Abstract
Peripartum depression (PPD) is a prevalent and debilitating disorder that adversely affects the development of mothers and infants. Recently, there has been a plea for increased mental health screening during the peripartum period; however, currently, there is no accurate screening tool to identify women at risk of PPD. In addition, some women do not respond to current treatment schemes and develop treatment-resistant depression. The current perspective aims to propose a unified understanding of the biological underpinnings of PPD (UmPPD) that considers the heterogeneity in the onset, symptoms cluster, and severity of PPD. Such a model could promote basic and applied research on PPD and suggest new treatment avenues. The central hub of the model is the kynurenine pathway (KP) and the KP-serotonin ratio. The forces and specific processes at play that cause an imbalance within the KP and between KP and serotonin are inflammation, stress, reproductive hormones (especially estradiol and progesterone), and oxytocin. UmPPD predicts that the most severe PPD would comprise prolonged inflammation, ongoing or multiple stressors, excessive estrogen, progesterone resistance, and avoidance of breastfeeding, skin-to-skin contact, and social proximity. These factors would be associated with a higher likelihood of developing PPD, early onset, and more significant symptom severity. In addition, subtypes of PPD would consist of different compositions and expressions of these components, with one central common factor. UmPPD could aid in directing future research and possibly detecting critical processes that could help discover, develop, and utilize novel treatments for PPD.