表观遗传修饰在应激诱发抑郁症中的作用

应激可以对个体的生理和行为产生负面影响, 甚至导致抑郁症, 但病因机制尚不清楚。近年来许多研究发现应激导致的表观遗传修饰变化影响抑郁症的发生。表观遗传是指DNA序列不发生变化, 但基因表达却发生了可遗传的改变。应激引起的HPA轴、单胺类递质、BDNF三个方面的表观遗传修饰的变化, 在抑郁症发生中发挥重要作用。最后提出了目前表观遗传机制研究的局限性和未来研究热点。     

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。     

成瘾相关记忆的表观遗传学机制 ——药物成瘾研究的新视角

成瘾相关记忆长期性的脑机制一直是药物成瘾研究领域的难点与热点,该文简要介绍了成瘾记忆长期性分子机制的研究脉络,提示表观遗传学修饰可能是研究药物成瘾的新视角。成瘾药物可以调节染色体不同亚型组蛋白乙酰化水平,不同基因DNA的甲基化程度从而改变染色体的空间结构,进而调节基因的表达导致成瘾,特别是DNA甲基化改变的相对的稳定性可能是成瘾记忆长期存在的分子基础。记忆再巩固过程中学习记忆相关脑区的记忆促进基因与记忆抑制基因的表观遗传学改变可能是未来研究的新趋势     

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。     

非药物成瘾的遗传学和神经生物学机制研究述评

非药物成瘾又称“非物质相关性成瘾”或“行为成瘾”。特征性表现包括对成瘾对象的渴望、受损的冲动控制、对成瘾对象的耐受、撤退反应和高复发率等。目前发现的非药物成瘾类型包括病理性赌博、网络成瘾、购物成瘾、游戏成瘾、性瘾以及贪食等。非药物成瘾与药物成瘾在症状学上表现出很高的相似性且具有较高的共病率, 提示二者之间可能存在着共同的发病机制。从遗传学和神经生物学的角度探讨非药物成瘾的机制具有重要的理论价值和临床应用价值。家庭研究和双生子研究发现, 男性的病理性赌博和贪食障碍具有中度以上的遗传度。分子遗传学研究发现, 单胺能神经递质相关基因, 如5-羟色胺转运体基因、多巴胺受体基因和单胺氧化酶A基因等, 与非药物成瘾有关。神经影像学研究发现, 非药物成瘾者脑内负责奖赏,线索加工和冲动控制的神经通路活动性异于正常对照。未来研究需要进一步从多个角度入手, 探讨非药物成瘾与药物成瘾的共性和特性。     

药物成瘾的易感性生物标记：从神经认知到分子遗传的证据

药物成瘾作为一种慢性复发性的脑疾病,具有从偶然性用药、规律性用药到强迫性用药的渐进式发展特征。研究提示,药物成瘾存在潜在的个体易感性机制,即在成瘾发生过程中不同个体接触药物后的成瘾风险并不相同,探索药物成瘾的神经生物标记是揭示成瘾易感性机制的重要途径。近十多年来,关于成瘾易感性标记的研究不断积聚。文章从神经认知、神经影像及脑电生理、分子遗传等层面梳理与药物成瘾生物标记有关的证据,试图在基因-大脑-心理-行为的理论框架下,对成瘾的发生发展机制进行综合阐释,期望为未来研究在探索药物成瘾的候选神经生物标记、寻找临床干预试验的精准靶点等方面提供更多理论参考。     

药物成瘾者的感觉寻求人格特征

药物成瘾具有明显的心理成因,其中,成瘾者的人格特点,特别是感觉寻求人格特质,是导致药物成瘾的重要病原性因素。中脑边缘体多巴胺系统是感觉寻求行为与药物成瘾行为共同的脑奖赏系统,而多巴胺受体的遗传表达至少部分建立在个体执行新奇寻求和药物成瘾的行为上。感觉寻求特质对药物成瘾的作用受环境因素（父母,同伴）调节。文章也评述了感觉寻求相关研究所采用的测量工具。     

