Perinatal depression and DNA methylation of oxytocin-related genes: a study of mothers and their children

King, Leonora; Robins, Stéphanie; Chen, Gang; Yerko, Volodymyr; Zhou, Yi; Nagy, Corina; Feeley, Nancy; Gold, Ian; Hayton, Barbara; Turecki, Gustavo; Zelkowitz, Phyllis

doi:10.1016/j.yhbeh.2017.09.006

Cited by 66 publications

(48 citation statements)

References 93 publications

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“…Oxytocin signaling is of particular importance to the promotion of mother-infant bonding in the early postnatal period, which is the same time period in which attachment insecurity assumes a uniquely strong association with depressive symptoms. Other authors have also reported roles for DNA methylation of the oxytocin receptor in risk for postpartum depression [27][28][29][30] . Additionally, oxytocin receptor gene polymorphisms have been shown to affect adult attachment insecurity 37 .…”

Section: Single-gene Dna Methylation Signature Within Oxtrmentioning

confidence: 95%

“…Later work from this dataset using a candidate-gene approach also identified alterations in methylation density within the oxytocin receptor gene in association with postpartum depression 27 . Other groups have also reported associations of oxytocin receptor DNA methylation with perinatal depression, in tissues such as saliva 28 , whole blood 29 , and placenta 30 .…”

Section: Molecular Pathways From Early Life Adversity To Adult Perinamentioning

confidence: 96%

“…Given extensive previous work on and interest in the oxytocin receptor and its clear relevance to both attachment security 37,38 and psychiatric morbidity in the perinatal period [27][28][29][30] , we also examined patterns of methylation density in association with perinatal depression, childhood trauma, and attachment insecurity within this candidate gene.…”

Section: Approachmentioning

confidence: 99%

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Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression

et al. 2020

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Early life adversity and insecure attachment style are known risk factors for perinatal depression. The biological pathways linking these experiences, however, have not yet been elucidated. We hypothesized that overlap in patterns of DNA methylation in association with each of these phenomena could identify genes and pathways of importance. Specifically, we wished to distinguish between allostatic-load and role-transition hypotheses of perinatal depression. We conducted a large-scale analysis of methylation patterns across 5 × 10 6 individual CG dinucleotides in 54 women participating in a longitudinal prospective study of perinatal depression, using clustering-based criteria for significance to control for multiple comparisons. We identified 1580 regions in which methylation density was associated with childhood adversity, 3 in which methylation density was associated with insecure attachment style, and 6 in which methylation density was associated with perinatal depression. Shorter telomeres were observed in association with childhood trauma but not with perinatal depression or attachment insecurity. A detailed analysis of methylation density in the oxytocin receptor gene revealed similar patterns of DNA methylation in association with perinatal depression and with insecure attachment style, while childhood trauma was associated with a distinct methylation pattern in this gene. Clinically, attachment style was strongly associated with depression only in pregnancy and the early postpartum, whereas the association of childhood adversity with depression was time-invariant. We concluded that the broad DNA methylation signature and reduced telomere length associated with childhood adversity could indicate increased allostatic load across multiple body systems, whereas perinatal depression and attachment insecurity may be narrower phenotypes with more limited DNA methylation signatures outside the CNS, and no apparent association with telomere length or, by extension, allostatic load. In contrast, the finding of matching DNA methylation patterns within the oxytocin receptor gene for perinatal depression and attachment insecurity is consistent with the theory that the perinatal period is a time of activation of existing attachment schemas for the purpose of structuring the mother-child relationship, and that such activation may occur in part through specific patterns of methylation of the oxytocin receptor gene.

