Immune Transcriptional Profiles in Mothers with Clinically Elevated Depression and Anxiety Symptoms Several Years Post-Delivery

Jennifer Nicoloro-SantaBarbara, PhD

Brigham and Women’s Hospital – Fellow
NicoloroSantaBarbara_Jenni poster

Scientific Abstract

Background: Most research on maternal mental health does not extend beyond 12 months postpartum. However, emerging evidence suggests that for some women (30%-50%), depression and anxiety may persist beyond the first year postpartum. Despite the high prevalence rates and devastating maternal-child consequences, our understanding of the underlying biological mechanisms of maternal mental health beyond the first year postpartum 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 2-3 yrs post-delivery and transcriptional control pathways relevant to inflammatory & antiviral processes.

Methods: Women (N=33) reported on their levels of depression, anxiety and PTSD and provided a blood sample approximately 2-3 yrs post-delivery. Bioinformatic analyses of differential gene expression (DGEs) to infer transcription factor activity were used. Gene expression was assayed by RNA sequencing & TELiS bioinformatics analysis of transcription factor-binding motifs in the promoters of differentially expressed genes.

Results: DGE analyses revealed women with clinically elevated symptoms of depression, anxiety &/or PTSD (n=16) showed upregulation of genes activated by transcription control pathways associated with inflammation (NFKB, p=0.004;JUN,p=0.02), including ꞵ-adrenergic responsive CREB (p=0.01) & reduced activation of genes associated with the antiviral response (IRFs, p=0.02) & the glucocorticoid signaling pathway (GR,p=0.02) compared to women without clinical symptoms (n=17).

Conclusions: Results suggest that clinically elevated symptoms of depression, anxiety and PTSD 2-3 yrs post-delivery are associated with a gene expression profile characterized by upregulated expression of pro-inflammatory genes & 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 ꞵ-adrenergic signaling & reduced hypothalamic pituitary adrenal axis activity.

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research Areas

Authors

Jennifer M. Nicoloro-SantaBarbara, PhD, Judith E. Carroll, PhD, Margo Minissian, PhD, Sarah J. Kilpatrick, MD, PhD, Steve Cole, PhD, C. Noel Bairey Merz, MD, & Eynav E. Accortt, PhD

Principal Investigator

Eynav E. Accortt, PhD