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Psychiatry Res. 2019 Nov 27:112711. doi: 10.1016/j.psychres.2019.112711. [Epub ahead of print]

DNA methylation biomarkers prospectively predict both antenatal and postpartum depression.

Author information

1
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
The Royal's Institute of Mental Health Research, University of Ottawa, 1145 Carling Avenue, Rm, 6458 Ottawa, Ontario, Canada.
4
Department of Psychiatry & Human Behavior, UC Irvine Genetic Epidemiology Research Institute, University of California, Irvine, CA, USA.
5
Development, Health and Disease Research Program, University of California, Irvine, CA, USA; Medical Psychology Department, Charité University Medicine Berlin, Berlin, Germany.
6
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA.
7
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Royal's Institute of Mental Health Research, University of Ottawa, 1145 Carling Avenue, Rm, 6458 Ottawa, Ontario, Canada; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: zachary.kaminsky@theroyal.ca.

Abstract

We sought to replicate and expand upon previous work demonstrating antenatal TTC9B and HP1BP3 gene DNA methylation is prospectively predictive of postpartum depression (PPD) with ~80% accuracy. In a preterm birth study from Emory, Illumina MethylEPIC microarray derived 1st but not 3rd trimester biomarker models predicted 3rd trimester Edinburgh Postnatal Depression Scale (EPDS) scores ≥ 13 with an AUC=0.8 (95% CI: 0.63-0.8). Bisulfite pyrosequencing derived biomarker methylation was generated using bisulfite pyrosequencing across all trimesters in a pregnancy cohort at UC Irvine and in 3rd trimester from an independent Johns Hopkins pregnancy cohort. A support vector machine model incorporating 3rd trimester EPDS scores, TTC9B, and HP1BP3 methylation status predicted 4 week to 6 week postpartum EPDS ≥ 13 from 3rd trimester blood in the UC Irvine cohort (AUC=0.78, 95% CI: 0.64-0.78) and from the Johns Hopkins cohort (AUC=0.84, 95% CI: 0.72-0.97), both independent of previous psychiatric diagnosis. Technical replicate predictions in a subset of the Johns Hopkins cohort exhibited strong cross experiment correlation. This study confirms the PPD prediction model has the potential to be developed into a clinical tool enabling the identification of pregnant women at future risk of PPD who may benefit from clinical intervention.

KEYWORDS:

Antenatal depression; DNA methylation; Epigenetic; HP1BP3; Postpartum depression; TTC9B; biomarker

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