Peripheral Nitrosative Stress in Pediatric Anxiety Disorders: Elevated Serum Nitric Oxide Levels

Background: The developing pediatric brain is vulnerable to nitrosative stress. This study investigated serum nitric oxide (NO), inducible nitric oxide synthase (iNOS), and S-nitrosothiols (SNOs) as peripheral biomarkers in children with anxiety disorders (ADs) and their associations with symptom severity.

Methods: Eighty-one participants aged 7-17 years were enrolled, including 40 drug-naive participants with ADs and 41 age- and sex-matched healthy controls (HCs). Diagnoses were established using the Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version, DSM-5— Turkish version (K-SADS-PL-DSM-5-T). Symptom severity was assessed using the Screen for Child Anxiety Related Emotional Disorders (SCARED) and the Clinical Global Impression–Severity (CGI-S) Scale. Data were analyzed using between-group comparisons, correlation analyses, covariance analyses (MANCOVA/ ANCOVA), controlling for age, sex, and body mass index (BMI), and receiver operating characteristic (ROC) analysis.

Results: Serum NO levels were significantly higher in the AD group compared with HCs (P = .028), whereas iNOS and SNO levels did not differ (P > .05). In adjusted analyses controlling for age, sex, and BMI, NO remained significantly higher, and iNOS and SNO levels were also significantly higher in the AD group. No marker (NO, iNOS, SNOs) correlated significantly with anxiety severity (all P > .05). Receiver operating characteristic analysis indicated modest diagnostic accuracy for NO (area under the curve (AUC) = 0.629, 95% CI: 0.506-0.752, P = .046), while iNOS and SNOs were not significant.

Conclusion: Elevated NO, alongside adjusted increases in iNOS and SNO, supports altered peripheral nitrosative signaling in pediatric ADs. Nitric oxide showed modest discriminative value.

Cite this article as: Okuyucu M, Ceylan MF, Hesapçıoğlu ST, Kafalı S, Neşelioğlu S, Erel Ö. Peripheral nitrosative stress in pediatric anxiety disorders: elevated serum nitric oxide levels. Eurasian J Med. 2026, 58(4), 1235, doi:10.5152/eurasianjmed.2026.251235.