Mental disorders (MDs) are emerging as a significant threat to global health, with their intricate pathogenesis making the discovery of effective treatments a challenging endeavor. Currently, nutritional intervention, especially polyunsaturated fatty acids (PUFAs), has garnered widespread attention. This review aims to explore the potential causal relationship between PUFAs and MDs using Mendelian randomization (MR) meta-analysis. The study employed two-sample MR technology to analyze the association between PUFAs (including omega-3, omega-3%, omega-6, omega-6%, and the omega-6:omega-3 ratio) and MDs. It utilized data from genome-wide association studies to assess the role of PUFAs in 12 major MDs. The MR analysis revealed a causal link between genetically predicted omega-3 and MDs such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% showed protective effects against certain diseases, including emotional personality disorder. Meanwhile, the inverse correlation between genetically predicted omega-6 and the risk of attention deficit/hyperactivity disorder, as well as the association between a high omega-6:omega-3 ratio and increased risk of depression and other mood disorders, were also supported by meta-analyses. These findings suggest that high levels of omega-3 and omega-3% may reduce the risk of MDs, while a high omega-6:omega-3 ratio may increase the risk. The study highlights the potential of PUFAs, particularly omega-3, in the prevention and treatment of MDs, while also noting the complex interactions between omega-3 and omega-6 and their impact on MDs, which necessitates further research. These findings provide a scientific basis for future clinical trials and the development of dietary intervention measures.

The authors have declared no competing interest.

This work was funded by the Zhejiang Medical and Health Science and Technology Project (Nos. 2023KY1271, 2024KY484), the Shaoxing Health Science and Technology Project (Nos. 2023SKY072, 2023SKY073), the Science and Technology Planning Project of Shaoxing City, China (No. 2023A14030), and the Shaoxing Seventh People's Hospital (No. 2022Q03), and Shaoxing University enterprise important horizontal topic (No. 2024USXH287 ).

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