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

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.

The Association between Plasma ERVWE1 Concentrations and Affective Symptoms during Pregnancy: Is This a Friendly Alien?

Human endogenous retroviruses (HERVs) comprise 8% of the human genome, and HERV DNA was reported to be essential in human embryonic development. Specifically, HERV-W encodes a protein, syncytin-1, alternatively known as ERVWE1 (Human Endogenous Retrovirus W EnvC7-1 Envelope Protein), participating in human placental morphogenesis and having a role in immune system regulation. Syncytin-1 activity is increased in neuropsychiatric disorders, autoimmune diseases, and cancer. In our study, forty-four women in the third trimester of pregnancy were tested for ERVWE1 plasma levels. In concomitance with blood samples the following rating scales were administered to women: the Edinburgh Postnatal Depression Scale (EPDS), State Anxiety Inventory (STAI-S), Trait Anxiety Inventory (STAI-T), and Prenatal Attachment Inventory (PAI). We found that higher ERVWE1 protein plasma levels were significantly associated with higher PAI scores (p = 0.02), an earlier gestational age at the time of blood collection (p = 0.01), a longer duration of symptoms (p = 0.03), and fewer lifetime attempted suicides (p = 0.02). Our results seem to support the role of ERVWE1 in maintaining clinical psychiatric symptoms as a result of potential prolonged inflammation. At the same time, this protein may have a protective role in pregnant women by a reduction of suicidal behavior and a better mother-fetus relationship.