Omega-3 polyunsaturated fatty acids (n‐3-PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may improve or prevent some psychiatric and neurodegenerative diseases in both experimental and clinical studies. As important membrane components, these PUFAs benefit brain health by modulating neuroimmune and apoptotic pathways, changing membrane function and/or competing with n‐6 PUFAs, the precursors of inflammatory mediators. However, the exact role of each fatty acid in neuroimmune modulation and neurogenesis, the interaction between EPA and DHA, and the best EPA:DHA ratios for improving brain disorders, remain unclear. It is also unknown whether EPA, as a DHA precursor, acts directly or via DHA. Here, we discuss recent evidence of EPA and DHA effects in the treatment of major depression and Alzheimer's disease, as well as their potential synergistic action on anti-inflammatory, antioxidant and neurotrophic processes in the brain. We further analyze the cellular and molecular mechanisms by which EPA, DHA or their combination may benefit these diseases. We also outline the limitations of current studies and suggest new genetic models and novel approaches to overcome these limitations. Finally, we summarize future strategies for translational research in this field.

Omega-3多不饱和脂肪酸（n-3-PUFA），主要是二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），可能在实验和临床研究中改善或预防某些精神疾病和神经退行性疾病。作为重要的膜成分，这些PUFA通过调节神经免疫和凋亡途径，改变膜功能和/或与炎性介质的前体n-6 PUFA竞争，从而有益于大脑健康。但是，每种脂肪酸在神经免疫调节和神经发生中的确切作用，EPA和DHA之间的相互作用以及改善脑部疾病的最佳EPA：DHA比例仍不清楚。EPA作为DHA的前体是直接发挥作用还是通过DHA发挥作用也不清楚。在这里，我们讨论了EPA和DHA在重度抑郁症和阿尔茨海默氏病治疗中的最新证据，以及它们对脑部抗炎，抗氧化和神经营养过程的潜在协同作用。我们进一步分析了EPA，DHA或其组合可能有益于这些疾病的细胞和分子机制。我们还概述了当前研究的局限性，并提出了新的遗传模型和新颖的方法来克服这些局限性。最后，我们总结了该领域翻译研究的未来策略。