Abstract
OBJECTIVE: To examine serum neuropeptide Y (NPY) levels and appetite changes in major depressive disorder (MDD) patients by sex and reproductive aging. METHODS: A total of 210 MDD were divided into male (n = 65), premenopausal women (n = 80), and postmenopausal women (n = 65) groups. Serum NPY levels were measured using ELISA, appetite changes were assessed with a visual analog scale (VAS), and depression severity was evaluated with the 17-item Hamilton Depression Rating Scale (HDRS-17). One-way ANOVA with post-hoc tests and stratified regression models were used to compare NPY levels and analyze the association between NPY and appetite changes across groups. RESULTS: One-way ANOVA showed significant group differences in serum NPY levels. Premenopausal women’NPY levels (280.80±35.50 pg/mL) were significantly higher than those of men (Δ = 30.30, p = 0.007) and postmenopausal women (Δ = 28.70, p = 0.009), whereas there is no difference between postmenopausal women and males (Δ = 1.60, p = 0.989). Similar group differences were observed for VAS scores. NPY was positively correlated with VAS scores, and the strength of this association differed across sex and reproductive aging groups: in the overall population, NPY is positively correlated with the VAS score (r = 0.422→0.437 after controlling for depression severity, p < 0.001), with the strongest association in premenopausal women (β = 0.027, p < 0.001), followed by males (β = 0.012, p = 0.017), and the weakest in postmenopausal women (β = 0.007, p = 0.021). CONCLUSION: Significant sex and reproductive aging differences exist in serum NPY levels, which are associated with appetite changes in MDD, particularly in premenopausal women, suggesting potential implications for individualized clinical consideration. However, without a healthy control group, it remains unclear whether these findings are specific to depression or reflect general population differences. CLINICAL TRIAL NUMBER: Not applicable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-025-07753-9.