Connecting the dots: Peripheral and central immune changes in mood disorders

Animal, genetic, epidemiologic, transcriptomic, imaging, and clinical studies provide evidence for a link between the immune system and mood disorders. Additionally, the immune system shows alterations in patients with BD and MDD. However, many uncertainties surround these findings, as most studies include small sample size, used only one methodological approach, did not replicate or validate findings, and did not control for other factors that are capable of influencing the immune system. Studies that compare central and peripheral immune changes directly have been lacking, hampering the functional translation of findings in the peripheral immune system in mood disorder patients. To conclude, the exact involvement of the immune system in mood disorders remains to be elucidated. This thesis aimed to explore the immune profile of mood disorder patients in several (high-risk) MDD and BD cohorts, and to link immune abnormalities in peripheral immune subsets and antibodies, and microglia to mood symptomatology.

1) In the first part of this thesis peripheral immune subsets, such as monocytes, T-cells and neuro-immune growth factors, were studied in two cohorts of increased familial risk for mood disorders.
2) The second part of this thesis explores different antibodies in blood of BD and high-risk populations for mood disorders. Antibodies directed against thyroidperoxidase, neuronal cell surface proteins and various neurotropic pathogens were measured in patients with bipolar disorder and postpartum psychosis.
3) To provide further insight in central immune abnormalities in mood disorders, part three of this thesis describes investigations to elucidate the role of the immune cells of the brain (microglia) in patients with BD and MDD. The phenotype and responsivity of microglia in bipolar disorder and major depressive disorder have been studied in depth.
4) In part 4 a summary of the findings is given. The summary shows that findings in the periphery cannot be clearly connected to findings in the central nervous system. Therefore, an additional structural review is presented in part four of this thesis that investigated the observed peripheral immune changes in patients with mood disorders in relation to abnormalities in the central nervous system and mood pathology.