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. 2025 Jul;15(7):e70645.
doi: 10.1002/brb3.70645.

Serum Nox1 and Gper Levels in Patients With Generalized Anxiety Disorder: A Cross-Sectional Study in Turkiye

Onur Hurşitoğlu  1 , Ergül Belge Kurutaş  2 , Ömer Faruk Uygur  3 , Nurinnisa Ozturk  4 , Hilal Uygur  5 , Fatih Saglam  6 , Rebecca Strawbridge  7
Affiliations

Serum Nox1 and Gper Levels in Patients With Generalized Anxiety Disorder: A Cross-Sectional Study in Turkiye

Onur Hurşitoğlu et al. Brain Behav. 2025 Jul.

Abstract

Purpose: Although the etiopathogenesis of generalized anxiety disorder (GAD) is not fully known, it is suggested that oxidative stress (OS) and estrogen play important roles. NADPH oxidase 1 (NOX1) is from the NADPH oxidase (NOX) family, which is known as a main source of reactive oxygen species (ROS). The G protein-coupled estrogen receptor (GPER) is a novel estrogen receptor that mediates the non-genomic rapid effects of estrogen. Recent work has shown GPER to be associated with OS, but it has not to our knowledge been examined in patient samples with GAD.

Method: We conducted a study comparing serum NOX1 and GPER levels of patients with GAD and healthy controls (HCs) matched for age, sex, and body mass index (BMI).

Finding: We found increased NOX1 and decreased GPER levels in patients with GAD compared with HCs. In addition, we showed that serum NOX1 levels have very good diagnostic performance for patients with GAD. We observed a weak positive correlation between serum NOX1 levels and GPER levels in the patient group.

Conclusion: Although we believe these results are important for a better understanding of the role of OS and estrogen in GAD patients, longitudinal studies should be performed in larger samples of GAD patients grouped by severity of symptoms.We investigated the levels of NOX1 and GPER in patients with GAD. We found increased NOX1 and decreased GPER levels in patients with GAD compared to healthy controls. In addition, we showed that serum NOX1 levels have very good diagnostic performance for patients with GAD.

Keywords: ERα; ERβ; biomarker; estrogen; oxidative stress; reactive oxygen species.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Boox plot graph for NADPH oxidase 1 (NOX1), representing highest, lowest, and mean values in both groups.
FIGURE 2
FIGURE 2
The relationship between NOX1‐HAM‐A and GPER‐HAM‐A in GAD patients and HCs.
FIGURE 3
FIGURE 3
ROC curve for NOX1 (Sensitivity, 100%; Specificity, 98.2%; AUC was 1.00 for NOX1, The cut‐off point was detected as 5.45 ng/mL. NOX1 NADPH oxidase 1; AUC, area under the curve; ROC, receiver operating characteristic).
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