Ünal K, Taş Torun Y, Erol ME, Özbaş C, Kurt ZK. 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; 15(2): 115284 [DOI: 10.5409/wjcp.v15.i2.115284]
Corresponding Author of This Article
Kübranur Ünal, MD, Associate Professor, Department of Medical Biochemistry, Gazi University, Faculty of Medicine, Emniyet, Gazi Hst., Yenimahalle, Ankara 06560, Türkiye. kubranurunal@gazi.edu.tr
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Psychology, Clinical
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Observational Study
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Jun 9, 2026 (publication date) through May 16, 2026
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World Journal of Clinical Pediatrics
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2219-2808
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Ünal K, Taş Torun Y, Erol ME, Özbaş C, Kurt ZK. 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; 15(2): 115284 [DOI: 10.5409/wjcp.v15.i2.115284]
World J Clin Pediatr. Jun 9, 2026; 15(2): 115284 Published online Jun 9, 2026. doi: 10.5409/wjcp.v15.i2.115284
Linkage of kynurenine pathway metabolites to neuroinflammation in drug-naive children with attention-deficit/hyperactivity disorder: A cross-sectional, case–control study
Kübranur Ünal, Yasemin Taş Torun, Mehmet Emre Erol, Cansu Özbaş, Zeynep Kübra Kurt
Kübranur Ünal, Department of Medical Biochemistry, Gazi University, Faculty of Medicine, Ankara 06560, Türkiye
Yasemin Taş Torun, Department of Child and Adolescent Mental Health and Diseases, Gazi University, Faculty of Medicine, Ankara 06560, Türkiye
Mehmet Emre Erol, Department of Medical Biochemistry, Gazi University, Institute of Health Sciences, Ankara 06560, Türkiye
Cansu Özbaş, Department of Public Health, Gazi University, Faculty of Medicine, Ankara 06560, Türkiye
Zeynep Kübra Kurt, Child Adolescent Psychiatric Clinic, Ankara Etlik City Hospital, Ankara 06170, Türkiye
Author contributions: Ünal K, Taş Torun Y, and Kurt ZK contributed to conceptualization, data acquisition and material preparation; Ünal K, Taş Torun Y, Kurt ZK, and Erol ME contributed to literature review; Özbaş C participated in formal analysis; Ünal K and Erol ME contributed to data interpretation and draft the original manuscript; Ünal K, Taş Torun Y, Erol ME, Özbaş C, and Kurt ZK revised and edited the manuscript. All authors have read and approved the final manuscript.
Institutional review board statement: The study was conducted in accordance with the principles of the Declaration of Helsinki and its later amendments. Ethical approval was obtained from the Clinical Research Ethics Committee of Gazi University (approval No. 025).
Informed consent statement: Written informed consent was obtained from the parents or legal guardians of all participating children. Additionally, age-appropriate verbal assent was obtained from the children enrolled in the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request. Due to ethical and privacy restrictions involving minors, raw datasets cannot be publicly shared.
Corresponding author: Kübranur Ünal, MD, Associate Professor, Department of Medical Biochemistry, Gazi University, Faculty of Medicine, Emniyet, Gazi Hst., Yenimahalle, Ankara 06560, Türkiye. kubranurunal@gazi.edu.tr
Received: October 15, 2025 Revised: December 2, 2025 Accepted: February 3, 2026 Published online: June 9, 2026 Processing time: 212 Days and 14.9 Hours
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.
Core Tip: This study examined the kynurenine pathway (KP) in drug-naive children with attention-deficit/hyperactivity disorder (ADHD), focusing on the balance between neuroprotective and neurotoxic metabolites. Serum kynurenic acid (KYNA) levels and the KYNA/quinolinic acid ratio were significantly lower in ADHD patients, while the neurotoxic quinolinic acid/KYNA ratio was higher compared to controls. These findings suggest an imbalance between excitotoxic and neuroprotective mechanisms and suggest that dysregulation of the KP may play a role in the pathophysiology of ADHD. Although diagnostic accuracy is low, the results highlight the potential of KP-derived indices as biomarkers of ADHD. Larger longitudinal studies will be necessary to determine causal relationships and assess the therapeutic modulation of KP activity.
