific pathways contributing to such disorders remain to be fully elucidated, it is known that PAG is structurally similar to catecholamines and can activate adrenergic receptors (Huynh, 2020).…”

Translational bioinformatics and data science for biomarker discovery in mental health: an analytical review

“…[ 101 ] linked 11 plasma metabolites to ASD outcomes, revealing disturbances in one-carbon metabolism and the tricarboxylic acid cycle. Tian et al ’s [ 102 ] ADHD study identified differentially changed metabolites including FAPy-adenine and dopamine 4-sulfate. Karabatsiakis et al ’s [ 103 ] PTSD research found 13 significant metabolite changes including glycerophospholipids and an endocannabinoid signaling metabolite.…”

A new type of sulfation reaction: C-sulfonation for α,β-unsaturated carbonyl groups by a novel sulfotransferase SULT7A1

“…In addition to its role in the “chemical defense” of living cells, sulfonation, as mediated by SULTs, plays a key role in maintaining the homeostasis of endogenous compounds, such as catecholamine hormones/neurotransmitters and thyroid/steroid hormones ( 4 , 5 ). Sulfonated metabolites of endogenous compounds, such as dopamine sulfate and cholesterol sulfate, have been emerging as potential biomarkers for disorders in hormone metabolism and other pathophysiological conditions ( 6 , 7 ). Thus, elucidating the physiological role of SULT-mediated sulfonation is an increasingly important issue.…”