Peripheral Blood Transcriptomic Features Distinguishing Postpartum Depression from Major Depressive Disorder and Healthy Postpartum Controls.

PURPOSE: Postpartum depression (PPD) is a common mental disorder, yet its pathogenesis remains incompletely understood. This study compared peripheral blood mononuclear cell (PBMC) transcriptomes across three cohorts-PPD, major depressive disorder (MDD), and healthy postpartum control (HPC)-to elucidate the molecular mechanisms underlying PPD and identify features that distinguish it from non-postpartum depression. PATIENTS AND METHODS: A total of 47 participants were recruited, including 11 with PPD, 16 HPC, and 20 with MDD. PBMCs were collected for transcriptome sequencing. Differentially expressed genes (DEGs) were identified using thresholds of |log2FC| ≥ 1 and P ≤ 0.05, followed by GO and KEGG enrichment analyses. RESULTS: Given that multiple testing correction identified only a limited number of DEGs, DEG analysis in this study was performed as an exploratory analysis using unadjusted P ≤ 0.05. Under this criterion, a total of 289 DEGs were identified in the PPD vs HPC comparison, and 335 DEGs in the PPD vs MDD comparison. The core molecular features of PPD included B cell-mediated humoral immune dysregulation, folate metabolic disruption, and blood-brain barrier matrix degradation. Key distinctions between PPD and MDD involved concurrent activation of host-microbe interactions and suppression of neurodevelopment. FOLR3 was the most significantly downregulated gene in PPD, whereas TNNT1 and MMP1 were characteristically upregulated in PPD compared with both MDD and HPC. CONCLUSION: The findings suggest peripheral transcriptomic alterations involving changes in humoral immunity, reduced FOLR3 expression, and increased TNNT1 and MMP1 expression, which may indicate altered folate-related immune-cell biology, muscle/motor dysregulation, and extracellular matrix remodeling relevant to peripheralcentral communication.