Influence of omega-3 fatty acids on post-traumatic stress disorder: prospective cohort study and Mendelian randomisation findings

<b>Background and Objectives:</b> Omega-3 fatty acids have positive effects on mental health. This study aimed to explore the association between plasma omega-3 fatty acid levels and the risk of post-traumatic stress disorder (PTSD).<b>Methods:</b> This study explored the association between plasma omega-3 fatty acid levels and risk of developing PTSD. In total, 82,391 adults from the UK Biobank were included in this study. PTSD screening was performed using a PCL-6 score greater than 13, based on responses to the online mental health questionnaire. Multivariate logistic regression analyses were performed to evaluate the association between omega-3 fatty acid levels and the risk of PTSD. Additionally, a two-sample bidirectional Mendelian randomisation (MR) analysis was used to investigate potential causal relationships.<b>Results:</b> A significant association was found between high omega-3 fatty acid levels and a lower risk of PTSD. For each 1 unit increase in omega-3 fatty acids, the adjusted odds ratio (OR) was 0.75 (<i>p</i> = 9.05E-05); for each 1% increase in total fatty acids, the adjusted OR was 0.95 (<i>p</i> = 4.30E-07). Among the population that has experienced catastrophic traumatic exposure, the results remained consistent. MR analysis indicated that high omega-3 levels and omega-3/total fatty acid ratios were causally linked to a reduced risk of PTSD (per 1 unit increase, OR = 0.99; <i>p</i> = .029; per 1% increase, OR = 0.98; <i>p</i> = .037). Conversely, PTSD was causally associated with lower omega-3 levels (beta = -0.203, <i>p</i> = 2.12E-05) and a lower omega-3/total fatty acids ratio (beta = -0.266, <i>p</i> = 1.52E-07). Subgroup analyses revealed that females might benefit more significantly (OR = 0.64, <i>p</i> = 3.59E-07; <i>p</i>-interaction = .010).<b>Conclusions:</b> This study suggests a negative association between PTSD and omega-3 fatty acids, indicating that omega-3 supplementation may be an effective preventive and therapeutic strategy for PTSD.