Prospective network analysis of proinflammatory proteins, lipid markers, and depression components in midlife community women

Abstract

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 that tested relationships between non-specific immune/endocrine markers and depression did not separate temporal inferences between people and within-person and how different immunometabolism markers related to unique depression symptoms. We thus used cross-lagged prospective network analyses (CLPN) to investigate this topic.

Methods: Community midlife women (n = 2224) completed the Center for Epidemiologic Studies-Depression scale and provided biomarker samples across five time-points spanning 9 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)], and 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, higher CRP and HDL predicted all three depression components (d = 0.131-2.112). Increased LDL preceded higher depressed mood and interpersonal issues (v. somatic symptoms) (d = 0.251-0.327). Elevated triglycerides predicted more somatic symptoms (v. depressed mood and interpersonal problems) (d = 0.131). More interpersonal problems forecasted elevated fibrinogen and LDL levels (d = 0.129-0.331), and stronger somatic symptoms preceded higher fibrinogen levels (d = 0.188).

Conclusions: Results supported both vulnerability and 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.

Keywords: Cross-lagged; depression; endocrine; immune; inflammation; interpersonal; network analysis; scar theory; vulnerability theory.

Fig. 1.

Within-person temporal network of proinflammatory proteins, lipid markers, and depression nodes. Note: crp, C-reactive protein; dep, depressed mood; fbr, fibrinogen; glc, fasting glucose; hdl, high density lipoprotein; ins, insulin; int, interpersonal problems; lip, lipid marker composite; ldl, low density lipoprotein; som, somatic symptoms; trg, triglycerides. Blue bold lines indicate statistically significant positive relations, whereas red dotted lines signal statistically significant negative relations and line boldness and thickness reflect strength of associations.

Fig. 2.

Within-person contemporaneous network of proinflammatory proteins, lipid markers, and depression nodes. Note: crp, C-reactive protein; dep, depressed mood; fbr, fibrinogen; glc, fasting glucose; hdl, high density lipoprotein; ins, insulin; int, interpersonal problems; lip, lipid marker composite; ldl, low density lipoprotein; som, somatic symptoms; trg, triglycerides. Blue bold lines indicate statistically significant positive relations, whereas red dotted lines signal statistically significant negative relations and line boldness and thickness reflect strength of associations.

Fig. 3.

Between-person network of proinflammatory proteins, lipid markers, and depression nodes. Note: crp, C-reactive protein; dep, depressed mood; fbr, fibrinogen; glc, fasting glucose; hdl, high density lipoprotein; ins, insulin; int, interpersonal problems; lip, lipid marker composite; ldl, low density lipoprotein; som, somatic symptoms; trg, triglycerides. Blue bold lines indicate statistically significant positive relations, whereas red dotted lines signal statistically significant negative relations and line boldness and thickness reflect strength of associations.