Current evidence on immune-driven depression.

Abstract

Purpose of review: This review summarizes recent evidence on immune-driven depression, a subtype of major depressive disorder (MDD) characterized by low-grade inflammation, energy-related symptoms and metabolic disturbances. This subtype is associated with worse outcomes and distinct antidepressant responses. Considering inflammatory features may help clinicians tailor MDD management, particularly by informing lifestyle measures and targeted interventions. The review highlights studies describing features of immune-driven depression, discussing mechanistic pathways, and evaluating mechanism-based interventions.

Recent findings: Novel mechanistic evidence includes sex-specific associations between inflammatory markers and depressive symptoms, effects of inflammation on motivation and immuno-metabolic interactions. These findings have informed stratified and enriched trial designs preselecting patients with inflammatory profiles. International initiatives integrate clinical, biomarker, neuroimaging and genetic data to define reproducible signatures. Novel interventions include GLP-1 receptor agonists, more focus on dopaminergic agents and low-dose interleukin-2.

Summary: Current evidence supports immune-driven depression as a clinically relevant MDD subtype. Indicators such as hsCRP, comorbid metabolic or inflammatory conditions and motivational anhedonia may help clinicians recognize at-risk patients. Most intervention trials remain limited by small, heterogeneous samples and nonspecific outcome measures. Advances in biomarker-guided stratification represent important steps toward precision psychiatry, aiming to develop tailored, mechanism-based treatments for MDD.