Vesta Steibliene

Background: Inflammatory mechanisms contribute to major depressive disorder (MDD) in a subset of patients. Lipopolysaccharide (LPS), a potent inflammatory endotoxin, can induce depressive-like symptoms, but its relationship with specific depressive symptom profiles remains unclear. Methods: In total, 95 adults with MDD (mean age was 44 ± 14 years) were recruited from psychiatric inpatient and outpatient services. Depressive symptom severity was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS). Serum concentrations of LPS, IL-10, TNF-α, IL-6, and IFN-γ were measured by ELISA. Associations between inflammatory markers and depressive symptoms were examined using group comparisons, correlation analyses, multivariable linear regression, quantile regression, and mediation analyses adjusted for demographic and clinical covariates. Results: Patients with severe depression exhibited significantly lower circulating LPS levels than those with mild-to-moderate depression (95.6 vs. 165.2 pg/mL, p = 0.007), despite no significant differences in cytokine concentrations. LPS levels were inversely associated with depression severity, anhedonia factor score, and MADRS item 8 (“inability to feel”). Lower LPS concentrations were independently predicted by higher inability to feel, reduced appetite and combined pharmacotherapy use. Quantile regression demonstrated heterogeneity across the LPS distribution, with symptom–LPS associations evident among patients with higher LPS concentrations. Higher LPS levels were associated with greater apparent sadness, concentration difficulties, and reduced sleep, but lower levels of anhedonia, less reduced appetite, less lassitude, lower inner tension, and lower suicidality. Mediation analyses indicated that anhedonia mediated the association between LPS levels and depression severity. Conclusions: Higher circulating LPS may characterize a biologically distinct subgroup of MDD patients with lower symptom severity and less anhedonia, supporting biological heterogeneity within MDD.

Background: Diffusion-prepared pseudo-continuous arterial spin labelling (DP-pCASL) can quantify the cerebral blood flow (CBF) and the water exchange rate (kw) across the blood–brain barrier (BBB). Little is known about the BBB water exchange in major depressive disorder (MDD). Objective: We aimed to explore the associations between kw, CBF, peripheral inflammation, and MDD. Methods: Using DP-pCASL, we measured the global and selected regional kw and CBF together with blood plasma levels of lipopolysaccharide (LPS) and inflammatory cytokines in 85 patients with MDD and 51 controls. Results: The global CBF was significantly lower in MDD patients compared with controls (means of 51 and 57 mL/100 g/min, respectively; p = 0.006), with similar reductions found in the dorsolateral and ventromedial prefrontal, anterior, and posterior cingulate regions, while no differences were found in the amygdala and the isthmic cingulate. There were no differences in the kw between groups globally (means of 128 min⁻¹; p = 0.958) and in the studied regions. Among MDD patients, the kw was weakly correlated with the MADRS scores (r = 0.231, p = 0.034). There were no associations between kw, CBF, and inflammatory markers (LPS, IL-6, IL-10, TNF-α, IFN-γ). Logistic regression showed that a combination of the regional CBF < 59.22 mL/100 g/min together with LPS > 143.58 pg/mL and/or IL-10 > 0 pg/mL distinguished MDD patients from controls with a moderate accuracy of 83.1% (sensitivity = 94.1%, specificity = 64.7%, AUC = 0.876). Conclusions: DP-pCASL imaging confirmed previous findings of reduced CBF in MDD, which together with LPS and IL-10 concentrations were independent significant predictors of MDD. However, no changes in the BBB water exchange were found, suggesting that it may not be as significant as CBF in MDD pathophysiology.