易感人格的工作记忆特征对药物成瘾的调节机制

药物成瘾是指持续使用成瘾药物, 出现耐受性和戒断症状并严重阻碍正常社会功能的精神疾病。工作记忆在调节药物成瘾行为中扮演了中心角色：在神经易感性和易感人格特质基础上, 低工作记忆容量导致危险决策和去抑制性, 进而影响寻求药物和复吸行为。目前的研究基于已经产生成瘾的个体, 无法区别神经易感性、人格特质以及工作记忆缺陷是药物成瘾的原因还是结果; 而且, 仅从认知角度研究药物成瘾的原因, 会忽视该行为受多个因素影响的事实。     

药物成瘾诱导相关大脑核团功能和行为改变的DNA甲基化机制

药物成瘾会导致相关神经环路的结构和功能长期改变.大量新的研究证据表明,在DNA序列不变的情况下,药物成瘾可通过影响不同亚型DNA甲基转移酶(DNMTs)的表达,使脑内多个相关核团发生DNA甲基化以及基因表达的改变,进而导致神经元功能的可塑性变化.因此,DNA甲基化被视作导致成瘾行为长期存在的可能机制之一.结合近几年来的重要发现,本文将重点讨论相关脑区的DNA甲基化在成瘾行为发生发展过程中的作用,以及成瘾药物影响DNA甲基化水平的可能机制,并试图提出可深入的研究展望.     

坚毅力的代际传递:父母教养方式的中介作用

从代际传递的角度,考察父母坚毅力和子女坚毅力的关系,同时检验教养方式在二者之间的中介作用。方法：采用问卷法对北京市三所中学初一、初二年级共302名青少年及其父母的数据进行调查,研究工具采用坚毅力问卷（Grit-Scales）、父母教养方式问卷（PBI）。结果：（1）父亲和母亲的坚毅力总分及两个维度兴趣一致性、坚持努力均可正向预测青少年坚毅力总分及各维度;（2）父亲教养方式的关爱维度在父亲坚毅力与孩子坚毅力之间起中介作用,母亲教养方式的关爱维度在母亲坚毅力与孩子坚毅力之间起中介作用。结论：坚毅力存在代际之间的传递,并且教养方式的关爱维度在代际传递过程中起部分中介作用。     

胚胎期可卡因、吗啡暴露影响子代成瘾相关行为的神经发育机制

孕期使用毒品可影响胎儿大脑的正常发育,导致脑内神经递质系统异常以及行为的改变.近年来不断有研究证据提示,胚胎期接触可卡因、吗啡等成瘾药物,可以影响神经细胞的增殖、迁移或凋亡等发育过程,使中脑皮层边缘系统中多巴胺、GABA、谷氨酸等神经元形态、受体功能以及突触可塑性发生改变,从而导致子代的学习记忆和成瘾易感性等行为异常.本文将从行为、神经发育、递质系统以及脑功能等层面归纳胚胎期用药对成瘾相关行为影响机制的重要研究进展,并试图提出可能的研究展望.     

Controlling the uncontrollable. Self-regulation and the dynamics of addiction

The multidisciplinary research on addictions generally promotes the assumption that addictive behavior is caused and maintained by the external psychoactive substance, which accordingly is considered to be ‘addictive in itself’. The present article challenges this widespread assumption by engaging in a detailed examination of the psychodynamic structures of addiction. Tracing addictive behavior back to problems in affect regulation, the article discusses the object, motivation, dynamics, and developmental origins of addiction. Linking the problem with the topic of transitional object relations, the article eventually argues that addictive behavior amounts to a desperate pursuit for self-control. The tragedy of the addict is that he or she only manages to replace one sense of uncontrollability with another.     

Psychopathologische und kognitive Veränderungen unter Rauschdrogen – Relevanz für die strafrechtliche Beurteilung

To properly estimate the effect of drug consumption in the context of criminal responsibility it is important to understand the nature and course of psychopathological alterations whilst under the influence of each particular drug. In addition, it is important to know about the addictive potential of the different street drugs and the pattern of withdrawal symptoms. In this review we are summarizing the existing evidence for the most widely used illegal drugs. We have considered both anecdotal evidence from and systematic surveys within the illegal drug scene as well as the results of experimental research with healthy volunteers. Finally, we evaluate how acute or subacute psychopathological drug effects effect the degree of criminal responsibility.     

