Baseline serum oxytocin and OXTR rs53576 genotype are not predictive of escitalopram response in generalized anxiety disorder

The oxytocin system is implicated in the pathophysiology of generalized anxiety disorder (GAD). However, its utility in predicting treatment outcomes with first-line antidepressants, such as escitalopram, remains unexplored. This study aimed to investigate whether baseline serum oxytocin levels and the oxytocin receptor gene polymorphism OXTR rs53576 can predict escitalopram response in patients with first-episode GAD. This prospective cohort study enrolled 60 drug-naïve patients with first-episode GAD and 60 age- and sex-matched healthy controls. Serum oxytocin levels were measured using enzyme-linked immunosorbent assay, and the OXTR rs53576 genotype was determined using TaqMan SNP Genotyping Assays. The patients received escitalopram monotherapy (10-20 mg/day). Anxiety severity was assessed using the Hamilton Anxiety Scale at baseline and weeks 2, 4, and 8. Treatment response was defined as a ≥ 50% reduction in Hamilton Anxiety Scale score. At baseline, patients with GAD had significantly higher oxytocin levels than healthy controls (147.99 ± 99.07 pg/ml vs. 76.86 ± 96.07 pg/ml, p < 0.001) and a higher prevalence of OXTR rs53576 AA genotype (71.67% vs. 25.00%, p < 0.001). Multiple linear regression analysis revealed that both higher oxytocin levels (p < 0.001) and the AA genotype (p < 0.001) were independently associated with greater baseline anxiety severity. However, after 8 weeks of treatment, neither baseline oxytocin levels nor the OXTR rs53576 genotype predicted treatment response at any time point (all p > 0.05). While the oxytocin system is dysregulated in GAD, baseline serum oxytocin and OXTR rs53576 genotypes are not clinically useful biomarkers for predicting short-term responses to escitalopram. This finding refines the search for predictive tools for personalized anxiety treatment.