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Antenatal prediction of postpartum depression with blood DNA methylation biomarkers

Molecular Psychiatry volume 19, pages 560–567 (2014)Cite this article

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A Corrigendum to this article was published on 22 October 2013

Abstract

Postpartum depression (PPD) affects ∼10–18% of women in the general population and results in serious consequences to both the mother and offspring. We hypothesized that predisposition to PPD risk is due to an altered sensitivity to estrogen-mediated epigenetic changes that act in a cell autonomous manner detectable in the blood. We investigated estrogen-mediated epigenetic reprogramming events in the hippocampus and risk to PPD using a cross-species translational design. DNA methylation profiles were generated using methylation microarrays in a prospective sample of the blood from the antenatal period of pregnant mood disorder patients who would and would not develop depression postpartum. These profiles were cross-referenced with syntenic locations exhibiting hippocampal DNA methylation changes in the mouse responsive to long-term treatment with 17β-estradiol (E2). DNA methylation associated with PPD risk correlated significantly with E2-induced DNA methylation change, suggesting an enhanced sensitivity to estrogen-based DNA methylation reprogramming exists in those at risk for PPD. Using the combined mouse and human data, we identified two biomarker loci at the HP1BP3 and TTC9B genes that predicted PPD with an area under the receiver operator characteristic (ROC) curve (area under the curve (AUC)) of 0.87 in antenatally euthymic women and 0.12 in a replication sample of antenatally depressed women. Incorporation of blood count data into the model accounted for the discrepancy and produced an AUC of 0.96 across both prepartum depressed and euthymic women. Pathway analyses demonstrated that DNA methylation patterns related to hippocampal synaptic plasticity may be of etiological importance to PPD.

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Acknowledgements

We thank The Solomon R and Rebecca D Baker Foundation for their generous support of this research. This work was funded, in part, by MH093967 to TDG and a NARSAD 2010 Young Investigator Award to ZK. The Sidney Kimmel Cancer Center Microarray Core Facility at Johns Hopkins University was supported by NIH Grant P30 CA006973. All animal treatments were approved by the University of Maryland, Baltimore Animal Care and Use Committee and were conducted in full accordance with the NIH Guide for the Care and Use of Laboratory Animals. Human subjects research was conducted under IRB protocol no. 00008149 and subjects were collected with funding from K23 MH074799-01A2 to JP.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, The Mood Disorders Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    J Guintivano, J L Payne & Z A Kaminsky

  2. Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA

    M Arad & T D Gould

  3. Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA

    T D Gould

  4. Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA

    T D Gould

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  1. J Guintivano
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Correspondence to Z A Kaminsky.

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Competing interests

ZK, JP and TDG are coinventors listed on a patent application for DNA methylation at biomarker loci related to PPD. The remaining authors declare no conflict of interest.

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Guintivano, J., Arad, M., Gould, T. et al. Antenatal prediction of postpartum depression with blood DNA methylation biomarkers. Mol Psychiatry 19, 560–567 (2014). https://doi.org/10.1038/mp.2013.62

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Keywords

  • biomarker
  • DNA methylation
  • estrogen
  • HP1BP3
  • postpartum depression
  • TTC9B

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