Research progress on the immune-inflammatory mechanisms of metabolic syndrome comorbid with depression
TL;DR
The roles of innate and adaptive immune responses in this context, including glial cell activation, blood-brain barrier disruption, microglial polarization, and T/B cell functional imbalance, which collectively contribute to a systemic chronic low-grade inflammatory state are focused on.
Abstract
Major depressive disorder (MDD) and metabolic syndrome (MetS) frequently exhibit high comorbidity, with the latter characterized primarily by insulin resistance, dyslipidemia, and abdominal obesity. Growing evidence suggests that immune-inflammatory dysregulation constitutes a shared pathobiological basis for both conditions. This review focuses on the roles of innate and adaptive immune responses in this context, including glial cell activation, blood-brain barrier disruption, microglial polarization, and T/B cell functional imbalance, which collectively contribute to a systemic chronic low-grade inflammatory state. We further integrate the bidirectional regulatory effects of key immune signaling pathways—such as TLR4–NF-κB, PI3K–Akt–mTOR, and JAK–STAT—in central neuroinflammation and peripheral metabolic dysfunction. These intertwined mechanisms influence mood regulation and synaptic plasticity while exacerbating insulin resistance and lipid abnormalities. Additionally, we discuss the potential value of immune markers, including GFAP, CTRP3, IL-6, and IFN-γ, in disease subtyping and risk assessment, and evaluate the prospects of novel anti-inflammatory intervention strategies for precision therapy. Finally, we highlight the current limitations in translational research and advocate for systematically integrated multi-omics and longitudinal cohort studies to advance precise interventions and personalized management of depressive-metabolic comorbidity.