We hypothesized that the discrepancy between the prepartum euthymic and depressed cohorts may be related to differences in blood cell-type counts between the two groups. Various experiments have identified elevated granulocytes and decreased CD8 and CD4 T-cell and associated cytokine profiles in individuals exhibiting depressed mood.29,30 Using DNA methylation proxies in the 19 prepartum depressed and 32 prepartum euthymic women, we determined that cell-type proportions of CD8 T cells, CD4 T cells, B cells and monocytes were significantly reduced in the depressed prepartum group, whereas cross-batch controls exhibited nonsignificant differences in the opposite direction (Supplementary Table 4). Pyrosequencing DNA methylation values for HP1BP3 were evaluated against all cell types in an additive linear model and identified a trend with monocyte proportions (b= −1.11±0.6, P=0.07). We subsequently evaluated the ratio of monocytes to the summed proportions of CD8 T cells, CD4 T cells, B cells and granulocytes, and observed a significant association with prepartum depression status (cell ratio, depressed=0.021±5.2×10−4, euthymic=0.032±3.3×10−4, P=2.1×10−4) but not PPD status (cell ratio, PPD=0.028±5×10−4, non-PPD=0.028±4.2×10−4, P=0.86) (Figure 3a), the distribution of which was similar but opposite to
