Linking inflammation to depression: evidence from blood plasma lipopolysaccharide and cytokines

Background: Chronic low-grade inflammation has been strongly implicated in the pathogenesis of major depressive disorder (MDD) [1]. In particular, cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), have been associated with diagnosis of MDD and depressive symptoms in a subset of patients. Preclinical studies have demonstrated that administration of lipopolysaccharide (LPS), a pro-inflammatory component of gram-negative bacterial membranes, induces inflammation and depressive-like behaviours in animal models [2,3]. While these findings provide strong experimental support for an inflammatory component in depression, clinical data on circulating LPS levels in individuals with MDD remain limited. This study aimed to investigate whether plasma concentrations of LPS, IL-6, and TNF-α differ between patients with MDD and healthy controls. Methods: This cross-sectional study included patients with MDD and a control group of subjects without psychiatric history. MDD diagnoses were based on ICD-10 diagnostic criteria and verified by experienced psychiatrists. Participants with unstable medical comorbidities or current anti-inflammatory treatment were excluded. Each study participant completed a sociodemographic questionnaire. Fasting venous blood samples were assayed for plasma LPS, IL-6 and TNF- α using commercial ELISA kits. Descriptive statistics were used to summarize sociodemographic and clinical characteristics. Continuous variables were presented as medians with interquartile ranges (IQR), assessed by the Shapiro-Wilk test. Between-group comparisons for continuous variables were conducted using the Mann-Whitney U test, as data did not meet the assumptions of normality. The Z-score and p-value were reported for each comparison. Results: A total of 143 participants were included in the analysis – 97 subjects with MDD and 46 controls. Demographic and clinical characteristics were comparable between MDD groups and controls with respect to age (Z= –0.801, p=0.423), female proportion (Z= –0.807, p=0.931), and body mass index (BMI) (Z= –0.713, p=0.476). Smoking prevalence was significantly higher in MDD group (Z= –3.513, p