Examining the Social Context of Bullying Behaviors in Early Adolescence

Familial and adult influences, peer relations, and distal contextual factors were tested as correlates of a continuous measure of bullying behavior within a sample of 558 middle school students. Only 19.5% of the sample reported exhibiting no bullying behavior in the past 30 days. Parental physical discipline, time spent without adult supervision, negative peer influences, and neighborhood safety concerns were each positively associated with bullying behavior. In contrast, positive adult role models were associated with less bullying behavior. Results suggest that counselors should focus prevention and intervention efforts on the risk factors within the larger social context of an adolescent's life.     

A genetically informed study of marital instability and its association with offspring psychopathology

Parental divorce is associated with a number of emotional and behavioral problems in young-adult offspring, but theoretical and empirical considerations suggest that the relation may be partially or fully accounted for by passive gene-environment correlation or environmental selection characteristics. The current study used the Children of Twins Design to explore whether shared environmental or genetic factors confound the relationship between parental marital instability and measures of psychopathology. Comparisons of the offspring of adult twins in Australia on 3 factors of abnormal behavior, including drug and alcohol, behavioral, and internalizing problems, suggest that environmental influences associated with divorce account for the higher rates of psychopathology. The results are consistent with a causal connection between marital instability and psychopathology in young-adult offspring.     

Addictions and the Quest to Control the Object

Most patients come into psychoanalytic treatment engaged in some form of repetitive, destructive behavior that is an externalization or projection of their internal struggles. One form of this object relational acting-out is the addictions, be they to alcohol, gambling, drugs, sex, procrastination, or other variations. The patient's experience is a "must do-can't stop" one that leaves them both desperate and relieved. Patients come to us wanting help in refraining from these addictive patterns. Sometimes, they are attending a 12-step program or are in a day treatment recovery program but need additional assistance in remaining free from their addictive behaviors. Others seek out psychoanalytic treatment while still involved in their addiction, but wish to stop the behavior and build a more positive plan for their lives. This paper examines the deeper object relational issues that lie behind the addictive process. The transference is often colored by acting-out, by sadomasochistic dynamics, by projective identification, and by fantasies of persecution and loss. Case material is used to explore these specific problems as well as the patient's general difficulties with paranoid-schizoid and depressive functioning.     

What is the role of mothers in the acquisition of termite-fishing behaviors in wild chimpanzees (Pan troglodytes schweinfurthii)?

This paper explores the role of maternal influences on the acquisition of a tool-using task in wild chimpanzees (Pan troglodytes schweinfurthii) in order to build on and complement previous work done in captivity. Young chimpanzees show a long period of offspring dependency on mothers and it is during this period that offspring learn several important skills, especially how to and on what to forage. At Gombe National Park, one skill that is acquired during dependency is termite-fishing, a complex behavior that involves inserting a tool made from the surrounding vegetation into a termite mound and extracting the termites that attack and cling to the tool. All chimpanzees observed at Gombe have acquired the termite-fishing skill by the age of 5.5 years. Since the mother is the primary source of information throughout this time period, I investigated the influence of mothers' individual termite-fishing characteristics on their offsprings' speed of acquisition and proficiency at the skill once acquired. Mother's time spent alone or with maternal family members, which is highly correlated to time spent termite-fishing, was positively correlated to offspring's acquisition of critical elements of the skill. I also investigated the specific types of social interactions that occur between mothers and offspring at the termite mound and found that mothers are highly tolerant to offspring, even when the behavior of the offspring may disrupt the termite-fishing attempt. However, no active facilitation by mothers of offsprings' attempts were observed. Electronic Supplementary Material Electronic supplementary material Supplementary material is available for this article at http://dx.doi.org/10.1007/s10071-005-0002-7 and accessible for authorised users.