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精神分裂症与昼夜节律紊乱:遗传、代谢及临床特征概述。

Schizophrenia and disruption of circadian rhythms: An overview of genetic, metabolic and clinical signs.

机构信息

Department of Psychiatry, Narcology and Medical Psychology, Poltava State Medical University, Poltava, Ukraine.

Department of Biosciences, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai-602105, Tamil Nadu, India.

出版信息

Schizophr Res. 2024 Feb;264:58-70. doi: 10.1016/j.schres.2023.12.002. Epub 2023 Dec 14.

Abstract

A molecular clock in the suprachiasmatic nucleus of the anterior hypothalamus, which is entrained by the dark-light cycle and controls the sleep-wake cycle, regulates circadian rhythms. The risk of developing mental disorders, such as schizophrenia, has long been linked to sleep abnormalities. Additionally, a common aspect of mental disorders is sleep disturbance, which has a direct impact on the intensity of the symptoms and the quality of life of the patient. This relationship can be explained by gene alterations such as CLOCK in schizophrenia which are also important components of the physiological circadian rhythm. The function of dopamine and adenosine in circadian rhythm should also be noted, as these hypotheses are considered to be the most popular theories explaining schizophrenia pathogenesis. Therefore, determining the presence of a causal link between the two can be key to identifying new potential targets in schizophrenia therapy, which can open new avenues for clinical research as well as psychiatric care. We review circadian disruption in schizophrenia at the genetic, metabolic, and clinical levels. We summarize data about clock and clock-controlled genes' alterations, neurotransmitter systems' impairments, and association with chronotype in schizophrenia patients. Our findings demonstrate that in schizophrenia either homeostatic or circadian processes of sleep regulation are disturbed. Also, we found an insufficient number of studies aimed at studying the relationship between known biological phenomena of circadian disorders and clinical signs of schizophrenia.

摘要

视交叉上核的分子钟受昼夜节律的影响,控制着睡眠-觉醒周期,调节着昼夜节律。精神障碍(如精神分裂症)的发病风险与睡眠异常有关,这一现象由来已久。此外,精神障碍的一个常见特征是睡眠障碍,它直接影响到患者症状的严重程度和生活质量。这种关系可以通过基因改变来解释,例如 CLOCK 在精神分裂症中的改变,这些改变也是生理昼夜节律的重要组成部分。还应该注意多巴胺和腺苷在昼夜节律中的作用,因为这些假说被认为是解释精神分裂症发病机制的最流行理论。因此,确定两者之间是否存在因果关系可能是确定精神分裂症治疗中潜在新靶点的关键,这为临床研究和精神保健开辟了新的途径。我们综述了精神分裂症在遗传、代谢和临床水平上的昼夜节律紊乱。我们总结了有关生物钟和时钟控制基因改变、神经递质系统损伤以及与精神分裂症患者昼夜类型关联的数据。我们的研究结果表明,在精神分裂症中,无论是睡眠调节的稳态过程还是昼夜节律过程都受到了干扰。此外,我们还发现,针对已知的昼夜节律紊乱的生物学现象与精神分裂症临床症状之间的关系进行研究的数量不足。

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