Peripheral Oxytocin Following Early-Life Stress: A Translational Systematic Review and Meta-Analysis of Human and Rodent Studies

Early-life stress (ELS) is associated with persistent oxytocinergic alterations, yet peripheral oxytocin (OT) changes in ELS-exposed adults remain inconsistent. To our knowledge, this translational systematic review and meta-analysis is the first to jointly synthesize human and rodent evidence on adult basal peripheral OT following ELS, with sex and biofluid type as moderators. A systematic search identified 12 human articles (k = 14; n = 1176) and four rodent articles (k = 6; n = 123). Random-effects meta-analyses revealed negative trends across humans (COR −0.18, 95% CI [−0.36, 0.02]; p = 0.0732) and rodents (SMD −0.53, 95% CI [−1.24, 0.18]; p = 0.1409), with a notable directional consistency across species. Biofluid type was the strongest moderator in human ELS–OT associations (χ24 = 19.18, p = 0.0007), with effects varying between sexes. Plasma was the only subgroup with a significant negative association (COR −0.28, 95% CI [−0.51, −0.03]) and a homogeneous signal in male cohorts (COR −0.34, 95% CI [−0.46, −0.21]; I2 = 0%). In rodents, sex was the significant moderator (χ22 = 13.17, p = 0.0014). GRADE certainty was very low across outcomes, reflecting the nascent state of this literature and the need for further research exploring sex differences and plasma-based quantification, among others.