HLA基因及儿童期经历在抑郁障碍发病机制中的作用及其交互影响关系(1)
摘要：在抑郁障碍的发病机制中，基因-环境交互作用学说得到了许多研究者的支持。同时抑郁障碍已经被许多研究广泛证实为与免疫密切相关的疾病，抑郁障碍患者中枢神经系统的免疫因子水平紊乱，个体对环境的高敏感状态等免疫系统亢进的表现已经被揭示。而儿童期遭遇的长期或重大的应激经历及创伤体验会显著增加个体罹患抑郁障碍的风险，这种早期的负性体验也会导致成年后机体免疫系统的亢进。HLA基因作为自身免疫过程的起点，其表达产物的类型及水平都会对个体的免疫系统产生重大影响。但是目前针对HLA基因在精神障碍的发病机制中的研究较为缺乏。本文分析了HLA基因对抑郁障碍发病可能存在的影响，总结了儿童期经历对个体抑郁障碍易感性的影响，并探索性的讨论了HLA基因以及儿童期经历在抑郁障碍发病机制中所起到的作用以及其相互间的交互作用存在的可能性机制。
关键词：抑郁障碍;童年期创伤;HLA基因多态性;基因环境交互学说;自身免疫
中图分类号：R749.4+1 文獻标识码：A DOI：10.3969/j.issn.1006-1959.2019.16.009
, 百拇医药
文章编号：1006-1959(2019)16-0027-03
Abstract：In the pathogenesis of depressive disorder， the theory of gene-environment interaction has been supported by many researchers. At the same time， depressive disorder has been widely confirmed by many studies as a disease closely related to immunity. The level of immune factors in the central nervous system of patients with depressive disorder is disordered， and the performance of the immune system such as the high sensitivity of the individual to the environment has been revealed. Long-term or significant stress experiences and traumatic experiences experienced during childhood can significantly increase the risk of depression in an individual. This early negative experience can also lead to an increase in the body's immune system in adulthood. As the starting point of the autoimmune process， the HLA gene has a significant impact on the individual's immune system. However， there is currently a lack of research on the pathogenesis of mental disorders in the HLA gene. This article analyzes the possible effects of HLA gene on the pathogenesis of depressive disorder， summarizes the impact of childhood experience on the susceptibility of individual depression， and explores the HLA gene and childhood experience in the pathogenesis of depression and the possible in mechanisms by which roles and their interactions exist.
, 百拇医药
Key words：Depression;Childhood trauma;HLA gene polymorphism;Genetic environment interaction theory; Autoimmune
随着社会经济水平的快速发展，工作压力及生活负担使得抑郁障碍的患病人群逐渐增加。最新发布的中国精神卫生调查(China Mental Health Survey，CMHS)结果[1]显示，在我国抑郁障碍的终生患病率为6.8%，12个月患病率为3.6%。而2017年世界卫生组织(WHO)发布的数据[2]显示全球范围内抑郁障碍患者已达3.22亿人，且10年间患者数量增加了18.4%。抑郁障碍的发病机制目前还尚未被完全揭示。患者除了出现情绪低落、兴趣丧失等临床表现以外，其体内环境中大脑内环境神经递质的紊乱、免疫水平的异常等表现也备受研究者的重视。随着对抑郁障碍病因学研究的深入，基因以及环境因素对抑郁障碍的交互作用越来越受到研究者的重视。英国精神病学家Michael Rutter首次提出遗传-环境交互学说[3](gene×environment interactions)，指出基因产物的调控作用与环境对疾病发展的干预作用在精神疾病的发病机制中占有主要地位，且二者存在相互影响。而后许多临床研究为这一假说提供了支持证据。因此，基因与环境的交互作用，可能是引起个体抑郁障碍的易感性差异、抑郁患者间症状的表现差异的主要机制。本文旨在探索性讨论HLA基因的多态性是否对抑郁障碍发病存在影响，且与其他基因类似，存在与环境因素的交互作用。, 百拇医药(程怡欣 卢瑾)
关键词：抑郁障碍;童年期创伤;HLA基因多态性;基因环境交互学说;自身免疫
中图分类号：R749.4+1 文獻标识码：A DOI：10.3969/j.issn.1006-1959.2019.16.009
, 百拇医药
文章编号：1006-1959(2019)16-0027-03
Abstract：In the pathogenesis of depressive disorder， the theory of gene-environment interaction has been supported by many researchers. At the same time， depressive disorder has been widely confirmed by many studies as a disease closely related to immunity. The level of immune factors in the central nervous system of patients with depressive disorder is disordered， and the performance of the immune system such as the high sensitivity of the individual to the environment has been revealed. Long-term or significant stress experiences and traumatic experiences experienced during childhood can significantly increase the risk of depression in an individual. This early negative experience can also lead to an increase in the body's immune system in adulthood. As the starting point of the autoimmune process， the HLA gene has a significant impact on the individual's immune system. However， there is currently a lack of research on the pathogenesis of mental disorders in the HLA gene. This article analyzes the possible effects of HLA gene on the pathogenesis of depressive disorder， summarizes the impact of childhood experience on the susceptibility of individual depression， and explores the HLA gene and childhood experience in the pathogenesis of depression and the possible in mechanisms by which roles and their interactions exist.
, 百拇医药
Key words：Depression;Childhood trauma;HLA gene polymorphism;Genetic environment interaction theory; Autoimmune
随着社会经济水平的快速发展，工作压力及生活负担使得抑郁障碍的患病人群逐渐增加。最新发布的中国精神卫生调查(China Mental Health Survey，CMHS)结果[1]显示，在我国抑郁障碍的终生患病率为6.8%，12个月患病率为3.6%。而2017年世界卫生组织(WHO)发布的数据[2]显示全球范围内抑郁障碍患者已达3.22亿人，且10年间患者数量增加了18.4%。抑郁障碍的发病机制目前还尚未被完全揭示。患者除了出现情绪低落、兴趣丧失等临床表现以外，其体内环境中大脑内环境神经递质的紊乱、免疫水平的异常等表现也备受研究者的重视。随着对抑郁障碍病因学研究的深入，基因以及环境因素对抑郁障碍的交互作用越来越受到研究者的重视。英国精神病学家Michael Rutter首次提出遗传-环境交互学说[3](gene×environment interactions)，指出基因产物的调控作用与环境对疾病发展的干预作用在精神疾病的发病机制中占有主要地位，且二者存在相互影响。而后许多临床研究为这一假说提供了支持证据。因此，基因与环境的交互作用，可能是引起个体抑郁障碍的易感性差异、抑郁患者间症状的表现差异的主要机制。本文旨在探索性讨论HLA基因的多态性是否对抑郁障碍发病存在影响，且与其他基因类似，存在与环境因素的交互作用。, 百拇医药(程怡欣 卢瑾)