Director Department of Blood Transfusion, Xiangya Hospital, NHC Key Laboratory of Cancer Proteomics, Central South University, Changsha, Hunan Province, China changsha, United States
Background/Case Studies: Depression poses a critical challenge to global health, with an estimated 300 million individuals affected worldwide. Recent studies have hinted at potential links between hematological parameters and depressive symptoms, while comprehensive evidence from large-scale, population-based analyses remains limited. This research aims to investigate whether peripheral blood cell indices are associated with the risk of developing depression, and whether such indices might serve as viable clinical biomarkers or targets for intervention.
Study
Design/Methods: Data from 393,124 participants enrolled in the UK Biobank were utilized. We employed multivariable logistic regression and Cox proportional hazards models to assess the linear associations between 29 predefined blood cell indices and the incidence of depression. Mendelian randomization (MR) analyses was used to infer potential causal relationships. Additionally, restricted cubic splines and piecewise linear regression were applied to evaluate possible non-linear trends. Blood indices were stratified into three categories: erythroid-related markers, immature erythrocyte parameters, and leukocyte indices. Depression diagnoses were ascertained via hospital inpatient records and validated mental health assessments, including PHQ-2 and PHQ-9.
Results/Findings: Across the primary and sensitivity analyses, ten blood cell indices exhibited significant associations with depression risk. Elevated erythroid markers—such as hemoglobin (HGB) and hematocrit (HCT)—were inversely associated with incident depression. In contrast, higher levels of immature red blood cells and certain leukocyte indices were positively correlated with depression onset. Notably, each standard deviation increases in HCT corresponded to a 10% reduction in depression risk over a median 13.6-year follow-up (HR = 0.90; 95% CI: 0.89–0.92). And this inverse association was further supported by MR findings, indicating causal effect between HCT and depression. Further investigation that an L-shaped dose–response relationship was observed between HCT levels and depression risk, with a turning point around 47.5%.
Conclusions: Our findings suggest a significant relationship between blood cell indices and the likelihood of developing depression. Especially, increased levels of red blood cell indices-HCT, appear to be protective in depression. Conversely, elevated immature erythroid and leukocyte parameters may confer increased depression risk. These observations underscore the potential utility of routine hematological testing in the early identification of individuals at elevated risk for depressive disorders. Furthermore, the results also indicated that may inform future preventive or therapeutic strategies in depression via red blood cell.
