Evaluating Levels of Lipopolysaccharide in Patients with Major Depressive Disorder

Abstract

Background: Accumulated scientific evidence has supported the importance of inflammatory processes, at least in the subgroup of patients with Major depressive disorder (MDD) [1]. Data suggest that plasma Lipopolysaccharides (LPS) or LPS-induced peripheral inflammation can induce neuroinflammation and sickness-like behavioral symptoms [2, 3]. Most of the evidence comes from numerous LPS-induced depression-like models in mice [4]. However, it is not known whether plasma LPS levels are elevated in patients with MDD. Thus, the aim of our study was to explore LPS concentrations of patients with MDD in comparison to healthy controls. Methods: This cross-sectional study included patients with MDD and a control group of subjects with no history of a mental disorder. The diagnosis of MDD was established by a psychiatrist according to the International Classification of Diseases 10th Revision diagnostic criteria. All participants had no medical comorbidities and did not take any anti-inflammatory drugs. All participants with MDD received pharmacological treatment for the disorder. Each study participant completed a socio-demographic questionnaire, and the severity of depression symptoms was evaluated using the structured interview guide for the Montgomery–Åsberg Depression Rating Scale (MADRS-SIGMA). Venous blood samples were taken to measure plasma LPS concentration using a commercial ELISA kit. At first, a Mann-Whitney’s U test and Spearman’s correlation was used to compare demographic and clinical characteristics, as well as plasma LPS concentrations of MDD patients and controls. Next, a multivariable regression analysis was conducted to investigate whether observed differences in plasma LPS concentrations were independent of gender and other inflammation-inducing factors such as older age, body mass index (BMI) and smoking status. Results: Overall, the study sample included 69 participants [n=55 with MDD and n=14 healthy controls]. The study groups differ statistically in severity of depressive symptoms (for MDD group MADRS-SIGMA median score [Q1-Q3] was 44 [35.0–58.0]) and for healthy controls MADRS-SIGMA median score [Q1-Q3] was 4.0 [2.0–7.3], p<0.001). Median age [Q1-Q3] of MDD group was 44 [35.0-58.0], 20.0 % [n=11] were men, 38.2 % [n=21] were smoking and 16.4 % [n=9] had BMI ≥30 kg/m2. The MDD group and control groups did not differ in age (p=0.132), gender (p=0.257), BMI (p=0.655), and smoking status (p=0.240). The concentration of plasma LPS was statistically significantly higher for participants with MDD than in the control group (MDD group median (Q1-Q3) - 84.9 (59.4–158.3) μg/ml vs. control group median [Q1-Q3] - 52.8 [39.6–111.8], p=0.024). We found positive correlation of diagnosis of MDD and plasma LPS concentration (r=0.280, p=0.019). The association remained significant in multivariable analysis including gender, age, BMI, and smoking status (β = 0.282; p = 0.025). Conclusions: LPS concentration was significantly higher in MDD patients, independent of potential inflammatory effects related to older age, obesity, smoking, and gender. Future studies could focus on the effect of reducing LPS concentrations as effective strategies for the treatment and prevention of MDD.