Immune mechanisms in bipolar disorder: Evidence and implications

Bipolar disorder (BD) is a severe mental illness associated with significant illness burden. The exact etiology of BD remains elusive, but inflammation is suggested to be one of the numerous causes leading to BD. Accumulating evidence also supports an association between BD and inflammation. In this chapter, we first discuss the role of inflammatory conditions such as infections and autoimmune disorders in BD pathophysiology. We then discuss how the gut microbiome can be one of the perpetrators of the inflammatory response seen in BD patients. We highlighted the inflammatory mechanisms involving inflammatory cytokines, oxidative stress production, mitochondrial dysfunction, and microglial activation. Moreover, we explain how they contribute to the development of BD. We also included scientific evidence of immune markers evaluated in blood, cerebrospinal fluid, and postmortem brain samples, which demonstrates the involvement of inflammation and immune-regulated pathways in the neurobiology of BD. Understanding the biological basis of BD pathophysiology will open up new targets for novel therapies.