Perinatal depression is associated with a higher polygenic risk for major depressive disorder than non-perinatal depression.

Distinctions between major depressive disorder (MDD) and perinatal depression (PND) reflect varying views of PND, from a unique etiological subtype of MDD to an MDD episode that happens to coincide with childbirth. This case-control study investigated genetic differences between PND and MDD outside the perinatal period (non-perinatal depression or NPD).We conducted a genome-wide association study using PND cases (Edinburgh Postnatal Depression Scale score ≥ 13) from the Australian Genetics of Depression Study 2018 data (n = 3804) and screened controls (n = 6134). Results of gene-set enrichment analysis were compared with those of women with non-PND. For six psychiatric disorders/traits, genetic correlations with PND were evaluated, and logistic regression analysis reported polygenic score (PGS) association with both PND and NPD.Genes differentially expressed in ovarian tissue were significantly enriched (stdBeta = 0.07, p = 3.3e-04), but were not found to be associated with NPD. The genetic correlation between PND and MDD was 0.93 (SE = 0.07; p = 3.5e-38). Compared with controls, PGS for MDD are higher for PND cases (odds ratio [OR] = 1.8, confidence interval [CI] = [1.7-1.8], p = 9.5e-140) than for NPD cases (OR = 1.6, CI = [1.5-1.7], p = 1.2e-49). Highest risk is for those reporting both antenatal and postnatal depression, irrespective of prior MDD history.PND has a high genetic overlap with MDD, but points of distinction focus on differential expression in ovarian tissue and higher MDD PGS, particularly for women experiencing both antenatal and postpartum PND.