Prospective Network Analysis of Proinflammatory Proteins, Lipid Markers, and Depression Components in Midlife Community Adult Women

Background: Vulnerability theories propose that suboptimal levels of lipid markers and proinflammatory proteins predict future heightened depression. Scar models posit the reverse association. However, most studies testing relations between non-specific immune/endocrine markers and depression have been cross-sectional, precluding within-person temporal inferences, and did not differentiate components. We thus used cross-lagged prospective network analyses (CLPN) to investigate this topic. Methods: Community midlife women (n = 2,224) completed the Center for Epidemiologic Studies-Depression scale and provided biomarker samples across five time-points spanning nine years. CLPN identified significant relations (edges) among components (nodes) of depression (depressed mood, somatic symptoms, interpersonal issues), lipid markers (insulin, fasting glucose, triglycerides, low-density lipoprotein-cholesterol (LDL), high-density lipoprotein-cholesterol (HDL)), proinflammatory proteins (C-reactive protein (CRP), fibrinogen), within and across time-points. All models adjusted for age, estradiol, follicle-stimulating hormone, and menopausal status. Results: In within-person temporal networks, CRP, fibrinogen, and HDL predicted all three depression components (|d| = 0.101 to 2.816). Reduced insulin and increased LDL preceded higher depressed mood and interpersonal issues (vs. somatic symptoms) (|d| = 0.327 to 0.943). Elevated triglycerides predicted more somatic symptoms (vs. depressed mood and interpersonal problems) (d = 0.174). Moreover, all depression components predicted higher fibrinogen and LDL levels (vs. other surrogate immunometabolism markers) (|d| = 0.108 to 0.441). Conclusions: Results offered more support for vulnerability (vs. scar models). Long-term dysregulated immunometabolism systems, social disengagement, and related patterns are possible mechanistic accounts. Cognitive-behavioral therapies that optimize nutrition and physical activity may effectively target depression.