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

心境障碍的终生患病率估计约为15%，心境障碍导致严重的社会损失和高自杀率。虽然抗抑郁药和情绪稳定剂的治疗已经建立，但仍有许多情绪障碍的治疗抵抗病例。这种疾病的病理生理学尚未可知，因此需要阐明病理生理学以确定这种疾病的预防和治疗。根据临床遗传学研究，如家系研究、双生子研究和收养研究，遗传因素被假设参与了心境障碍的病因学。此外，心境障碍患者的单胺类神经递质异常和精神药物的单胺类神经递质作用机制提示，单胺类神经递质异常参与了心境障碍的病理生理过程。这两点导致了情绪障碍的单胺能遗传学研究。然而，没有获得可重复的结果。一 关于我们 障碍的原因之一是心境障碍是病因异质性障碍。因此，我们必须掌握家族史、对精神药物的反应、个性、养育经验和临床资料，以阐明病理生理学。此外，随着分子生物学的发展，我们可以探索过去无法探索的单胺能分子遗传机制。因此，我们在获得心境障碍患者的药物反应、其他生物学资料、生育经历、人格特征和临床特征后，开始研究心境障碍患者的单胺能分子遗传背景，并采用抑郁症的TC-1人格特征进行研究。结果表明，抑郁程度与伤害回避呈显著正相关，与自我导向、合作性呈显著负相关。此外，在抗抑郁药治疗后，好反应者变得接近正常值，但差反应者没有改变。另一方面，在使用PBI的养育经验中，抑郁症和强迫症患者表现出较低的父母关怀和较高的母亲保护。另外，特应性皮炎患者对TCI的伤害回避程度高，对PBI无特征。另一方面，根据季节性情感障碍的分子遗传学研究，5-HTT多态性与疾病相关，但5-HT 1a，1b，1d，2a，我们将继续进行分子遗传学研究，以获得药物反应的标志物，并为新药的开发开辟道路。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。2)情绪障碍的频率和环境因素在劳动者和一般医疗条件下的病人。3)认知行为疗法对抑郁症的疗效。少

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