Background: The primary prevention of illness at the population level, the ultimate aim of medicine, seems out of reach for schizophrenia. Schizophrenia has a strong genetic component, and its pathogenesis begins long before the emergence of psychosis, as early as fetal brain development. Cholinergic neurotransmission at nicotinic receptors is a pathophysiological mechanism related to one aspect of this genetic risk. Choline activates these nicotinic receptors during fetal brain development. Dietary supplementation of maternal choline thus emerges as a possible intervention in pregnancy to alter the earliest developmental course of the illness.
Aim: Review available literature on the relationship of choline supplementation or choline levels during pregnancy and fetal brain development.
Methods: A Medline search was used to identify studies assessing effects of choline in human fetal development. Studies of other prenatal risk factors for schizophrenia and the role of cholinergic neurotransmission in its pathophysiology were also identified.
Results: Dietary requirements for choline are high during pregnancy because of its several uses, including membrane biosynthesis, one-carbon metabolism, and cholinergic neurotransmission. Its ability to act directly at high concentrations as a nicotinic agonist is critical for normal brain circuit development. Dietary supplementation in the second and third trimesters with phosphatidyl-choline supports these functions and is associated generally with better fetal outcome. Improvement in inhibitory neuronal functions whose deficit is associated with schizophrenia and attention deficit disorder has been observed.
Conclusion: Prenatal dietary supplementation with phosphatidyl-choline and promotion of diets rich in choline-containing foods (meats, soybeans, and eggs) are possible interventions to promote fetal brain development and thereby decrease the risk of subsequent mental illnesses. The low risk and short (sixmonth) duration of the intervention makes it especially conducive to population-wide adoption. Similar findings with folate for the prevention of cleft palate led to recommendations for prenatal pharmacological supplementation and dietary improvement. However, definitive proof of the efficacy of prenatal choline supplementation will not be available for decades (because of the 20-year lag until the onset of schizophrenia), so public health officials need to decide whether or not promoting choline supplementation is justified based on the limited information available.
背景: 医学的最终目的是在人群中对疾病进行一级预防，这对精神分裂症而言似乎是难以实现的。精神分裂症的病因早在胎儿大脑发育时期就开始出现，远远早于病症的出现。基因因素是精神分裂症的主要病因之一，作用于烟碱型胆碱能受体上的胆碱能神经递质的传递是与此遗传风险相关的病理生理机制之一。在胎儿大脑发育过程中，胆碱可以激活上述烟碱型受体。因而通过孕期膳食补充胆碱可能是在更早期预防精神分裂症发生发展的一种干预手段。.
目的: 对有关孕期和胎儿大脑发育过程中补充胆碱或胆碱水平与疾病关系的文献进行综述。.
方法: 在Medline上检索评估胆碱对人类胎儿发育影响的研究，还检索了有关精神分裂症的其他产前危险因素的研究以及胆碱能神经传递对精神分裂症病理生理作用的研究。.
结果: 孕期饮食中胆碱含量要高，因为膜的生物合成、一碳单位代谢和胆碱能神经传递等都需要胆碱。高浓度胆碱能够直接作为烟碱型受体激动剂，这对正常的大脑环路发育是至关重要的。在孕中、晚期的膳食中补充磷脂酰胆碱可以增强上述胆碱的功能，更有利于胎儿的发育。有研究观察到膳食补充磷脂酰胆碱能改善抑制性神经元功能，而该功能不足与精神分裂症和注意缺陷障碍相关。.
结论: 产前膳食补充磷脂酰胆碱，提倡食用富含胆碱的食物（肉类、大豆、鸡蛋），可能会促进胎儿大脑发育，从而降低今后发生精神疾病的风险。这种短期（6个月）干预风险低，特别适用于普通人群。这类似于以往研究发现叶酸能预防腭裂，因而建议产前补充相应的药物并改善饮食。然而，数十年内还无法获得产前补充胆碱有效性的确切证据（因为精神分裂症的发生要滞后约20年），所以公共卫生领域的官员只能根据现有的有限信息来决定是否提倡补充胆碱。.
中文全文: 本文全文中文版从2015年6月6日起在http://dx.doi.org/10.11919/j.issn.1002-0829.215006可供免费阅览下载.
Keywords: choline; fetal development; nicotinic; pregnancy; prevention; receptors; schizophrenia.