ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Psychopharmacology
OXTR rs2254298 polymorphism influences escitalopram response in Generalized Anxiety Disorder: a sex-specific role for oxytocin signaling
Provisionally accepted
- Third People's Hospital of Huzhou, Huzhou, China
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Objective: This study aimed to investigate whether the functional OXTR rs2254298 polymorphism moderates escitalopram response in Generalized Anxiety Disorder (GAD) through oxytocin (OT) neuroendocrine signaling, with specific consideration of sex-specific effects. Methods: 88 patients with GAD and 92 matched healthy controls (HCs) were enrolled. All participants underwent OXTR rs2254298 genotyping and baseline serum OT measurement. GAD patients then received 8 weeks of escitalopram monotherapy. Anxiety severity was assessed using the Hamilton Anxiety Scale (HAMA) at baseline and weeks 2, 4, and 8. Results: Baseline serum OT levels were significantly elevated in GAD patients compared to HCs (126.28 ± 88.41 vs. 92.77 ± 47.51 pg/mL, p = 0.006), a difference that was primarily driven by female patients (p = 0.037). OT levels were positively correlated with baseline HAMA scores (r = 0.197, p = 0.008). After 8 weeks of treatment, the OXTR rs2254298 genotype distribution significantly differed between treatment responders and non-responders (p = 0.049), with GG homozygotes showing a lower response rate. Conclusion: Our findings suggest that the OXTR rs2254298 polymorphism may influence escitalopram response in GAD via OT neuroendocrine mechanisms, exhibiting prominent sexual dimorphism. Integrating genetic profiling with endocrine biomarkers holds promise for personalizing anxiety treatment.
Keywords: generalized anxiety disorder, Oxytocin, OXTR gene, Pharmacogenetics, Sex, differences, treatment response, SSRI
Received: 03 Oct 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Liang, Fen and Hong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xue Liang, xl02087334067@126.com
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