Antenatal Depression and Adverse Pregnancy Outcomes (ADAPT)

Project: Research project

Project Details

Description

One in seven women experience an episode of major depressive disorder (MDD) during pregnancy or the puerperium. While it is common practice to screen for postpartum depression, a substantial number of depressive episodes start before or during pregnancy.1 In women, MDD is usually co-morbid with anxiety disorder(s). Given the co-occurrence of these disorders, I will focus this application on MDD with the understanding that both depressive and anxiety symptomatology contribute to maternal distress and impaired function. Untreated antenatal depression has been associated with adverse consequences in the developing offspring, including intrauterine growth restriction (IUGR)2-4, preterm birth (PTB)2,5,6, and neurobehavioral impairment.7-10 As such, perinatal depression has enormous public health impact.
Evidence suggests that, outside of pregnancy, inflammation is associated with MDD.11-17 Our pilot work has extended this finding to pregnancy and demonstrated that pregnant women with depressive symptomatology have higher levels of cerebrospinal fluid inflammatory cytokines. However the mechanism that leads to overproduction of these cytokines, and whether the increase in inflammation associated with perinatal depression represents the mechanism underlying the association between antenatal depression and adverse obstetric outcomes have not been elucidated. This critical gap in knowledge has limited our ability to develop interventions to prevent the obstetric and perinatal sequelae of antenatal depression.
One possible etiology for cytokine overproduction is that depression is associated with altered lymphocytic regulation. An example of these regulatory cells is CD4+CD25+ T regulatory (Treg) cells, which normally suppress the immune response during pregnancy and promote tolerance of the fetus.18-21 Depletion of Tregs results in an increased expression of inflammatory cytokines, and has been associated with MDD in animal models and human studies. Yet, the role of Tregs in perinatal depression has not been examined.22,23 Natural killer (NK) cells are another potential source of immune dysregulation.24 The development of MDD has been associated with a suppression of NK quantity and function.25,26 At rest, NK cells serve to maintain macrophages and dendritic cells in a non-inflammatory state.27,28 When activated, NK cells are a major source of IFNγ, an inflammatory cytokine, and granulysin, a family of immunoregulatory cytokines. The larger 15 kD isoform of granulysin is not cytolytic but rather induces the differentiation of monocytes into dendritic cells, while the smaller 9 kD isoform is found in cytotoxic granules together with perforin and granzyme B which are cytotoxic to trophoblasts.29,30 Thus, dysregulated NK cell release of granulysin may link perinatal depression with adverse pregnancy outcomes, but this particular pathway has yet to be studied.
My long-term goal is to develop an integrated research program examining the obstetric and perinatal sequelae of perinatal depression with the ultimate goal of developing preventive treatments for these vulnerable pregnant women and their offspring. The goals of this project include determining the association of perinatal depressive symptoms and syndromal MDD with peripheral lymphocyte profiles, with a particular focus on immune regulation. My hypothesis is that aberrant regulation of lymphocytes and/or their secreted cytokines is associated with perinatal depression. The specific aims include:
Aim 1: Examine the association between antenatal depressive symptoms or MDD and altered perip
StatusFinished
Effective start/end date10/1/173/1/18

Funding

  • Foundation for SMFM (Agmt 10/1/17)

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