Preliminary insights into the genetic architecture of postpartum depressive symptom severity using polygenic risk scores

Background Genetic factors influence susceptibility to postpartum mood disorders (PPMDs). However, the genetic architecture of PPMDs remains poorly understood. This study explored the genetic architecture of depressive symptom severity in a transdiagnostic sample of Canadian women with self-report PPMDs. Methods Women with self-reported current or past postpartum depression (PPD) or past postpartum psychosis (PPP) were recruited online via social media from across Canada. Postpartum depressive symptom severity was measured by self-report using the Edinburgh Postnatal Depression Scale (EPDS) through an iPhone application that is part of a large international study. Polygenic risk scoring (PRS) was applied to evaluate the genetic relationship between EPDS score and six non-perinatal psychiatric disorders (anxiety, bipolar disorder, depression, neuroticism, obsessive compulsive disorder, schizophrenia) and three putative PPMD biomarkers (C reactive protein (CRP), thyroxine (T4), progesterone). Exploratory Mendelian randomization was performed to evaluate causal relationships between biomarker levels and EPDS score. Results Polygenic risk scores for (1) bipolar disorder, (2) depression, and (3) serum CRP levels were positively associated with EPDS score among women with PPMDs (p < 0.05 after multiple testing correction). Mendelian randomization did not suggest a causal relationship between CRP levels and EPDS scores, but lacked sufficient statistical power. Conclusions This transdiagnostic study provides preliminary insights into the genetic architecture of postpartum depressive symptom severity as a dimensional trait. Our findings suggest there are shared genetic risk factors for postpartum depressive symptom severity and susceptibility to mood disorders outside the perinatal window, and highlight the potential role of inflammation in influencing postpartum depressive symptom severity.