Robert K McNamara, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45219, United States.
World J Psychiatry. 2015 Mar 22;5(1):15-34. doi: 10.5498/wjp.v5.i1.15.
Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In non-human primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with long-standing deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder (ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.
越来越多的转化证据表明，长链ω-3 脂肪酸二十二碳六烯酸（DHA）在皮质回路的成熟和稳定中发挥作用，而这些回路在不同的复发性精神障碍中受到损害。具体来说，啮齿动物和细胞培养研究发现，DHA 优先积累在突触和生长锥膜中，并促进神经突生长、树突棘稳定性和突触发生。额外的证据表明，DHA 可能在小胶质细胞介导的突触修剪以及髓鞘发育和弹性中发挥作用。在非人类灵长类动物中，围产期 n-3 脂肪酸不足会导致成年额皮质网络的功能连接广泛缺陷，而在 DHA 强化饮食中饲养的灵长类动物则没有这种缺陷。非人类灵长类动物和人类的早产与皮质 DHA 积累早期缺陷有关。人类早产与髓鞘完整性和皮质回路连接的长期缺陷以及注意力缺陷/多动障碍（ADHD）、情绪和精神病障碍的风险增加有关。一般来说，ADHD 和情绪及精神病障碍最初出现在皮质回路快速成熟期间，其特征是 DHA 缺乏、髓鞘病理和皮质回路连接受损。这些关联表明，胎儿大脑 DHA 积累的早期和未纠正的缺陷可能是精神障碍皮质回路成熟缺陷的可改变风险因素，因此可能对告知早期干预和预防策略具有重要意义。
