Associations of adiposity, atherogenic lipid phenotypes, systemic immune-inflammatory indices, and vascular aging markers with depression in US adults: NHANES 2005-2020.

Moderate-to-severe depression prevalence differed substantially by sex among the 17,011 NHANES participants studied.

• Total sample included 17,011 participants from NHANES 2005-2020, with 8477 women and 8534 men.
• Moderate-to-severe depression prevalence was 10.9% in women and 6.2% in men.
• Depression was defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥ 10.
• Data spanned the NHANES cycles from 2005 to 2020.

Higher BMI was significantly associated with greater odds of moderate-to-severe depression in fully adjusted models.

• The association was identified using weighted logistic regression with full covariate adjustment.
• Associations were generally stronger in women than in men.
• BMI was examined as a measure of adiposity alongside other cardiometabolic markers.
• The analysis controlled for sociodemographic and clinical factors.

Multiple atherogenic lipid phenotypes were significantly associated with greater odds of depression, with sex differences observed.

• Higher atherogenic index of plasma, triglyceride/HDL-C ratio, and Castelli indices were each significantly associated with greater odds of depression in fully adjusted models.
• HDL-C showed an inverse association with depression specifically in women.
• Associations for atherogenic lipid indices were generally stronger in women than in men.
• Non-HDL-C was also examined among the atherogenic lipid profile markers.

Multiple systemic immune-inflammatory indices were significantly associated with greater odds of moderate-to-severe depression.

• Higher systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-platelet ratio were each significantly associated with greater odds of depression in fully adjusted models.
• Platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were also examined as immune-inflammatory indices.
• Associations for inflammatory markers were generally stronger in women than in men.
• These associations were independent of sociodemographic and clinical factors.

Both vascular aging markers — estimated pulse wave velocity and urinary albumin-to-creatinine ratio — were significantly associated with greater odds of depression.

• Higher estimated pulse wave velocity was significantly associated with greater odds of depression in fully adjusted models.
• Higher urinary albumin-to-creatinine ratio was significantly associated with greater odds of depression in fully adjusted models.
• These associations were independent of adiposity, lipid, and inflammatory markers.
• These findings support the role of vascular aging pathways in depression pathogenesis.

Predictive models incorporating cardiometabolic and inflammatory indices improved classification of moderate-to-severe depression beyond sociodemographic and clinical factors alone.

• Area under the curve (AUC) increases ranged from 0.024 to 0.045 when these indices were added to base models.
• All improvements in AUC were statistically significant (all P < .05).
• Receiver operating characteristic analyses were used to assess predictive performance.
• The improvement was demonstrated across models incorporating adiposity, lipid, inflammatory, and vascular aging markers.

Sex was a significant moderator of the associations between cardiometabolic/inflammatory markers and depression, with stronger associations generally observed in women.

• Associations between atherogenic lipid indices and depression were generally stronger in women than in men.
• Associations between inflammatory markers and depression were generally stronger in women than in men.
• HDL-C showed an inverse association with depression only in women, not men.
• Overall depression prevalence was higher in women (10.9%) than men (6.2%).