Summary: Women who experience postpartum mood disorders including PTSD, depression, and anxiety two to three years after giving birth had irregular immune system responses, researchers report.
Source: Cedar Sinai Medical Center
Women with prolonged mental health problems up to three years after childbirth may be suffering from irregular immune system responses, according to new research by Cedars-Sinai investigators.
The findings are published in the American Journal of Reproductive Immunology.
“We found that women who had clinically elevated symptoms of depression, anxiety, and/or post-traumatic stress disorder (PTSD) two to three years after delivery had genetic evidence of a higher prevalence of immune system defense mechanism activation,”said Eynav Accortt, Ph.D., principal investigator of the study and director of the Reproductive Psychology Program at Cedars-Sinai.
“These women also appeared to have a reduction in the activity of genes related to antiviral immune responses that can offer the body protection from pathogens,” said Accortt, a clinical psychologist.
According to the Centers for Disease Control and Prevention, about 1 in 8 women experience significant symptoms of perinatal mood and anxiety disorders that can interfere with overall health, daily activities and family life. Much of the research into maternal mental health to date has focused on the perinatal period and the first year after childbirth.
Cedars-Sinai investigators surveyed 33 women about their mental health over a longer period, two to three years after giving birth. Study participants also provided a blood sample, and scientists performed bioinformatic analyses of differential gene expression.
Much of the research into maternal mental health to date has focused on the perinatal period and the first year after childbirth. Image is in the public domain
“Delayed or persistent postpartum anxiety, depression and PTSD is an area that is woefully understudied,” said Sarah Kilpatrick, MD, Ph.D., chair of the Department ofSarah Kilpatrick, MD, Ph.D., chair of the department of Obstetrics and Gynecology at Cedars-Sinai and one of the study’s co-authors.
“In this preliminary research, we have identified genetic differences related to inflammation when comparing women experiencing prolonged symptoms of mood and anxiety disorders to those who did not report poor mental health. Additional studies will be needed for a deeper dive into the role inflammation may play in postpartum mental illness,” said Kilpatrick.
A primary goal of this work is to design a blood test that would detect which women are at the highest risk for serious and prolonged postpartum mood disorders, according to Accortt.
“A blood test could help us develop early interventions that provide medical and mental health treatments and support. We want to figure out why some women are at greater risk for depression, anxiety and PTSD. No one should have to suffer for years after childbirth,” said Accortt.
Immune transcriptional profiles in mothers with clinically elevated depression and anxiety symptoms several years post‐delivery
Most research on maternal mental health focuses on the perinatal period and does not extend beyond 12 months postpartum. However, emerging evidence suggests that for some women (30%–50%), psychological symptoms may persist beyond the first year postpartum or even emerge later increasing the risk of chronic mood and anxiety symptoms. Despite the high prevalence rates and devastating maternal-child consequences, studies examining maternal depression, anxiety, and post-traumatic stress disorder (PTSD) beyond the first year postpartum are rare and our understanding of the underlying biological mechanisms is incomplete. Inflammatory processes are thought to be involved in the pathophysiology of depression, anxiety, & PTSD outside of the postpartum period. Therefore, the purpose of the current investigation was to examine the relationship between depression, anxiety, and PTSD two to three years post-delivery, and transcriptional control pathways relevant to inflammatory and antiviral processes.
Women over 18 years of age enrolled in ongoing research studies at Cedars Sinai Medical Center who were 2–3 years postpartum were invited to participate in the current study. Women (N = 33) reported on their levels of depression, anxiety, and PTSD and provided a blood sample approximately 2–3 years post-delivery. Bioinformatic analyses of differential gene expression (DGEs) to infer transcription factor activity were used. Gene expression was assayed by RNA sequencing and TELiS bioinformatics analysis of transcription factor-binding motifs in the promoters of differentially expressed genes.
DGE analyses revealed that women with clinically elevated symptoms of depression, anxiety and PTSD (n = 16) showed upregulation of genes activated by transcription control pathways associated with inflammation (NF-ΚB, p = 0.004; JUN, p = 0.02), including β-adrenergic responsive CREB (p = 0.01) and reduced activation of genes associated with the antiviral response (IRFs, p = 0.02) and the glucocorticoid signaling pathway (GR, p = 0.02) compared to women without clinical symptoms (n = 17).
This is one of the first investigations into the immune signaling pathways involved in depression, anxiety, and PTSD two to three years post-delivery. The results of this study suggest that clinically elevated symptoms of depression, anxiety, and PTSD two to three years post-delivery are associated with a gene expression profile characterized by upregulated expression of pro-inflammatory genes and downregulated expression of antiviral genes. The data also point to two potential stress responsive pathways linking symptoms to increased inflammatory signaling in immune cells: sympathetic nervous system mediated β-adrenergic signaling and reduced hypothalamic pituitary adrenal axis activity. Together, these findings highlight the need for investigations into maternal mental health beyond the first year postpartum.