Genetic Evidence for Null Association Between Polyunsaturated Fatty Acids Levels and Postpartum Depression Risk: A Mendelian Randomization Study

Background: Previous observational studies suggest that polyunsaturated fatty acids (PUFAs) may influence the risk of postpartum depression (PPD) by modulating neuroinflammation and synaptic function. However, causal evidence remains limited. This study employs a genetic approach to investigate the causal relationship between omega-3 and omega-6 PUFAs, including their subtypes, as well as the risk of PPD. Methods: Genetic instrumental variables (IVs) associated with PUFA levels were selected based on genome-wide association study (GWAS) data from European populations. The inverse variance-weighted (IVW) method, along with additional Mendelian randomization (MR) approaches, were applied to analyze the associations between genetically predicted PUFA levels and PPD risk. Results: The results indicate that genetically predicted levels of omega-3, omega-6, and their subtypes were not causally associated with the risk of PPD in European women (odds ratio [OR] for omega-3 PUFAs = 1.026 [95% confidence interval [CI]: 0.949–1.109], p = 0.926; OR for docosahexaenoic acid (DHA) = 0.937 [95% CI: 0.808–1.087], p = 0.39; OR for eicosapentaenoic acid (EPA) = 0.798 [95% CI: 0.561–1.136], p = 0.211; OR for omega-6 PUFAs = 1.053 [95% CI: 0.939–1.181], p = 0.377; OR for linoleic acid (LA) = 1.046 [95% CI: 0.938–1.167], p = 0.418; and OR for arachidonic acid (AA) = 1.001 [95% CI: 0.941–1.063], p = 0.997). Conclusions: The genetic evidence from this study does not support a causal role for omega-3 and omega-6 PUFAs, or their subtypes, in the prevention of PPD. Although the genetic evidence from this study does not support a causal role for omega-3 and omega-6 PUFAs, or their subtypes, in the prevention of PPD, these results do not preclude potential benefits in specific subgroups. Future biomarker-guided trials targeting individuals with baseline PUFA deficiency may still be warranted.