遗传和早期环境对血清素系统的影响：对大脑发育的后果及精神病理学风险
Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology.
作者信息
Booij Linda, Tremblay Richard E, Szyf Moshe, Benkelfat Chawki
机构信息
Sainte-Justine Hospital Research Center & University of Montréal, Montréal, Que.; Department of Psychology and Psychiatry, Queen's University, Kingston, Ont.; Department of Psychiatry, McGill University, Montréal, Que.; Department of Psychiatry, University of Montréal, Montréal, Que.
Sainte-Justine Hospital Research Center & University of Montréal, Montréal, Que.; Departments of Psychology and Pediatrics, University of Montréal, Montréal, Que.; School of Public Health and Population Sciences, University College Dublin, Dublin, Ireland.
出版信息
J Psychiatry Neurosci. 2015 Jan;40(1):5-18. doi: 10.1503/jpn.140099.
BACKGROUND
Despite more than 60 years of research in the role of serotonin (5-HT) in psychopathology, many questions still remain. From a developmental perspective, studies have provided more insight into how 5-HT dysfunctions acquired in utero or early in life may modulate brain development. This paper discusses the relevance of the developmental role of 5-HT for the understanding of psychopathology. We review developmental milestones of the 5-HT system, how genetic and environmental 5-HT disturbances could affect brain development and the potential role of DNA methylation in 5-HT genes for brain development.
METHODS
Studies were identified using common databases (e.g., PubMed, Google Scholar) and reference lists.
RESULTS
Despite the widely supported view that the 5-HT system matures in early life, different 5-HT receptors, proteins and enzymes have different developmental patterns, and development is brain region-specific. A disruption in 5-HT homeostasis during development may lead to structural and functional changes in brain circuits that modulate emotional stress responses, including subcortical limbic and (pre)frontal areas. This may result in a predisposition to psychopathology. DNA methylation might be one of the underlying physiologic mechanisms.
LIMITATIONS
There is a need for prospective studies. The impact of stressors during adolescence on the 5-HT system is understudied. Questions regarding efficacy of drugs acting on 5-HT still remain.
CONCLUSION
A multidisciplinary and longitudinal approach in designing studies on the role of 5-HT in psychopathology might help to bring us closer to the understanding of the role of 5-HT in psychopathology.
背景
尽管在血清素（5-羟色胺，5-HT）在精神病理学中的作用方面已经进行了60多年的研究，但仍有许多问题存在。从发育的角度来看，研究已经更深入地了解了子宫内或生命早期获得的5-HT功能障碍如何调节大脑发育。本文讨论了5-HT的发育作用对于理解精神病理学的相关性。我们回顾了5-HT系统的发育里程碑、遗传和环境因素导致的5-HT紊乱如何影响大脑发育以及5-HT基因中的DNA甲基化在大脑发育中的潜在作用。
方法
通过常用数据库（如PubMed、谷歌学术）和参考文献列表来识别研究。
结果
尽管人们普遍认为5-HT系统在生命早期成熟，但不同的5-HT受体、蛋白质和酶具有不同的发育模式，并且发育具有脑区特异性。发育过程中5-HT稳态的破坏可能导致调节情绪应激反应的脑回路发生结构和功能变化，包括皮层下边缘系统和（前额）额叶区域。这可能导致易患精神病理学疾病。DNA甲基化可能是潜在的生理机制之一。
局限性
需要进行前瞻性研究。青春期应激源对5-HT系统的影响研究不足。关于作用于5-HT的药物疗效的问题仍然存在。
结论
采用多学科和纵向研究方法来设计关于5-HT在精神病理学中作用的研究，可能有助于我们更深入地理解5-HT在精神病理学中的作用。
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