The study shows that people with generalized anxiety have higher blood levels of the hormone oxytocin, especially women, and that a common genetic variation (OXTR rs2254298) predicts who will respond less well to the antidepressant escitalopram. The effect is different between men and women, suggesting a sex‑specific role of oxytocin signaling in anxiety treatment.

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. 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. Baseline serum OT levels were significantly elevated in GAD patients compared to HCs (126.28 &#xb1; 88.41 vs. 92.77 &#xb1; 47.51 pg/mL, p = 0.006), a difference that was primarily driven by female patients (<i>p</i> = 0.037). OT levels were positively correlated with baseline HAMA scores (<i>r</i> = 0.197, <i>p</i> = 0.008). After 8 weeks of treatment, the OXTR rs2254298 genotype distribution significantly differed between treatment responders and non-responders (<i>p</i> = 0.049), with GG homozygotes showing a lower response rate. 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.