Immune dysregulation and neuroinflammation in bipolar disorder: Pathophysiological insights and therapeutic perspectives

Bipolar disorder (BD) is increasingly associated with immune system dysregulation encompassing both peripheral and central components. Peripheral low-grade inflammation, marked by elevated proinflammatory cytokines and impaired anti-inflammatory responses, contributes to systemic immune imbalance in BD. This peripheral inflammatory state may compromise blood–brain barrier (BBB) integrity, facilitating the entry of peripheral immune mediators into the central nervous system (CNS) and triggering neuroinflammatory cascades. Within the CNS, neuroinflammation is orchestrated primarily by microglial and astrocytic activation, which disrupts neuronal homeostasis and synaptic function. Additionally, oxidative stress acts as a crucial mediator, exacerbating neuronal damage. Based on current findings, this review synthesises evidence linking both central and peripheral inflammation to the pathophysiology of BD, offering a perspective on its underlying biology. A comprehensive understanding of the dynamic interplay between peripheral inflammation and central neuroimmune responses is essential for identifying novel therapeutic targets and developing interventions that effectively address both systemic and CNS components of BD pathophysiology.