Understanding the genetics of peripartum depression: Research challenges, strategies, and opportunities

Abstract

Peripartum depression (PD) is a common mood disorder associated with negative outcomes for mother and child. PD is an understudied disorder in psychiatric genetics, and progress characterizing its genetic architecture has been limited by a lack of disorder-specific research, heterogeneous and evolving phenotypic definitions, inadequate representation of global populations, low-powered studies, and insufficient data amenable to large meta-analyses. The increasing availability of large-scale, population-level efforts, like biobanks, have the potential to accelerate scientific discovery and translational research by leveraging clinical, molecular, and self-report data from hundreds of thousands of individuals. Although these efforts will not fully equip researchers to confront every challenge posed by systemic issues in data collection, such as the reliance on minimal phenotyping strategies, the field is in a position to learn from other successful psychiatric genetic investigations. This review summarizes the current state of PD genetics research and highlights research challenges, including the impact of phenotype depth, measurement, and definition on the replicability and interpretability of genomic research. Recommendations for advancing health equity and improving the collection, analysis, discussion, and reporting of measures for PD research are provided.

Keywords: depression; genetics; genome-wide association studies; major depressive disorder; peripartum depression; polygenic risk scores; postpartum depression; women’s mental health.

FIGURE 1

Impact of Phenotypic Definition on Peripartum Depression Case Status. This figure illustrates how the same medical history would be classified in a case-control study of peripartum depression (PD) based on the evolving criteria for diagnosis that have appeared in the Diagnostic and Statistical Manual (DSM). For each subpanel, green ovals indicate pregnancies, and squares indicate depressive episodes. Black squares indicate depressive episodes that meet diagnostic criteria for PD, and yellow squares indicate depressive episodes that do not meet PD diagnostic criteria. The diagnostic window for each definition is denoted by vertical grey boxes in the center section. For DSM-IV, the narrow vertical grey box represents the 4 week window following pregnancy when the postpartum specifier would be applied to MD episodes onsetting during that time period. The diagnostic window is much larger for DSM-5 and includes all of pregnancy. Note that before 1994, researchers would have had to apply their own definition because no specifier or diagnosis was included in the DSM before DSM-IV. MD, major depression; MDE, major depressive episode; PD, peripartum depression; DSM, Diagnostic and Statistical Manual.