Nonlinear Association Between NHHR and Suicide Attempts in First-Episode Untreated Depression With a Threshold Effect

To investigate, with an emphasis on possible nonlinearity, the relationship between suicide attempts (SAs) and the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) in patients with first-episode untreated (FEU) major depressive disorder (MDD).

A total of 1718 FEU MDD were included in this cross-sectional study. NHHR was calculated from the fasting lipid profiles. Multivariable logistic regression was used to assess the independent association between the NHHR and SA across the three adjusted models. Restricted cubic splines (RCSs) and two-piecewise logistic regression were applied to characterize the dose-response relationship and identify the inflection point.

SA occurred in 346 (20.1%) patients. SA prevalence increased progressively across the NHHR tertiles: 10.82% (T1), 17.13% (T2), and 32.46% (T3) (p < 0.001). Higher SA risk was independently linked to each unit increase in NHHR in the fully adjusted model (OR = 1.08, 95% CI: 1.01-1.16). At NHHR = 5.76, a significant nonlinear threshold effect was found; below the limit, every unit increase in NHHR was associated with a 27% greater likelihood of SA (OR = 1.27, 95% CI: 1.12-1.43, p < 0.001), while outside the limits, no significant association emerged (OR = 0.85, p = 0.092).

NHHR was independently and nonlinearly associated with SA in patients with FEU MDD, with a clinically meaningful threshold of 5.76. As a readily available lipid-derived marker calculable from standard fasting panels, NHHR may serve as a practical tool for early suicide risk stratification in clinical settings.