Elucidate the meaning of chronobiological genotype for etiological mechanism of mood disorders

阐明时间生物学基因型对情绪障碍病因机制的意义

• 批准号: 13670999
• 负责人: OZEKI Yuji
• 金额: $ 2.3万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670999/
• 关键词: mood disorder; chronotxpe; biological rhythm; bipolar disorder; morningness-eveningness score; snp; hper1; hper2; 時間関連遺伝子; 時間遺伝子; ポリモルフィズム; per2; per; clock

Disruptions in circadian rhythm such as the sleep-wake cycle, body temperature, frequently characterize mood disorder. Researchers have developed chronobiological theories to explain such observation. And social rhythm therapy, which grew from the chronobiological model of mood disorder, is an effective psychotherapy specially designed for the treatment. Therefore, mood disorder is thought to be associated with disturbed circadian rhythms, and there is a chance that polymorphism of the circadian gene might influence mood disorder.To test this hypothesis, mutation screening was performed in the reported area of the human hper2, in which are a mutation accelerates human circadian rhythm, in bipolar disorder patients and controls. We screened 88 patients with bipolar disorder and 127 normal controls. But we cannot find any relation between genotype and phenotype.We also try to realize the hper1 influences with sleep habituation by using the Horne-Osberg morningness-evening score. We find one SNP with amino acid substitution in hper1 gene. But there was no relation between hper1 new haprotype and sleep habituation of 134 normal controls.To find a molecular mechanism of chronobiological theory of mood disorder, further investigation of clock relevant gene may need.

昼夜节律的紊乱，例如睡眠-觉醒周期、体温，常常是情绪障碍的特征。研究人员开发了时间生物学理论来解释这种观察结果。而从情绪障碍的时间生物学模型发展而来的社会节律疗法，是专门针对该治疗而设计的一种有效的心理疗法。因此，情绪障碍被认为与昼夜节律紊乱有关，并且昼夜节律基因的多态性有可能影响情绪障碍。为了检验这一假设，在双相情感障碍患者和对照中，对人类 hper2 的报道区域进行了突变筛查，其中突变加速了人类昼夜节律。我们筛查了 88 名双相情感障碍患者和 127 名正常对照者。但我们找不到基因型和表型之间的任何关系。我们还尝试通过使用Horne-Osberg早晚评分来认识hper1对睡眠习惯的影响。我们在hper1基因中发现了一个氨基酸取代的SNP。但hper1新单体型与134名正常对照的睡眠习惯之间没有关系。要找到情绪障碍时间生物学理论的分子机制，可能需要对时钟相关基因进行进一步研究。

项目成果

Shiino Y, Nakajima S, Ozeki Y, Isono T, Yamada N: "Mutation screening of the human period gene in bipolar disorder"Neuroscience Letter. 338. 82-84 (2000)

Shiino Y、Nakajima S、Ozeki Y、Isono T、Yamada N：“双相情感障碍中人类周期基因的突变筛查”神经科学快报。

Yayoi Shiino: "Mutation screening of the human period2 gene in bipolar disorder"Neuroscience Letters. 20. 82-84 (2003)

椎野弥生：“双相情感障碍中人类 period2 基因的突变筛查”《神经科学快报》。

Yayoi Shiino, Satoru Nakajima, Yuji Ozeki, Takahiro Isono, Naoto Yamada: "Mutation screening of the human period 2003gene in bipolar disorder"Neuroscience Letters. 388-1. 82-84 (2003)

Yayoi Shiino、Satoru Nakajima、Yuji Ozeki、Takahiro Isono、Naoto Yamada：“双相情感障碍中人类 2003 期基因的突变筛查”神经科学快报。