2026 ECNP Congress

PS04-4149

Rethinking inflammation in attention-deficit/hyperactivity disorder: decreased neutrophil gelatinase-associated lipocalin and tumor necrosis factor-alpha levels in a pediatric sample

Gözdenur Bozkurt Ünal — H. Ayraler Taner, B. Akın Sarı, D. Kaba, E.S. Türkoğlu, H.E. Özturan Özer, M. Yavuz Çolak · Başkent University Faculty of Medicine, Child and Adolescent Psychiatry, Ankara, Türkiye

2026 ECNP Congress

Introduction

Evidence from human and animal studies suggests a potential role of neuroinflammation in the pathophysiology of attention-deficit/hyperactivity disorder(ADHD),with inflammatory cytokines such as IL-6, IL-1β, and TNF-α implicated in its etiology [1,2]. Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein involved in immune processes and originally identified in neutrophils [3], has emerged as a potential biomarker in psychiatric disorders. Experimental studies in NGAL-null mice have demonstrated anxiety- and depression-like behaviors and cognitive impairments [4]. However, NGAL has not yet been investigated in ADHD.

This study aimed to investigate whether NGAL and TNF-α levels play a role in the etiology of the disorder by comparing their levels in treatment-naive children with ADHD and healthy controls.

Methods

The study included 128 children aged 6–12 years (64 with ADHD diagnosed according to DSM-5 and 64 healthy controls). Diagnoses were established using the Turkish version of the K-SADS-PL, and parents completed the Conners Parent Rating Scale. Participants were treatment-naive for at least 6 months, and those with comorbid psychiatric, neurological, genetic, or chronic systemic diseases, or extreme BMI percentiles (<5th or >95th), were excluded.

Venous blood samples were collected without fasting requirements and samples were allowed to clot for 15 minutes at room temperature,centrifuged at 2000-3000 rpm for 20 minutes and serum was aliquoted stored at −80°C until analysis. Serum NGAL and TNF-α levels were measured using ELISA kits; neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) were also assessed. Statistical analyses were performed using IBM SPSS Statistics version 25.0, with p < 0.05 considered significant.

Results

There is no statistically significant difference in neutrophil count or the neutrophil-to-lymphocyte ratio in children diagnosed with ADHD compared with the healthy control group. Serum NGAL and TNF-α levels were significantly lower in children with ADHD compared to healthy controls (NGAL: 120.33 ± 88.65 vs. 146.91 ± 99.05, p = 0.009; TNF-α: 184.07 ± 173.84 vs. 201.16 ± 163.95, p = 0.025). NGAL and TNF-α levels were strongly correlated with each other (r = 0.697, p < 0.001) and showed negative correlations with ADHD symptom severity (NGAL: r = -0.203, p = 0.021; TNF-α: r = -0.205, p = 0.021).

Conclusion

Serum NGAL and TNF-α levels were significantly lower in treatment-naive children with ADHD and were inversely associated with symptom severity. Although previous studies have focused on ADHD and pro-inflammatory processes, recent studies suggest that there are changes in inflammatory processes in ADHD, as evidenced by specific symptoms [5]. As the first study to examine NGAL in pediatric ADHD, this work adds novel evidence to the emerging literature on neuroimmune mechanisms in the disorder. Future research should also explore whether these biomarkers can serve as potential diagnostic or prognostic indicators and whether they may inform individualized treatment approaches in pediatric ADHD. Further longitudinal and mechanistic studies are needed to clarify the underlying pathways and clinical implications.

References

  1. . Leffa DT, Bellaver B, de Oliveira C, de Macedo IC, de Freitas JS, Grevet EH, et al. Increased oxidative parameters and decreased cytokine levels in an animal model of attention-deficit/hyperactivity disorder. Neurochem Res. 2017;42(11):3084–3092. https://doi.org/10.1007/s11064-017-2341-6
  2. . Leffa DT, Torres ILS, Rohde LA. A review on the role of inflammation in attention-deficit/hyperactivity disorder. Neuroimmunomodulation. 2019;25(5-6):328–333. https://doi.org/10.1159/000489635
  3. . Abella V, Scotece M, Conde J, Pino J, Gonzalez-Gay MA, Gómez-Reino JJ, et al. The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases. Biomarkers. 2015;20(8):565–571. https://doi.org/10.3109/1354750X.2015.1123354
  4. . Ferreira AC, Pinto V, Da Mesquita S, Novais A, Sousa JC, Correia-Neves M, et al. Lipocalin-2 is involved in emotional behaviors and cognitive function. Front Cell Neurosci. 2013;7:122. https://doi.org/10.3389/fncel.2013.00122
  5. Schnorr, I., Siegl, A., Luckhardt, S., Wenz, S., Friedrichsen, H., El Jomaa, H., Steinmann, A., Kilencz, T., Arteaga-Henríquez, G., Ramos-Sayalero, C., Ibanez-Jimenez, P., Rosales-Ortiz, S. K., Bitter, I., Fadeuilhe, C., Ferrer, M., Lavebratt, C., Réthelyi, J. M., Richarte, V., Rommelse, N., Ramos-Quiroga, J. A., … Schiweck, C. (2024). Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome. Translational psychiatry, 14(1), 37. https://doi.org/10.1038/s41398-023-02729-3