CpG methylation levels at two loci within the HP1BP3 and TTC9B genes were identified as biomarkers predictive of PPD. Both genes have ties to estrogen signaling, as HP1BP3 was identified to associate with estrogen receptor β based on tandem affinity purification assays performed on MCF-7 breast cancer cells37 and TTC9B expression has been shown to be responsive to gonadal hormones.38 Owing to the circulating nature of estrogen, the identification of these markers in peripheral blood may be a marker of estrogen-mediated epigenetic changes occurring in the hippocampus and potentially conferring risk to phenotype based on its actions in the brain. The functional relevance of TTC9B may be linked to hippocampal synaptic plasticity as tetratricopeptide repeat containing domains such as that found in TTC9B have been shown to inhibit HSP90-mediated trafficking of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) receptors critical for hippocampal long-term potentiation/long-term depression.39
