West Virginia University Research & Scholarship Advancement Award
B Cells as a Predictor for Postpartum Mood and Anxiety Disturbances in Mice and Humans
*aka MADPIG (Mood/Anxiety Disturbances & Peri/postpartum Immunology Grant)
We think that postpartum mood and anxiety disturbances (PMAD) may result from a failure of a properly sequenced immune recovery, particularly of T cells and B cells.
Public Health Relevance
Mood and anxiety disturbances (PMAD), including depression, anxiety, and obsessive-compulsive disorder, are the most common complications of pregnancy affecting 1 in 7 mothers (Luca et al., 2019; Wenzel et al., 2016). PMAD are associated with adverse outcomes for mother and baby, including poor nutrition, drug use, and self-harm in mothers, and delays in infant development and growth, anxiety and depression in children, difficulty breastfeeding, and interference with parent-infant bonding. Further, PMAD cost the United States an estimated 14.2 billion dollars per year. Thus there is a pressing need to determine causes of PMAD so we can find new intervention targets to help millions of women and children worldwide.
Scientific Premise
Disruptions in the immune system, such as increased inflammatory cytokines (substances released by immune cells, i.e. IL-6, IFN-ɣ, and TNF-α) may be related to mood disturbances (Payne & Osborn, 2020). Importantly, pregnancy is associated with immense changes in the immune system (i.e., MacLean et al., 1992; Watanabe et al., 1997) characterized by immune suppression during gestation following by a rapid upregulation of immune cells in the weeks and months following parturition. Given that anxiety and mood disorders are associated with changes in the immune system, and that pregnancy dramatically affects the immune system, it is theorized that abnormal immune disruptions during pregnancy or a failure of suppressed immune features to recover appropriately (e.g., too much inflammation during or post pregnancy) may cause PMAD (Osborne et al., 2019).
Aim 1
Determine if B:T Cell Profiles Relate to Postpartum Anxiety and Depression-like Behaviors in Mice
Dr. Engler-Chiurazzi, with her expertise in conducting mouse model studies and assessing immune cells and her preliminary data in mice that implicate B cells in the control of mood, will execute Aim 1. Our team will measure T and B cell numbers in three groups of mice, a group who were never pregnant, a group who were recently pregnant, and a final group who were previously pregnant, and determine if stress response behaviors of these groups differ.
Aim 2
Determine if B:T Cell Profiles Are Related to PMAD and Can Predict Development of These Symptoms
Dr. Steinman, with her expertise recruiting and evaluating human participants with mood and anxiety disorders and pregnant women, will execute Aim 2. Our team will measure T and B cell numbers in the blood of women at 4 time points (during their pregnancy, at birth, and in the postpartum period) and correlate these values with the extent of PMAD symptoms displayed by these mothers.
Outcomes
Our work will further the immune theory of disordered mood and suggest novel therapeutic targets to prevent and treat PMAD, benefitting millions of mothers and offspring worldwide. Moreover, this work will support the career development of two early stage investigators/mothers/colleagues/friends via the production of posters at international conventions, high-impact publications, and pilot data for National Institutes of Health grant submissions.