Differentially expressed transcripts associated with depressive symptoms during pregnancy and postpartum

Mol Psychiatry. 2025 Jun 5. doi: 10.1038/s41380-025-03068-z. Online ahead of print.

ABSTRACT

Peripartum depression can have severe impact on the mother’s and the infant’s health. Yet, its biological underpinnings are largely unknown. The present study sought to identify transcriptomic signatures of depressive symptoms during pregnancy and postpartum. Blood samples were collected during late pregnancy or early postpartum for mRNA isolation and sequencing, while depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Based on the timepoint when the samples were collected, differentially expressed genes (DEGs) were identified by (1) comparing mRNA levels between the depression symptom trajectory groups, and (2) correlating with EPDS scores. DEGs for samples collected during late pregnancy, but not postpartum, were associated with depressive symptoms occurring only during pregnancy or persisting postpartum, compared with controls. There were 16 upregulated and 109 downregulated DEGs significantly associated with EPDS score at week 32 among samples collected during late pregnancy. Gene Set Enrichment Analysis identified immune response and cell motility as processes linked to these DEGs. Hypothesis-based analysis on previously identified postpartum depressive symptoms-related DEGs replicated a positive association between expression of immune-related genes ISG15 and RSAD2 with postpartum-onset depressive symptoms, both in samples taken during late pregnancy and postpartum. The present findings point to transcriptomic signatures associated with peripartum depressive symptoms, mostly related to immune system dysregulation.

PMID:40473930 | DOI:10.1038/s41380-025-03068-z