The aberrant immune system in bipolar disorder

The aim of this chapter is to provide an overview of various perspectives of the aberrant immune system in bipolar disorder (BD) in light of the search for new therapy options. The chapter follows the macrophage-T cell theory of mood disorders formulated in the 1990’s, and the theory was founded on high serum levels of pro-inflammatory and T cell regulating cytokines in mood disorder patients. Besides higher levels of pro-inflammatory cytokines depending on the episodic activity of the disorder, BD patients also show a higher prevalence of auto-immune diseases and minor numerical T cell deficiencies. These minor T cell deficiencies go together with a proneness of T helper subsets (such as Th17 cells) to overreact, for T regulatory cells to be deficient, and for monocytes/macrophages to react pro-inflammatory. These various aberrant immune reactions are thought to have their effect on BD illness progression, via alterations in the tryptophan catabolism and via dysfunction of glial cells, such as the microglia and oligodendrocytes. Therapeutic immune interventions in BD have thus far mainly been focused on non-steroidal anti-inflammatory drugs (NSAID), omega-3-fatty acids and N- acetylcysteine (NAC). More recently, scientific attention has been directed to the gut-brain-axis, with emphasis on increased intestinal permeability of immune stimulants and microbiome disturbances driving the inflammatory dysregulation. Based on the research that is becoming more extensive and global, this field seems promising for potential treatment options in this severe mental illness.