The Methylation of Clock Genes in Perinatal Depression: Which Role for Oxytocin?

Abstract

Background: Perinatal Depression (PD) is a widespread disabling condition that is hypothesized to be associated with abnormalities in circadian rhythms and neuropeptide release including oxytocin (OXT).Methods: Fourty-four pregnant women (28 with PD, and 16 controls) were evaluated through the Edinburgh Postnatal Depression Scale (EPDS), the State/Trait Anxiety Inventory Form Y (STAI-Y), and the Prenatal Attachment Inventory (PAI). A blood sample was collected from all participants, and OXT plasma levels, DNA methylation of clock genes, as well as of FOXp3 and HERV-W were measured. Linear regression analyses were performed to assess the effect of oxytocin on the methylation of selected genes. Continuous ordinal regression models was further applied to see if the score of rating scales was associated to gene methylation, adjusting for oxytocin-methylation interaction.Results: OXT plasma levels were positively associated with CRY1 methylation. Women with higher OXT plasma levels showed an association between higher degree of CRY2 methylation (thus, reduced expression) and lower EPDS (OR = 0.21; P = 0.043) and STAI-S scores (OR = 6.96; P = 0.019). Finally, with high OXT levels, hypermethylation of CRY1 was associated to higher scores on the PAI (OR = 2.74; P = 0.029) while higher methylation of HERV-W related to lower PAI scores (OR = 0.273; P = 0.019).Conclusion: Our results suggest a possible protective role played by oxytocin in the development of PD by promoting a favorable methylation profile characterized by reduced expression of CRY1 and CRY2. Moreover, oxytocin strengthens the association between maternal prenatal attachment with a favorable pattern of methylation of clock genes and HERV-W, which is essential for pregnancy outcomes.

Air Pollution and Perinatal Mental Health: A Comprehensive Overview

“…Moreover, short-and long-term exposure to PM was found to be associated with increased plasma levels of cytokines such as IL-6, IL-1β, and TNFα [65,66]. As mentioned in the introduction, the effects of neuroinflammation during the perinatal period are particularly detrimental for the role of neuropeptides and circadian rhythms for the physiological functioning of women in this specific phase of life [25].…”

“…In particular, transcriptional/translational feedback mechanisms involving CLOCK-BMAL, a protein dimer complex, have been identified as the main regulators of circadian rhythms [23,24]. Recent studies have highlighted that epigenetic modifications in clock and other genes (different degrees of methylation) can contribute to the development of depression and anxiety disorders during the perinatal period [25], as a result of hypomethylation of clock genes CRY1 and CRY2 [9] and modulation of HERV-W, the latter implicated in maternal immune tolerance during pregnancy [26]. Women during the perinatal period are particularly vulnerable to the negative effects of air pollution as it was demonstrated, even in physiological pregnancy, that a delay of circadian rhythms, particularly in the third trimester, prepare breastfeeding [27].…”