Depression during and after pregnancy affects up to 20% of pregnant women, but the biological underpinnings remain incompletely understood. As pregnancy progresses, the immune system changes to facilitate fetal development, leading to distinct fluctuations in the production of pro-inflammatory factors and neuroactive tryptophan metabolites throughout the peripartum period. Therefore, it is possible that depression in pregnancy could constitute a specific type of inflammation-induced depression. Both inflammatory factors and kynurenine metabolites impact neuroinflammation and glutamatergic neurotransmission and can therefore affect mood and behavior. To determine whether cytokines and kynurenine metabolites can predict the development of depression in pregnancy, we analyzed blood samples and clinical symptoms in 114 women during each trimester and the postpartum. We analyzed plasma IL-1β, IL-2, -6, -8, -10, TNF, kynurenine, tryptophan, serotonin, kynurenic- quinolinic- and picolinic acids and used mixed-effects models to assess the association between biomarkers and depression severity. IL-1β and IL-6 levels associated positively with severity of depressive symptoms across pregnancy and the postpartum, and that the odds of experiencing significant depressive symptoms increased by >30% per median absolute deviation for both IL-1β and IL-6 (both P = 0.01). A combination of cytokines and kynurenine metabolites in the 2nd trimester had a >99% probability of accurately predicting 3rd trimester depression, with an ROC AUC > 0.8. Altogether, our work shows that cytokines and tryptophan metabolites can predict depression during pregnancy and could be useful as clinical markers of risk. Moreover, inflammation and kynurenine pathway enzymes should be considered possible therapeutic targets in peripartum depression.

The prevalence of anxiety, mood and trauma- and stress-related disorders are on the rise; however, efforts to develop new and effective treatment strategies have had limited success. To identify novel therapeutic targets, a comprehensive understanding of the disease etiology is needed, especially in the context of the holobiont, i.e., the superorganism consisting of a human and its microbiotas. Much emphasis has been placed on the role of the gut microbiota in the development, exacerbation, and persistence of psychiatric disorders; however, data for the oral microbiota are limited. The oral cavity houses the second most diverse microbial community in the body, with over 700 bacterial species that colonize the soft and hard tissues. Periodontal diseases encompass a group of infectious and inflammatory diseases that affect the periodontium. Among them, periodontitis is defined as a chronic, multi-bacterial infection that elicits low-grade systemic inflammation via the release of pro-inflammatory cytokines, as well as local invasion and long-distance translocation of periodontal pathogens. Periodontitis can also induce or exacerbate other chronic systemic inflammatory diseases such as atherosclerosis and diabetes and can lead to adverse pregnancy outcomes. Recently, periodontal pathogens have been implicated in the etiology and pathophysiology of neuropsychiatric disorders (such as depression and schizophrenia), especially as dysregulation of the immune system also plays an integral role in the etiology and pathophysiology of these disorders. This review will discuss the role of the oral microbiota associated with periodontal diseases in anxiety, mood and trauma- and stress-related disorders. Epidemiological data of periodontal diseases in individuals with these disorders will be presented, followed by a discussion of the microbiological and immunological links between the oral microbiota and the central nervous system. Pre-clinical and clinical findings on the oral microbiota related to periodontal diseases in anxiety, mood and trauma- and stress-related phenotypes will be reviewed, followed by a discussion on the bi-directionality of the oral-brain axis. Lastly, we will focus on the oral microbiota associated with periodontal diseases as a target for future therapeutic interventions to alleviate symptoms of these debilitating psychiatric disorders.