Latalova Klara, Sery Omar, Hosakova Kristyna, Hosak Ladislav
Department of Psychiatry, Palacky University Olomouc, School of Medicine and University Hospital Olomouc, Olomouc, Czech Republic.
Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
Neuropsychiatr Dis Treat. 2020 May 6;16:1147-1156. doi: 10.2147/NDT.S238522. eCollection 2020.
Mental disorders affect about one-third of the human population, are typically chronic and significantly decrease the quality of life. Presently, the treatment of mental illnesses is far from adequate with a substantial proportion of the patients being pharmacoresistant and suffering from relapses. One of the reasons for this complicated situation is that we do not precisely know about the causes of mental disorders, so their treatment cannot be causal. The etiology of a mental disorder is typically based on a combination of molecular (genetic) and environmental factors.
The aim of the project is to discover the gene-environment interactions (GxE) in a wide spectrum of mental disorders.
The design of our study is innovative in the sense that we intend to study large groups of associated mental disorders as a whole instead of in isolation. This would enable us to map out the possible environmental causal factors in detail in relation to their character, magnitude and timing. The project also allows a study of genetics (including epigenetics and microbiomes) as well as the environment simultaneously. We plan on involving three study groups: the first group are patients suffering from schizophrenia or a mood disorder such as major depression, recurrent depressive disorder and bipolar affective disorder; the second group of patients have anxiety disorders; and the third group are healthy volunteers from the general population who are genetically unrelated. All of the study subjects will undergo the following assessments: a psychiatric examination, the identification of stressful life events with the aid of a questionnaire, the examination of their reaction to stress, genetic and epigenetic (microRNA) assessments and the analysis of oral and gut microbiome.
We expect that some of the genetic as well as environmental factors in the studied mental disorders are shared, while some others are specific. We also expect that the GxE (gene-environment interaction) in schizophrenic and affective disorders will be different from the GxE in anxiety disorders and that the GxE in the studied mental disorders will differ generally from the GxE in healthy volunteers. Our results can help in the prevention and individualized treatment of a range of mental disorders.
精神障碍影响着约三分之一的人口,通常为慢性疾病,会显著降低生活质量。目前,精神疾病的治疗远未达到理想状态,相当一部分患者存在药物抵抗并遭受复发困扰。造成这种复杂情况的原因之一是我们并不确切了解精神障碍的病因,因此其治疗无法做到有的放矢。精神障碍的病因通常基于分子(遗传)和环境因素的综合作用。
该项目的目的是发现广泛的精神障碍中的基因-环境相互作用(GxE)。
我们研究的设计具有创新性,因为我们打算将大量相关的精神障碍作为一个整体而非孤立地进行研究。这将使我们能够详细描绘出可能的环境因果因素,包括其特征、程度和时机。该项目还允许同时研究遗传学(包括表观遗传学和微生物群)以及环境。我们计划纳入三个研究组:第一组是患有精神分裂症或情绪障碍(如重度抑郁症、复发性抑郁症和双相情感障碍)的患者;第二组是患有焦虑症的患者;第三组是来自普通人群的无亲缘关系的健康志愿者。所有研究对象都将接受以下评估:精神病学检查、借助问卷识别应激性生活事件、检查他们对压力的反应、基因和表观遗传学(微小RNA)评估以及口腔和肠道微生物群分析。
我们预计在所研究的精神障碍中,一些遗传和环境因素是共同的,而另一些则是特定的。我们还预计精神分裂症和情感障碍中的基因-环境相互作用(GxE)将与焦虑症中的GxE不同,并且所研究的精神障碍中的GxE总体上与健康志愿者中的GxE也会有所不同。我们的研究结果有助于一系列精神障碍的预防和个体化治疗。