Pregnancy-related inflammatory markers and their association with perinatal mental illness: a systematic review

Abstract

Introduction. This study investigates the relationship between immune dysregulation and perinatal mental disorders by analyzing clinical data and biomarker profiles in pregnant individuals with varying severity of psychiatric symptoms. Understanding these associations may support the development of early screening tools and targeted interventions to improve maternal and infant mental health outcomes. Material and methods. A comprehensive literature review was conducted using PubMed, MEDLINE, and Scopus, covering studies published through 2025. Key proinflammatory and anti-inflammatory cytokines, including IL-6, TNF-α, IL-1β, CRP, IL-8, and IL-10, were extracted from peer-reviewed articles. When numerical values were unavailable, data were estimated from published figures using digitization tools. Extracted data were standardized and analyzed using Python (Pandas, Matplotlib). Statistical procedures included correlation analysis, ROC curve modelling, and ANOVA testing to assess group differences and diagnostic performance of biomarkers. Results. Analysis revealed strong associations between cytokine levels and perinatal depressive symptoms. In one dataset, nine cytokines were inversely correlated with postpartum depression severity (Pearson r = –0.79, p = 0.004; Spearman rₛ = –0.87, p = 0.00085; Kendall τ = –0.72, p = 0.0031), and ANOVA confirmed significant group differences (F = 5.8, p = 0.022). Other studies reported elevated IL-6 and TNF-α levels in postpartum depression (p < 0.05). Co-expression of IL-2, IL-6, IL8, and TNF-α was very high (r = 0.9991, p = 0.00006), likely reflecting cytokine collinearity and limited sample size, with ANOVA indicating significant elevation in affected individuals (F = 45.42, p = 0.0151). ROC analyses identified IL-8, IL-6, CRP, and TNF-α as reliable markers of perinatal depression and psychosis. Tryptophan metabolites and MCP-1 were more specific for psychosis, while IFN-γ showed a regulatory rather than a diagnostic function. Conclusions. Perinatal mental disorders are associated with significant immune alterations. IL-6, IL-8, IL-2, and TNF-α appear to play a central role in the pathophysiology of postpartum depression. The findings support the utility of cytokine profiling for early detection and differential diagnosis of perinatal psychiatric conditions.