Molecular regulation of circadian rhythm and psychiatric disorders: a systematic review

ABSTRACT Objective The article aims to investigate the clock genes that are most associated with psychiatric disorders, the functions, and locations of these genes, as well as to investigate the main disorder, method and model in the analyzes. The paper seeks to summarize the findings and discuss the impact of this research on scientific knowledge. Methods This review used a systematic methodology (Prospero; ID 152031) and followed the PRISMA guidelines. The studies were searched in the PubMed/MEDLINE and Scientific Electronic Library Online databases and the terms of the Medical Subject Headings Terms were used. Quantitative studies with conclusive results regarding the association of psychiatric disorders with the molecular regulation of circadian rhythm were selected. The useful information was extracted and used for the elaboration of graphs and tables. Results We included 24 articles in our study. Bipolar disorder was the most commonly addressed psychiatric disorder (40% of studies); The participants’ Polish nationality also stood out in 39% of the works. Additionally, the PER gene was the most studied (25%) and the cerebral cortex was the main region in which the evaluated clock genes express themselves (34%). Finally, common PCR was the most used method (38%) and serotonin metabolism was the main function performed by gene products (16%). Conclusions Taken together, the results suggest that bipolar disorder is the most prevalent psychiatric disorder among research related to circadian genes, expressed mainly in the cerebral cortex of humans, especially the PER gene.摘要 目的：本研究旨在探究与精神疾病关联最为密切的时钟基因，阐明此类基因的功能与表达位点，同时厘清相关分析中所采用的主要疾病类型、实验方法及研究模型；并旨在总结现有研究成果，探讨本综述对相关科学认知的影响。 方法：本综述采用系统综述方法（Prospero平台；编号ID 152031），并遵循PRISMA报告规范。研究检索了PubMed/MEDLINE与科学电子在线图书馆（Scientific Electronic Library Online, SciELO）数据库，使用医学主题词（Medical Subject Headings, MeSH）进行检索。最终纳入针对精神疾病与昼夜节律分子调控存在明确关联的定量研究，提取有效信息用于图表绘制与表格编制。 结果：本研究共纳入24篇文献。双相情感障碍是最受关注的精神疾病（占比40%）；波兰籍受试者在39%的研究中占比突出。此外，PER基因是研究最为广泛的时钟基因（占比25%），大脑皮层是所评估时钟基因的主要表达区域（占比34%）。最后，聚合酶链式反应（Polymerase Chain Reaction, PCR）是最常用的实验方法（占比38%），血清素代谢是基因产物的主要功能（占比16%）。 结论：综合来看，研究结果表明，在昼夜节律时钟基因相关的精神疾病研究中，双相情感障碍是最受关注的研究主题，相关基因主要在人类大脑皮层中表达，其中尤以PER基因最为典型。