Lipid Ratio Biomarkers as Protective Factors for Depressive Symptoms in Newly Diagnosed Metabolic Syndrome: Evidence From Regression Modeling

J Integr Neurosci. 2026 Apr 22;25(4):49628. doi: 10.31083/JIN49628.

ABSTRACT

BACKGROUND: Obesity and depression have a bidirectional relationship. Previous work has shown that obesity increases the risk of depression, while atypical depression can elevate the risk of obesity. This study aimed to investigate the associations between anthropometric markers, lipid and insulin resistance biomarkers, inflammatory cytokines, and adipokines with depressive symptom severity in individuals with newly diagnosed metabolic syndrome (MetS).

METHODS: 88 treatment-naïve adults with newly identified MetS, without known coronary artery disease, were included. Clinical assessments comprised anthropometric measures, while laboratory analyses measured lipid metabolism markers, insulin resistance indicators, inflammatory cytokines, and adipokines. Depressive symptom severity was assessed using the von Zerssen Depression Scale (DS), validated for the Bulgarian population. To explore latent structures within biomarker domains, principal component analyses (PCA) were performed. Associations between depressive symptoms and biomarkers were then examined in two steps: first, using linear regression with PCA-derived component scores, and second, through hierarchical multiple regression focusing on selected individual biomarkers, controlling for covariates such as age and gender.

RESULTS: PCA identified distinct latent structures within anthropometric, lipid, insulin resistance, and cytokine domains, though regression analyses using PCA-derived component scores did not yield significant associations with depressive symptoms (all p > 0.050). Hierarchical multiple regression with selected biomarkers showed that lower low-density lipoprotein cholesterol (LDLc)/Apolipoprotein B (ApoB) ratios were consistently associated with higher depressive symptom severity (Model 1: β = -0.332, p = 0.011; Model 2: β = -0.326, p = 0.012; Model 3: β = -0.319, p = 0.013), while higher interleukin-6 (IL-6) levels were independently linked to greater symptom severity (Model 1: β = 0.217, p = 0.052; Model 3: β = 0.230, p = 0.033). ApoB/apolipoprotein A1 (ApoA1) ratios and age showed weaker or non-significant effects.

CONCLUSIONS: LDLc/ApoB ratio and IL-6 levels are independently associated with depressive symptom severity in newly diagnosed MetS, highlighting their potential as clinically relevant biomarkers. These findings highlight perspectives for integrating lipid and inflammatory profiles in the assessment of depression risk within MetS populations.

PMID:42052758 | DOI:10.31083/JIN49628