Association between C-reactive protein and depression among alcohol users in the United States: A population-based analysis of National Health and Nutrition Examination Survey (NHANES) 2015-2020.

BACKGROUND

Inflammation and alcohol use are linked to depression, but whether their effects are independent or interactive remains unclear.

OBJECTIVE

To examine inflammation as an independent correlate of depression among U.S. adults who consume alcohol and a modifier of the alcohol-depression association.

METHODS

Cross-sectional analysis of NHANES 2015-2020 including adults aged ≥18 reporting past-year alcohol use(n = 3019). Depression was assessed using the PHQ-9, with scores categorized as no depression(0), minimal(1-4), mild(5-9), and moderate-severe(10-27). Inflammation was measured using high-sensitivity CRP, categorized as low(≤1 mg/L), average(1-3 mg/L), and high(>3 mg/L). Alcohol use was classified as light, moderate, or heavy based on drinks/week and binge frequency. Modified Poisson regression with robust variance estimated prevalence ratios for depressive symptoms across CRP levels, adjusting for covariates (alcohol severity, age, sex, race/ethnicity, income, BMI, smoking, physical activity, sleep, comorbidities, drug use). Survey-weighted GLM models tested CRP-alcohol interactions.

RESULTS

High CRP was associated with 13% higher mild and 22% higher moderate-severe depression prevalence (p < 0.0001) vs. low CRP. CRP-alcohol interactions were statistically significant with high CRP associated with increased depression prevalence among light drinkers (PR = 1.06,95% CI:1.05-1.07) and moderate drinkers (PR = 1.03,95% CI:1.01-1.04). Among heavy drinkers, high CRP showed an 8.2% increase, not statistically significant, likely due to limited power and dilution by acute inflammation. Sensitivity analyses excluding CRP >10 mg/L showed stronger effects (6-11% increase); high CRP × heavy drinking became significant (PR = 1.11,95% CI:1.05-1.18, p < 0.0001).

CONCLUSION

CRP was associated with higher depression and modified alcohol-depression associations. Inflammation amplified depression risk across drinking levels.