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.
Zhong et al. (Wed,) studied this question.