U-shaped association between serum hs-CRP and medication status in acute-phase major depressive disorder

To investigate the correlation and potential non-linear relationship between serum high-sensitivity C-reactive protein (hs-CRP) levels and medication status in patients with acute-phase major depressive disorder (MDD). This single-center retrospective cross-sectional study included 492 acute-phase MDD inpatients (2020–2025). Patients were classified as medicated ( n = 355) or unmedicated ( n = 137) based on antipsychotic, antidepressant, or sedative-hypnotic use at admission. Sociodemographic data, duration of MDD, and biochemical parameters (hs-CRP, blood count, glucose-lipid metabolism, and thyroid function) were collected. Multivariable logistic regression was used to assess the hs-CRP–medication status association. Generalized additive model-based smooth curve fitting and piecewise regression were employed to detect nonlinearity and threshold effects, with subgroup analyses stratified by sex, age, duration of MDD, diabetes, and hypertension. Among the 492 participants, 114 (23.2%) were male and 378 (76.8%) were female, with a mean age of 53.15 ± 19.45 years and a median duration of MDD of 6 years. The unmedicated group had significantly lower hs‑CRP levels than the medicated group (median 0.83 vs. 1.13 mg/L, p = 0.04, Cohen’s d = 0.30). In multivariable logistic regression, each 1.0 mg/L increase in hs‑CRP was associated with an 18% increase in the odds of current medication use (OR = 1.18, 95% CI: 1.00–1.38, p = 0.048). Smooth curve fitting revealed a U‑shaped nonlinear association between hs‑CRP and medication status (P for nonlinearity = 0.04), with a turning point at 0.79 mg/L. Below this threshold, each 0.1 mg/L increment in hs‑CRP was associated with 17% lower odds of being on medication (OR = 0.83, 95% CI: 0.72–0.95, p = 0.007); at or above 0.79 mg/L, each 1.0 mg/L increase corresponded to 172% higher odds of current pharmacotherapy (OR = 2.72, 95% CI: 1.11–6.65, p = 0.03). Subgroup analyses yielded consistent directional findings across all strata (all interaction p > 0.05). A U-shaped non-linear association exists between serum hs-CRP levels and medication status in patients with acute-phase MDD, with 0.79 mg/L identified as a exploratory turning point. Below the turning point of 0.79 mg/L, higher hs-CRP levels were associated with a reduced likelihood of being on medication; above this point, higher hs-CRP levels were associated with an increased likelihood of being on medication.