Immune Cell Abundance as a Biomarker of Depressive Symptom Severity and Response to Anti-inflammatory Treatment in Major Depression Restricted; Files & ToC
Balidemaj, Nora (Spring 2025)
Abstract
Introduction: Major Depressive Disorder (MDD) is a prevalent psychiatric condition significantly contributing to global disability, yet a substantial proportion of patients exhibit treatment-resistant depression (TRD), characterized by insufficient responses to standard antidepressants. Emerging evidence implicates inflammation as a pivotal factor in the etiology and persistence of depressive symptoms, particularly anhedonia, anxiety, and psychomotor slowing.
Methods: This study explored the association between immune cell abundance and depressive symptoms, focusing specifically on monocytes and lymphocytes, within a cohort of 60 treatment-resistant depressed patients undergoing a 12-week randomized controlled trial with either infliximab, a TNF-α inhibitor, or placebo. A secondary replication cohort of 149 medication-free, medically stable individuals with major depression (MD) was analyzed cross-sectionally to confirm initial findings.
Results: Results indicated that higher percentages of circulating monocytes were significantly correlated with increased anhedonia severity in both cohorts, supporting the hypothesis of monocyte-mediated inflammation contributing to specific depressive phenotypes. Further stratified analysis revealed this relationship was moderated by severe obesity, emphasizing the role of metabolic factors in depressive inflammation.Longitudinal analysis demonstrated that infliximab treatment resulted in a significant increase in lymphocyte counts at week 12 compared to placebo. Notably, this lymphocyte increase was significantly associated with a reduction in anxiety symptoms specifically in the infliximab group, indicating a potential immunomodulatory mechanism for therapeutic benefit.
Discussion: This investigation underscores the clinical relevance of peripheral immune cell populations as biomarkers for depression severity and response to anti-inflammatory treatments. The positive correlation between monocyte abundance and anhedonia suggests potential avenues for targeted anti-inflammatory interventions. Moreover, infliximab’s ability to modulate lymphocyte abundance and improve anxiety symptoms highlights immune modulation as a viable therapeutic approach for TRD. Collectively, these findings provide compelling evidence for inflammation-targeted treatments in managing depressive symptoms. Further research into specific immune subtypes and inflammatory pathways is warranted to refine personalized therapeutic strategies for individuals suffering from depression characterized by heightened inflammatory states.
Table of Contents
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