Georgetown University, Interdisciplinary Program in Neuroscience, Washington DC, United States.
Department of Psychology, The University of Texas at El Paso, El Paso, TX 79968, United States.
Curr Pharm Des. 2020;26(20):2385-2401. doi: 10.2174/1381612826666200429094158.
Omega-3 (N3) fatty acids are dietary nutrients that are essential for human health. Arguably, one of their most critical contributions to health is their involvement in the structure and function of the nervous system. N3 fatty acids accumulate in neuronal membranes through young adulthood, becoming particularly enriched in a brain region known to be the locus of cognitive control of behavior-the prefrontal cortex (PFC). The PFC undergoes a surge in development during adolescence, coinciding with a life stage when dietary quality and intake of N3 fatty acids tend to be suboptimal. Such low intake may impact neurodevelopment and normative development of cognitive functions suggested to be protective for the risk of subsequent substance and alcohol use disorders (UD). While multiple genetic and environmental factors contribute to risk for and resilience to substance and alcohol use disorders, mounting evidence suggests that dietary patterns early in life may also modulate cognitive and behavioral factors thought to elevate UD risk (e.g., impulsivity and reward sensitivity). This review aims to summarize the literature on dietary N3 fatty acids during childhood and adolescence and risk of executive/ cognitive or behavioral dysfunction, which may contribute to the risk of subsequent UD. We begin with a review of the effects of N3 fatty acids in the brain at the molecular to cellular levels-providing the biochemical mechanisms ostensibly supporting observed beneficial effects. We continue with a review of cognitive, behavioral and neurodevelopmental features thought to predict early substance and alcohol use in humans. This is followed by a review of the preclinical literature, largely demonstrating that dietary manipulation of N3 fatty acids contributes to behavioral changes that impact drug sensitivity. Finally, a review of the available evidence in human literature, suggesting an association between dietary N3 fatty and neurodevelopmental profiles associated with risk of adverse outcomes including UD. We conclude with a brief summary and call to action for additional research to extend the current understanding of the impact of dietary N3 fatty acids and the risk of drug and alcohol UD.
ω-3（N3）脂肪酸是对人体健康至关重要的膳食营养素。可以说，它们对健康最重要的贡献之一是参与神经系统的结构和功能。N3 脂肪酸在成年早期积累在神经元膜中，在一个已知是行为认知控制的大脑区域（前额叶皮层，PFC）中特别丰富。PFC 在青春期经历了一次发育高峰，与饮食质量和 N3 脂肪酸摄入往往不理想的生命阶段相吻合。这种低摄入量可能会影响神经发育和认知功能的正常发展，而这些认知功能被认为可以预防随后的物质和酒精使用障碍（UD）的风险。虽然多种遗传和环境因素会导致物质和酒精使用障碍的风险和韧性，但越来越多的证据表明，生命早期的饮食模式也可能调节被认为会增加 UD 风险的认知和行为因素（例如，冲动和奖励敏感性）。本综述旨在总结儿童和青少年时期饮食 N3 脂肪酸与执行/认知或行为功能障碍风险的相关文献，这些因素可能会增加随后 UD 的风险。我们首先回顾了 N3 脂肪酸在大脑中的分子到细胞水平的作用，提供了支持观察到的有益效果的生化机制。然后我们回顾了被认为可以预测人类早期物质和酒精使用的认知、行为和神经发育特征。接下来，我们回顾了临床前文献，这些文献主要表明饮食中 N3 脂肪酸的操纵会导致影响药物敏感性的行为变化。最后，我们回顾了人类文献中的现有证据，这些证据表明饮食 N3 脂肪酸与与不良结果（包括 UD）相关的神经发育特征之间存在关联。最后，我们简要总结并呼吁开展更多研究，以扩展对饮食 N3 脂肪酸的影响以及药物和酒精 UD 风险的现有认识。
