IL-18 and NFE2L2/NRF2 in Adult ADHD: An Inflammation–Redox Framework for Salivary Biomarker Research
- 1Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania
- 2Sf. Spiridon County Clinical Emergency Hospital, 700111 Iasi, Romania
- 3Institute of Psychiatry Socola, 36 Bucium Street, 700282 Iasi, Romania
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder, and increasing evidence suggests that inflammatory and oxidative processes may contribute to its biological complexity. Despite these observations, no molecular biomarker has yet been established for clinical diagnosis. In this narrative review, we examine interleukin-18 (IL-18) and the NFE2L2/NRF2 antioxidant pathway as two potentially complementary components of the inflammation–redox landscape in adult ADHD, with particular attention to their possible assessment in saliva. For this purpose, we conducted a focused search of PubMed/MEDLINE, Scopus, and Web of Science, bringing together evidence from human ADHD studies, mechanistic and experimental research, and studies investigating the feasibility of salivary biomarkers. IL-18 is closely associated with inflammasome-mediated inflammatory signaling, whereas NFE2L2 encodes NRF2, a major regulator of antioxidant and cytoprotective responses. The evidence for these two targets in adult ADHD is not equally developed. Direct human data on IL-18 remain limited, while more recent studies have identified alterations in NRF2-related antioxidant defenses in adults with ADHD. Both IL-18 and NRF2 can be measured in human saliva, although the available evidence comes from clinical populations other than ADHD. Their detection in saliva therefore demonstrates analytical feasibility but does not establish their validity as ADHD biomarkers. At present, neither marker has been validated in the saliva of adults with ADHD. Studying them together may nevertheless provide a useful way to explore the relationship between inflammatory activity and antioxidant regulation. Future studies will require standardized saliva collection, careful assessment of oral health, and characterization of systemic inflammatory and metabolic conditions, medication use, and smoking. Initial studies should also include paired saliva and blood samples to determine how salivary measurements relate to circulating levels and whether they capture biologically meaningful variation in adult ADHD.
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BibTeX
@article{hurjui2026il18,
title = {{IL-18 and NFE2L2/NRF2 in Adult ADHD: An Inflammation–Redox Framework for Salivary Biomarker Research}},
author = {Ion Andrei Hurjui and Ionela Lacramioara Serban and Loredana Liliana Hurjui and Raluca Jipu and Ion Hurjui and Daniela Maria Tanase and Cristina Claudia Tarniceriu and Carina Balcos and Irina Dobrin and Romeo Petru Dobrin},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219732},
url = {https://www.mdpi.com/1422-0067/27/21/9732},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - IL-18 and NFE2L2/NRF2 in Adult ADHD: An Inflammation–Redox Framework for Salivary Biomarker Research
AU - Ion Andrei Hurjui
AU - Ionela Lacramioara Serban
AU - Loredana Liliana Hurjui
AU - Raluca Jipu
AU - Ion Hurjui
AU - Daniela Maria Tanase
AU - Cristina Claudia Tarniceriu
AU - Carina Balcos
AU - Irina Dobrin
AU - Romeo Petru Dobrin
PY - 2026
DA - 2026/10/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219732
UR - https://www.mdpi.com/1422-0067/27/21/9732
AB - Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder, and increasing evidence suggests that inflammatory and oxidative processes may contribute to its biological complexity. Despite these observations, no molecular biomarker has yet been established for clinical diagnosis. In this narrative review, we examine interleukin-18 (IL-18) and the NFE2L2/NRF2 antioxidant pathway as two potentially complementary components of the inflammation–redox landscape in adult ADHD, with particular attention to their possible assessment in saliva. For this purpose, we conducted a focused search of PubMed/MEDLINE, Scopus, and Web of Science, bringing together evidence from human ADHD studies, mechanistic and experimental research, and studies investigating the feasibility of salivary biomarkers. IL-18 is closely associated with inflammasome-mediated inflammatory signaling, whereas NFE2L2 encodes NRF2, a major regulator of antioxidant and cytoprotective responses. The evidence for these two targets in adult ADHD is not equally developed. Direct human data on IL-18 remain limited, while more recent studies have identified alterations in NRF2-related antioxidant defenses in adults with ADHD. Both IL-18 and NRF2 can be measured in human saliva, although the available evidence comes from clinical populations other than ADHD. Their detection in saliva therefore demonstrates analytical feasibility but does not establish their validity as ADHD biomarkers. At present, neither marker has been validated in the saliva of adults with ADHD. Studying them together may nevertheless provide a useful way to explore the relationship between inflammatory activity and antioxidant regulation. Future studies will require standardized saliva collection, careful assessment of oral health, and characterization of systemic inflammatory and metabolic conditions, medication use, and smoking. Initial studies should also include paired saliva and blood samples to determine how salivary measurements relate to circulating levels and whether they capture biologically meaningful variation in adult ADHD.
SN - 1422-0067
ER -