"Inflammation and the kynurenine pathway are involved in multiple physiological and pathophysiological states, however their role in depression during and after pregnancy, suicidality, and pre-eclampsia remain to be understood. Here, we sought to understand how the kynurenine pathway and its metabolites as well as their interactions with inflammation may influence these conditions. First, we analyzed suicide warning in women with mood and anxiety disorders. We identified a distinct immunobiological profile linked to cross-diagnostic suicide risk in women with mood disorders, attending a psychiatric outpatient clinic. This consisted of a strong proinflammatory profile, containing white blood cell count and polymononuclear leukocyte cell count which may be associated with the underlying pathobiology of suicide warning.. Next, we analyzed inflammation and the kynurenine pathway in peripartum depression and postpartum depression and suicidality to understand how they could influence psychiatric health. We found plasma IL-6 predicted depression scores throughout the first, second, and third trimester. In the third trimester we found increased neurotoxic kynurenine metabolite quinolinic acid in the plasma of women with depression compared to health controls. Additionally, we found plasma IL-1beta and IL-6 correlated with placental tissue expression of indolamine 2,3-dioxygenase 1 (IDO) connecting the placenta with peripheral inflammation in the plasma. There was a different inflammatory profile in postpartum depression and suicidality, with increased IL-8 and decreased IL-2, indicating the mechanisms causing peripartum depression and postpartum depression may be different. Finally, we looked at placentas from women with pre-eclampsia compared to healthy controls and found they had dysregulated tryptophan metabolism. There was a decrease of IDO, a compensatory increase in expression of tryptophan-2,3-dioxygenase, and this was associated with a decrease of serum amyloid A. Collectively, this dissertation highlights the importance of inflammation and the kynurenine pathway in the pathophysiology of psychiatric disorders and pregnancy states in females. Further research of inflammation and the kynurenine pathway may lead to screening panels and treatments for suicide, peripartum depression, postpartum depression and suicidality, and pre-eclampsia."--Pages ii-iii.
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