创伤后应激障碍的组蛋白修饰机制

创伤后应激障碍是一种具有复杂病因学的精神疾病, 多发生于个体受到重大创伤事件后。创伤后应激障碍的发生发展过程受到环境和遗传易感性的共同作用, 存在着较大的个体差异; 而表观遗传学作为一门研究多变环境因素调控基因表达的可遗传变化的学科, 近年来在创伤后应激障碍的研究中受到越来越多的重视。表观遗传机制之一——组蛋白修饰机制在创伤后应激障碍的发生中起着重要作用, 并且由于组蛋白修饰可以受到多种酶的调控, 其灵活的可逆化和精细调控为相应的药物研发提供了可能性和便利。因此, 深入探讨创伤后应激障碍的组蛋白修饰机制, 对于相关疾病的临床治疗及药物研发具有十分重要的意义。当前创伤后应激障碍的组蛋白修饰研究主要使用动物模型, 临床研究较少; 组蛋白的类型则主要关注组蛋白H3和H4乙酰化; 此外, 同以往的研究结果一致, 组蛋白修饰水平的变化主要发生在前额叶、海马体和杏仁核区域, 参与免疫系统、血清素系统和神经肽Y能系统等相关通路的调节。当前PTSD组蛋白修饰的研究结果间还存在较大的异质性, 未来的研究应采用更加一致和实用的分析和报道方法, 以最大限度地发挥研究的影响。     

应激对兴奋性突触传递的影响及其分子机制

应激与抑郁症、心血管疾病及肿瘤等重大疾病的发生有着密切关系。前额叶皮层和海马是调控应激反应的重要组织,也是应激作用的靶器官。兴奋性突触传递是大脑功能活动的重要基础,应激通过改变递质的释放和代谢及受体的转运和表达,影响突触传递功能。包括表观遗传在内的多种细胞内信号通路参与了应激的作用机制。揭示这些信号通路可为研发治疗应激相关疾病的药物提供潜在的靶点。     

亲代孕前成瘾药物暴露对子代行为的影响及其表观遗传机制

孕前成瘾药物暴露不仅危害使用者的身体健康,而且会对子代的生理行为造成影响,近年来研究发现表观遗传机制在其中发挥重要作用。孕前成瘾药物暴露会对子代的成瘾易感性和焦虑样行为造成影响,引起子代的抑郁样行为和认知受损。这些现象可能是成瘾药物通过引起亲代生殖细胞内表观遗传修饰变化所致,其中包括印记基因、神经递质系统、BDNF三个方面的表观遗传修饰变化。此外,未来除了加强以上三个方面基因的研究,也需要增加其他方面基因的研究,以及寻找能预测子代异常行为的表观遗传生物标志物。     

早期经历影响个体成年后行为的表观遗传学机制

既往研究已证实早期经历与个体成年后的行为密切相关,然而早期经历对个体成年后的行为产生长期影响的分子生物机制并不清楚。近年来越来越多的研究表明表观遗传因素在早期经历调控成年个体行为中发挥了重要功能。表观遗传是研究没有DNA序列变化,但是可遗传和可逆转的基因组功能的调控。本文试图从早期经历参与调控个体成年后行为表现以及基因表达的相关表观遗传学修饰进行综述。     

DNA表观遗传修饰在药物成瘾记忆中的作用及机制

DNA表观遗传修饰主要包括DNA甲基转移酶介导的DNA甲基化和10-11易位酶介导的DNA去甲基化。这两种表观遗传修饰都可以响应环境刺激,调控基因表达,引起神经功能和行为的改变。已有大量研究表明DNA甲基化是调控成瘾记忆的重要机制之一,近年来也发现DNA去甲基化参与调控恐惧记忆及成瘾行为,提示DNA表观遗传修饰在成瘾记忆中的作用需要重新评估。本文将重点讨论DNA甲基化和去甲基化可能共同调控成瘾记忆,探讨其调控机制,并试图提出可深入的研究展望。     

抑郁遗传效应的发展动态性

抑郁的遗传效应存在发展动态性。一方面,在发展过程中,抑郁的遗传率会发生改变,抑郁的风险基因及其与环境的交互作用模式也存在动态变化。另一方面,遗传因素会影响抑郁的发展变化模式。通过梳理既有相关研究,本文从生理成熟因素、表观遗传和发展级联效应三方面分析抑郁遗传效应发展动态性的原因。未来研究应区分重要发展阶段,增加脑功能、性激素、神经生物蛋白以及表观遗传等指标考察抑郁遗传效应的变化模式及其发生机制。     

