Distinct Genetic Profiles in Postpartum Depression With Different Trajectory of Illness

Abstract

BackgroundPostpartum depression (PPD) is a common and highly heritabledisorder in the postnatal period of new mothers. The development of PPD is shown to affectneurodevelopment in children and recent evidence suggests thatthe trajectory of PPDisalso associated with children’s neurodevelopment and mental conditions. Thus, early identification and intervention for individuals at high risk of PPD are urgently needed.Additionally, it is not clear whether genetic factors affect thetrajectory of PPD. Therefore, using a polygenic risk score (PRS) approach, we investigated if PRS for depression (Depression-PRS) and bipolar disorder (Bipolar-PRS) are associated with the development and clinical course of PPD.Methods Usingrecent large genome-wide association studies(GWAS) of depression and bipolar disorder as discovery cohorts, we calculatedDepression-PRS and Bipolar-PRS in each individual. Then, we investigated the possible association between Depression-PRS and Bipolar-PRS with the development andtrajectory of PPD insubjects from the Hamamatsu Birth Cohort for mothers and children (n = 136). Depressive symptoms were assessed using the Edinburgh Postpartum Depression Scale. Gene-set enrichment analyses were used to identify pathways underlying these conditions. ResultsDepression-PRS was significantly higher in subjects with PPD than in those without PPD(t = -3.283, P = 0.002)and logistic analysis showed that Depression-PRS significantly increases therisk of developing PPD(OR [SE] = 2.274 [0.585], P = 0.002). Furthermore, Depression-PRS was positively associated with continuity of PPD (β [SE]=1.621 [0.672]; P = 0.032).Gene-set enrichment analyses revealed that pathways such as“response to hormone”(β[SE] -2.285[1.002], P < 0.001) and “epigenetic regulation”(β[SE] 2.831 [1.317], P < 0.001) were involved in the continuity of PPD. ConclusionThese preliminary findings indicate that the genetic component plays an important role not only in the development but also inthe continuity of PPD. A polygenic risk score approach could be useful to identify subjects at risk for PPD, especially for persistent PPD,who needcareful monitoring and intervention after delivery.

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

“…Polygenic scores (PGS) that index an individual's liability to a given disorder have been used to investigate the genetic overlap between PND and MDD, as well as the personality trait neuroticism (Jermy et al, 2021;Pouget et al, 2021) and other psychiatric disorders, including bipolar disorder (BIP) (Bauer et al, 2019;Byrne et al, 2014;Jermy et al, 2021;Pouget et al, 2021;Rantalainen et al, 2020;Takahashi et al, 2020), schizophrenia (SCZ) (Rantalainen et al, 2020), and cross disorder, which includes attention deficit hyperactivity disorder (ADHD) and anorexia (Rantalainen et al, 2020), with inconsistent results. For example, compared to heterogeneous depression, PND has been associated with higher PGS for BIP (Byrne et al, 2014), and higher PGS for MDD and neuroticism (Jermy et al, 2021), but other studies have reported no association between PND and BIP PGS (Rantalainen et al, 2020;Takahashi et al, 2020) or neuroticism PGS (Pouget et al, 2021).…”