Blood metabolomic and postpartum depression: a mendelian randomization study.

ABSTRACT

BACKGROUND: Postpartum depression is a complex mental health condition that often occurs after childbirth and is characterized by persistent sadness, anxiety, and fatigue. Recent research suggests a metabolic component to the disorder. This study aims to investigate the causal relationship between blood metabolites and postpartum depression using mendelian randomization (MR). METHODS: This study used a bi-directional MR framework to investigate the causal relationship between 1,400 metabolic biomarkers and postpartum depression. We used two specific genome-wide association studies datasets one with single nucleotide polymorphisms data from mothers diagnosed with postpartum depression and another with blood metabolite data, both of which focused on people of European ancestry. Genetic variants were chosen as instrumental variables from both datasets using strict criteria to improve the robustness of the MR analysis. The combination of these datasets enabled a thorough examination of genetic influences on metabolic profiles associated with postpartum depression. Statistical analyses were conducted using techniques such as inverse variance weighting, weighted median, and model-based estimation, which enabled rigorous causal inference from the observed associations. postpartum depression was defined using endpoint definitions approved by the FinnGen study's clinical expert groups, which included leading experts in their respective medical fields. RESULTS: The MR analysis identified seven metabolites that could be linked to postpartum depression. Out of these, one metabolite was found to be protective, while six were associated with an increased risk of developing the condition. The results were consistent across multiple MR methods, indicating a significant correlation. CONCLUSIONS: This study emphasizes the potential of metabolomics for understanding postpartum depression. The discovery of specific metabolites associated with the condition sheds new insights on its pathophysiology and opens up possibilities for future research into targeted treatment strategies.