Association of genetic polymorphisms with drug-response and personality in mood disorders

情绪障碍中基因多态性与药物反应和人格的关联

• 批准号: 10670923
• 负责人: OZAKI Norio
• 金额: $ 2.05万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670923/
• 关键词: MOOD DISOREDERS; GENE; DRUG-RESPONSE; PERSONALITY; BREEDING EXPERIENCE; 免疫学

Lifetime prevalence of mood disorders is estimated about 15% and mood disorders cause a serious social loss and a high suicide rate. There are many treatment-resistant cases with mood disorders although the treatment by antidepressants and mood stabilizers has been established. The pathophysiology of this disorders has not yet unknown, thus the elucidation of the pathophysiology is required to establish the prevention and treatment of this condition. According to the clinical genetic studies, such as the family study, the twin study, and the adopted study, genetic factors are hypothesized to participate in the etiology of mood disorders. In addition, abnormal monoamines in patients with mood disorders and monoaminergic mechanisms of psychotropic drugs suggest that abnormality of monoamines participates in the pathophysiology of mood disorders. These two points mentioned above lead to the monoaminergic genetic studies of mood disorders. No reproducible result, however, has acquired. One … More of the reasons for the obstacle is that mood disorders are etiologically heterogeneous disorders. Therefore, we have to grasp the family history, the response to psychotropic drugs, the personality, the breeding experience and the clinical information in order to elucidate the pathophysiology. In addition, by progress of molecular biology, we can search for monoaminergic molecular genetic mechanisms that is used to be impossible. Thus, we started to examine the monoaminergic molecular genetic background in patients with mood disorders after we obtained their drug-response, other biological data, their breeding experience, personality and the clinical features.We examined the personality using the TC1 in depression. As a result, the severity of depression showed the positive correlation with Harm Avoidance, and the negative correlation with Self-Directedness and Cooperativeness. Furthermore, good responders became close to normal values after an antidepressant treatment, but bad responders did not change. On the other hand, on the breeding experience using PBI, patients with depression and OCD showed a low caring of parents and a high protection of a mother. In addition, patients with atopic dermatitis had high Harm Avoidance with TCI and no characteristics with PBI.On the other hand, according to the molecular genetic study of seasonal affective disorder, the 5HTT polymorphism had the association with the disease, but the 5-HT1a, 1b, 1d, 2a, 2c do not.We are going to continue the molecular genetic research to obtain a marker for the drug response and open the road to the development of a new drug. Furthermore, we are carrying out researches to aim at goals as follows. 1) Developing a tool for early discovery of depression. 2) Frequency of mood disorders and an environment factor in laborers and patient with general medical conditions. 3) Effectiveness of cognitive behavior therapy for depression. Less

情绪障碍的终生患病率估计约为 15%，情绪障碍会导致严重的社会损失和高自杀率，尽管抗抑郁药和情绪稳定剂的治疗已经确定，但仍有许多情绪障碍的治疗耐药病例。疾病尚不为人所知，因此需要阐明其病理生理学来建立该疾病的预防和治疗方法。根据临床遗传学研究，如家系研究、双胞胎研究和收养研究，开创了遗传因素。此外，情绪障碍患者的单胺异常和精神药物的单胺能机制提示单胺异常参与了情绪障碍的病理生理学，这两点引发了单胺能遗传学研究。然而，尚未获得可重复的结果，其中一个障碍是情绪障碍是一种病因学上异质性的疾病，因此，我们必须掌握其家族史和反应。结合精神药物、性格、饲养经验和临床信息来阐明病理生理学。此外，通过分子生物学的进步，我们可以从遗传上寻找过去不可能的单胺能分子机制。在获得情绪障碍患者的药物反应、其他生物学数据、繁殖经历、性格和临床特征后，我们检查了情绪障碍患者的单胺能分子遗传背景。我们使用 TC1 来检查抑郁症患者的性格，从而确定抑郁症的严重程度。抑郁症与伤害避免呈正相关，与自我导向性和合作性呈负相关。此外，良好的反应者在抗抑郁治疗后变得接近正常值，但不良反应者则没有变化。根据PBI的繁殖经验，抑郁症和强迫症患者表现出对父母的关心程度较低，而对母亲的保护程度较高。此外，特应性皮炎患者在TCI中具有较高的伤害避免率，而在PBI中则没有特征。根据季节性情感障碍的分子遗传学研究，5HTT多态性与该疾病有关联，而5-HT1a、1b、1d、2a、2c则没有。我们将继续进行分子遗传学研究，以获得标记此外，我们正在开展研究以实现以下目标：1）开发早期发现抑郁症的工具。情绪障碍和环境因素对患有一般疾病的劳动者和患者的影响 3) 认知行为疗法对抑郁症的有效性 较少。

项目成果

Hibiya M, Ichinose H, Ozaki N, Fujita K, Nishimoto T, Yoshikawa T, Asano Y, Nagatsu T: "Normal value and age-dependent changes in GTP cyclohydrase I activity in stimulated mononuclear blood cells measured by high-performance liquid chromatography."Journal

Hibiya M、Ichinose H、Ozaki N、Fujita K、Nishimoto T、Yoshikawa T、Asano Y、Nagatsu T：“通过高效液相色谱法测量受刺激的单核血细胞中 GTP 环化酶 I 活性的正常值和年龄依赖性变化。

Kusunoki K, Ozaki N, Sawada M, Sato T, Hirano S, Narita T: "Serum levels of dihydroneopterin and soluble cytokine receptors in major depression"Pteridines. 10. 24-26 (1999)

Kusunoki K、Ozaki N、Sawada M、Sato T、Hirano S、Narita T：“重度抑郁症中二氢新蝶呤和可溶性细胞因子受体的血清水平”蝶啶。