| 李则宣.抑郁症的表观遗传学机制：涉及认知灵活性的证据[J].济宁医学院学报,2017,40(5):361-365 |
| 抑郁症的表观遗传学机制：涉及认知灵活性的证据 |
| Mechanism of epigenetics in depression:evidence for involvement of cognitive flexibility |
| 投稿时间：2017-07-13 |
| DOI：10.3969/j.issn.1000-9760.2017.05.012 |
| 中文关键词: 抑郁症;表观遗传学;应激;认知灵活性 |
| 英文关键词: Depression;Epigenetics;Stress;Cognitive flexibility |
| 基金项目:国家科技支撑计划（2015BAI13B02） |
| 作者 | 单位 | | 李则宣 | 中南大学湘雅二医院精神卫生研究所
国家精神心理疾病临床研究中心(长沙), 长沙 410011 |
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| 中文摘要: |
| 抑郁症是全球高负担疾病，严重影响人们的职业功能、生活质量和幸福感。遗传和环境在抑郁症的易感中共同发挥作用，这可能是通过表观遗传学机制（如DNA甲基化）而最终影响基因表达来介导的。一方面，应激作为普遍而显著的环境因素可引起多种基因的甲基化改变而导致抑郁症，另一方面，神经心理学认知研究的证据支持认知异常尤其是认知灵活性异常在抑郁症病理机制中的核心作用。目前神经生物学研究也支持抑郁症表观遗传学机制涉及认知灵活性的调节异常，但缺乏直接而具体的证据。对此进行研究将进一步促进抑郁症的理解、诊断和治疗。 |
| 英文摘要: |
| As one most common mental disorder with high prevalence rate,depression accounts for an increasingly substantial proportion of the global burden of disease and has a devastating impact on occupational functioning,quality of life and well-being.In general,it is well admitted that genetic and environmental factors together play an important role in the vulnerability to depression.However,current data has showed that no specific gene(s) is/are responsible for depression.For the time being,the genes found for leading to MDD can not be well repeated at all.One reason for this may be that there exists great heterogeneity in the mechanisms underlying depression.On the other hand,another explanation for this in the context of gene-environment interaction is that depression may be more mediated by epigenetic mechanism(e.g.,methylation of DNA) that can eventually influence gene expression.It has be well suggested that stresses as common and significant environmental factors enable depression by recruiting abnormal methylation of many DNAs such as that of brain derived neurotrophic factor(BDNF),5-hydroxytryptamine transporter(5-HTT)and glucocorticoid receptor(GR)that are also associated with cognitive flexibility.One latest development in neurocognitive science including epigenetics shows that Rac1,a small G protein of Rho family GTPase,plays an important role in cognitive flexibility and that its expression is reduced in the nucleus accumbens(NAc,an area related to reward in brain) of stress-induced depressed animals and deceased patients with major depressive disorder.Overall,in view of the body of evidence from neuropsychological studies supporting that cognitive abnormality,esp.the impairment of cognitive flexibility,exert a central role in the episode,maintenance and treatment of depression,the epigenetic mechanism of depression may involve the abnormality of cognitive flexibility as psychological dimension.However,there is lack of special and direct research related to this area.So,in the future study one can hypothesize that abnormally increased hyper-methylation and reduced mRNA expression of Rac1gene in addition to abnormal methylation and mRNA expression of BDNF gene,5-HTT gene,GR gene and so on relating to abnormal cognitive flexibility in depression which may be considered as certain psychobiological marker(s).Conduction of this kind of research would further contribute to understanding of mechanisms and insight to the diagnosis and therapy for depression. |
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