Linkage of kynurenine pathway metabolites to neuroinflammation in drug-naive children with attention-deficit/hyperactivity disorder: A cross-sectional, case-control study

World J Clin Pediatr. 2026 Jun 9;15(2):115284. doi: 10.5409/wjcp.v15.i2.115284. eCollection 2026 Jun 9.

ABSTRACT

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder that causes psychological, social, academic, and occupational impairments. Despite numerous studies, its etiopathogenesis remains incompletely understood.

AIM: To compare serum kynurenine pathway (KP) metabolite levels and metabolite ratios between drug-naive children with ADHD and healthy controls.

METHODS: The study included 51 drug-naive children with ADHD and 36 age- and gender-matched healthy controls. Serum tryptophan, kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) levels were measured. Ratios reflecting the activities of KP enzymes, namely KYN/tryptophan, KYNA/KYN, and QUIN/KYN, were measured, and the neurotoxic (QUIN/KYNA) and neuroprotective (KYNA/QUIN) indices were calculated.

RESULTS: Compared with controls, serum KYNA levels and the KYNA/QUIN ratio (neuroprotective index) were significantly lower in the ADHD group, while the QUIN/KYNA ratio (neurotoxic index) was significantly higher (P = 0.023, 0.025, and 0.029, respectively). There were no significant differences between groups in other KP metabolites or their ratios (P > 0.05).

CONCLUSION: These findings support the hypothesis that neuroinflammatory imbalance in the KP contributes to the pathogenesis of ADHD and highlight the importance of new biomarkers for the development of targeted therapies.

PMID:42220958 | PMC:PMC13217210 | DOI:10.5409/wjcp.v15.i2.115284