早期应激对抑郁相关行为及神经内分泌反应的长期影响

临床研究发现,早期创伤性经历是导致成年抑郁症易感性增加的高风险因素之一。但早期应激通过何种途径对抑郁发病产生长期的影响,目前尚不清楚。本文综述了近年来有关的实验动物研究,从早期应激的动物模型建立、早期应激对成年动物抑郁相关行为及神经内分泌反应的长期影响等方面进行了系统论述和分析,进而提出了早期应激并不影响动物的本能行为,但早期应激影响与行为动机和应激应对等认知相关的行为的观点,进一步论证了早期应激是通过增加个体潜在的易患病素质对抑郁症发病产生影响     

多巴胺相关基因甲基化、家庭环境与创造力的关系

“遗传与环境”的争论一直是创造力研究的核心问题, 但目前对于环境以及遗传与环境交互作用对创造力影响的分子生物机制还未有研究涉及。近年来, 随着表观遗传学的兴起, 揭示影响心理行为的表观遗传机制现已成为心理学研究的热点。作为环境与基因组之间的纽带, 表观遗传学研究为揭示环境以及遗传与环境交互作用对创造力影响的分子生物机制提供了机遇。本研究以多巴胺相关基因、家庭环境以及两者对于创造力的交互作用为切入点, 对影响创造力的表观遗传机制进行考察, 并在此基础之上, 对环境以及遗传与环境交互作用对创造力影响的分子生物机制进行探索。具体研究内容包括：(1)通过对多巴胺相关基因甲基化模式与创造力关系的系统考察, 筛选出甲基化模式与创造力有关的基因; (2)对筛选出的基因, 进一步考察其甲基化模式在家庭环境及其遗传多态性与家庭环境交互作用对创造力影响中的中介作用。本研究有助于揭示创造力的表观遗传机制, 深化关于遗传与环境对创造力影响的作用机制的理解。     

心理社会应激的免疫反应规律与机制

心理社会应激会引起免疫系统发生免疫防御、免疫自稳和免疫监视方面的功能变化, 并随着应激刺激的时间和强度的变化而发生着异常与正常之间的动态转变。其机制与遗传、神经内分泌、自由基代谢和肠道菌群变化等生物学因素相关, 且小胶质细胞可能在其中起着重要的中介作用。诸多的生物学因素与年龄、性别和经济地位等人口学因素共同决定着心理社会应激的免疫反应发生发展。在其干预中, 运动疗法中的体育锻炼是极为值得重视的一种手段。     

不同应激范式对大鼠行为和脑神经颗粒素含量的影响

为探讨慢性情绪应激、生理应激对大鼠旷场行为和脑神经颗粒素（Neurogranin,NG）含量的不同作用,以及NG含量变化与应激性行为效应之间的相互关系。分别以不确定性空瓶刺激和饮水剥夺,建立情绪应激和生理应激动物模型。将40只雄性SD大鼠随机分为情绪应激组（ES）、生理应激组（PS）、定时饮水组（C1）和正常对照组（C2）（n=10）。以旷场行为任务来评定大鼠应激后的行为变化,Western blotting方法测定海马和前脑皮层中的NG含量。结果表明：应激后四组大鼠海马的NG含量差异无显著性;ES组前脑皮层的NG含量低于C2组,差异具有显著性,p<0.01;PS组的前脑皮层NG含量也下降,但与C2组相比差异无显著性; 应激后ES组、PS组修饰行为多于C2组,差异具有显著性,分别为p<0.01,p<0.05;前脑皮层NG含量与修饰行为之间的相关达显著水平。提示慢性情绪和生理应激均能导致前脑皮层NG含量下降,修饰行为增加,情绪应激作用更显著。修饰行为可能是反映情绪状态的较敏感行为指标,前脑皮层NG水平可能是预测情绪应激所致焦虑或抑郁行为的较敏感生物学指标。     

Affective Processing and Emotion Regulation in Dysphoria and Depression: Cognitive Biases and Deficits in Cognitive Control

In this article, we take a closer look at the cognitive processing of emotional material in dysphoria and depression and link cognitive biases and deficits to individual differences in emotion regulation, an important risk factor for depression. Specifically, we propose that cognitive biases are associated with individual differences in the initial appraisal and reappraisal of emotion‐eliciting events. In addition, deficits in cognitive control result in prolonged processing of negative, goal‐irrelevant aspects of information as well as in decreased accessibility of mood‐incongruent material. These deficits further affect people’s ability to regulate negative affect by setting the stage for ruminative responses and by interfering with the use of reappraisal after the onset of an emotional response. This article provides a brief summary of findings that support these propositions and outlines implications for future research on the relation among affective processing, cognitive control, and emotion regulation in dysphoria and depression.     

