Show simple item record

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

dc.contributor.authorRoth, Marissa C.
dc.contributor.authorHumphreys, Kathryn L.
dc.identifier.citationRobakis, T. K., Zhang, S., Rasgon, N. L., Li, T., Wang, T., Roth, M. C., Humphreys, K. L., Gotlib, I. H., Ho, M., Khechaduri, A., Watson, K., Roat-Shumway, S., Budhan, V. V., Davis, K. N., Crowe, S. D., Ellie Williams, K., & Urban, A. E. (2020). Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression. Translational psychiatry, 10(1), 48.
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at
dc.description.abstractEarly 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 x 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.en_US
dc.description.sponsorshipT.K.R. was supported by a NIMH T32 training grant to the Stanford University Department of Psychiatry (5T32MH019938-19; PI: Schatzberg; trainee: Robakis), by a 2014 Brain and Behavior Research Foundation Young Investigator Grant (PI: Robakis), and by a 2018 Stanford University Precision Health and Integrated Diagnostics seed grant (PI: Robakis). Support for this project was also provided by NIH Grants R21-HD090493 and R21-MH111978 to I.H.G. A.E.U. is a Tashia and John Morgridge Faculty Fellow of the Stanford Child Health Research Institute, is a Project-PI of the Stanford Center of Excellence in Genomics - Center for Personal Dynamic Regulomes (NIH HG007735-0, Center PI Chang), and acknowledges funding from and helpful discussions with Bruce Blackie. The sequencing data were generated on an Illumina HiSeq 4000 that was purchased with funds from NIH under award number S10OD018220. J.T.L. and T.W. are affiliated with Accura Science, LLC, and were financially recompensed for their expert biostatistical analysis. We thank Jue Lin, PhD, for assistance with the telomere assay, Brian Holder-Chow Lin On and Nikos Daskalakis, MD, PhD for early biostatistical assistance, Booil Jo, PhD, for additional statistical guidance, and Lin Lee, CNM, Maria Greulich, CNM, and Nicole Wilcox, MD for their invaluable assistance with recruitment. We would also like to thank all of the women who so generously provided their time, information, and biological samples to this work.en_US
dc.publisherTranslational Psychiatryen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
dc.titleEpigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depressionen_US

Files in this item


This item appears in the following Collection(s)

Show simple item record