Disentangling the complex role of endogenous and exogenous oxytocin (Pitocin) in postpartum depression and anxiety

About This Grant

The postpartum is a high-risk period for depression and anxiety in women. Because of the risks that postpartum depression and anxiety pose to the mother and infant, there is a pressing need to understand their neurobiology to develop biomarkers to identify those at risk, and develop early, targeted treatments and prevention strategies. Lower endogenous oxytocin levels in pregnancy are a promising biomarker that has been associated with risk for postpartum depression and anxiety. Synthetic oxytocin (Pitocin) is widely used to induce and augment labor and after delivery for placenta expulsion and postpartum hemorrhage prevention and management. Despite its widespread use, it is unknown whether Pitocin protects against (or increases risk for) postpartum mood and anxiety disorders. Most previous studies lack quantitative Pitocin dosing data, and most lack measures of both exogenous Pitocin dose and endogenous oxytocin levels. No study to date has examined the combined impact of endogenous oxytocin levels and Pitocin dose on risk for postpartum depression and anxiety disorders. Another key limitation is that most studies only measure peripheral oxytocin (blood), as cerebrospinal fluid (CSF) collection via lumbar puncture is invasive. However, the extent to which blood oxytocin levels reflect central oxytocin levels in pregnancy is unknown. The proposed study will allow us to address the gaps in knowledge described above by harnessing CSF collected during standard neuraxial anesthesia procedures indicated as treatment as usual. The proposed study design is a prospective pregnancy cohort. We will recruit our study participants in 2nd or 3rd trimester of pregnancy, and follow them until 3 months postpartum, when we will measure depression and anxiety symptoms. Our overall goal in the proposed study is to elucidate the complex role of endogenous and exogenous oxytocin (Pitocin) in postpartum depression and anxiety. Aim 1A will quantify central (CSF) and peripheral (blood) oxytocin levels in pregnancy. Aim 1B will examine whether endogenous CSF oxytocin levels in pregnancy are prospectively associated with depression and anxiety symptom severity 3 months postpartum. Aim 2 will examine whether exogenous Pitocin dose received is prospectively associated with depression and anxiety symptom severity 3 months postpartum in a dose-dependent manner. Aim 3 will elucidate the combined effect of endogenous oxytocin levels and exogenous Pitocin dose received on depression and anxiety symptoms 3 months postpartum. Our exploratory Aim will examine whether CSF and blood endogenous oxytocin levels and exogenous Pitocin dose predict maternal caregiving behavior 3 months postpartum.