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.
DNA methylation variation at HP1BP3 and TTC9B is modified by estrogen exposure in the rodent hippocampus and was previously shown to be prospectively predictive of postpartum depression (PPD) when modeled in antenatal blood.
Using a statistical model trained on DNA methylation data from N=51 high-risk women, we prospectively predicted PPD status in an independent N=51 women using first trimester antenatal gene expression levels of HP1BP3 and TTC9B, with an area under the receiver operator characteristic curve (AUC) of 0.81 (95% CI: 0.69-0.92, p<5 × 10(-4)).
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.
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.