Inflammatory matters: Exploring the underlying pathophysiology of unipolar and bipolar disorder

Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD) are high ranking among the most prevalent and severely disabling disorders worldwide. The accurate diagnosis of BD is often delayed for many years and this has significant clinical implications. If we could understand more about the underlying disease mechanisms of these disorders, it might help us to differentiate them. Over the years two theories regarding the development of mood disorders have gained attention. The first considers dysregulation of the immune system as the driving force behind mood disorders. The other states that a dysregulated stress system can cause mood disorders. However, the immune and stress system can influence each other on multiple levels. Therefore, this thesis explored different aspects of the immune and stress system of BD and MDD patients. Differences between BD and MDD patients were found in all examined parts of the immune system: in cytokines, T helper cell differentiation and in the innate immune response. These findings point to structural biological differences between the two disorders. Furthermore, when examining the stress system, significant differences were found again between both patient groups. Finally, the interrelatedness of both systems was examined, and we found that especially the combination of high immune activity and a dysregulated stress system increased the risk of bipolar depression. This stresses the importance of considering these systems simultaneously. With this thesis we hope to have added some missing pieces to the puzzle, thereby increasing our understanding of the underlying disease mechanism of mood disorders.