Neuroinflammatory mechanisms have long been implicated in the pathophysiology of depression, particularly in treatment-resistant depression (TRD). Peripheral immune markers such as monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-platelet ratio (NPR) may reflect chronic or acute immune activation and could serve as potential biomarkers for treatment response. We analyzed differential blood cell counts and inflammatory ratios (MLR, NLR, NPR), as well as interleukin-6 (IL-6) and C-reactive protein (CRP) levels, in 196 patients with severe depression. Patients were grouped into unmedicated (UDC), TRD with medication only (TRD-M), and TRD with electroconvulsive therapy (TRD-ECT), and were assessed at baseline and after four weeks. TRD patients showed significantly higher monocyte and MLR levels than non-TRD patients. Within TRD, ECT responders exhibited lower monocyte and MLR values compared to non-responders. NLR levels were significantly higher in the ECT group. A positive correlation was found between NPR changes and symptom improvement based on Beck Depression Inventory-II scores (BDI-II). Our findings suggest that TRD is associated with a chronic inflammatory profile, and that ECT may induce a shift toward acute immune activation, potentially contributing to treatment response. MLR, NLR, and NPR may serve as potential biomarkers and should be evaluated in prospective studies with larger samples and detailed immune phenotyping.
Hwach et al. (2026) studied this question.