Preadolescent Clues to Understanding Depression in Girls

Between the ages of 10 and 15, increases in depression among girls result in a rate that is twice as high as the rate of depression in boys. This sex difference remains throughout early and middle adulthood. Prior to early adolescence, there is essentially no sex difference in the rate of depression. The aim of the present review is to examine whether the preadolescent period is a time during which precursors to depression in girls can be identified. First, existing areas of research on explaining sex differences in depression, including cognitive and affiliative style and the socialization of emotion, are reviewed. Second, the hypothesis that for some girls, preadolescent precursors to depression take the form of excessive empathy, compliance and regulation of negative emotions is articulated. Third, ways of building on existing models by including the proposed preadolescent precursors are proposed. Finally, approaches to testing the hypotheses that individual differences in these domains during preadolescence may explain later individual differences in adolescent onset depression are explored.     

Life Stress and Major Depression

ABSTRACT— People have long believed that adversity and stress contribute to emotional problems in general and to depression in particular. A considerable body of research has supported this intuition, documenting a consistent association between major stressful life events and the onset of clinical depression. However, most individuals under stress do not become depressed, sometimes depression develops without prior stress, and distinguishing psychological distress from major depression can be diagnostically challenging. In varying forms and degrees, life stress may play multiple roles in relation to major depression. In this article, we outline the opportunities and obstacles associated with conceptualizing depression from a life-stress perspective and discuss the implications for future research.     

Developments in Genetic and Epigenetic Data Protection in Behavioral and Mental Health Spaces

The legal system has been preparing for an explosion of epigenetic issues in public health, environmental regulation and litigation. So far, this explosion has been muted, and for now epigenetic data protection merely seems to be “enjoying” the same technological and legal challenges experienced by other clinical and research data. However, three areas of development suggest where epigenetic data protection may prove problematic. This article examines these three issues, noting the rapid expansion of research based on EMR-sourced clinical data, the large number of data protection models that can apply to genetic data (including point-of-use prohibitions on discrimination and confidentiality), and the increasing and controversial dangers of deidentified information being reidentified. Copyright © 2015 John Wiley & Sons, Ltd.     

Clinical risk factors for the generation of life events in major depression.

This study examines the relationship of anxiety disorder and dysthymia comorbidity to the generation of life events prior to major depression episode onset in a cross-sectional community sample of 76 women. Those with comorbid anxiety and dysthymia experienced higher rates of events that were at least partly dependent on their own behavior but did not differ from those without these clinical risk factors on independent life events outside of their control. This relationship remained significant even after controlling for overall severity of depression and demographic covariates. The implications of these results for understanding the increased rates of major depression onset and recurrence among those with comorbid anxiety and dysthymia are discussed as avenues of future research.     

青少年抑郁及其自动情绪调节的研究概述

本文旨在梳理近年来国内外青少年抑郁及其自动情绪调节在相关研究领域的研究成果,以进一步促进青少年抑郁的自动情绪调节研究。首先,阐明了青少年脑发展与抑郁之间的关系,并概括了三种青少年抑郁模型。然后,澄清了自动情绪调节的内涵和经典范式,而且从时间和空间方面,总结了青少年抑郁的自动情绪调节的神经机制的相关文献。最后,未来要加强功能连接研究,采用经颅直流电刺激(t DCS)、重复经颅磁刺激(r TMS)技术开展干预研究。     

Patterns of Adolescent Depression to Age 20: The Role of Maternal Depression and Youth Interpersonal Dysfunction

Considerable research has focused on youth depression, but further information is needed to characterize different patterns of onset and recurrence during adolescence. Four outcome groups by age 20 were defined (early onset-recurrent, early-onset-desisting, later-onset, never depressed) and compared on three variables predictive of youth depression: gender, maternal depression, and interpersonal functioning. Further, it was hypothesized that the association between maternal depression and youth depression between 15 and 20 is mediated by early-onset depression and interpersonal dysfunction by age 15. Eight hundred sixteen community youth selected for depression risk by history (or absence) of maternal depression were interviewed at age 15, and 699 were included in the 5-year follow-up. Controlling for gender, early onset and interpersonal dysfunction mediated the link between maternal depression and late adolescent major depression. Different patterns for males and females were observed. For males maternal depression’s effect was mediated by early onset but not interpersonal difficulties, while for females maternal depression’s effect was mediated by interpersonal difficulties but not early onset. Maternal depression did not predict first onset of major depression after age 15. The results suggest the need for targeting the impact of maternal depression’s gender-specific effects on early youth outcomes, and also highlight the different patterns of major depression in youth and their likely implications for future course of depression.