Depression, immune-metabolic alterations and mortality in haemodialysis: a prospective cohort study

Depressive symptom heterogeneity and mortality in a prospective U.S. cohort.

Immune disturbances cluster around specific depressive phenotypes under conditions of structural adversity

Higher and lower hs-CRP profiles clustered around distinct latent depressive phenotypes, supporting biologically heterogeneous depressive presentations within a socially exposed urban population.

Metabolomic and Lipidomic Signatures of Depressive Symptoms in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Background Depression is a highly prevalent condition with a substantial health burden and known links to metabolic dysfunction. We investigated plasma metabolites and lipids associated with depressive symptoms at baseline, including sex- and race-specific differences, and subsequently examined longitudinal associations of baseline metabolites and lipids with depressive symptoms over follow-up. Methods Baseline plasma samples were profiled for 162 metabolites and 195 lipid species using targeted mass spectrometry in the REasons for Geographic And Racial Differences in Stroke (REGARDS) stroke case-cohort. Depressive symptoms were assessed using the 4-item Center for Epidemiologic Studies Depression Scale (CES-D-4) at baseline and during follow-up. Cross-sectional associations were evaluated using weighted logistic regression, and longitudinal associations were assessed using weighted generalized estimating equations. Effect modification by sex and race was examined. Model 1 was adjusted for age, race, and sex (and time in longitudinal analyses). Model 2 was further adjusted for body mass index, smoking status, alcohol use, physical activity, perceived stress, and incident stroke. False discovery rate (FDR) correction was applied to account for multiple testing. Results Of 1,938 participants, 205 had depressive symptoms at baseline. At baseline, several metabolites (e.g., glycine, cyclic AMP) and lipid species were nominally associated with depressive symptoms, though none remained significant after FDR correction. In longitudinal analyses, stronger and more consistent associations emerged. Higher levels of anserine (OR=1.27, 95% CI: 1.16-1.39) and glucose (OR=1.36, 95% CI: 1.10-1.68) were associated with increased odds of depressive symptoms, with anserine remaining significant after FDR correction. Multiple lipid species, particularly phosphatidylethanolamines (PEs) and triglycerides (TGs), were significantly associated with depressive symptoms after FDR correction in longitudinal models. Significant sex interactions were observed for several lipid species, with stronger positive associations in females and attenuated or inverse associations in males. Conclusions In this stroke-enriched case-cohort, PEs and TGs were associated with depressive symptoms over time. Sex-specific lipid differences highlight biological heterogeneity. These results identify amino acid, phospholipid, and triacylglycerol pathways in depressive symptoms, supporting further mechanistic and biomarker investigations.

Depressive symptoms in the association between herpes zoster and heart disease in middle-aged and older adults: A longitudinal cohort study.

BACKGROUND Herpes zoster (HZ) has been linked to elevated cardiovascular risk, but the mechanisms remain unclear. Depressive symptoms, particularly specific domains of symptoms, may show statistical mediation in this association. This study examined the longitudinal association between HZ and heart disease, assessed whether depressive symptoms showed statistical mediation, and conducted exploratory internal prediction analyses using machine-learning survival models. METHODS Based on the data from the Health and Retirement Study (HRS), we used Cox proportional hazards models to estimate the association between HZ and heart disease and mediation analyses to evaluate the role of total, cognitive-affective, and somatic depressive symptoms in middle-aged and older adults. In addition, five survival prediction models, including Cox, RSF, GBM, LASSO-Cox, and XGBoost, were evaluated using the concordance index (C-index). RESULTS Among 16,195 participants, HZ was associated with an increased risk of heart disease (adjusted HR 1.22, 95% CI 1.09-1.38, P = 0.001). Significant statistical indirect effects were observed for total (P = 0.003) and somatic depressive symptoms (P = 0.001), whereas no significant indirect effect was observed for cognitive-affective symptoms. Among the evaluated models, Cox and LASSO-Cox showed the highest discrimination, with C-indices of approximately 0.67. CONCLUSION HZ was associated with an increased risk of incident heart disease. Statistical indirect effects were observed through depressive symptoms, particularly somatic symptoms, under the assumed temporal ordering. HZ and depressive symptoms provided modest additional predictive information in exploratory internal analyses.

Sleep Duration and the Association Between Systemic Inflammatory Response Index and Depressive Symptoms Among Emerging Adults: Evidence from NHANES 2005-2023.

Higher SIRI levels were associated with increased odds of depressive symptoms among emerging adults, and sleep duration played a modest suppressor role in this relationship, suggesting complex interactions between inflammation, sleep, and mental health warranting further investigation through prospective studies.

Longitudinal association between insulin resistance and depressive symptoms in older adults: the mediating role of inflammation in the ELSA cohort

Background Insulin resistance (IR) has been implicated in depression, yet the dynamic interplay between concurrent changes in IR and depressive symptoms over time, and whether systemic inflammation mediates this relationship, remains unclear. Methods Data were obtained from 3,404 older adults (aged ≥50 years) in the English Longitudinal Study of Ageing (ELSA) across Waves 2, 4, and 6. IR was assessed using the estimated glucose disposal rate (eGDR). Depressive symptoms were measured with the CES-D scale (0-8). C-reactive protein (CRP) was log-transformed as the mediator. Linear mixed models were used to assess the longitudinal association between changes in eGDR and CES-D score. Restricted cubic splines were applied to explore potential nonlinear dose-response relationships. Mediation analysis was conducted to test whether CRP mediated the association. Subgroup and sensitivity analyses were performed to evaluate the robustness of the findings. Results In the overall population, eGDR was significantly associated with CES-D score (P = 0.003), with no evidence of nonlinearity (P = 0.074). The overall eGDR × time interaction was not significant (P = 0.349). When stratified by joint trajectories of eGDR and CES-D, significant eGDR × time interactions were observed in two groups: the decrease-increase group (eGDR declined and CES-D increased, β = –0.018, P < 0.001), and the increase-decrease group, (eGDR increased and CES-D decreased, β = 0.021, P < 0.001). CRP partially mediated the association, with an indirect effect of -0.00092 (95% CI: -0.00155 to -0.00042), accounting for 10.8% of the total effect. Subgroup and sensitivity analyses confirmed robustness. Conclusions The longitudinal association between IR and depressive symptoms differs across developmental trajectories and appears to be partially mediated by systemic inflammation. Our findings suggest that improvements in insulin sensitivity are associated with a lower risk of depressive symptoms in older adults.