The Role of Oxytocin in Relation to the HPA axis and Differential Receptor Methylation Patterns in the Prognosis and Prevention of Postpartum Depression
Introduction: Postpartum depression, which effects as many as 30% of mothers, impairs mother-infant interactions and can have a profound effect on both child development and motherhood.1 Oxytocin is a key regulatory hormone that is known to buffer stress reactivity, support positive mood, and promote healthy mothering behaviors.2 While emerging research focuses on oxytocin levels during and after childbirth, the complex action of oxytocin and oxytocin receptors needs to be fully understood. Research on oxytocin in the PVN of the hypothalamus as a modulator of the HPA axis stress response perinatally along with discoveries about differential oxytocin receptor DNA methylation patterns has further illuminated the potential dysregulation that can occur in the context of PPD mothers who have an “at risk” methylation phenotype. Methods: In a postpartum depression rat model, gestation restraint stress induced depressive-like behaviors and higher plasma cortisol levels in rats.3 Oxytocin (20 ng) was injected locally into the PVN to determine its effects on the depressive-like behaviors and oxytocin’s role in the appearance/treatment of those behaviors.3 Percent methylation data for the OXTR gene and IGR AVP was generated for protein-coding and tissue-specific enhancing regions to determine whether the experience of PPD for 4 groups of women stratified based on EPDS score was associated with differential methylation of the OXTR gene and/or AVP/OXT IGR.4 Results: In PPD rats, there was a significant decrease in the mRNA expression of OXT in the PVN and increase in depressive-like behaviors compared to non-GRS rats.3 Local injection of oxytocin into the PVN significantly reversed both depressive-like GRS-induced behaviors and increased plasma cortisol levels in rats.3 Mothers with persistent PPD had significantly higher overall exon 3 OXTR methylation and lower AVP IGR methylation.4 Conclusions: GRS successfully induced PPD in rats based on decreased mRNA OXT level in the PVN and subsequent increased depressive-like behaviors.3 Central oxytocin treatment induces and antidepressant-like response in the PPD rat model and reverses oxytocin dysregulation that led to increased cortisol levels in the HPA axis.3 Persistent PPD is associated with significant differential methylation patterns in regions that may have downstream effects on the entire OXT system during the postpartum period, contributing to the hypothesis that an “at-risk” phenotype makes women more susceptible to PPD.4 The direct effect of oxytocin in the PVN on depressive behaviors and cortisol levels may be altered in mothers with an at-risk phenotype based on OXTR methylation patterns through oxytocin-HPA axis buffering dysfunction.
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- King L, Robins S, Chen G, Yerko V, Zhou Y, Nagy C, Feeley N, Gold I, Hayton B, Turecki G, Zelkowitz P. Perinatal depression and DNA methylation of oxytocin-related genes: a study of mothers and their children. Horm Behav. 2017 Nov;96:84-94. doi: 10.1016/j.yhbeh.2017.09.006.