Prognostic Nutritional Index and Post-Stroke Depression: Insights from a Cross-Sectional Analysis of NHANES 2005–2018 Data

• First national-representative analysis linking the Prognostic Nutritional Index (PNI) to post-stroke depression (PSD) via NHANES 2005–2018 data. • Higher PNI levels are independently associated with a reduced risk of PSD in stroke survivors. • Socioeconomic status (poverty-income ratio) modulates the protective effect of PNI on PSD. • PNI acts as a low-cost, clinically feasible biomarker for PSD risk screening in stroke populations. : The Prognostic Nutritional Index (PNI), a composite biomarker that integrates nutritional reserve (albumin) and immune competence (lymphocyte count), has demonstrated prognostic utility across diverse clinical settings. However, its association with post-stroke depression (PSD) remains insufficiently elucidated, particularly in nationally representative large-scale cohorts. : For this investigation, we obtained data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005–2018, a nationally representative cross-sectional survey. PNI was computed as 10 × serum albumin (g/dL) + 5 × total lymphocyte count (×10⁹/L). PSD was ascertained when participants had a Patient Health Questionnaire-9 (PHQ-9) score ≥10. Participants were categorized into quartiles according to their PNI values. Multivariable logistic regression (via three sequential models) and restricted cubic spline (RCS) analysis were employed to characterize the association between PNI and PSD. Subgroup and interaction analyses investigated potential heterogeneity across demographic subgroups (e.g., age, sex) and clinical subgroups (e.g., BMI, comorbidities). : Among 32,220 participants, 220 (0.7%) fulfilled diagnostic criteria for PSD. In the fully adjusted Model 3, continuous PNI exhibited an inverse association with the risk of PSD (OR = 0.95, 95% CI: 0.92–0.99, p = 0.009). Participants in the highest PNI quartile (Q4: 44.02–56.01) demonstrated a 55% reduction in PSD risk compared to those in the lowest quartile (Q1: 12.01–40.01; OR = 0.45, 95% CI: 0.27–0.76, p = 0.003). Restricted cubic spline analysis verified a linear relationship between PNI and PSD (p = 0.825 for non-linearity). Subgroup analysis demonstrated a significant interaction solely with the poverty-income ratio (PIR, p = 0.005), and no heterogeneity was observed in other strata (all p > 0.05). : PNI exhibits a significant inverse linear association with PSD risk, supporting its role as a clinically feasible marker for PSD risk stratification. The PNI–PIR interaction highlights the need to contextualize PNI within socioeconomic frameworks when interpreting its prognostic value in PSD.