Objective: Serum cholesterol was reported to be associated with depressed mood, but the studies conducted among household population are rare.

Methods: We used the data of 4115 men and 4275 women aged 18 or older, who completed a depression screening interview and had blood collected as a part of the National Health and Nutrition Examination Survey, 2005–2008. The serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were gender-specifically categorized into lower, intermediate, and upper quartiles. Depression was measured using the Patient Health Questionnaire, a 9-item screening instrument asking about the frequency of depression symptoms over the past 2 weeks.

Results: After adjustment for socio-demographics and behavioral risks, a U-shaped association was detected between severe depression and LDL-C among men. The odds ratios (ORs) of severe depression were 5.13 (95% CI = 1.74–15.09), 1 (reference) and 2.28 (1.07–4.86) respectively for the men with lower (< 169 mg/dL), intermediate (169–221 mg/dL), and upper quartile (≥ 222 mg/dL) LDL-C. Among women, lower HDL-C was significantly associated with an elevated odds of severe depression [OR = 2.96 (1.59–5.52)] compared with upper quartile of HDL-C, the association diminished after adjustment for covariates [OR = 1.24 (0.66–2.32)]. No clear pattern of association between cholesterol and moderate depression was observed from either men or women.

Limitation: The inherent limitation of cross-sectional design prevented the authors from investigating causality.

Conclusions: A U-shaped association was identified between LDL-C and severe depression among men. Further studies are necessary to explore the biological mechanism and identify the clinical implication among populations vulnerable to psychiatric disorders.