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Section: Single-gene Dna Methylation Signature Within Oxtrmentioning

confidence: 95%

Section: Molecular Pathways From Early Life Adversity To Adult Perinamentioning

confidence: 96%

Section: Approachmentioning

confidence: 99%

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Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression

et al. 2020

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“…A CpG dinucleotide flanks the 5’ end of the CHRE but its potential role in the epigenetic regulation of Oxt in the PVN has not been examined. Previous work in humans has investigated DNA methylation in the entire Oxt promoter region, including the CHRE [22,23], and the enhancer in the Oxt/Avp intergenic region [24]. However, because peripheral tissues were examined in these studies, it is not known whether DNA methylation at this locus is involved in the regulation of Oxt transcript abundance in the brain.…”

Section: Introductionmentioning

confidence: 99%

Early-life Temperature Exposure Affects Thyroid Hormone Receptor Signaling and Epigenetic Regulation of the Paraventricular Nucleus in Female Rat Pups

Lauby¹,

McGowan

2020

Preprint

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Early-life maternal care received has a profound effect on later-life behaviour in adult offspring and previous studies have suggested epigenetic mechanisms (e.g., DNA methylation) are involved. Changes in thyroid hormone receptor signaling might be related to differences in maternal care received and DNA methylation modifications. We investigated the effects of two factors in the maternal environment, temperature exposure (a proxy of maternal contact) and licking-like tactile stimulation, on these processes in week-old female rat pups. We assessed thyroid hormone receptor signaling by measuring circulating triiodothyronine and transcript abundance of thyroid hormone receptors and the thyroid hormone-responsive genes DNA methyltransferase 3a and oxytocin in the paraventricular nucleus of the hypothalamus. DNA methylation of the oxytocin promoter was assessed in relation to changes in thyroid hormone receptor binding. Repeated room temperature exposure was associated with a decrease in thyroid hormone receptor signaling measures relative to nest temperature exposure, while acute room temperature exposure was associated with an increase. Repeated room temperature exposure also increased thyroid hormone receptor binding and DNA methylation at the oxytocin promoter. These findings suggest that repeated room temperature exposure may affect DNA methylation levels as a consequence of alterations in thyroid hormone receptor signaling.

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“…[1][2][3][4][5] However, we direct the reader to other more up-to-date studies and reviews of the epigenetics of mothering that describe the very exciting work that is presently ongoing in this field. [6][7][8] Portions of this brief review are based on other articles and reviews we have published and to which we refer throughout. [1][2][3][4][5][9][10][11]…”

Section: Introductionmentioning

confidence: 99%

Molecular and Genetic Bases of Mammalian Maternal Behavior

Fleming

Kraemer

2019

Gender and the Genome

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New mammalian mothers undergo an increase in their maternal responsiveness with the birth of their infants. Associated with changes in responsiveness are how attracted mothers are to infant cues, mothers' affective state, and their cognitive and executive function. In comparison to nonmothers, new mothers are more attracted to infant odors and are more easily alerted to their vocalizations; they undergo a reduction in withdrawal behaviors and anxiety, but increased lability. Their maternal sensitivity (human or licking intensity, rat) is associated with higher levels of attention and working memory. Maternal responsiveness and these associated behaviors are associated with large shifts in maternal hormones across parturition. Changes in expression of neuropeptides and neurotransmitters are affected by mothers' prior experiences, including their very early experiences in their families of origin. The present review describes the regulation of mothering and associated behaviors by the neurotransmitters, oxytocin, dopamine, and serotonin, in a rat model and in humans. Emphasis is then given to studies that focus on the role of genes and what we know about their expression in the functioning of these 3 neurochemical systems in new mothers. Studies of early experience, genetics, and human mothering show gene-by-environment interplays (interactions) for a number of DNA singlenucleotide polymorphism within both the oxytocin and serotonin systems, where associations between mothers' early experiences and mothering/affect depend on mothers' genotype. Studies also show associations between different dopamine genes and many aspects of both mothering and maternal affect. Where known, we also discuss evidence that the relation between early experience and mothering is often an indirect one, mediated through an effect of experience on mothers' affect or executive function. In many cases, mothers' genetic profile moderates these relations. Finally, preliminary evidence suggests a role of epigenetic mechanisms in these processes.

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Perinatal depression and DNA methylation of oxytocin-related genes: a study of mothers and their children

Cited by 66 publications

References 93 publications

Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression

Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression

Early-life Temperature Exposure Affects Thyroid Hormone Receptor Signaling and Epigenetic Regulation of the Paraventricular Nucleus in Female Rat Pups

Molecular and Genetic Bases of Mammalian Maternal Behavior

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